Robert L. Barbieri, MD

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

All mammalian life is dependent on a continuous supply of molecular oxygen. Molecular oxygen is carried to cells by noncovalent binding to the iron moiety in the hemoglobin of red blood cells. It is utilized within cells by noncovalent binding to the iron moiety in various microsomal and mitochondrial proteins, including myoglobin and cytochromes. Consequently, to efficiently utilize molecular oxygen all mammalian life is dependent on an adequate supply of iron. Surprisingly, in an era of high technology precision medicine, many pregnant women are iron deficient, anemic, and not receiving adequate iron supplementation.

Iron deficiency is prevalent in women and pregnant women

Women often become iron deficient because of pregnancy or heavy menstrual bleeding. During pregnancy, maternal iron is provided to supply the needs of the fetus and placenta. Additional iron is needed to expand maternal red blood cell volume and replace iron lost due to bleeding at delivery. In the National Health and Nutrition Examination Survey (NHANES) of 1988–1994, 11% of women aged 16 to 49 years were iron deficient. By contrast, less than 1% of men aged 16 to 49 years were iron deficient.¹

In a NHANES study from 1999–2006, risk factors for iron deficiency included multiparity, current pregnancy, and regular menstrual cycles. Use of hormonal contraception reduced the rate of iron deficiency.² Using the same data, the prevalences of iron deficiency during the first, second, and third trimesters of pregnancy were reported to be 7%, 14%, and 30%, respectively.³ In addition to pregnancy and menstrual bleeding there are many other medical problems that may contribute to iron deficiency, including Helicobacter pylori (H pylori) infection, gastritis, celiac disease, and bariatric surgery.

Iron deficiency anemia may be associated with adverse pregnancy outcomes

In a retrospective study of 75,660 singleton pregnancies, 7,977 women were diagnosed with iron deficiency anemia when they were admitted for delivery. Compared with pregnant women without iron deficiency, the presence of iron deficiency increased the risk of:

• blood transfusion (odds ratio [OR], 5.48; 95% confidence interval [CI], 4.57–6.58)
• preterm delivery (OR, 1.54; 95% CI, 1.36–1.76)
• cesarean delivery (OR, 1.30; 95% CI, 1.13–1.49)
• 5-minute Apgar score <7 (OR, 2.21; 95% CI, 1.84–2.64)
• intensive care unit (ICU) admission (OR, 1.28; 95% CI, 1.20–1.39).⁴

In a systematic review and meta-analysis of 26 studies, maternal anemia (mostly iron deficiency anemia) was associated with a higher risk of low birth weight (relative risk [RR], 1.31; 95% CI, 1.13–1.51), preterm birth (RR, 1.63; 95% CI, 1.33–2.01), perinatal mortality (RR, 1.51; 95% CI, 1.30–1.76), and neonatal mortality (RR, 2.72; 95% CI, 1.19–6.25).⁵

In a clinical trial, pregnant women were randomly assigned to receive folic acid alone; folic acid plus iron supplements; or 15 vitamins and minerals, including folic acid and iron. At delivery, women in the iron-folic acid and the 15 vitamin and minerals groups had higher hemoglobin concentrations than the folic acid monotherapy group. Among 4,697 live births, women in the iron-folic acid group had significantly fewer preterm births (<34 weeks’ gestation) than the folic acid group (RR, 0.50; 95% CI, 0.27–0.94; P = .031).⁶ Data from additional randomized trials are needed to further clarify the effect of iron supplementation on obstetric outcomes.

Related article:
Treating polycystic ovary syndrome: Start using dual medical therapy

The diagnosis of iron deficiency is optimized by measuring serum ferritin

Serum ferritin measurement is an excellent test of iron deficiency. We recommend that all pregnant women have serum ferritin measured at the first prenatal visit and at the beginning of the third trimester to assess maternal iron stores. In pregnancy, the Centers for Disease Control and Prevention and the World Health Organization define anemia as a hemoglobin level of less than 11 g/dL or hematocrit less than 33% in the first and third trimesters. If a pregnant woman is not anemic, a serum ferritin level less than 15 ng/mL indicates iron deficiency.⁷ Some experts believe that in pregnant women who are not anemic, a serum ferritin level between 15 and 30 ng/mL may also indicate iron deficiency.⁸ If the pregnant woman is anemic and does not have another cause of the anemia, a serum ferritin level less than 40 ng/mL is indicative of iron deficiency.⁷

Ferritin is an acute phase reactant and levels may be falsely elevated due to chronic or acute inflammation, liver disease, renal failure, metabolic syndrome, or malignancy. Some women with iron deficiency due to bariatric surgery or malabsorption also have vitamin B12 and, less commonly, folate deficiency, which can contribute to the development of anemia (see “Diagnosis of anemia, iron deficiency, and iron deficiency anemia in pregnancy.”) Clinicians are often advised that a mean corpuscular volume demonstrating microcytosis is the “best test” to assess a patient for iron deficiency. However, reduced iron availability and low ferritin precede microcytosis. Hence microcytosis is a lagging measure and iron deficiency is diagnosed at an earlier stage by ferritin.

Dietary iron

Iron in food is present in heme (meat, poultry, fish) and non-heme forms (grains, plant food, supplements). Heme iron is better absorbed than non-heme iron. Foods rich in non-heme iron include spinach, lentils, prune juice, dried prunes, and fortified cereals. Absorption of non-heme iron can be increased by vitamin C or vitamin C–rich foods (broccoli, bell peppers, cantaloupe, grapefruit, oranges, strawberries, and tomatoes). Absorption of non-heme iron is reduced by consumption of dairy products, coffee, tea, and chocolate.

Oral iron treatment

Oral iron is an effective treatment for iron deficiency^9,10 and is inexpensive, safe, and widely available. The CDC recommends that all pregnant women take a 30 mg/day iron supplement, unless they have hemochromatosis.¹¹ For women with a low ferritin level and anemia, iron supplementation should be increased to 30 to 120 mg daily.¹¹ Not all prenatal vitamins contain iron; those that do typically contain 17 to 28 mg of elemental iron per dose.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy.¹² Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.¹³

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. Greater doses do not result in more iron absorption and are associated with more side effects.^14,15 (See “Start using alternate-day oral iron dosing, and stop using daily iron dosing.”)

Oral iron should not be taken in close approximation to the consumption of milk, cereals, tea, coffee, eggs, or calcium supplements. The absorption of oral iron is enhanced by the consumption of orange juice or 250 mg of vitamin C. Gastrointestinal side effects include nausea, flatulence, constipation, diarrhea, epigastric distress, and vomiting. If gastrointestinal side effects occur, interventions that might improve tolerability include: reduce the dose of iron or administer intermittently or use a low dose of oral iron, where dosing can be more easily titrated.

We re-check ferritin and hemoglobin levels 2 to 4 weeks after initiation of oral iron therapy and expect to see a hemoglobin rise of 1 g/dL if the therapy is effective.

Intravenous iron treatment

For women with iron deficiency anemia who cannot tolerate oral iron or in whom oral iron treatment has not resolved their anemia, intravenous (IV) iron treatment may be an optimal approach. Women in the third trimester of pregnancy with iron deficiency anemia have very little time to consume sufficient quantities of oral iron in food and supplements to restore their deficiency and reverse their anemia. Consequently, treatment with IV iron may be especially appropriate for women with iron deficiency anemia in the third trimester of pregnancy. Prior gastric surgery, including gastric bypass, results in reduced gastric acid production and causes severe impairment of intestinal absorption of iron. Patients with malabsorption syndromes, including celiac disease, also may have limited absorption of oral iron. These populations of pregnant women may particularly benefit from the use of IV iron. In pregnant women IV iron has fewer gastrointestinal side effects than oral iron.¹⁶

Many severely iron deficient patients need 1,000 mg of iron to resolve their deficit. In order to avoid giving multiple standard doses (200 mg per infusion, with 5 infusions over many days), some centers have explored the use of 1 large dose of IV iron (1,000 mg of low molecular weight iron dextran administered over 1 hour) (INFeD, Watson Pharma).^17–19 This is not a regimen that is specifically approved by the US Food and Drug Administration. An alternative regimen is to administer 750 mg of ferrous carboxymaltose (Injectafer, Luitpold Pharmaceuticals) over 15 minutes, which is an FDA-approved regimen.¹⁸ Many hematologists prefer to administer multiple smaller doses of iron. For example, in our practice, pregnant women are commonly treated with IV iron sucrose (300 mg) every 2 weeks for 3 doses. To increase access of pregnant women to IV iron treatment, obstetricians need to work with hematologists and infusion centers to create collaborative protocols to expeditiously treat women in the third trimester.

There is an epidemic of iron deficiency in pregnant women in the United States. In an era of high technology medicine, it is surprising that iron deficiency remains an unsolved obstetric problem in our country.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Obstetrician-gynecologists are deeply committed to reducing maternal mortality and severe morbidity. Hypertensive diseases of pregnancy, including preeclampsia and eclampsia, are important contributors to both maternal mortality and severe morbidity. Among US live births from 2011–2013 there were 1,078 pregnancy-related maternal deaths, and 10% were attributed to preeclampsia or eclampsia.¹ Hypertensive disease of pregnancy is also a major cause of severe maternal morbidity, with an increased risk of acute renal failure, respiratory failure, and cerebrovascular events.² Preeclampsia is associated with a 4-fold increased risk of thrombocytopenia and coagulopathy and a 2-fold increased risk of postpartum hemorrhage.³

Severe hypertension is defined as a systolic blood pressure (BP) ≥160 mm Hg or a diastolic BP ≥110 mm Hg on 2 measurements within 15 minutes.^4,5 Severe hypertensive disease of pregnancy is a common clinical problem in obstetrics, requiring clinicians to respond expeditiously and decisively to minimize adverse maternal outcomes. Following the identification of severe hypertension, a diagnosis and management plan should be initiated within 30 to 60 minutes.⁴ Some experts recommend that treatment be initiated within 15 minutes of identifying severe hypertension in a pregnant woman.⁶

The American College of Obstetricians and Gynecologists recommends that obstetric programs adopt standardized guidelines for the management of women with preeclampsia or eclampsia.⁴ The National Partnership for Maternal Safety recommends that all obstetric programs develop care bundles to respond to severe hypertension.⁵ Key points in managing severe hypertension are summarized below.

Related article:
2017 Update on obstetrics: Preeclampsia prevention

1. Expeditiously initiate treatment of severe hypertension…

…with intravenous (IV) labetalol (administered as 20 mg/40 mg/80 mg sequential doses as needed) or hydralazine (administered as 10 mg/10 mg/20 mg/40 mg sequential doses as needed). Our preferred agent is labetalol, administered as a 20-mg IV infusion over 2 minutes. If the patient’s BP remains elevated 10 min after the initial dose, administer labetalol 40 mg as an IV infusion over 2 min. If her BP remains elevated 10 min after this dose, administer 80 mg of labetalol. If the BP continues to be elevated, hydralazine treatment can be initiated as described below.

Occasionally there are national shortages of labetalol or a patient has a low heart rate or contraindication such as heart disease or asthma prohibiting its use. If labetalol is not available, we use hydralazine administered as a 10-mg IV bolus over 2 min. If the BP remains elevated, every 20 min, an escalating dose of hydralazine is administered, first by repeating the 10-mg dose, then administering 20 mg, and finally 40 mg.

For women without IV access, we use oral nifedipine 10 mg to control hypertension only while awaiting the placement of an IV. If BP remains elevated after 30 min, a second dose of oral nifedipine 20 mg can be given with a plan to transition to IV agents as soon as possible. The risks of maternal tachycardia or overshoot hypotension with immediate release oral nifedipine limit its use in our clinical practice to this circumstance.

Once the BP is controlled, start maintenance oral hypertension therapy. Our first-line agent is labetalol 200 mg twice per day with a maximum dose of 800 mg 3 times daily (2,400 mg maximal daily dose).

2. Initiate treatment with magnesium sulfate

If the patient’s BP is ≥160/110 mm Hg or if her BP is ≥140/90 mm Hg with coexisting symptoms of severe preeclampsia (for example a severe headache), initiate magnesium sulfate treatment. A standard regimen is magnesium sulfate 4 to 6 g administered as an IV bolus over 20 min followed by the IV infusion of 2 g per hour. In our clinical opinion, if you plan on initiating IV antihypertensive treatment for severe hypertension you also should strongly consider starting magnesium sulfate to reduce the risk of an eclamptic seizure.

We also start magnesium sulfate therapy for women with severe hypertension and clinical symptoms or laboratory signs of preeclampsia even in the absence of proteinuria. Approximately 2% of women with preeclampsia will develop an eclamptic seizure and magnesium sulfate treatment significantly reduces the risk of seizure and may also reduce maternal mortality.^7,8

Magnesium sulfate is contra-indicated in women with myasthenia gravis. In women with renal dysfunction, the loading dose can be given, but the continuous magnesium sulfate infusion should not be initiated until serum magnesium levels are assessed.

3. Consider administering maternal betamethasone

Treatment with betamethasone advances fetal maturation if the pregnancy is preterm (for example, <34 weeks of gestation). A major cause of neonatal morbidity and mortality for pregnancy complicated by severe hypertensive disease is premature delivery. Maternal glucocorticoid treatment reduces the risk of neonatal morbidity and mortality if preterm delivery is anticipated. However, do not delay delivery for antenatal corticosteroids for women with severe and persistent hypertension or symptoms of preeclampsia that do not resolve following treatment.

We also consider women with eclampsia, placental abruption, pulmonary edema, or severe laboratory derangements too unstable to delay delivery for 48 hours to achieve the maximum benefit of steroid treatment. If antenatal corticosteroids are administered in the late preterm period between 34 0/7 weeks and 36 6/7 weeks of gestation, obstetric management should not be altered and delivery should not be delayed.⁹

Related article:
Start offering antenatal corticosteroids to women delivering between 34 0/7 and 36 6/7 weeks of gestation to improve newborn outcomes

4. Preeclampsia plus a severe headache is a toxic combination

For patients with this constellation either have a plan for delivery or keep them under close surveillance. Occasionally a woman >20 weeks pregnant with new onset hypertension and a headache is seen in an emergency department and is not assessed for proteinuria or other preeclampsia laboratory abnormalities. If the woman is diagnosed as having a migraine or tension headache and discharged home with a headache medicine they are at high risk for serious morbidity, including stroke.

Read about preeclampsia and thrombocytopenia, HELLP syndrome, more.

5. Preeclampsia plus thrombocytopenia complicates anesthesia options

If the platelet count falls too low (for instance, <70,000 platelets per µL), many anesthesiologists will not provide a regional anesthetic for delivery because of the risk of peridural bleeding. In addition, a low platelet count (<50,000 platelets per µL) significantly increases the risk of obstetric hemorrhage. Transfer of the patient to an obstetrics unit with a full-service blood bank capable of supporting multiple platelet transfusions may be warranted.

6. Preeclampsia plus dyspnea or chest pain increases the risk of severe maternal morbidity

Authors of a prospective study of 2,023 women with preeclampsia reported an increase in adverse maternal outcomes when the following factors were present: early gestational age, dyspnea, chest pain, oxygen saturation of SpO₂ <93%, thrombocytopenia, elevated creatinine, or elevated aspartate transaminase concentration.¹⁰ If dyspnea is present, the patient may have pulmonary edema, pulmonary embolism, heart failure, acute asthma, or pneumonia. If the patient has chest pain the differential diagnosis includes pulmonary embolism, cardiac ischemia, cardiomyopathy, or another cardiac disease.

Consider obtaining a chest radiograph for pregnant women with dyspnea and a computed tomography pulmonary angiogram or lung scintigraphy (ventilation perfusion scan) if the chest radiograph is normal for women with chest pain.^6,11 We obtain a transthoracic echocardiogram in cases of pulmonary edema to evaluate for the possibility of peripartum cardiomyopathy.

7. HELLP syndrome

The triad of hemolysis, elevated liver enzymes, and low platelet count (HELLP) is associated with an increased risk of maternal mortality and severe morbidity.¹² In a study of 171 women with HELLP, factors that increased the risk for adverse maternal outcomes included¹²:

• aspartate aminotransferase (AST) levels >316 U/L
• alanine aminotransferase (ALT) levels >217 U/L
• total bilirubin levels >2.0 mg/dL
• lactate dehydrogenase (LDH) levels >1,290 U/L
• blood urea nitrogen test results >44 mg/dL
• platelet count <50,000 platelets per µL.

The clinical course of HELLP syndrome is characterized by progression and the potential for sudden and catastrophic deterioration. For example, some women with HELLP will suddenly develop a ruptured liver, pulmonary edema, or a stroke. The Society for Maternal-Fetal Medicine recommends against expectant management of women with HELLP syndrome.¹³

Related article:
Optimal obstetric care for women aged 40 and older

8. Delivery or expectant management?

Currently the only cure for preeclampsia is delivery. The Society for Maternal-Fetal Medicine recommends against expectant management of severe preeclampsia if certain problems occur (BOX).¹³ For women with preeclampsia who are less than 34 weeks’ gestation and do not have a contraindication to expectant management, consider transferring the patient to a tertiary maternal care center. In our practice, pregnant women with a hypertensive disorder are scheduled for an induction of labor and delivery at 37 weeks’ gestation.
 

In the United States, major obstetric causes of pregnancy-related death include sepsis, venous thromboembolism-pulmonary embolism, hemorrhage, and hypertensive disease of pregnancy. Other important causes of pregnancy-related death include cardiac disease, stroke, and pre-existing major medical disease including advanced cancer. In the United States there are approximately 17 pregnancy-related maternal deaths per 100,000 live births.¹ Obstetricians are dedicated to reducing this excessively high rate of maternal death.

Given the US maternal death rate of 1 maternity death per 5,880 live births, over the course of a 40-year career, most obstetrician-gynecologists will have 1 or 2 of their pregnant patients die. From the perspective of an individual clinician, maternal death is an extremely rare event, with 1 death during every 20 years of practice. However, from a population perspective, maternal death in the United States is all too common compared to other developed countries. We can only reduce the rate of maternal death by working in interdisciplinary teams to ensure our obstetrics units are prepared to expeditiously diagnose and treat the most common obstetric causes of death and severe morbidity.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Obstetrician-gynecologists are deeply committed to reducing maternal mortality and severe morbidity. Hypertensive diseases of pregnancy, including preeclampsia and eclampsia, are important contributors to both maternal mortality and severe morbidity. Among US live births from 2011–2013 there were 1,078 pregnancy-related maternal deaths, and 10% were attributed to preeclampsia or eclampsia.¹ Hypertensive disease of pregnancy is also a major cause of severe maternal morbidity, with an increased risk of acute renal failure, respiratory failure, and cerebrovascular events.² Preeclampsia is associated with a 4-fold increased risk of thrombocytopenia and coagulopathy and a 2-fold increased risk of postpartum hemorrhage.³

Severe hypertension is defined as a systolic blood pressure (BP) ≥160 mm Hg or a diastolic BP ≥110 mm Hg on 2 measurements within 15 minutes.^4,5 Severe hypertensive disease of pregnancy is a common clinical problem in obstetrics, requiring clinicians to respond expeditiously and decisively to minimize adverse maternal outcomes. Following the identification of severe hypertension, a diagnosis and management plan should be initiated within 30 to 60 minutes.⁴ Some experts recommend that treatment be initiated within 15 minutes of identifying severe hypertension in a pregnant woman.⁶

The American College of Obstetricians and Gynecologists recommends that obstetric programs adopt standardized guidelines for the management of women with preeclampsia or eclampsia.⁴ The National Partnership for Maternal Safety recommends that all obstetric programs develop care bundles to respond to severe hypertension.⁵ Key points in managing severe hypertension are summarized below.

Related article:
2017 Update on obstetrics: Preeclampsia prevention

1. Expeditiously initiate treatment of severe hypertension…

…with intravenous (IV) labetalol (administered as 20 mg/40 mg/80 mg sequential doses as needed) or hydralazine (administered as 10 mg/10 mg/20 mg/40 mg sequential doses as needed). Our preferred agent is labetalol, administered as a 20-mg IV infusion over 2 minutes. If the patient’s BP remains elevated 10 min after the initial dose, administer labetalol 40 mg as an IV infusion over 2 min. If her BP remains elevated 10 min after this dose, administer 80 mg of labetalol. If the BP continues to be elevated, hydralazine treatment can be initiated as described below.

Occasionally there are national shortages of labetalol or a patient has a low heart rate or contraindication such as heart disease or asthma prohibiting its use. If labetalol is not available, we use hydralazine administered as a 10-mg IV bolus over 2 min. If the BP remains elevated, every 20 min, an escalating dose of hydralazine is administered, first by repeating the 10-mg dose, then administering 20 mg, and finally 40 mg.

For women without IV access, we use oral nifedipine 10 mg to control hypertension only while awaiting the placement of an IV. If BP remains elevated after 30 min, a second dose of oral nifedipine 20 mg can be given with a plan to transition to IV agents as soon as possible. The risks of maternal tachycardia or overshoot hypotension with immediate release oral nifedipine limit its use in our clinical practice to this circumstance.

Once the BP is controlled, start maintenance oral hypertension therapy. Our first-line agent is labetalol 200 mg twice per day with a maximum dose of 800 mg 3 times daily (2,400 mg maximal daily dose).

2. Initiate treatment with magnesium sulfate

If the patient’s BP is ≥160/110 mm Hg or if her BP is ≥140/90 mm Hg with coexisting symptoms of severe preeclampsia (for example a severe headache), initiate magnesium sulfate treatment. A standard regimen is magnesium sulfate 4 to 6 g administered as an IV bolus over 20 min followed by the IV infusion of 2 g per hour. In our clinical opinion, if you plan on initiating IV antihypertensive treatment for severe hypertension you also should strongly consider starting magnesium sulfate to reduce the risk of an eclamptic seizure.

We also start magnesium sulfate therapy for women with severe hypertension and clinical symptoms or laboratory signs of preeclampsia even in the absence of proteinuria. Approximately 2% of women with preeclampsia will develop an eclamptic seizure and magnesium sulfate treatment significantly reduces the risk of seizure and may also reduce maternal mortality.^7,8

Magnesium sulfate is contra-indicated in women with myasthenia gravis. In women with renal dysfunction, the loading dose can be given, but the continuous magnesium sulfate infusion should not be initiated until serum magnesium levels are assessed.

3. Consider administering maternal betamethasone

Treatment with betamethasone advances fetal maturation if the pregnancy is preterm (for example, <34 weeks of gestation). A major cause of neonatal morbidity and mortality for pregnancy complicated by severe hypertensive disease is premature delivery. Maternal glucocorticoid treatment reduces the risk of neonatal morbidity and mortality if preterm delivery is anticipated. However, do not delay delivery for antenatal corticosteroids for women with severe and persistent hypertension or symptoms of preeclampsia that do not resolve following treatment.

We also consider women with eclampsia, placental abruption, pulmonary edema, or severe laboratory derangements too unstable to delay delivery for 48 hours to achieve the maximum benefit of steroid treatment. If antenatal corticosteroids are administered in the late preterm period between 34 0/7 weeks and 36 6/7 weeks of gestation, obstetric management should not be altered and delivery should not be delayed.⁹

Related article:
Start offering antenatal corticosteroids to women delivering between 34 0/7 and 36 6/7 weeks of gestation to improve newborn outcomes

4. Preeclampsia plus a severe headache is a toxic combination

For patients with this constellation either have a plan for delivery or keep them under close surveillance. Occasionally a woman >20 weeks pregnant with new onset hypertension and a headache is seen in an emergency department and is not assessed for proteinuria or other preeclampsia laboratory abnormalities. If the woman is diagnosed as having a migraine or tension headache and discharged home with a headache medicine they are at high risk for serious morbidity, including stroke.

Read about preeclampsia and thrombocytopenia, HELLP syndrome, more.

5. Preeclampsia plus thrombocytopenia complicates anesthesia options

If the platelet count falls too low (for instance, <70,000 platelets per µL), many anesthesiologists will not provide a regional anesthetic for delivery because of the risk of peridural bleeding. In addition, a low platelet count (<50,000 platelets per µL) significantly increases the risk of obstetric hemorrhage. Transfer of the patient to an obstetrics unit with a full-service blood bank capable of supporting multiple platelet transfusions may be warranted.

6. Preeclampsia plus dyspnea or chest pain increases the risk of severe maternal morbidity

Authors of a prospective study of 2,023 women with preeclampsia reported an increase in adverse maternal outcomes when the following factors were present: early gestational age, dyspnea, chest pain, oxygen saturation of SpO₂ <93%, thrombocytopenia, elevated creatinine, or elevated aspartate transaminase concentration.¹⁰ If dyspnea is present, the patient may have pulmonary edema, pulmonary embolism, heart failure, acute asthma, or pneumonia. If the patient has chest pain the differential diagnosis includes pulmonary embolism, cardiac ischemia, cardiomyopathy, or another cardiac disease.

Consider obtaining a chest radiograph for pregnant women with dyspnea and a computed tomography pulmonary angiogram or lung scintigraphy (ventilation perfusion scan) if the chest radiograph is normal for women with chest pain.^6,11 We obtain a transthoracic echocardiogram in cases of pulmonary edema to evaluate for the possibility of peripartum cardiomyopathy.

7. HELLP syndrome

The triad of hemolysis, elevated liver enzymes, and low platelet count (HELLP) is associated with an increased risk of maternal mortality and severe morbidity.¹² In a study of 171 women with HELLP, factors that increased the risk for adverse maternal outcomes included¹²:

• aspartate aminotransferase (AST) levels >316 U/L
• alanine aminotransferase (ALT) levels >217 U/L
• total bilirubin levels >2.0 mg/dL
• lactate dehydrogenase (LDH) levels >1,290 U/L
• blood urea nitrogen test results >44 mg/dL
• platelet count <50,000 platelets per µL.

The clinical course of HELLP syndrome is characterized by progression and the potential for sudden and catastrophic deterioration. For example, some women with HELLP will suddenly develop a ruptured liver, pulmonary edema, or a stroke. The Society for Maternal-Fetal Medicine recommends against expectant management of women with HELLP syndrome.¹³

Related article:
Optimal obstetric care for women aged 40 and older

8. Delivery or expectant management?

Currently the only cure for preeclampsia is delivery. The Society for Maternal-Fetal Medicine recommends against expectant management of severe preeclampsia if certain problems occur (BOX).¹³ For women with preeclampsia who are less than 34 weeks’ gestation and do not have a contraindication to expectant management, consider transferring the patient to a tertiary maternal care center. In our practice, pregnant women with a hypertensive disorder are scheduled for an induction of labor and delivery at 37 weeks’ gestation.
 

In the United States, major obstetric causes of pregnancy-related death include sepsis, venous thromboembolism-pulmonary embolism, hemorrhage, and hypertensive disease of pregnancy. Other important causes of pregnancy-related death include cardiac disease, stroke, and pre-existing major medical disease including advanced cancer. In the United States there are approximately 17 pregnancy-related maternal deaths per 100,000 live births.¹ Obstetricians are dedicated to reducing this excessively high rate of maternal death.

Given the US maternal death rate of 1 maternity death per 5,880 live births, over the course of a 40-year career, most obstetrician-gynecologists will have 1 or 2 of their pregnant patients die. From the perspective of an individual clinician, maternal death is an extremely rare event, with 1 death during every 20 years of practice. However, from a population perspective, maternal death in the United States is all too common compared to other developed countries. We can only reduce the rate of maternal death by working in interdisciplinary teams to ensure our obstetrics units are prepared to expeditiously diagnose and treat the most common obstetric causes of death and severe morbidity.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Obstetrician-gynecologists are deeply committed to reducing maternal mortality and severe morbidity. Hypertensive diseases of pregnancy, including preeclampsia and eclampsia, are important contributors to both maternal mortality and severe morbidity. Among US live births from 2011–2013 there were 1,078 pregnancy-related maternal deaths, and 10% were attributed to preeclampsia or eclampsia.¹ Hypertensive disease of pregnancy is also a major cause of severe maternal morbidity, with an increased risk of acute renal failure, respiratory failure, and cerebrovascular events.² Preeclampsia is associated with a 4-fold increased risk of thrombocytopenia and coagulopathy and a 2-fold increased risk of postpartum hemorrhage.³

Severe hypertension is defined as a systolic blood pressure (BP) ≥160 mm Hg or a diastolic BP ≥110 mm Hg on 2 measurements within 15 minutes.^4,5 Severe hypertensive disease of pregnancy is a common clinical problem in obstetrics, requiring clinicians to respond expeditiously and decisively to minimize adverse maternal outcomes. Following the identification of severe hypertension, a diagnosis and management plan should be initiated within 30 to 60 minutes.⁴ Some experts recommend that treatment be initiated within 15 minutes of identifying severe hypertension in a pregnant woman.⁶

The American College of Obstetricians and Gynecologists recommends that obstetric programs adopt standardized guidelines for the management of women with preeclampsia or eclampsia.⁴ The National Partnership for Maternal Safety recommends that all obstetric programs develop care bundles to respond to severe hypertension.⁵ Key points in managing severe hypertension are summarized below.

Related article:
2017 Update on obstetrics: Preeclampsia prevention

1. Expeditiously initiate treatment of severe hypertension…

…with intravenous (IV) labetalol (administered as 20 mg/40 mg/80 mg sequential doses as needed) or hydralazine (administered as 10 mg/10 mg/20 mg/40 mg sequential doses as needed). Our preferred agent is labetalol, administered as a 20-mg IV infusion over 2 minutes. If the patient’s BP remains elevated 10 min after the initial dose, administer labetalol 40 mg as an IV infusion over 2 min. If her BP remains elevated 10 min after this dose, administer 80 mg of labetalol. If the BP continues to be elevated, hydralazine treatment can be initiated as described below.

Occasionally there are national shortages of labetalol or a patient has a low heart rate or contraindication such as heart disease or asthma prohibiting its use. If labetalol is not available, we use hydralazine administered as a 10-mg IV bolus over 2 min. If the BP remains elevated, every 20 min, an escalating dose of hydralazine is administered, first by repeating the 10-mg dose, then administering 20 mg, and finally 40 mg.

For women without IV access, we use oral nifedipine 10 mg to control hypertension only while awaiting the placement of an IV. If BP remains elevated after 30 min, a second dose of oral nifedipine 20 mg can be given with a plan to transition to IV agents as soon as possible. The risks of maternal tachycardia or overshoot hypotension with immediate release oral nifedipine limit its use in our clinical practice to this circumstance.

Once the BP is controlled, start maintenance oral hypertension therapy. Our first-line agent is labetalol 200 mg twice per day with a maximum dose of 800 mg 3 times daily (2,400 mg maximal daily dose).

2. Initiate treatment with magnesium sulfate

If the patient’s BP is ≥160/110 mm Hg or if her BP is ≥140/90 mm Hg with coexisting symptoms of severe preeclampsia (for example a severe headache), initiate magnesium sulfate treatment. A standard regimen is magnesium sulfate 4 to 6 g administered as an IV bolus over 20 min followed by the IV infusion of 2 g per hour. In our clinical opinion, if you plan on initiating IV antihypertensive treatment for severe hypertension you also should strongly consider starting magnesium sulfate to reduce the risk of an eclamptic seizure.

We also start magnesium sulfate therapy for women with severe hypertension and clinical symptoms or laboratory signs of preeclampsia even in the absence of proteinuria. Approximately 2% of women with preeclampsia will develop an eclamptic seizure and magnesium sulfate treatment significantly reduces the risk of seizure and may also reduce maternal mortality.^7,8

Magnesium sulfate is contra-indicated in women with myasthenia gravis. In women with renal dysfunction, the loading dose can be given, but the continuous magnesium sulfate infusion should not be initiated until serum magnesium levels are assessed.

3. Consider administering maternal betamethasone

Treatment with betamethasone advances fetal maturation if the pregnancy is preterm (for example, <34 weeks of gestation). A major cause of neonatal morbidity and mortality for pregnancy complicated by severe hypertensive disease is premature delivery. Maternal glucocorticoid treatment reduces the risk of neonatal morbidity and mortality if preterm delivery is anticipated. However, do not delay delivery for antenatal corticosteroids for women with severe and persistent hypertension or symptoms of preeclampsia that do not resolve following treatment.

We also consider women with eclampsia, placental abruption, pulmonary edema, or severe laboratory derangements too unstable to delay delivery for 48 hours to achieve the maximum benefit of steroid treatment. If antenatal corticosteroids are administered in the late preterm period between 34 0/7 weeks and 36 6/7 weeks of gestation, obstetric management should not be altered and delivery should not be delayed.⁹

Related article:
Start offering antenatal corticosteroids to women delivering between 34 0/7 and 36 6/7 weeks of gestation to improve newborn outcomes

4. Preeclampsia plus a severe headache is a toxic combination

For patients with this constellation either have a plan for delivery or keep them under close surveillance. Occasionally a woman >20 weeks pregnant with new onset hypertension and a headache is seen in an emergency department and is not assessed for proteinuria or other preeclampsia laboratory abnormalities. If the woman is diagnosed as having a migraine or tension headache and discharged home with a headache medicine they are at high risk for serious morbidity, including stroke.

Read about preeclampsia and thrombocytopenia, HELLP syndrome, more.

5. Preeclampsia plus thrombocytopenia complicates anesthesia options

If the platelet count falls too low (for instance, <70,000 platelets per µL), many anesthesiologists will not provide a regional anesthetic for delivery because of the risk of peridural bleeding. In addition, a low platelet count (<50,000 platelets per µL) significantly increases the risk of obstetric hemorrhage. Transfer of the patient to an obstetrics unit with a full-service blood bank capable of supporting multiple platelet transfusions may be warranted.

6. Preeclampsia plus dyspnea or chest pain increases the risk of severe maternal morbidity

Authors of a prospective study of 2,023 women with preeclampsia reported an increase in adverse maternal outcomes when the following factors were present: early gestational age, dyspnea, chest pain, oxygen saturation of SpO₂ <93%, thrombocytopenia, elevated creatinine, or elevated aspartate transaminase concentration.¹⁰ If dyspnea is present, the patient may have pulmonary edema, pulmonary embolism, heart failure, acute asthma, or pneumonia. If the patient has chest pain the differential diagnosis includes pulmonary embolism, cardiac ischemia, cardiomyopathy, or another cardiac disease.

Consider obtaining a chest radiograph for pregnant women with dyspnea and a computed tomography pulmonary angiogram or lung scintigraphy (ventilation perfusion scan) if the chest radiograph is normal for women with chest pain.^6,11 We obtain a transthoracic echocardiogram in cases of pulmonary edema to evaluate for the possibility of peripartum cardiomyopathy.

7. HELLP syndrome

The triad of hemolysis, elevated liver enzymes, and low platelet count (HELLP) is associated with an increased risk of maternal mortality and severe morbidity.¹² In a study of 171 women with HELLP, factors that increased the risk for adverse maternal outcomes included¹²:

• aspartate aminotransferase (AST) levels >316 U/L
• alanine aminotransferase (ALT) levels >217 U/L
• total bilirubin levels >2.0 mg/dL
• lactate dehydrogenase (LDH) levels >1,290 U/L
• blood urea nitrogen test results >44 mg/dL
• platelet count <50,000 platelets per µL.

The clinical course of HELLP syndrome is characterized by progression and the potential for sudden and catastrophic deterioration. For example, some women with HELLP will suddenly develop a ruptured liver, pulmonary edema, or a stroke. The Society for Maternal-Fetal Medicine recommends against expectant management of women with HELLP syndrome.¹³

Related article:
Optimal obstetric care for women aged 40 and older

8. Delivery or expectant management?

Currently the only cure for preeclampsia is delivery. The Society for Maternal-Fetal Medicine recommends against expectant management of severe preeclampsia if certain problems occur (BOX).¹³ For women with preeclampsia who are less than 34 weeks’ gestation and do not have a contraindication to expectant management, consider transferring the patient to a tertiary maternal care center. In our practice, pregnant women with a hypertensive disorder are scheduled for an induction of labor and delivery at 37 weeks’ gestation.
 

In the United States, major obstetric causes of pregnancy-related death include sepsis, venous thromboembolism-pulmonary embolism, hemorrhage, and hypertensive disease of pregnancy. Other important causes of pregnancy-related death include cardiac disease, stroke, and pre-existing major medical disease including advanced cancer. In the United States there are approximately 17 pregnancy-related maternal deaths per 100,000 live births.¹ Obstetricians are dedicated to reducing this excessively high rate of maternal death.

Given the US maternal death rate of 1 maternity death per 5,880 live births, over the course of a 40-year career, most obstetrician-gynecologists will have 1 or 2 of their pregnant patients die. From the perspective of an individual clinician, maternal death is an extremely rare event, with 1 death during every 20 years of practice. However, from a population perspective, maternal death in the United States is all too common compared to other developed countries. We can only reduce the rate of maternal death by working in interdisciplinary teams to ensure our obstetrics units are prepared to expeditiously diagnose and treat the most common obstetric causes of death and severe morbidity.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In 2015 more than 30,000 deaths from opioid overdose were reported (FIGURE).¹ More than 50% of the deaths were due to prescription opioids. The opioid crisis is a public health emergency and clinicians are diligently working to reduce both the number of opioid prescriptions and the doses prescribed per prescription.

In obstetrics, there is growing concern that narcotics used for the treatment of pain in women who are breastfeeding may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the US Food and Drug Administration (FDA) and the American College of Obstetricians and Gynecologists (ACOG) recommend against the use of codeine and tramadol in women who are breastfeeding because their newborns may have adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems.^2–4 In addition, there is growing concern that the use of oxycodone and hydrocodone should also be limited in women who are breastfeeding. In this article, I discuss the rationale for these recommendations.

Related article:
Landmark women’s health care remains law of the land

Codeine

Codeine is metabolized to morphine by CYP2D6 and CYP2D7. Both codeine and morphine are excreted into breast milk. Some women are ultrarapid metabolizers of codeine because of high levels of CYP2D6, resulting in higher concentrations of morphine in their breast milk and their breast fed newborn.^2,5 In many women who are ultra-rapid metabolizers of codeine, CYP2D6 gene duplication or multiplication is the cause of the increased enzyme activity.⁶ Genotyping can identify some women who are ultrarapid metabolizers, but it is not currently utilized widely in clinical practice.

In the United States approximately 5% of women express high levels of CYP2D6 and are ultra-rapid metabolizers of codeine.⁴ In Ethiopia as many as 29% of women are ultrarapid metabolizers.⁷ Newborn central nervous system (CNS) depression is the most common adverse effect of fetal ingestion of excessive codeine and mor-phine from breast milk and may present as sedation, apnea, bradycardia, or cyanosis.⁸ Multiple newborn fatalities have been re-ported in the literature when lactating mothers who were ultrarapid metabolizers took co-deine. The FDA and ACOG recommend against the use of codeine in lactating women.

Hydrocodone

Hydrocodone, a hydrogenated ketone derivative of codeine, is metabolized by CYP2D6 to hydromorphone. Both hydrocodone and hydromorphone are present in breast milk. In lactating mothers taking hydrocodone, up to 9% of the dose may be ingested by the breastfeeding newborn.⁹ There is concern that hydrocodone use by women who are breastfeeding and are ultrarapid metabolizers may cause increased fetal consumption of hydromorphone resulting in adverse outcomes in the newborn. The AAP cautions against the use of hydrocodone.²

Oxycodone

Oxycodone is metabolized by CYP2D6 to oxymorphone and is concentrated into breast milk.¹⁰ Oxymorphone is more than 10 times more potent than oxycodone. In one study of lactating women taking oxycodone, codeine, or acetaminophen, the rates of neonate CNS depression were 20%, 17%, and 0.5%, respectively.¹¹ The authors concluded that for mothers who are breastfeeding oxycodone was no safer than codeine because both medications were associated with a high rate of depression in the neonate. Newborns who develop CNS depression from exposure to oxycodone in breast milk will respond to naloxone treatment.¹² The AAP recommends against prescribing oxycodone for women who are breastfeeding their infants.²

In a recent communication, the Society for Obstetric Anesthesia and Perinatology (SOAP) observed that in the United States, following cesarean delivery the majority of women receive oxycodone or hydrocodone.¹³ SOAP disagreed with the AAP recommendation against the use of oxycodone or hydrocodone in breastfeeding women. SOAP noted that all narcotics can produce adverse effects in newborns of breastfeeding women and that there are no good data that the prescription of oxycodone or hydrocodone is more risky than morphine or hydromorphone. However, based on their assessment of risk and benefit, pediatricians prioritize the use of acetaminophen and morphine and seldom use oxycodone or hydrocodone to treat moderate to severe pain in babies and children.

Tramadol

Tramadol is metabolized by CYP2D6 to O-desmethyltramadol. Both tramadol and O-desmethyltramadol are excreted into breast milk. In ultrarapid metabolizers, a greater concentration of O-desmethyltramadol is excreted into breast milk. The FDA reported that they identified no serious neonatal adverse events in the literature due to the use of tramadol by women who are breastfeeding. However, given that tramadol and its CYP2D6 metabolite enter breast milk and the potential for life-threatening respiratory de-pression in the infant, the FDA included tramadol in its warning about codeine.³

Codeine, hydrocodone, oxycodone, and tramadol are all metabolized to more potent metabolites by the CYP2D6 enzyme. Individuals with low CYP2D6 activity, representing about 5% of the US population, cannot fully activate these narcotics. Hence they may not get adequate pain relief when treated with codeine, oxycodone, hydrocodone, or tramadol. Given their resistance to these medications they may first be placed on a higher dose of the narcotic and then switched from a high ineffective dose of one of the agents activated by CYP2D6 to a high dose of morphine or hydromorphone. This can be dangerous because they may then receive an excessive dose of narcotic and develop respiratory depression.¹⁴

Read about how other pain medications affect breast milk.

Aspirin

There are very little high quality data about the use of aspirin in women breastfeeding and the effect on the neonate. If a mother takes aspirin, the drug will enter breast milk. It is estimated that the nursing baby receives about 4% to 8% of the mother’s dose. The World Health Organization recommends that aspirin is compatible with breastfeeding in occasional small doses, but repeated administration of aspirin in normal doses should be avoided in women who are breastfeeding. If chronic or high-dose aspirin therapy is recommended, the infant should be monitored for side effects including metabolic acidosis¹⁵ and coagulation disorders.¹⁶ The National Reye’s Syndrome Foundation recommends against the use of aspirin in women who are breastfeeding because of the theoretical risk of triggering Reye syndrome.¹⁷ Acetaminophen and ibuprofen are recommended by the WHO for chronic treatment of pain during breastfeeding.¹⁶

Acetaminophen and ibuprofen

For the medication treatment of pain in women who are breastfeeding, the WHO recommends the use of acetaminophen and ibuprofen.¹⁶ Acetaminophen is transferred from the maternal circulation into breast milk, but it is estimated that the dose to the nursing neonate is <0.3% of the maternal dose.¹⁸ In mothers taking ibuprofen 1600 mg daily, the concentration of ibuprofen in breast milk was below the level of laboratory detection (<1 mg/L).¹⁹ Ibuprofen treatment is thought to be safe for women who are breastfeeding because of its short half-life (2 hours), low excretion into milk, and few reported adverse effects in infants.

Morphine

Morphine is not metabolized by CYP2D6 and is excreted into breast milk. Many experts believe that women who are breastfeeding may take standard doses of oral morphine with few adverse effects in the newborn.^20,21 For the treatment of moderate to severe pain in opioid-naive adults, morphine doses in the range of 10 mg orally every 4 hours up to 30 mg orally every 4 hours are prescribed. When using a solution of morphine, standard doses are 10 mg to 20 mg every 4 hours, as needed to treat pain. When using morphine tablets, standard doses are 15 mg to 30 mg every 4 hours. The WHO states that occasional doses of morphine are usually safe for women breastfeeding their newborn.¹⁶ The AAP recommends the use of morphine and hydromorphone when narcotic agents are needed to treat pain in breastfeeding women.²

Hydromorphone

Hydromorphone, a hydrogenated ketone derivative of morphine, is not metabolized by CYP2D6 and is excreted into breast milk. There are limited data on the safety of hydromorphone during breastfeeding. Breast milk concentrations of hydromorphone are low, and an occasional dose is likely associated with few adverse effects in the breastfeeding newborn.²² For the treatment of moderate to severe pain in opioid-naive adults, hydromorphone doses in the range of 2 mg orally every 4 hours up to 4 mg orally every 4 hours are prescribed. Like all narcotics, hydromorphone can result in central nervous system depression. If a mother ingests sufficient quantities of hydromorphone, respiratory depression in the breastfeeding newborn can occur. In one case report, a nursing mother was taking hydromorphone 4 mg every 4 hours for pain following a cesarean delivery. On day 6 following birth, her newborn was lethargic and she brought the infant to an emergency room. In the emergency room the infant became apneic and was successfully treated with naloxone, suggesting anarcotic overdose due to the presence of hydromorphone in breast milk.²³ Hydromorphone should only be used at the lowest effective dose and for the shortest time possible.

Related article:
Should coffee consumption be added as an adjunct to the postoperative care of gynecologic oncology patients?

The bottom line

Pediatricians seldom prescribe codeine, oxycodone, hydrocodone, or tramadol for the treatment of pain in newborns or children. Pediatricians generally use acetaminophen and morphine for the treatment of pain in newborns. Although data from large, high quality clinical trials are not available, expert opinion recommends that acetaminophen and ibuprofen should be prescribed as first-line medications for the treatment of pain in women who are breastfeeding. Use of narcotics that are metabolized by CYP2D6 should be minimized or avoided in women who are breastfeeding. If narcotic medication is necessary, the lowest effective dose of morphine or hy-dromorphone should be prescribed for the shortest time possible. If morphine is prescribed to wo-men who are breastfeeding, they should be advised to observe their baby for signs of narcotic excess, including drowsiness, poor nursing, slow breathing, or low heart rate.

The goal of reducing morbidity and mortality from opioid use is a top public health priority. Obstetrician-gynecologists can contribute through the optimal use of opioid analgesics. Reducing the number of opioid prescriptions and the quantity of medication prescribed per prescription is an important first step in our effort to reduce opioid-related deaths.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In 2015 more than 30,000 deaths from opioid overdose were reported (FIGURE).¹ More than 50% of the deaths were due to prescription opioids. The opioid crisis is a public health emergency and clinicians are diligently working to reduce both the number of opioid prescriptions and the doses prescribed per prescription.

In obstetrics, there is growing concern that narcotics used for the treatment of pain in women who are breastfeeding may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the US Food and Drug Administration (FDA) and the American College of Obstetricians and Gynecologists (ACOG) recommend against the use of codeine and tramadol in women who are breastfeeding because their newborns may have adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems.^2–4 In addition, there is growing concern that the use of oxycodone and hydrocodone should also be limited in women who are breastfeeding. In this article, I discuss the rationale for these recommendations.

Related article:
Landmark women’s health care remains law of the land

Codeine

Codeine is metabolized to morphine by CYP2D6 and CYP2D7. Both codeine and morphine are excreted into breast milk. Some women are ultrarapid metabolizers of codeine because of high levels of CYP2D6, resulting in higher concentrations of morphine in their breast milk and their breast fed newborn.^2,5 In many women who are ultra-rapid metabolizers of codeine, CYP2D6 gene duplication or multiplication is the cause of the increased enzyme activity.⁶ Genotyping can identify some women who are ultrarapid metabolizers, but it is not currently utilized widely in clinical practice.

In the United States approximately 5% of women express high levels of CYP2D6 and are ultra-rapid metabolizers of codeine.⁴ In Ethiopia as many as 29% of women are ultrarapid metabolizers.⁷ Newborn central nervous system (CNS) depression is the most common adverse effect of fetal ingestion of excessive codeine and mor-phine from breast milk and may present as sedation, apnea, bradycardia, or cyanosis.⁸ Multiple newborn fatalities have been re-ported in the literature when lactating mothers who were ultrarapid metabolizers took co-deine. The FDA and ACOG recommend against the use of codeine in lactating women.

Hydrocodone

Hydrocodone, a hydrogenated ketone derivative of codeine, is metabolized by CYP2D6 to hydromorphone. Both hydrocodone and hydromorphone are present in breast milk. In lactating mothers taking hydrocodone, up to 9% of the dose may be ingested by the breastfeeding newborn.⁹ There is concern that hydrocodone use by women who are breastfeeding and are ultrarapid metabolizers may cause increased fetal consumption of hydromorphone resulting in adverse outcomes in the newborn. The AAP cautions against the use of hydrocodone.²

Oxycodone

Oxycodone is metabolized by CYP2D6 to oxymorphone and is concentrated into breast milk.¹⁰ Oxymorphone is more than 10 times more potent than oxycodone. In one study of lactating women taking oxycodone, codeine, or acetaminophen, the rates of neonate CNS depression were 20%, 17%, and 0.5%, respectively.¹¹ The authors concluded that for mothers who are breastfeeding oxycodone was no safer than codeine because both medications were associated with a high rate of depression in the neonate. Newborns who develop CNS depression from exposure to oxycodone in breast milk will respond to naloxone treatment.¹² The AAP recommends against prescribing oxycodone for women who are breastfeeding their infants.²

In a recent communication, the Society for Obstetric Anesthesia and Perinatology (SOAP) observed that in the United States, following cesarean delivery the majority of women receive oxycodone or hydrocodone.¹³ SOAP disagreed with the AAP recommendation against the use of oxycodone or hydrocodone in breastfeeding women. SOAP noted that all narcotics can produce adverse effects in newborns of breastfeeding women and that there are no good data that the prescription of oxycodone or hydrocodone is more risky than morphine or hydromorphone. However, based on their assessment of risk and benefit, pediatricians prioritize the use of acetaminophen and morphine and seldom use oxycodone or hydrocodone to treat moderate to severe pain in babies and children.

Tramadol

Tramadol is metabolized by CYP2D6 to O-desmethyltramadol. Both tramadol and O-desmethyltramadol are excreted into breast milk. In ultrarapid metabolizers, a greater concentration of O-desmethyltramadol is excreted into breast milk. The FDA reported that they identified no serious neonatal adverse events in the literature due to the use of tramadol by women who are breastfeeding. However, given that tramadol and its CYP2D6 metabolite enter breast milk and the potential for life-threatening respiratory de-pression in the infant, the FDA included tramadol in its warning about codeine.³

Codeine, hydrocodone, oxycodone, and tramadol are all metabolized to more potent metabolites by the CYP2D6 enzyme. Individuals with low CYP2D6 activity, representing about 5% of the US population, cannot fully activate these narcotics. Hence they may not get adequate pain relief when treated with codeine, oxycodone, hydrocodone, or tramadol. Given their resistance to these medications they may first be placed on a higher dose of the narcotic and then switched from a high ineffective dose of one of the agents activated by CYP2D6 to a high dose of morphine or hydromorphone. This can be dangerous because they may then receive an excessive dose of narcotic and develop respiratory depression.¹⁴

Read about how other pain medications affect breast milk.

Aspirin

There are very little high quality data about the use of aspirin in women breastfeeding and the effect on the neonate. If a mother takes aspirin, the drug will enter breast milk. It is estimated that the nursing baby receives about 4% to 8% of the mother’s dose. The World Health Organization recommends that aspirin is compatible with breastfeeding in occasional small doses, but repeated administration of aspirin in normal doses should be avoided in women who are breastfeeding. If chronic or high-dose aspirin therapy is recommended, the infant should be monitored for side effects including metabolic acidosis¹⁵ and coagulation disorders.¹⁶ The National Reye’s Syndrome Foundation recommends against the use of aspirin in women who are breastfeeding because of the theoretical risk of triggering Reye syndrome.¹⁷ Acetaminophen and ibuprofen are recommended by the WHO for chronic treatment of pain during breastfeeding.¹⁶

Acetaminophen and ibuprofen

For the medication treatment of pain in women who are breastfeeding, the WHO recommends the use of acetaminophen and ibuprofen.¹⁶ Acetaminophen is transferred from the maternal circulation into breast milk, but it is estimated that the dose to the nursing neonate is <0.3% of the maternal dose.¹⁸ In mothers taking ibuprofen 1600 mg daily, the concentration of ibuprofen in breast milk was below the level of laboratory detection (<1 mg/L).¹⁹ Ibuprofen treatment is thought to be safe for women who are breastfeeding because of its short half-life (2 hours), low excretion into milk, and few reported adverse effects in infants.

Morphine

Morphine is not metabolized by CYP2D6 and is excreted into breast milk. Many experts believe that women who are breastfeeding may take standard doses of oral morphine with few adverse effects in the newborn.^20,21 For the treatment of moderate to severe pain in opioid-naive adults, morphine doses in the range of 10 mg orally every 4 hours up to 30 mg orally every 4 hours are prescribed. When using a solution of morphine, standard doses are 10 mg to 20 mg every 4 hours, as needed to treat pain. When using morphine tablets, standard doses are 15 mg to 30 mg every 4 hours. The WHO states that occasional doses of morphine are usually safe for women breastfeeding their newborn.¹⁶ The AAP recommends the use of morphine and hydromorphone when narcotic agents are needed to treat pain in breastfeeding women.²

Hydromorphone

Hydromorphone, a hydrogenated ketone derivative of morphine, is not metabolized by CYP2D6 and is excreted into breast milk. There are limited data on the safety of hydromorphone during breastfeeding. Breast milk concentrations of hydromorphone are low, and an occasional dose is likely associated with few adverse effects in the breastfeeding newborn.²² For the treatment of moderate to severe pain in opioid-naive adults, hydromorphone doses in the range of 2 mg orally every 4 hours up to 4 mg orally every 4 hours are prescribed. Like all narcotics, hydromorphone can result in central nervous system depression. If a mother ingests sufficient quantities of hydromorphone, respiratory depression in the breastfeeding newborn can occur. In one case report, a nursing mother was taking hydromorphone 4 mg every 4 hours for pain following a cesarean delivery. On day 6 following birth, her newborn was lethargic and she brought the infant to an emergency room. In the emergency room the infant became apneic and was successfully treated with naloxone, suggesting anarcotic overdose due to the presence of hydromorphone in breast milk.²³ Hydromorphone should only be used at the lowest effective dose and for the shortest time possible.

Related article:
Should coffee consumption be added as an adjunct to the postoperative care of gynecologic oncology patients?

The bottom line

Pediatricians seldom prescribe codeine, oxycodone, hydrocodone, or tramadol for the treatment of pain in newborns or children. Pediatricians generally use acetaminophen and morphine for the treatment of pain in newborns. Although data from large, high quality clinical trials are not available, expert opinion recommends that acetaminophen and ibuprofen should be prescribed as first-line medications for the treatment of pain in women who are breastfeeding. Use of narcotics that are metabolized by CYP2D6 should be minimized or avoided in women who are breastfeeding. If narcotic medication is necessary, the lowest effective dose of morphine or hy-dromorphone should be prescribed for the shortest time possible. If morphine is prescribed to wo-men who are breastfeeding, they should be advised to observe their baby for signs of narcotic excess, including drowsiness, poor nursing, slow breathing, or low heart rate.

The goal of reducing morbidity and mortality from opioid use is a top public health priority. Obstetrician-gynecologists can contribute through the optimal use of opioid analgesics. Reducing the number of opioid prescriptions and the quantity of medication prescribed per prescription is an important first step in our effort to reduce opioid-related deaths.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In 2015 more than 30,000 deaths from opioid overdose were reported (FIGURE).¹ More than 50% of the deaths were due to prescription opioids. The opioid crisis is a public health emergency and clinicians are diligently working to reduce both the number of opioid prescriptions and the doses prescribed per prescription.

In obstetrics, there is growing concern that narcotics used for the treatment of pain in women who are breastfeeding may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the US Food and Drug Administration (FDA) and the American College of Obstetricians and Gynecologists (ACOG) recommend against the use of codeine and tramadol in women who are breastfeeding because their newborns may have adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems.^2–4 In addition, there is growing concern that the use of oxycodone and hydrocodone should also be limited in women who are breastfeeding. In this article, I discuss the rationale for these recommendations.

Related article:
Landmark women’s health care remains law of the land

Codeine

Codeine is metabolized to morphine by CYP2D6 and CYP2D7. Both codeine and morphine are excreted into breast milk. Some women are ultrarapid metabolizers of codeine because of high levels of CYP2D6, resulting in higher concentrations of morphine in their breast milk and their breast fed newborn.^2,5 In many women who are ultra-rapid metabolizers of codeine, CYP2D6 gene duplication or multiplication is the cause of the increased enzyme activity.⁶ Genotyping can identify some women who are ultrarapid metabolizers, but it is not currently utilized widely in clinical practice.

In the United States approximately 5% of women express high levels of CYP2D6 and are ultra-rapid metabolizers of codeine.⁴ In Ethiopia as many as 29% of women are ultrarapid metabolizers.⁷ Newborn central nervous system (CNS) depression is the most common adverse effect of fetal ingestion of excessive codeine and mor-phine from breast milk and may present as sedation, apnea, bradycardia, or cyanosis.⁸ Multiple newborn fatalities have been re-ported in the literature when lactating mothers who were ultrarapid metabolizers took co-deine. The FDA and ACOG recommend against the use of codeine in lactating women.

Hydrocodone

Hydrocodone, a hydrogenated ketone derivative of codeine, is metabolized by CYP2D6 to hydromorphone. Both hydrocodone and hydromorphone are present in breast milk. In lactating mothers taking hydrocodone, up to 9% of the dose may be ingested by the breastfeeding newborn.⁹ There is concern that hydrocodone use by women who are breastfeeding and are ultrarapid metabolizers may cause increased fetal consumption of hydromorphone resulting in adverse outcomes in the newborn. The AAP cautions against the use of hydrocodone.²

Oxycodone

Oxycodone is metabolized by CYP2D6 to oxymorphone and is concentrated into breast milk.¹⁰ Oxymorphone is more than 10 times more potent than oxycodone. In one study of lactating women taking oxycodone, codeine, or acetaminophen, the rates of neonate CNS depression were 20%, 17%, and 0.5%, respectively.¹¹ The authors concluded that for mothers who are breastfeeding oxycodone was no safer than codeine because both medications were associated with a high rate of depression in the neonate. Newborns who develop CNS depression from exposure to oxycodone in breast milk will respond to naloxone treatment.¹² The AAP recommends against prescribing oxycodone for women who are breastfeeding their infants.²

In a recent communication, the Society for Obstetric Anesthesia and Perinatology (SOAP) observed that in the United States, following cesarean delivery the majority of women receive oxycodone or hydrocodone.¹³ SOAP disagreed with the AAP recommendation against the use of oxycodone or hydrocodone in breastfeeding women. SOAP noted that all narcotics can produce adverse effects in newborns of breastfeeding women and that there are no good data that the prescription of oxycodone or hydrocodone is more risky than morphine or hydromorphone. However, based on their assessment of risk and benefit, pediatricians prioritize the use of acetaminophen and morphine and seldom use oxycodone or hydrocodone to treat moderate to severe pain in babies and children.

Tramadol

Tramadol is metabolized by CYP2D6 to O-desmethyltramadol. Both tramadol and O-desmethyltramadol are excreted into breast milk. In ultrarapid metabolizers, a greater concentration of O-desmethyltramadol is excreted into breast milk. The FDA reported that they identified no serious neonatal adverse events in the literature due to the use of tramadol by women who are breastfeeding. However, given that tramadol and its CYP2D6 metabolite enter breast milk and the potential for life-threatening respiratory de-pression in the infant, the FDA included tramadol in its warning about codeine.³

Codeine, hydrocodone, oxycodone, and tramadol are all metabolized to more potent metabolites by the CYP2D6 enzyme. Individuals with low CYP2D6 activity, representing about 5% of the US population, cannot fully activate these narcotics. Hence they may not get adequate pain relief when treated with codeine, oxycodone, hydrocodone, or tramadol. Given their resistance to these medications they may first be placed on a higher dose of the narcotic and then switched from a high ineffective dose of one of the agents activated by CYP2D6 to a high dose of morphine or hydromorphone. This can be dangerous because they may then receive an excessive dose of narcotic and develop respiratory depression.¹⁴

Read about how other pain medications affect breast milk.

Aspirin

There are very little high quality data about the use of aspirin in women breastfeeding and the effect on the neonate. If a mother takes aspirin, the drug will enter breast milk. It is estimated that the nursing baby receives about 4% to 8% of the mother’s dose. The World Health Organization recommends that aspirin is compatible with breastfeeding in occasional small doses, but repeated administration of aspirin in normal doses should be avoided in women who are breastfeeding. If chronic or high-dose aspirin therapy is recommended, the infant should be monitored for side effects including metabolic acidosis¹⁵ and coagulation disorders.¹⁶ The National Reye’s Syndrome Foundation recommends against the use of aspirin in women who are breastfeeding because of the theoretical risk of triggering Reye syndrome.¹⁷ Acetaminophen and ibuprofen are recommended by the WHO for chronic treatment of pain during breastfeeding.¹⁶

Acetaminophen and ibuprofen

For the medication treatment of pain in women who are breastfeeding, the WHO recommends the use of acetaminophen and ibuprofen.¹⁶ Acetaminophen is transferred from the maternal circulation into breast milk, but it is estimated that the dose to the nursing neonate is <0.3% of the maternal dose.¹⁸ In mothers taking ibuprofen 1600 mg daily, the concentration of ibuprofen in breast milk was below the level of laboratory detection (<1 mg/L).¹⁹ Ibuprofen treatment is thought to be safe for women who are breastfeeding because of its short half-life (2 hours), low excretion into milk, and few reported adverse effects in infants.

Morphine

Morphine is not metabolized by CYP2D6 and is excreted into breast milk. Many experts believe that women who are breastfeeding may take standard doses of oral morphine with few adverse effects in the newborn.^20,21 For the treatment of moderate to severe pain in opioid-naive adults, morphine doses in the range of 10 mg orally every 4 hours up to 30 mg orally every 4 hours are prescribed. When using a solution of morphine, standard doses are 10 mg to 20 mg every 4 hours, as needed to treat pain. When using morphine tablets, standard doses are 15 mg to 30 mg every 4 hours. The WHO states that occasional doses of morphine are usually safe for women breastfeeding their newborn.¹⁶ The AAP recommends the use of morphine and hydromorphone when narcotic agents are needed to treat pain in breastfeeding women.²

Hydromorphone

Hydromorphone, a hydrogenated ketone derivative of morphine, is not metabolized by CYP2D6 and is excreted into breast milk. There are limited data on the safety of hydromorphone during breastfeeding. Breast milk concentrations of hydromorphone are low, and an occasional dose is likely associated with few adverse effects in the breastfeeding newborn.²² For the treatment of moderate to severe pain in opioid-naive adults, hydromorphone doses in the range of 2 mg orally every 4 hours up to 4 mg orally every 4 hours are prescribed. Like all narcotics, hydromorphone can result in central nervous system depression. If a mother ingests sufficient quantities of hydromorphone, respiratory depression in the breastfeeding newborn can occur. In one case report, a nursing mother was taking hydromorphone 4 mg every 4 hours for pain following a cesarean delivery. On day 6 following birth, her newborn was lethargic and she brought the infant to an emergency room. In the emergency room the infant became apneic and was successfully treated with naloxone, suggesting anarcotic overdose due to the presence of hydromorphone in breast milk.²³ Hydromorphone should only be used at the lowest effective dose and for the shortest time possible.

Related article:
Should coffee consumption be added as an adjunct to the postoperative care of gynecologic oncology patients?

The bottom line

Pediatricians seldom prescribe codeine, oxycodone, hydrocodone, or tramadol for the treatment of pain in newborns or children. Pediatricians generally use acetaminophen and morphine for the treatment of pain in newborns. Although data from large, high quality clinical trials are not available, expert opinion recommends that acetaminophen and ibuprofen should be prescribed as first-line medications for the treatment of pain in women who are breastfeeding. Use of narcotics that are metabolized by CYP2D6 should be minimized or avoided in women who are breastfeeding. If narcotic medication is necessary, the lowest effective dose of morphine or hy-dromorphone should be prescribed for the shortest time possible. If morphine is prescribed to wo-men who are breastfeeding, they should be advised to observe their baby for signs of narcotic excess, including drowsiness, poor nursing, slow breathing, or low heart rate.

The goal of reducing morbidity and mortality from opioid use is a top public health priority. Obstetrician-gynecologists can contribute through the optimal use of opioid analgesics. Reducing the number of opioid prescriptions and the quantity of medication prescribed per prescription is an important first step in our effort to reduce opioid-related deaths.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

There are no large randomized clinical trials exploring the relationship between COCs and the risk of developing cancer. Many epidemiological studies, however, have investigated the possible association between COC use and the risk of cancer. Such prospective and retrospective studies consistently report that the use of COCs significantly decreases the risk of ovarian and endometrial cancer. The epidemiological data are less consistent concerning the possible association between COC use and the risk of breast cancer. Meta-analyses conclude that current use of COCs may be associated with a small increase in breast cancer risk. In addition, prolonged use of COCs may be associated with an increased risk of cervical cancer.

Ovarian cancer

• 0.78 (0.73–0.83) for 2.4 years
• 0.64 (0.59–0.69) for 6.8 years
• 0.56 (0.50–0.62) for 11.6 years
• 0.42 (0.36–0.49) for 18.3 years.

In the Royal College of General Practitioners Oral Contraceptive (RCGPOC) study, about 23,000 womenwho did not use COCs and 23,000 current users of COCs were recruited around 1968 and followed for a median of 41 years. In this study, current and recent use of COCs was associated with a decreased RR for ovarian cancer (0.49) and the risk reduction persisted for at least 35 years following COC discontinuation (RR, 0.50; 99% CI, 0.29–0.84).²

In the prospective Nurses’ Health Study (NHS) I, 121,700 nurses were recruited in 1976 and followed for more than 30 years.³ For nurses who reported using COCs for more than 5 years, the rate ratio for ovarian cancer at 20 years or less and greater than 20 years since last use was 0.58 (95% CI, 0.61–0.87) and 0.92 (95% CI, 0.61–1.39), respectively. These studies show that the association between COC use and a decreased risk of ovarian cancer persists for many years after discontinuing COCs.

Endometrial cancer

In the RCGPOC study of 46,000 women, the RR of endometrial cancer among current and recent users of COCs was 0.61, and the reduced risk (0.83) persisted for more than 35 years after discontinuing the COC.²

Related article:
2016 Update on cancer: Endometrial cancer

It is thought that the progestin in the COC provides most of the beneficial effect. Progestin-only contraceptives, such as depotmedroxyprogesterone acetate, progestin implants, and levonorgestrel-releasingintrauterine devices (LNG-IUDs) are also thought to reduce endometrial cancer risk. For instance, in a study of 93,842 Finnish women who used the LNG-IUD, the standardized incidence ratio for endometrial cancer was 0.50 among LNG-IUD users compared with the general population.⁵

Read about the effects of COC use in breast and cervical cancer.

Breast cancer

In the prospective NHS study of 116,608 nurses with 1,246,967 years of follow-up, the multivariate relative risk (mRR) of breast cancer with current COC use was 1.33 (95% CI, 1.03–1.73). Past use of COCs was not associated with a significantly increased risk of breast cancer (mRR, 1.12; 95% CI, 0.95–1.33; NS).⁷

In the RCGPOC study (approximately 46,000 women), current use of COCs was associated with an increased risk of breast cancer (incidence rate ratio [IRR], 1.48; 95% CI,1.10–1.97). Five to 15 years after stopping COCs, there was no significant association between prior COC use and breast cancer (IRR, 1.12; 99% CI, 0.91–1.39; NS).²

Related article:
Webcast: Oral contraceptives and breast cancer: What’s the risk?

It is important to note that it is not possible to conclude from these data whether the reported association between current use of COCs and breast cancer is due to early and accelerated diagnosis of breast cancer, the biological effects of hormones contained in COCs on breast tissue and nascent tumors, or both. In addition, formulations of COCs prescribed in the 1960s and 1970s contained higher doses of estrogen, raising the possibility that the association between COCs and breast cancer is due to COC formulations that are no longer prescribed. However, in animal models and postmenopausal women certain combinations of estrogen plus progestin clearly influence breast cancer biology and cancer risk.^8,9

Cervical cancer

• less than 5 years, 0.73 (95% CI, 0.52–1.03)
• 5 to 9 years, 2.82 (95% CI, 1.46–5.42)
• ≥10 years, 4.03 (95% CI, 2.09–8.02).

It is not possible to conclude from these data whether the association between COC use and cervical cancer is due to the biological effects of hormones on the initiation and progression of HPV disease or confounding factors that have yet to be identified. It is known that estrogens and progestins influence the immune defense system of the lower genital tract, and this may be a pathway that influences the acquisition and progression of viral disease.¹² From a clinical perspective, cervical cancer is largely preventable with HPV vaccination and screening. Therefore, the risk between COC use and cervical cancer is likely limited to women who have not been vaccinated and who are not actively participating in cervical cancer screening.

The bottom line

COC use markedly reduces the risk of ovarian and endometrial cancers, and slightly increases the risk of breast cancer. Prolonged COC use may be associated with an increased risk of cervical cancer. Using available epidemiological data, investigators attempted to project the impact of these competing risks on the approximate 12,300,000 females who live in Australia. Based on the pattern of COC use and the cancer incidence in Australia in 2010, the investigators calculated that COC use would cause about 105 breast and 52 cervical cancers and prevent 1,032 endometrial and 308 ovarian cancers.¹³ This analysis indicates that the balance of risks and benefits related to COC use and cancer generally favors COC use.

Prevention of unintended pregnancy is a major public health goal. Many women choose COCs as their preferred approach to preventing unintended pregnancy. Evaluated from a whole-life perspective the health benefits of COCs are substantial and represent a great advance in women’s health.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

There are no large randomized clinical trials exploring the relationship between COCs and the risk of developing cancer. Many epidemiological studies, however, have investigated the possible association between COC use and the risk of cancer. Such prospective and retrospective studies consistently report that the use of COCs significantly decreases the risk of ovarian and endometrial cancer. The epidemiological data are less consistent concerning the possible association between COC use and the risk of breast cancer. Meta-analyses conclude that current use of COCs may be associated with a small increase in breast cancer risk. In addition, prolonged use of COCs may be associated with an increased risk of cervical cancer.

Ovarian cancer

• 0.78 (0.73–0.83) for 2.4 years
• 0.64 (0.59–0.69) for 6.8 years
• 0.56 (0.50–0.62) for 11.6 years
• 0.42 (0.36–0.49) for 18.3 years.

In the Royal College of General Practitioners Oral Contraceptive (RCGPOC) study, about 23,000 womenwho did not use COCs and 23,000 current users of COCs were recruited around 1968 and followed for a median of 41 years. In this study, current and recent use of COCs was associated with a decreased RR for ovarian cancer (0.49) and the risk reduction persisted for at least 35 years following COC discontinuation (RR, 0.50; 99% CI, 0.29–0.84).²

In the prospective Nurses’ Health Study (NHS) I, 121,700 nurses were recruited in 1976 and followed for more than 30 years.³ For nurses who reported using COCs for more than 5 years, the rate ratio for ovarian cancer at 20 years or less and greater than 20 years since last use was 0.58 (95% CI, 0.61–0.87) and 0.92 (95% CI, 0.61–1.39), respectively. These studies show that the association between COC use and a decreased risk of ovarian cancer persists for many years after discontinuing COCs.

Endometrial cancer

In the RCGPOC study of 46,000 women, the RR of endometrial cancer among current and recent users of COCs was 0.61, and the reduced risk (0.83) persisted for more than 35 years after discontinuing the COC.²

Related article:
2016 Update on cancer: Endometrial cancer

It is thought that the progestin in the COC provides most of the beneficial effect. Progestin-only contraceptives, such as depotmedroxyprogesterone acetate, progestin implants, and levonorgestrel-releasingintrauterine devices (LNG-IUDs) are also thought to reduce endometrial cancer risk. For instance, in a study of 93,842 Finnish women who used the LNG-IUD, the standardized incidence ratio for endometrial cancer was 0.50 among LNG-IUD users compared with the general population.⁵

Read about the effects of COC use in breast and cervical cancer.

Breast cancer

In the prospective NHS study of 116,608 nurses with 1,246,967 years of follow-up, the multivariate relative risk (mRR) of breast cancer with current COC use was 1.33 (95% CI, 1.03–1.73). Past use of COCs was not associated with a significantly increased risk of breast cancer (mRR, 1.12; 95% CI, 0.95–1.33; NS).⁷

In the RCGPOC study (approximately 46,000 women), current use of COCs was associated with an increased risk of breast cancer (incidence rate ratio [IRR], 1.48; 95% CI,1.10–1.97). Five to 15 years after stopping COCs, there was no significant association between prior COC use and breast cancer (IRR, 1.12; 99% CI, 0.91–1.39; NS).²

Related article:
Webcast: Oral contraceptives and breast cancer: What’s the risk?

It is important to note that it is not possible to conclude from these data whether the reported association between current use of COCs and breast cancer is due to early and accelerated diagnosis of breast cancer, the biological effects of hormones contained in COCs on breast tissue and nascent tumors, or both. In addition, formulations of COCs prescribed in the 1960s and 1970s contained higher doses of estrogen, raising the possibility that the association between COCs and breast cancer is due to COC formulations that are no longer prescribed. However, in animal models and postmenopausal women certain combinations of estrogen plus progestin clearly influence breast cancer biology and cancer risk.^8,9

Cervical cancer

• less than 5 years, 0.73 (95% CI, 0.52–1.03)
• 5 to 9 years, 2.82 (95% CI, 1.46–5.42)
• ≥10 years, 4.03 (95% CI, 2.09–8.02).

It is not possible to conclude from these data whether the association between COC use and cervical cancer is due to the biological effects of hormones on the initiation and progression of HPV disease or confounding factors that have yet to be identified. It is known that estrogens and progestins influence the immune defense system of the lower genital tract, and this may be a pathway that influences the acquisition and progression of viral disease.¹² From a clinical perspective, cervical cancer is largely preventable with HPV vaccination and screening. Therefore, the risk between COC use and cervical cancer is likely limited to women who have not been vaccinated and who are not actively participating in cervical cancer screening.

The bottom line

COC use markedly reduces the risk of ovarian and endometrial cancers, and slightly increases the risk of breast cancer. Prolonged COC use may be associated with an increased risk of cervical cancer. Using available epidemiological data, investigators attempted to project the impact of these competing risks on the approximate 12,300,000 females who live in Australia. Based on the pattern of COC use and the cancer incidence in Australia in 2010, the investigators calculated that COC use would cause about 105 breast and 52 cervical cancers and prevent 1,032 endometrial and 308 ovarian cancers.¹³ This analysis indicates that the balance of risks and benefits related to COC use and cancer generally favors COC use.

Prevention of unintended pregnancy is a major public health goal. Many women choose COCs as their preferred approach to preventing unintended pregnancy. Evaluated from a whole-life perspective the health benefits of COCs are substantial and represent a great advance in women’s health.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

There are no large randomized clinical trials exploring the relationship between COCs and the risk of developing cancer. Many epidemiological studies, however, have investigated the possible association between COC use and the risk of cancer. Such prospective and retrospective studies consistently report that the use of COCs significantly decreases the risk of ovarian and endometrial cancer. The epidemiological data are less consistent concerning the possible association between COC use and the risk of breast cancer. Meta-analyses conclude that current use of COCs may be associated with a small increase in breast cancer risk. In addition, prolonged use of COCs may be associated with an increased risk of cervical cancer.

Ovarian cancer

• 0.78 (0.73–0.83) for 2.4 years
• 0.64 (0.59–0.69) for 6.8 years
• 0.56 (0.50–0.62) for 11.6 years
• 0.42 (0.36–0.49) for 18.3 years.

In the Royal College of General Practitioners Oral Contraceptive (RCGPOC) study, about 23,000 womenwho did not use COCs and 23,000 current users of COCs were recruited around 1968 and followed for a median of 41 years. In this study, current and recent use of COCs was associated with a decreased RR for ovarian cancer (0.49) and the risk reduction persisted for at least 35 years following COC discontinuation (RR, 0.50; 99% CI, 0.29–0.84).²

In the prospective Nurses’ Health Study (NHS) I, 121,700 nurses were recruited in 1976 and followed for more than 30 years.³ For nurses who reported using COCs for more than 5 years, the rate ratio for ovarian cancer at 20 years or less and greater than 20 years since last use was 0.58 (95% CI, 0.61–0.87) and 0.92 (95% CI, 0.61–1.39), respectively. These studies show that the association between COC use and a decreased risk of ovarian cancer persists for many years after discontinuing COCs.

Endometrial cancer

In the RCGPOC study of 46,000 women, the RR of endometrial cancer among current and recent users of COCs was 0.61, and the reduced risk (0.83) persisted for more than 35 years after discontinuing the COC.²

Related article:
2016 Update on cancer: Endometrial cancer

It is thought that the progestin in the COC provides most of the beneficial effect. Progestin-only contraceptives, such as depotmedroxyprogesterone acetate, progestin implants, and levonorgestrel-releasingintrauterine devices (LNG-IUDs) are also thought to reduce endometrial cancer risk. For instance, in a study of 93,842 Finnish women who used the LNG-IUD, the standardized incidence ratio for endometrial cancer was 0.50 among LNG-IUD users compared with the general population.⁵

Read about the effects of COC use in breast and cervical cancer.

Breast cancer

In the prospective NHS study of 116,608 nurses with 1,246,967 years of follow-up, the multivariate relative risk (mRR) of breast cancer with current COC use was 1.33 (95% CI, 1.03–1.73). Past use of COCs was not associated with a significantly increased risk of breast cancer (mRR, 1.12; 95% CI, 0.95–1.33; NS).⁷

In the RCGPOC study (approximately 46,000 women), current use of COCs was associated with an increased risk of breast cancer (incidence rate ratio [IRR], 1.48; 95% CI,1.10–1.97). Five to 15 years after stopping COCs, there was no significant association between prior COC use and breast cancer (IRR, 1.12; 99% CI, 0.91–1.39; NS).²

Related article:
Webcast: Oral contraceptives and breast cancer: What’s the risk?

It is important to note that it is not possible to conclude from these data whether the reported association between current use of COCs and breast cancer is due to early and accelerated diagnosis of breast cancer, the biological effects of hormones contained in COCs on breast tissue and nascent tumors, or both. In addition, formulations of COCs prescribed in the 1960s and 1970s contained higher doses of estrogen, raising the possibility that the association between COCs and breast cancer is due to COC formulations that are no longer prescribed. However, in animal models and postmenopausal women certain combinations of estrogen plus progestin clearly influence breast cancer biology and cancer risk.^8,9

Cervical cancer

• less than 5 years, 0.73 (95% CI, 0.52–1.03)
• 5 to 9 years, 2.82 (95% CI, 1.46–5.42)
• ≥10 years, 4.03 (95% CI, 2.09–8.02).

It is not possible to conclude from these data whether the association between COC use and cervical cancer is due to the biological effects of hormones on the initiation and progression of HPV disease or confounding factors that have yet to be identified. It is known that estrogens and progestins influence the immune defense system of the lower genital tract, and this may be a pathway that influences the acquisition and progression of viral disease.¹² From a clinical perspective, cervical cancer is largely preventable with HPV vaccination and screening. Therefore, the risk between COC use and cervical cancer is likely limited to women who have not been vaccinated and who are not actively participating in cervical cancer screening.

The bottom line

COC use markedly reduces the risk of ovarian and endometrial cancers, and slightly increases the risk of breast cancer. Prolonged COC use may be associated with an increased risk of cervical cancer. Using available epidemiological data, investigators attempted to project the impact of these competing risks on the approximate 12,300,000 females who live in Australia. Based on the pattern of COC use and the cancer incidence in Australia in 2010, the investigators calculated that COC use would cause about 105 breast and 52 cervical cancers and prevent 1,032 endometrial and 308 ovarian cancers.¹³ This analysis indicates that the balance of risks and benefits related to COC use and cancer generally favors COC use.

Prevention of unintended pregnancy is a major public health goal. Many women choose COCs as their preferred approach to preventing unintended pregnancy. Evaluated from a whole-life perspective the health benefits of COCs are substantial and represent a great advance in women’s health.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During the past 45 years, the cesarean delivery (CD) rate in the United States has increased from 5.5% in 1970 to 33% from 2009 to 2013, followed by a small decrease to 32% in 2014 and 2015.¹ Many clinical problems cause clinicians and patients to decide that CD is an optimal birth route, including: abnormal labor progress, abnormal or indeterminate fetal heart rate pattern, breech presentation, multiple gestation, macrosomia, placental and cord abnormalities, preeclampsia, prior uterine surgery, and prior CD.² Recent secular trends that contribute to the current rate of CD include an adversarial liability environment,^3,4 increasing rates of maternal obesity,⁵ and widespread use of continuous fetal-heart monitoring during labor.⁶

Wide variation in CD rate has been reported among countries, states, and hospitals. The variation is due, in part, to different perspectives about balancing the harms and benefits of vaginal delivery versus CD. In Europe, in 2010 the CD rates in Sweden and Italy were 17.1% and 38%, respectively.⁷ In 2010, among the states, Alaska had the lowest rate of CD at 22% and Kentucky had the highest rate at 40%.⁸ In 2015, the highest rate was 38%, in Mississippi (FIGURE).⁹ In 2014, among Massachusetts hospitals with more than 2,500 births, the CD rate ranged from a low of 22% to a high of 37%.¹⁰

Clinicians, patients, policy experts, and the media are perplexed and troubled by the “high” US CD rate and the major variation in rate among countries, states, and hospitals. Labor management practices likely influence the rate of CD and diverse approaches to labor management likely account for the wide variation in CD rates.

A nationwide effort to standardize and continuously improve labor management might result in a decrease in the CD rate. Building on this opportunity, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) have jointly recommended new labor management guidelines that may reduce the primary CD rate.⁸

The ACOG/SMFM guidelines encourage obstetricians to extend the time for labor progress in both the 1st and 2nd stages prior to recommending a CD.⁸ These new guidelines emphasize that for a modern obstetrician, patience is a virtue. There are 2 important caveats to this statement: to safely extend the length of time of labor requires both (1) a reassuring fetal heart rate tracing and (2) stable maternal health. If the fetus demonstrates a persistent worrisome Category II or a Category IIIheart-rate tracing, decisive intervention is necessary and permitting an extended labor would not be optimal. Similarly, if the mother has rapidly worsening preeclampsia it may not be wise to extend an induction of labor (IOL) over many days.

There are risks with extending the length of labor. An extended duration of the 1st stage of labor is associated with an increased rate of maternal chorioamnionitis and shoulder dystocia at birth.¹¹ An extended duration of the 2nd stage of labor is associated with an increase in the rate of maternal chorioamnionitis, anal sphincter injury, uterine atony, and neonatal admission to an intensive care unit.¹² Clinicians who adopt practices that permit an extended length of labor must weigh the benefits of avoiding a CD against these maternal and fetal complications.

Active phase redefined

Central to the ACOG/SMFM guidelines is a new definition of the active phase of labor. The research of Dr. Emmanuel Friedman indicated that at approximately 4 cm of cervical dilation many women in labor transition from the latent phase, a time of slow change in cervical dilation, to the active phase, a time of more rapid change in cervical dilation.^13,14 However, more recent research indicates that the transition between the latent and active phase is difficult to precisely define, but more often occurs at about 6 cm of cervical dilation and not 4 cm of dilation.¹⁵ Adopting these new norms means that laboring women will spend much more time in the latent phase, a phase of labor in which patience is a virtue.

The ACOG/SMFM guidelines

Main takeaways from the ACOG/SMFM guidelines are summarized below. Interventions that address common obstetric issues and labor abnormalities are outlined below.

Do not perform CD for a prolonged latent phase of labor, defined as regular contractions of >20 hours duration in nulliparous women and >14 hours duration in multiparous women. Patience with a prolonged latent phase will be rewarded by the majority of women entering the active phase of labor. Alternatively, if appropriate, cervical ripening followed by oxytocin IOL and amniotomy will help the patient with a prolonged latent phase to enter the active phase of labor.¹⁶

For women with an unfavorable cervix as assessed by the Bishop score, cervical ripening should be performed prior to IOL. Use of cervical ripening prior to IOL increases the chance of achieving vaginal delivery within 24 hours and may result in a modest decrease in the rate of CD.^17,18

Related article:
Should oxytocin and a Foley catheter be used concurrently for cervical ripening in induction of labor?
 

Failed IOL in the latent phase should only be diagnosed following 12 to 18 hours of both ruptured membranes and adequate contractions stimulated with oxytocin. The key ingredients for the successful management of the latent phase of labor are patience, oxytocin, and amniotomy.¹⁶

CD for the indication of active phase arrest requires cervical dilation ≥6 cm with ruptured membranes and no change in cervical dilation for ≥4 hours of adequate uterine activity. In the past, most obstetricians defined active phase arrest, a potential indication for CD, as the absence of cervical change for 2 or more hours in the presence of adequate uterine contractions and cervical dilation of at least 4 cm. Given the new definition of active phase arrest, slow but progressive progress in the 1st stage of labor is not an indication for CD.^11,19

“A specific absolute maximum length of time spent in the 2nd stage beyond which all women should be offered an operative delivery has not been identified.”⁸ Diagnosis of arrest of labor in the 2nd stage may be considered after at least 2 hours of pushing in multiparous women and 3 hours of pushing in nulliparous women, especially if no fetal descent is occurring. The guidelines also state “longer durations may be appropriate on an individualized basis (eg, with use of epidural analgesia or with fetal malposition)” as long as fetal descent is observed.

Patience is a virtue, especially in the management of the 2nd stage of labor. Extending the 2nd stage up to 4 hours appears to be reasonably safe if the fetal status is reassuring and the mother is physiologically stable. In a study from San Francisco of 42,268 births with normal newborn outcomes, the 95th percentile for the length of the 2nd stage of labor for nulliparous women was 3.3 hours without an epidural and 5.6 hours with an epidural.²⁰

In a study of 53,285 births, longer duration of pushing was associated with a small increase in the rate of neonatal adverse outcomes. In nulliparous women the rate of adverse neonatal outcomes increased from 1.3% with less than 60 minutes of pushing to 2.4% with greater than 240 minutes of pushing. Remarkably, even after 4 hours of pushing, 78% of nulliparous women who continued to push had a vaginal delivery.²¹ In this study, among nulliparous women the rate of anal sphincter injury increased from 5% with less than 60 minutes of pushing to 16% with greater than 240 minutes of pushing, and the rate of postpartum hemorrhage increased from 1% with less than 60 minutes of pushing to 3.3% with greater than 240 minutes of pushing.

I am not enthusiastic about patiently watching a labor extend into the 5th hour of the 2nd stage, especially if the fetus is at +2 station or lower. In a nulliparous woman, after 4 hours of managing the 2nd stage of labor, my patience is exhausted and I am inclined to identify a clear plan for delivery, either by enhanced labor coaching, operative vaginal delivery, or CD.

Operative vaginal delivery in the 2nd stage of labor is an acceptable alternative to CD. The rate of operative vaginal delivery in the United States has declined over the past 2 decades (TABLE). In Sweden in 2010 the operative vaginal delivery rate was 7.6% with a CD rate of 17.1%.⁷ In the United States in 2010 the operative delivery rate was 3.6%, and the CD rate was 33%.¹ A renewed focus on operative vaginal delivery with ongoing training and team simulation for the procedure would increase our use of operative delivery and decrease the overall rate of CD.

Related article:
STOP using instruments to assist with delivery of the head at cesarean
 

Encourage the detection of persistent fetal occiput posterior position by physical examination and/or ultrasound and consider manual rotation of the fetal occiput from the posterior to anterior position in the 2nd stage. Persistent occiput posterior is the most common fetal malposition.²² This malposition is associated with an increased rate of CD.²³ There are few randomized trials of manual rotation of the fetal occiput from posterior to anterior position in the 2nd stage of labor, and the evidence is insufficient to determine the efficacy of manual rotation.²⁴ Small nonrandomized studies report that manual rotation of the occiput from posterior to anterior position may reduce the CD rate.^25–27

For persistent 2nd stage fetal occiput posterior position in a woman with an adequate pelvis, where manual rotation was not successful and the fetus is at +2 station or below, operative vaginal delivery is an option. “Vacuum or forceps?” and “If forceps, to rotate or not to rotate?” those are the clinical questions. Forceps delivery is more likely to be successfulthan vacuum delivery.²⁸ Direct forceps delivery of the occiput posterior fetus is associated with more anal sphincter injuries than forceps delivery after successful rotation, but few clinicians regularly perform rotational forceps.²⁹ In a study of 2,351 women in the 2nd stage of labor with the fetus at +2 station or below, compared with either forceps or vacuum delivery, CD was associated with more maternal infections and fewer perineal lacerations. Neonatal composite morbidity was not significantly different among the 3 routes of operative delivery.³⁰

Amnioinfusion for repetitive variable decelerations of the fetal heart rate may reduce the risk of CD for an indeterminate fetal heart-rate pattern.³¹

IOL in a well-dated pregnancy at 41 weeks will reduce the risk of CD. In a large clinical trial, 3,407 women at 41 weeks of gestation were randomly assigned to IOL or expectant management. The rate of CD was significantly lower in the women assigned to IOL compared with expectant management (21% vs 25%, respectively; P = .03).³² The rate of neonatal morbidity was similar in the 2 groups.

Women with twin gestations and the first twin in a cephalic presentation may elect vaginal delivery. In a large clinical trial, 1,398 women with a twin gestation and the first twin in a cephalic presentation were randomly assigned to planned vaginal delivery (with cesarean only if necessary) or planned CD.³³ The rate of CD was 44% and 91% for the women in the planned-vaginal and planned-cesarean groups, respectively. There was no significant difference in composite fetal or neonatal death or serious morbidity. The authors concluded that, for twin pregnancy with the presenting twin in the cephalic presentation, there were no demonstrated benefits of planned CD.

Develop maternity care systems that encourage the use of trial of labor after cesarean (TOLAC). The ACOG/SMFM guidelines focus on interventions to reduce the rate of primary CD and do not address the role of TOLAC in reducing CD rates. There are little data from clinical trials to assess the benefits and harms from TOLAC versus scheduled repeat CD.³⁴ However, our experience with TOLAC in the 1990s strongly suggests that encouraging TOLAC will decrease the rate of CD. In 1996 the US rate of vaginal birth after cesarean (VBAC) peaked at 28%, and the rate of CD achieved a recent historic nadir of 21%. Growing concerns that TOLAC occasionally results in fetal harm was followed by a decrease in the VBAC rate to 12% in 2015.¹ A recent study of obstetric practices in countries with high and low VBAC rates concluded that patient and clinician commitment and comfort with prioritizing TOLAC over scheduled repeat CD greatly influenced the VBAC rate.³⁵

Related article:
Should lower uterine segment thickness measurement be included in the TOLAC decision-making process?

Labor management is an art

During labor obstetricians must balance the unique needs of mother and fetus, which requires great clinical skill and patience. Evolving concepts of normal labor progress necessitate that we change our expectations concerning the acceptable rate of progress in the 1st and 2nd stage of labor. Consistent application of these new labor guidelines may help to reduce the rate of CD.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During the past 45 years, the cesarean delivery (CD) rate in the United States has increased from 5.5% in 1970 to 33% from 2009 to 2013, followed by a small decrease to 32% in 2014 and 2015.¹ Many clinical problems cause clinicians and patients to decide that CD is an optimal birth route, including: abnormal labor progress, abnormal or indeterminate fetal heart rate pattern, breech presentation, multiple gestation, macrosomia, placental and cord abnormalities, preeclampsia, prior uterine surgery, and prior CD.² Recent secular trends that contribute to the current rate of CD include an adversarial liability environment,^3,4 increasing rates of maternal obesity,⁵ and widespread use of continuous fetal-heart monitoring during labor.⁶

Wide variation in CD rate has been reported among countries, states, and hospitals. The variation is due, in part, to different perspectives about balancing the harms and benefits of vaginal delivery versus CD. In Europe, in 2010 the CD rates in Sweden and Italy were 17.1% and 38%, respectively.⁷ In 2010, among the states, Alaska had the lowest rate of CD at 22% and Kentucky had the highest rate at 40%.⁸ In 2015, the highest rate was 38%, in Mississippi (FIGURE).⁹ In 2014, among Massachusetts hospitals with more than 2,500 births, the CD rate ranged from a low of 22% to a high of 37%.¹⁰

Clinicians, patients, policy experts, and the media are perplexed and troubled by the “high” US CD rate and the major variation in rate among countries, states, and hospitals. Labor management practices likely influence the rate of CD and diverse approaches to labor management likely account for the wide variation in CD rates.

A nationwide effort to standardize and continuously improve labor management might result in a decrease in the CD rate. Building on this opportunity, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) have jointly recommended new labor management guidelines that may reduce the primary CD rate.⁸

The ACOG/SMFM guidelines encourage obstetricians to extend the time for labor progress in both the 1st and 2nd stages prior to recommending a CD.⁸ These new guidelines emphasize that for a modern obstetrician, patience is a virtue. There are 2 important caveats to this statement: to safely extend the length of time of labor requires both (1) a reassuring fetal heart rate tracing and (2) stable maternal health. If the fetus demonstrates a persistent worrisome Category II or a Category IIIheart-rate tracing, decisive intervention is necessary and permitting an extended labor would not be optimal. Similarly, if the mother has rapidly worsening preeclampsia it may not be wise to extend an induction of labor (IOL) over many days.

There are risks with extending the length of labor. An extended duration of the 1st stage of labor is associated with an increased rate of maternal chorioamnionitis and shoulder dystocia at birth.¹¹ An extended duration of the 2nd stage of labor is associated with an increase in the rate of maternal chorioamnionitis, anal sphincter injury, uterine atony, and neonatal admission to an intensive care unit.¹² Clinicians who adopt practices that permit an extended length of labor must weigh the benefits of avoiding a CD against these maternal and fetal complications.

Active phase redefined

Central to the ACOG/SMFM guidelines is a new definition of the active phase of labor. The research of Dr. Emmanuel Friedman indicated that at approximately 4 cm of cervical dilation many women in labor transition from the latent phase, a time of slow change in cervical dilation, to the active phase, a time of more rapid change in cervical dilation.^13,14 However, more recent research indicates that the transition between the latent and active phase is difficult to precisely define, but more often occurs at about 6 cm of cervical dilation and not 4 cm of dilation.¹⁵ Adopting these new norms means that laboring women will spend much more time in the latent phase, a phase of labor in which patience is a virtue.

The ACOG/SMFM guidelines

Main takeaways from the ACOG/SMFM guidelines are summarized below. Interventions that address common obstetric issues and labor abnormalities are outlined below.

Do not perform CD for a prolonged latent phase of labor, defined as regular contractions of >20 hours duration in nulliparous women and >14 hours duration in multiparous women. Patience with a prolonged latent phase will be rewarded by the majority of women entering the active phase of labor. Alternatively, if appropriate, cervical ripening followed by oxytocin IOL and amniotomy will help the patient with a prolonged latent phase to enter the active phase of labor.¹⁶

For women with an unfavorable cervix as assessed by the Bishop score, cervical ripening should be performed prior to IOL. Use of cervical ripening prior to IOL increases the chance of achieving vaginal delivery within 24 hours and may result in a modest decrease in the rate of CD.^17,18

Related article:
Should oxytocin and a Foley catheter be used concurrently for cervical ripening in induction of labor?
 

Failed IOL in the latent phase should only be diagnosed following 12 to 18 hours of both ruptured membranes and adequate contractions stimulated with oxytocin. The key ingredients for the successful management of the latent phase of labor are patience, oxytocin, and amniotomy.¹⁶

CD for the indication of active phase arrest requires cervical dilation ≥6 cm with ruptured membranes and no change in cervical dilation for ≥4 hours of adequate uterine activity. In the past, most obstetricians defined active phase arrest, a potential indication for CD, as the absence of cervical change for 2 or more hours in the presence of adequate uterine contractions and cervical dilation of at least 4 cm. Given the new definition of active phase arrest, slow but progressive progress in the 1st stage of labor is not an indication for CD.^11,19

“A specific absolute maximum length of time spent in the 2nd stage beyond which all women should be offered an operative delivery has not been identified.”⁸ Diagnosis of arrest of labor in the 2nd stage may be considered after at least 2 hours of pushing in multiparous women and 3 hours of pushing in nulliparous women, especially if no fetal descent is occurring. The guidelines also state “longer durations may be appropriate on an individualized basis (eg, with use of epidural analgesia or with fetal malposition)” as long as fetal descent is observed.

Patience is a virtue, especially in the management of the 2nd stage of labor. Extending the 2nd stage up to 4 hours appears to be reasonably safe if the fetal status is reassuring and the mother is physiologically stable. In a study from San Francisco of 42,268 births with normal newborn outcomes, the 95th percentile for the length of the 2nd stage of labor for nulliparous women was 3.3 hours without an epidural and 5.6 hours with an epidural.²⁰

In a study of 53,285 births, longer duration of pushing was associated with a small increase in the rate of neonatal adverse outcomes. In nulliparous women the rate of adverse neonatal outcomes increased from 1.3% with less than 60 minutes of pushing to 2.4% with greater than 240 minutes of pushing. Remarkably, even after 4 hours of pushing, 78% of nulliparous women who continued to push had a vaginal delivery.²¹ In this study, among nulliparous women the rate of anal sphincter injury increased from 5% with less than 60 minutes of pushing to 16% with greater than 240 minutes of pushing, and the rate of postpartum hemorrhage increased from 1% with less than 60 minutes of pushing to 3.3% with greater than 240 minutes of pushing.

I am not enthusiastic about patiently watching a labor extend into the 5th hour of the 2nd stage, especially if the fetus is at +2 station or lower. In a nulliparous woman, after 4 hours of managing the 2nd stage of labor, my patience is exhausted and I am inclined to identify a clear plan for delivery, either by enhanced labor coaching, operative vaginal delivery, or CD.

Operative vaginal delivery in the 2nd stage of labor is an acceptable alternative to CD. The rate of operative vaginal delivery in the United States has declined over the past 2 decades (TABLE). In Sweden in 2010 the operative vaginal delivery rate was 7.6% with a CD rate of 17.1%.⁷ In the United States in 2010 the operative delivery rate was 3.6%, and the CD rate was 33%.¹ A renewed focus on operative vaginal delivery with ongoing training and team simulation for the procedure would increase our use of operative delivery and decrease the overall rate of CD.

Related article:
STOP using instruments to assist with delivery of the head at cesarean
 

Encourage the detection of persistent fetal occiput posterior position by physical examination and/or ultrasound and consider manual rotation of the fetal occiput from the posterior to anterior position in the 2nd stage. Persistent occiput posterior is the most common fetal malposition.²² This malposition is associated with an increased rate of CD.²³ There are few randomized trials of manual rotation of the fetal occiput from posterior to anterior position in the 2nd stage of labor, and the evidence is insufficient to determine the efficacy of manual rotation.²⁴ Small nonrandomized studies report that manual rotation of the occiput from posterior to anterior position may reduce the CD rate.^25–27

For persistent 2nd stage fetal occiput posterior position in a woman with an adequate pelvis, where manual rotation was not successful and the fetus is at +2 station or below, operative vaginal delivery is an option. “Vacuum or forceps?” and “If forceps, to rotate or not to rotate?” those are the clinical questions. Forceps delivery is more likely to be successfulthan vacuum delivery.²⁸ Direct forceps delivery of the occiput posterior fetus is associated with more anal sphincter injuries than forceps delivery after successful rotation, but few clinicians regularly perform rotational forceps.²⁹ In a study of 2,351 women in the 2nd stage of labor with the fetus at +2 station or below, compared with either forceps or vacuum delivery, CD was associated with more maternal infections and fewer perineal lacerations. Neonatal composite morbidity was not significantly different among the 3 routes of operative delivery.³⁰

Amnioinfusion for repetitive variable decelerations of the fetal heart rate may reduce the risk of CD for an indeterminate fetal heart-rate pattern.³¹

IOL in a well-dated pregnancy at 41 weeks will reduce the risk of CD. In a large clinical trial, 3,407 women at 41 weeks of gestation were randomly assigned to IOL or expectant management. The rate of CD was significantly lower in the women assigned to IOL compared with expectant management (21% vs 25%, respectively; P = .03).³² The rate of neonatal morbidity was similar in the 2 groups.

Women with twin gestations and the first twin in a cephalic presentation may elect vaginal delivery. In a large clinical trial, 1,398 women with a twin gestation and the first twin in a cephalic presentation were randomly assigned to planned vaginal delivery (with cesarean only if necessary) or planned CD.³³ The rate of CD was 44% and 91% for the women in the planned-vaginal and planned-cesarean groups, respectively. There was no significant difference in composite fetal or neonatal death or serious morbidity. The authors concluded that, for twin pregnancy with the presenting twin in the cephalic presentation, there were no demonstrated benefits of planned CD.

Develop maternity care systems that encourage the use of trial of labor after cesarean (TOLAC). The ACOG/SMFM guidelines focus on interventions to reduce the rate of primary CD and do not address the role of TOLAC in reducing CD rates. There are little data from clinical trials to assess the benefits and harms from TOLAC versus scheduled repeat CD.³⁴ However, our experience with TOLAC in the 1990s strongly suggests that encouraging TOLAC will decrease the rate of CD. In 1996 the US rate of vaginal birth after cesarean (VBAC) peaked at 28%, and the rate of CD achieved a recent historic nadir of 21%. Growing concerns that TOLAC occasionally results in fetal harm was followed by a decrease in the VBAC rate to 12% in 2015.¹ A recent study of obstetric practices in countries with high and low VBAC rates concluded that patient and clinician commitment and comfort with prioritizing TOLAC over scheduled repeat CD greatly influenced the VBAC rate.³⁵

Related article:
Should lower uterine segment thickness measurement be included in the TOLAC decision-making process?

Labor management is an art

During labor obstetricians must balance the unique needs of mother and fetus, which requires great clinical skill and patience. Evolving concepts of normal labor progress necessitate that we change our expectations concerning the acceptable rate of progress in the 1st and 2nd stage of labor. Consistent application of these new labor guidelines may help to reduce the rate of CD.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During the past 45 years, the cesarean delivery (CD) rate in the United States has increased from 5.5% in 1970 to 33% from 2009 to 2013, followed by a small decrease to 32% in 2014 and 2015.¹ Many clinical problems cause clinicians and patients to decide that CD is an optimal birth route, including: abnormal labor progress, abnormal or indeterminate fetal heart rate pattern, breech presentation, multiple gestation, macrosomia, placental and cord abnormalities, preeclampsia, prior uterine surgery, and prior CD.² Recent secular trends that contribute to the current rate of CD include an adversarial liability environment,^3,4 increasing rates of maternal obesity,⁵ and widespread use of continuous fetal-heart monitoring during labor.⁶

Wide variation in CD rate has been reported among countries, states, and hospitals. The variation is due, in part, to different perspectives about balancing the harms and benefits of vaginal delivery versus CD. In Europe, in 2010 the CD rates in Sweden and Italy were 17.1% and 38%, respectively.⁷ In 2010, among the states, Alaska had the lowest rate of CD at 22% and Kentucky had the highest rate at 40%.⁸ In 2015, the highest rate was 38%, in Mississippi (FIGURE).⁹ In 2014, among Massachusetts hospitals with more than 2,500 births, the CD rate ranged from a low of 22% to a high of 37%.¹⁰

Clinicians, patients, policy experts, and the media are perplexed and troubled by the “high” US CD rate and the major variation in rate among countries, states, and hospitals. Labor management practices likely influence the rate of CD and diverse approaches to labor management likely account for the wide variation in CD rates.

A nationwide effort to standardize and continuously improve labor management might result in a decrease in the CD rate. Building on this opportunity, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) have jointly recommended new labor management guidelines that may reduce the primary CD rate.⁸

The ACOG/SMFM guidelines encourage obstetricians to extend the time for labor progress in both the 1st and 2nd stages prior to recommending a CD.⁸ These new guidelines emphasize that for a modern obstetrician, patience is a virtue. There are 2 important caveats to this statement: to safely extend the length of time of labor requires both (1) a reassuring fetal heart rate tracing and (2) stable maternal health. If the fetus demonstrates a persistent worrisome Category II or a Category IIIheart-rate tracing, decisive intervention is necessary and permitting an extended labor would not be optimal. Similarly, if the mother has rapidly worsening preeclampsia it may not be wise to extend an induction of labor (IOL) over many days.

There are risks with extending the length of labor. An extended duration of the 1st stage of labor is associated with an increased rate of maternal chorioamnionitis and shoulder dystocia at birth.¹¹ An extended duration of the 2nd stage of labor is associated with an increase in the rate of maternal chorioamnionitis, anal sphincter injury, uterine atony, and neonatal admission to an intensive care unit.¹² Clinicians who adopt practices that permit an extended length of labor must weigh the benefits of avoiding a CD against these maternal and fetal complications.

Active phase redefined

Central to the ACOG/SMFM guidelines is a new definition of the active phase of labor. The research of Dr. Emmanuel Friedman indicated that at approximately 4 cm of cervical dilation many women in labor transition from the latent phase, a time of slow change in cervical dilation, to the active phase, a time of more rapid change in cervical dilation.^13,14 However, more recent research indicates that the transition between the latent and active phase is difficult to precisely define, but more often occurs at about 6 cm of cervical dilation and not 4 cm of dilation.¹⁵ Adopting these new norms means that laboring women will spend much more time in the latent phase, a phase of labor in which patience is a virtue.

The ACOG/SMFM guidelines

Main takeaways from the ACOG/SMFM guidelines are summarized below. Interventions that address common obstetric issues and labor abnormalities are outlined below.

Do not perform CD for a prolonged latent phase of labor, defined as regular contractions of >20 hours duration in nulliparous women and >14 hours duration in multiparous women. Patience with a prolonged latent phase will be rewarded by the majority of women entering the active phase of labor. Alternatively, if appropriate, cervical ripening followed by oxytocin IOL and amniotomy will help the patient with a prolonged latent phase to enter the active phase of labor.¹⁶

For women with an unfavorable cervix as assessed by the Bishop score, cervical ripening should be performed prior to IOL. Use of cervical ripening prior to IOL increases the chance of achieving vaginal delivery within 24 hours and may result in a modest decrease in the rate of CD.^17,18

Related article:
Should oxytocin and a Foley catheter be used concurrently for cervical ripening in induction of labor?
 

Failed IOL in the latent phase should only be diagnosed following 12 to 18 hours of both ruptured membranes and adequate contractions stimulated with oxytocin. The key ingredients for the successful management of the latent phase of labor are patience, oxytocin, and amniotomy.¹⁶

CD for the indication of active phase arrest requires cervical dilation ≥6 cm with ruptured membranes and no change in cervical dilation for ≥4 hours of adequate uterine activity. In the past, most obstetricians defined active phase arrest, a potential indication for CD, as the absence of cervical change for 2 or more hours in the presence of adequate uterine contractions and cervical dilation of at least 4 cm. Given the new definition of active phase arrest, slow but progressive progress in the 1st stage of labor is not an indication for CD.^11,19

“A specific absolute maximum length of time spent in the 2nd stage beyond which all women should be offered an operative delivery has not been identified.”⁸ Diagnosis of arrest of labor in the 2nd stage may be considered after at least 2 hours of pushing in multiparous women and 3 hours of pushing in nulliparous women, especially if no fetal descent is occurring. The guidelines also state “longer durations may be appropriate on an individualized basis (eg, with use of epidural analgesia or with fetal malposition)” as long as fetal descent is observed.

Patience is a virtue, especially in the management of the 2nd stage of labor. Extending the 2nd stage up to 4 hours appears to be reasonably safe if the fetal status is reassuring and the mother is physiologically stable. In a study from San Francisco of 42,268 births with normal newborn outcomes, the 95th percentile for the length of the 2nd stage of labor for nulliparous women was 3.3 hours without an epidural and 5.6 hours with an epidural.²⁰

In a study of 53,285 births, longer duration of pushing was associated with a small increase in the rate of neonatal adverse outcomes. In nulliparous women the rate of adverse neonatal outcomes increased from 1.3% with less than 60 minutes of pushing to 2.4% with greater than 240 minutes of pushing. Remarkably, even after 4 hours of pushing, 78% of nulliparous women who continued to push had a vaginal delivery.²¹ In this study, among nulliparous women the rate of anal sphincter injury increased from 5% with less than 60 minutes of pushing to 16% with greater than 240 minutes of pushing, and the rate of postpartum hemorrhage increased from 1% with less than 60 minutes of pushing to 3.3% with greater than 240 minutes of pushing.

I am not enthusiastic about patiently watching a labor extend into the 5th hour of the 2nd stage, especially if the fetus is at +2 station or lower. In a nulliparous woman, after 4 hours of managing the 2nd stage of labor, my patience is exhausted and I am inclined to identify a clear plan for delivery, either by enhanced labor coaching, operative vaginal delivery, or CD.

Operative vaginal delivery in the 2nd stage of labor is an acceptable alternative to CD. The rate of operative vaginal delivery in the United States has declined over the past 2 decades (TABLE). In Sweden in 2010 the operative vaginal delivery rate was 7.6% with a CD rate of 17.1%.⁷ In the United States in 2010 the operative delivery rate was 3.6%, and the CD rate was 33%.¹ A renewed focus on operative vaginal delivery with ongoing training and team simulation for the procedure would increase our use of operative delivery and decrease the overall rate of CD.

Related article:
STOP using instruments to assist with delivery of the head at cesarean
 

Encourage the detection of persistent fetal occiput posterior position by physical examination and/or ultrasound and consider manual rotation of the fetal occiput from the posterior to anterior position in the 2nd stage. Persistent occiput posterior is the most common fetal malposition.²² This malposition is associated with an increased rate of CD.²³ There are few randomized trials of manual rotation of the fetal occiput from posterior to anterior position in the 2nd stage of labor, and the evidence is insufficient to determine the efficacy of manual rotation.²⁴ Small nonrandomized studies report that manual rotation of the occiput from posterior to anterior position may reduce the CD rate.^25–27

For persistent 2nd stage fetal occiput posterior position in a woman with an adequate pelvis, where manual rotation was not successful and the fetus is at +2 station or below, operative vaginal delivery is an option. “Vacuum or forceps?” and “If forceps, to rotate or not to rotate?” those are the clinical questions. Forceps delivery is more likely to be successfulthan vacuum delivery.²⁸ Direct forceps delivery of the occiput posterior fetus is associated with more anal sphincter injuries than forceps delivery after successful rotation, but few clinicians regularly perform rotational forceps.²⁹ In a study of 2,351 women in the 2nd stage of labor with the fetus at +2 station or below, compared with either forceps or vacuum delivery, CD was associated with more maternal infections and fewer perineal lacerations. Neonatal composite morbidity was not significantly different among the 3 routes of operative delivery.³⁰

Amnioinfusion for repetitive variable decelerations of the fetal heart rate may reduce the risk of CD for an indeterminate fetal heart-rate pattern.³¹

IOL in a well-dated pregnancy at 41 weeks will reduce the risk of CD. In a large clinical trial, 3,407 women at 41 weeks of gestation were randomly assigned to IOL or expectant management. The rate of CD was significantly lower in the women assigned to IOL compared with expectant management (21% vs 25%, respectively; P = .03).³² The rate of neonatal morbidity was similar in the 2 groups.

Women with twin gestations and the first twin in a cephalic presentation may elect vaginal delivery. In a large clinical trial, 1,398 women with a twin gestation and the first twin in a cephalic presentation were randomly assigned to planned vaginal delivery (with cesarean only if necessary) or planned CD.³³ The rate of CD was 44% and 91% for the women in the planned-vaginal and planned-cesarean groups, respectively. There was no significant difference in composite fetal or neonatal death or serious morbidity. The authors concluded that, for twin pregnancy with the presenting twin in the cephalic presentation, there were no demonstrated benefits of planned CD.

Develop maternity care systems that encourage the use of trial of labor after cesarean (TOLAC). The ACOG/SMFM guidelines focus on interventions to reduce the rate of primary CD and do not address the role of TOLAC in reducing CD rates. There are little data from clinical trials to assess the benefits and harms from TOLAC versus scheduled repeat CD.³⁴ However, our experience with TOLAC in the 1990s strongly suggests that encouraging TOLAC will decrease the rate of CD. In 1996 the US rate of vaginal birth after cesarean (VBAC) peaked at 28%, and the rate of CD achieved a recent historic nadir of 21%. Growing concerns that TOLAC occasionally results in fetal harm was followed by a decrease in the VBAC rate to 12% in 2015.¹ A recent study of obstetric practices in countries with high and low VBAC rates concluded that patient and clinician commitment and comfort with prioritizing TOLAC over scheduled repeat CD greatly influenced the VBAC rate.³⁵

Related article:
Should lower uterine segment thickness measurement be included in the TOLAC decision-making process?

Labor management is an art

During labor obstetricians must balance the unique needs of mother and fetus, which requires great clinical skill and patience. Evolving concepts of normal labor progress necessitate that we change our expectations concerning the acceptable rate of progress in the 1st and 2nd stage of labor. Consistent application of these new labor guidelines may help to reduce the rate of CD.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Using the Rotterdam criteria, the diagnosis of polycystic ovary syndrome (PCOS) is made in the presence of 2 of the following 3 criteria¹:

1. oligo-ovulation or anovulation
2. hyperandrogenism manifested by the presence of either hirsutism or elevated hormone levels (including serum testosterone androstenedione and/or dehydroepiandrosterone sulfate)
3. ultrasonography evidence of multifollicular ovaries (≥12 follicles with a diameter of 2 mm to 9 mm in one or both ovaries; FIGURE) or ovarian stromal volume of 10 mL or more.

Illustration: Kimberly Martens for OBG Management

Among reproductive-age women, the prevalence of PCOS has been reported to range from 8% to 13% for different populations.² Most clinicians initiate treatment for PCOS with oral estrogen−progestin (OEP) monotherapy. OEP treatment has many beneficial hormonal effects, including:

• a resulting decrease in pituitary luteinizing hormone (LH) secretion, which decreases ovarian androgen production
• an increase in liver production of sex hormone−binding globulin (SHBG), which decreases free testosterone levels
• protection against the development of endometrial hyperplasia
• induction of regular uterine withdrawal bleeding.

However, OEP therapy neither improves metabolic indices (insulin sensitivity and visceral fat secretion of adipokines) nor blocks androgen action in the skin.

Dual medical treatment for PCOS can address the issues that monotherapy cannot and, along with providing guidance on improving diet and exercise, many experts support the initial therapy of PCOS with dual medical therapy (OEP plus metformin or spironolactone).

Advantages of OEP plus metformin

For many women with PCOS, the syndrome is characterized by abnormalities in both the reproductive (increase in LH secretion) and metabolic (insulin resistance and increased adipokines) systems. OEP monotherapy does not improve the metabolic abnormalities of PCOS. Combination treatment with both OEP plus metformin, along with diet and exercise, can best treat these combined abnormalities.

Data support dual therapy with metformin. In one small, randomized trial in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater reduction in serum androstenedione and a greater increase in SHBG than OEP monotherapy.³ In addition, weight loss and a reduction in waist-to-hip ratio only occurred in the OEP plus metformin group.³ In another small randomized study in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater decrease in free androgen index than OEP monotherapy.⁴

In my clinical opinion, women who may best benefit from OEP plus metformin therapy have one of the following factors indicating the presence of insulin resistance⁵:

• body mass index >30 kg/m²
• waist-to-hip ratio ≥0.85
• waist circumference >35 in (89 cm)
• acanthosis nigricans
• personal history of gestational diabetes
• family history of type 2 diabetes mellitus (T2DM) in a first-degree relative
• diagnosis of the metabolic syndrome.

My preferred treatment approach

Metformin is a low cost and safe treatment for metabolic dysfunction due to insulin resistance and excess adipokines. I often start PCOS treatment for my patients with an OEP plus metformin extended release (XR) 750 mg with dinner. If the patient tolerates this dose, I increase the dose to metformin XR 1,500 mg with dinner.

Adverse effects. The most common side effects of metformin are gastrointestinal, including abdominal discomfort, flatulence, borborygmi, diarrhea, and nausea. Metformin reduces serum vitamin B12 levels by 5% to 10%; therefore, ensuring adequate vitamin B12 intake (2.6 µg daily) is helpful.⁶ Although metformin does reduce vitamin B12 levels, there is no strong relationship between metformin and anemia or peripheral neuropathy.⁷ Lactic acidosis is a rare complication of ­metformin.

Beneficial effects. In the treatment of PCOS, metformin may have many beneficial effects, including⁸:

• decrease in insulin resistance
• decrease in harmful adipokines
• reduction in visceral fat
• reduction in the incidence of T2DM.

OEP plus spironolactone

Many women with PCOS have increased LH secretion and increased androgen activity in the skin due to increased 5-alpha reductase enzyme activity, which catalyzes the conversion of testosterone to the powerful intracellular androgen dihydrotestosterone.⁹ Women with PCOS may present with a chief problem report of hirsutism, acne, or female androgenetic alopecia. OEP plus spironolactone may be an optimal initial treatment for women with a dominant dermatologic manifestation of PCOS. OEP treatment results in a decrease in pituitary LH secretion and ovarian androgen production. Spironolactone adds to this therapeutic effect by blocking androgen action in the skin.

The data on dual therapy with spironolactone. Many dermatologists recommend spironolactone in combination with cosmetic measures for the treatment of acne, but there are only a few randomized trials that demonstrate its efficacy.¹⁰ In one trial spironolactone was demonstrated to be superior to placebo for the treatment of inflammatory acne.¹⁰ Authors of multiple randomized trials report that the antiandrogens, spironolactone, or finasteride are superior to metformin to treat hirsutism.¹¹ In addition, a few small trials report that spironolactone plus OEP is superior to either OEP or metformin monotherapy for hirsutism.¹¹ Clinical trials of spironolactone for hirsutism have been rated as “low quality” and additional controlled trials of OEP monotherapy versus OEP plus spironolactone are ­warranted.¹²

My preferred treatment approach

Spironolactone is effective in the treatment of hirsutism at doses ranging from 50 mg to 200 mg daily. I ­routinely use a dose of spironolactone 100 mg daily because this dose is near of the top of the dose-response curve and has few adverse effects (such as intermittent uterine bleeding or spotting). With spironolactone monotherapy at a dose of 200 mg, irregular uterine bleeding or spotting is common, but concomitant treatment with an OEP tends to minimize this side effect. In my practice I rarely have patients report irregular uterine bleeding or spotting with the combination treatment of an OEP and spironolactone­ 100 mg ­daily.

Contraindications. Spironolactone should not be given to women with renal insufficiency because it can cause hyperkalemia. However, it is not necessary to check potassium levels in young women taking spironolactone with normal creatinine levels.¹³

Triple therapy: OEP plus metformin plus spironolactone

Some experts strongly recommend the initial treatment of PCOS in adolescents and young women with triple therapy: OEP plus an insulin sensitizer plus an antiandrogen.¹⁴ This recommendation is based in part on the observation that OEP monotherapy may be associated with an increase in circulating adipokines and visceral fat mass as determined by dual-energy x-ray absorptiometry.¹⁵ By contrast, triple treatment with an OEP plus metformin plus an antiandrogen is associated with a decrease in circulating adipokines and visceral fat mass.

What is the best progestin for PCOS?

Any OEP is better than no OEP, regardless of the progestin used to treat the PCOS because ethinyl estradiol plus any synthetic progestin suppresses pituitary secretion of LH and decreases ovarian androgen production. However, for the treatment of acne, using a progestin that is less androgenic may be ­beneficial.¹⁶

In one study, 2,147 consecutive women who were taking a contraceptive and presented for treatment of acne were asked if their contraceptive had a positive impact on their acne. The percentage of women reporting that their contraceptive significantly improved their acne ranged from 26% for those taking drospirenone-ethinyl estradiol (EE) to 1% for those taking the etonogestrel subdermal implant (FIGURE).¹⁶ The US Food and Drug Administration has approved 4 OEP contraceptives for the treatment of acne (TABLE). The OEPs with drospirenone, norgestimate, desogestrel, or norethindrone acetate may be optimal choices for the treatment of acne caused by PCOS.

The bottom line

PCOS is a common endocrine disorder treated primarily by obstetricians-gynecologists. Among adolescents and young women with PCOS chief problem reports include irregular menses, hirsutism, obesity, acne, and infertility. Among mid-life women the presentation of PCOS often evolves into chronic medical problems, including obesity, metabolic syndrome, hyperlipidemia, hypertension, T2DM, cardiovascular disease, and endometrial cancer.^17–19 To optimally treat the multiple pathophysiologic disorders manifested in PCOS, I recommend initial dual medical therapy with an OEP plus metformin or an OEP plus spironolactone.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Using the Rotterdam criteria, the diagnosis of polycystic ovary syndrome (PCOS) is made in the presence of 2 of the following 3 criteria¹:

1. oligo-ovulation or anovulation
2. hyperandrogenism manifested by the presence of either hirsutism or elevated hormone levels (including serum testosterone androstenedione and/or dehydroepiandrosterone sulfate)
3. ultrasonography evidence of multifollicular ovaries (≥12 follicles with a diameter of 2 mm to 9 mm in one or both ovaries; FIGURE) or ovarian stromal volume of 10 mL or more.

Illustration: Kimberly Martens for OBG Management

Among reproductive-age women, the prevalence of PCOS has been reported to range from 8% to 13% for different populations.² Most clinicians initiate treatment for PCOS with oral estrogen−progestin (OEP) monotherapy. OEP treatment has many beneficial hormonal effects, including:

• a resulting decrease in pituitary luteinizing hormone (LH) secretion, which decreases ovarian androgen production
• an increase in liver production of sex hormone−binding globulin (SHBG), which decreases free testosterone levels
• protection against the development of endometrial hyperplasia
• induction of regular uterine withdrawal bleeding.

However, OEP therapy neither improves metabolic indices (insulin sensitivity and visceral fat secretion of adipokines) nor blocks androgen action in the skin.

Dual medical treatment for PCOS can address the issues that monotherapy cannot and, along with providing guidance on improving diet and exercise, many experts support the initial therapy of PCOS with dual medical therapy (OEP plus metformin or spironolactone).

Advantages of OEP plus metformin

For many women with PCOS, the syndrome is characterized by abnormalities in both the reproductive (increase in LH secretion) and metabolic (insulin resistance and increased adipokines) systems. OEP monotherapy does not improve the metabolic abnormalities of PCOS. Combination treatment with both OEP plus metformin, along with diet and exercise, can best treat these combined abnormalities.

Data support dual therapy with metformin. In one small, randomized trial in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater reduction in serum androstenedione and a greater increase in SHBG than OEP monotherapy.³ In addition, weight loss and a reduction in waist-to-hip ratio only occurred in the OEP plus metformin group.³ In another small randomized study in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater decrease in free androgen index than OEP monotherapy.⁴

In my clinical opinion, women who may best benefit from OEP plus metformin therapy have one of the following factors indicating the presence of insulin resistance⁵:

• body mass index >30 kg/m²
• waist-to-hip ratio ≥0.85
• waist circumference >35 in (89 cm)
• acanthosis nigricans
• personal history of gestational diabetes
• family history of type 2 diabetes mellitus (T2DM) in a first-degree relative
• diagnosis of the metabolic syndrome.

My preferred treatment approach

Metformin is a low cost and safe treatment for metabolic dysfunction due to insulin resistance and excess adipokines. I often start PCOS treatment for my patients with an OEP plus metformin extended release (XR) 750 mg with dinner. If the patient tolerates this dose, I increase the dose to metformin XR 1,500 mg with dinner.

Adverse effects. The most common side effects of metformin are gastrointestinal, including abdominal discomfort, flatulence, borborygmi, diarrhea, and nausea. Metformin reduces serum vitamin B12 levels by 5% to 10%; therefore, ensuring adequate vitamin B12 intake (2.6 µg daily) is helpful.⁶ Although metformin does reduce vitamin B12 levels, there is no strong relationship between metformin and anemia or peripheral neuropathy.⁷ Lactic acidosis is a rare complication of ­metformin.

Beneficial effects. In the treatment of PCOS, metformin may have many beneficial effects, including⁸:

• decrease in insulin resistance
• decrease in harmful adipokines
• reduction in visceral fat
• reduction in the incidence of T2DM.

OEP plus spironolactone

Many women with PCOS have increased LH secretion and increased androgen activity in the skin due to increased 5-alpha reductase enzyme activity, which catalyzes the conversion of testosterone to the powerful intracellular androgen dihydrotestosterone.⁹ Women with PCOS may present with a chief problem report of hirsutism, acne, or female androgenetic alopecia. OEP plus spironolactone may be an optimal initial treatment for women with a dominant dermatologic manifestation of PCOS. OEP treatment results in a decrease in pituitary LH secretion and ovarian androgen production. Spironolactone adds to this therapeutic effect by blocking androgen action in the skin.

The data on dual therapy with spironolactone. Many dermatologists recommend spironolactone in combination with cosmetic measures for the treatment of acne, but there are only a few randomized trials that demonstrate its efficacy.¹⁰ In one trial spironolactone was demonstrated to be superior to placebo for the treatment of inflammatory acne.¹⁰ Authors of multiple randomized trials report that the antiandrogens, spironolactone, or finasteride are superior to metformin to treat hirsutism.¹¹ In addition, a few small trials report that spironolactone plus OEP is superior to either OEP or metformin monotherapy for hirsutism.¹¹ Clinical trials of spironolactone for hirsutism have been rated as “low quality” and additional controlled trials of OEP monotherapy versus OEP plus spironolactone are ­warranted.¹²

My preferred treatment approach

Spironolactone is effective in the treatment of hirsutism at doses ranging from 50 mg to 200 mg daily. I ­routinely use a dose of spironolactone 100 mg daily because this dose is near of the top of the dose-response curve and has few adverse effects (such as intermittent uterine bleeding or spotting). With spironolactone monotherapy at a dose of 200 mg, irregular uterine bleeding or spotting is common, but concomitant treatment with an OEP tends to minimize this side effect. In my practice I rarely have patients report irregular uterine bleeding or spotting with the combination treatment of an OEP and spironolactone­ 100 mg ­daily.

Contraindications. Spironolactone should not be given to women with renal insufficiency because it can cause hyperkalemia. However, it is not necessary to check potassium levels in young women taking spironolactone with normal creatinine levels.¹³

Triple therapy: OEP plus metformin plus spironolactone

Some experts strongly recommend the initial treatment of PCOS in adolescents and young women with triple therapy: OEP plus an insulin sensitizer plus an antiandrogen.¹⁴ This recommendation is based in part on the observation that OEP monotherapy may be associated with an increase in circulating adipokines and visceral fat mass as determined by dual-energy x-ray absorptiometry.¹⁵ By contrast, triple treatment with an OEP plus metformin plus an antiandrogen is associated with a decrease in circulating adipokines and visceral fat mass.

What is the best progestin for PCOS?

Any OEP is better than no OEP, regardless of the progestin used to treat the PCOS because ethinyl estradiol plus any synthetic progestin suppresses pituitary secretion of LH and decreases ovarian androgen production. However, for the treatment of acne, using a progestin that is less androgenic may be ­beneficial.¹⁶

In one study, 2,147 consecutive women who were taking a contraceptive and presented for treatment of acne were asked if their contraceptive had a positive impact on their acne. The percentage of women reporting that their contraceptive significantly improved their acne ranged from 26% for those taking drospirenone-ethinyl estradiol (EE) to 1% for those taking the etonogestrel subdermal implant (FIGURE).¹⁶ The US Food and Drug Administration has approved 4 OEP contraceptives for the treatment of acne (TABLE). The OEPs with drospirenone, norgestimate, desogestrel, or norethindrone acetate may be optimal choices for the treatment of acne caused by PCOS.

The bottom line

PCOS is a common endocrine disorder treated primarily by obstetricians-gynecologists. Among adolescents and young women with PCOS chief problem reports include irregular menses, hirsutism, obesity, acne, and infertility. Among mid-life women the presentation of PCOS often evolves into chronic medical problems, including obesity, metabolic syndrome, hyperlipidemia, hypertension, T2DM, cardiovascular disease, and endometrial cancer.^17–19 To optimally treat the multiple pathophysiologic disorders manifested in PCOS, I recommend initial dual medical therapy with an OEP plus metformin or an OEP plus spironolactone.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Using the Rotterdam criteria, the diagnosis of polycystic ovary syndrome (PCOS) is made in the presence of 2 of the following 3 criteria¹:

1. oligo-ovulation or anovulation
2. hyperandrogenism manifested by the presence of either hirsutism or elevated hormone levels (including serum testosterone androstenedione and/or dehydroepiandrosterone sulfate)
3. ultrasonography evidence of multifollicular ovaries (≥12 follicles with a diameter of 2 mm to 9 mm in one or both ovaries; FIGURE) or ovarian stromal volume of 10 mL or more.

Illustration: Kimberly Martens for OBG Management

Among reproductive-age women, the prevalence of PCOS has been reported to range from 8% to 13% for different populations.² Most clinicians initiate treatment for PCOS with oral estrogen−progestin (OEP) monotherapy. OEP treatment has many beneficial hormonal effects, including:

• a resulting decrease in pituitary luteinizing hormone (LH) secretion, which decreases ovarian androgen production
• an increase in liver production of sex hormone−binding globulin (SHBG), which decreases free testosterone levels
• protection against the development of endometrial hyperplasia
• induction of regular uterine withdrawal bleeding.

However, OEP therapy neither improves metabolic indices (insulin sensitivity and visceral fat secretion of adipokines) nor blocks androgen action in the skin.

Dual medical treatment for PCOS can address the issues that monotherapy cannot and, along with providing guidance on improving diet and exercise, many experts support the initial therapy of PCOS with dual medical therapy (OEP plus metformin or spironolactone).

Advantages of OEP plus metformin

For many women with PCOS, the syndrome is characterized by abnormalities in both the reproductive (increase in LH secretion) and metabolic (insulin resistance and increased adipokines) systems. OEP monotherapy does not improve the metabolic abnormalities of PCOS. Combination treatment with both OEP plus metformin, along with diet and exercise, can best treat these combined abnormalities.

Data support dual therapy with metformin. In one small, randomized trial in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater reduction in serum androstenedione and a greater increase in SHBG than OEP monotherapy.³ In addition, weight loss and a reduction in waist-to-hip ratio only occurred in the OEP plus metformin group.³ In another small randomized study in women with PCOS, OEP plus metformin (1,500 mg daily) resulted in a greater decrease in free androgen index than OEP monotherapy.⁴

In my clinical opinion, women who may best benefit from OEP plus metformin therapy have one of the following factors indicating the presence of insulin resistance⁵:

• body mass index >30 kg/m²
• waist-to-hip ratio ≥0.85
• waist circumference >35 in (89 cm)
• acanthosis nigricans
• personal history of gestational diabetes
• family history of type 2 diabetes mellitus (T2DM) in a first-degree relative
• diagnosis of the metabolic syndrome.

My preferred treatment approach

Metformin is a low cost and safe treatment for metabolic dysfunction due to insulin resistance and excess adipokines. I often start PCOS treatment for my patients with an OEP plus metformin extended release (XR) 750 mg with dinner. If the patient tolerates this dose, I increase the dose to metformin XR 1,500 mg with dinner.

Adverse effects. The most common side effects of metformin are gastrointestinal, including abdominal discomfort, flatulence, borborygmi, diarrhea, and nausea. Metformin reduces serum vitamin B12 levels by 5% to 10%; therefore, ensuring adequate vitamin B12 intake (2.6 µg daily) is helpful.⁶ Although metformin does reduce vitamin B12 levels, there is no strong relationship between metformin and anemia or peripheral neuropathy.⁷ Lactic acidosis is a rare complication of ­metformin.

Beneficial effects. In the treatment of PCOS, metformin may have many beneficial effects, including⁸:

• decrease in insulin resistance
• decrease in harmful adipokines
• reduction in visceral fat
• reduction in the incidence of T2DM.

OEP plus spironolactone

Many women with PCOS have increased LH secretion and increased androgen activity in the skin due to increased 5-alpha reductase enzyme activity, which catalyzes the conversion of testosterone to the powerful intracellular androgen dihydrotestosterone.⁹ Women with PCOS may present with a chief problem report of hirsutism, acne, or female androgenetic alopecia. OEP plus spironolactone may be an optimal initial treatment for women with a dominant dermatologic manifestation of PCOS. OEP treatment results in a decrease in pituitary LH secretion and ovarian androgen production. Spironolactone adds to this therapeutic effect by blocking androgen action in the skin.

The data on dual therapy with spironolactone. Many dermatologists recommend spironolactone in combination with cosmetic measures for the treatment of acne, but there are only a few randomized trials that demonstrate its efficacy.¹⁰ In one trial spironolactone was demonstrated to be superior to placebo for the treatment of inflammatory acne.¹⁰ Authors of multiple randomized trials report that the antiandrogens, spironolactone, or finasteride are superior to metformin to treat hirsutism.¹¹ In addition, a few small trials report that spironolactone plus OEP is superior to either OEP or metformin monotherapy for hirsutism.¹¹ Clinical trials of spironolactone for hirsutism have been rated as “low quality” and additional controlled trials of OEP monotherapy versus OEP plus spironolactone are ­warranted.¹²

My preferred treatment approach

Spironolactone is effective in the treatment of hirsutism at doses ranging from 50 mg to 200 mg daily. I ­routinely use a dose of spironolactone 100 mg daily because this dose is near of the top of the dose-response curve and has few adverse effects (such as intermittent uterine bleeding or spotting). With spironolactone monotherapy at a dose of 200 mg, irregular uterine bleeding or spotting is common, but concomitant treatment with an OEP tends to minimize this side effect. In my practice I rarely have patients report irregular uterine bleeding or spotting with the combination treatment of an OEP and spironolactone­ 100 mg ­daily.

Contraindications. Spironolactone should not be given to women with renal insufficiency because it can cause hyperkalemia. However, it is not necessary to check potassium levels in young women taking spironolactone with normal creatinine levels.¹³

Triple therapy: OEP plus metformin plus spironolactone

Some experts strongly recommend the initial treatment of PCOS in adolescents and young women with triple therapy: OEP plus an insulin sensitizer plus an antiandrogen.¹⁴ This recommendation is based in part on the observation that OEP monotherapy may be associated with an increase in circulating adipokines and visceral fat mass as determined by dual-energy x-ray absorptiometry.¹⁵ By contrast, triple treatment with an OEP plus metformin plus an antiandrogen is associated with a decrease in circulating adipokines and visceral fat mass.

What is the best progestin for PCOS?

Any OEP is better than no OEP, regardless of the progestin used to treat the PCOS because ethinyl estradiol plus any synthetic progestin suppresses pituitary secretion of LH and decreases ovarian androgen production. However, for the treatment of acne, using a progestin that is less androgenic may be ­beneficial.¹⁶

In one study, 2,147 consecutive women who were taking a contraceptive and presented for treatment of acne were asked if their contraceptive had a positive impact on their acne. The percentage of women reporting that their contraceptive significantly improved their acne ranged from 26% for those taking drospirenone-ethinyl estradiol (EE) to 1% for those taking the etonogestrel subdermal implant (FIGURE).¹⁶ The US Food and Drug Administration has approved 4 OEP contraceptives for the treatment of acne (TABLE). The OEPs with drospirenone, norgestimate, desogestrel, or norethindrone acetate may be optimal choices for the treatment of acne caused by PCOS.

The bottom line

PCOS is a common endocrine disorder treated primarily by obstetricians-gynecologists. Among adolescents and young women with PCOS chief problem reports include irregular menses, hirsutism, obesity, acne, and infertility. Among mid-life women the presentation of PCOS often evolves into chronic medical problems, including obesity, metabolic syndrome, hyperlipidemia, hypertension, T2DM, cardiovascular disease, and endometrial cancer.^17–19 To optimally treat the multiple pathophysiologic disorders manifested in PCOS, I recommend initial dual medical therapy with an OEP plus metformin or an OEP plus spironolactone.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Endometriosis is a common gynecologic problem in adolescents and women. It often presents with pelvic pain, an ovarian endometrioma, and/or subfertility. In a prospective study of 116,678 nurses, the incidence of a new surgical diagnosis of endometriosis was greatest among women aged 25 to 29 years and lowest among women older than age 44.¹ Using the incidence data from this study, the calculated prevalence of endometriosis in this large cohort of women of reproductive age was approximately 8%.

Although endometriosis is known to be a very common gynecologic problem, many studies report that there can be long delays between onset of pelvic pain symptoms and the diagnosis of endometriosis (Figure 1).²⁻⁶ Combining the results from 5 studies, involving 1,187 women, the mean age of onset of pelvic pain symptoms was 22.1 years, and the mean age at the diagnosis of endometriosis was 30.7 years. This is a difference of 8.6 years between the age of symptom onset and age at diagnosis.²⁻⁶

What factors contribute to the diagnosis delay?

Both patient and physician factors contribute to the reported lengthy delay between symptom onset and endometriosis diagnosis.^7,8 Differentiating dysmenorrhea due to primary and secondary causes is difficult for both patients and physicians. Women may conceal the severity of menstrual pain to avoid both the embarrassment of drawing attention to themselves and being stigmatized as unable to cope. Most disappointing is that many women with endometriosis reported that they asked their clinician if endometriosis could be the cause of their severe dysmenorrhea and were told, “No.”^7,8

Of interest, the reported delay in the diagnosis of endometriosis is much shorter for women who pre-sent with infertility than for women who present with pelvic pain. In one study from the United States, the delay to diagnosis was 3.13 years for women who presented with infertility and 6.35 years for women who presented with severe pelvic pain.³ This suggests that clinicians and patients more rapidly pursue the diagnosis of endometriosis in women with infertility, but not pelvic pain.

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Initial treatment of pelvic pain with NSAIDs and estrogen—progestin contraceptives

Many women with undiagnosed endometriosis present with pelvic pain symptoms including moderate to severe dysmenorrhea. These women are often empirically treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and combination estrogen−progestin contraceptives in either a cyclic or continuous manner.^9,10 Since many women with endometriosis will have a reduction in their pelvic pain with NSAID and contraceptive treatment, diagnosis of their endometriosis may be delayed until their disease progresses years after their initial presentation. It is important to gently alert these women to the possibility that they have undiagnosed endometriosis as the cause of their pain symptoms and encourage them to report any worsening pain symptoms in a timely manner.

Sometimes women with pelvic pain are treated with NSAIDs and contraceptives but no significant reduction in pain symptoms occurs. For these women, speedy consideration should be given to offering a laparoscopy to determine the cause of their pain.

Related article:
Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain

Diagnosing endometriosis relies on identifying flags in the patient’s history

The gold standard for endometriosis diagnosis is surgical visualization of endometriosis lesions, most often with laparoscopy, plus histologic confirmation of endometriosis on a tissue biopsy.^9,10 A key to reducing the time between onset of symptoms and diagnosis of endometriosis is identifying adolescents and women who are at high risk for having the disease. These women should be offered a laparoscopy procedure. In women with moderate to severe pelvic pain of at least 6 months duration, medical history, physical examination, and imaging studies can be helpful in identifying those at increased risk for endometriosis.

Items from the patient history that might raise the likelihood of endometriosis include:

• abdominopelvic pain, dysmenorrhea, menorrhagia, subfertility, dyspareunia and/or postcoital bleeding¹¹
• symptoms of dysmenorrhea and/or dyspareunia that are not responsive to NSAIDs or estrogen−progestin contraceptives¹²
• symptoms of dysmenorrhea and/or dyspareunia associated with absenteeism from school or work¹³
• multiple visits to the emergency department for severe dysmenorrhea
• endometriosis in the patient’s mother or sister
• subfertility with regular ovulation, patent fallopian tubes, and a partner with a normal semen analysis
• urinary frequency, urgency, and/or pain on urination
• diarrhea, constipation, nausea, dyschezia, bowel cramping, abdominal distention, and early satiety.

A daunting clinical challenge is that symptoms of endometriosis overlap with other gynecologic and nongynecologic problems including pelvic infection, adhesions, ovarian cysts, fibroids, irritable bowel syndrome, inflammatory bowel disease, interstitial cystitis, myofascial pain, depression, and history of sexual abuse.

Diagnosing endometriosis relies on identifying flags on physical exam

Physical examination findings that raise the likelihood that the patient has endometriosis include:

• fixed and retroverted uterus
• adnexal mass
• lesions of the cervix or posterior fornix that visually appear to be endometriosis
• uterosacral ligament abnormalities, including tenderness, thickening, and/or nodularity^14,15
• lateral displacement of the cervix (FIGURE 2)^16,17
• severe cervical stenosis.

Illustration: Marcia Hartsock for OBG Management

In one study of 57 women with a surgical diagnosis of endometriosis, uterosacral ligament abnormalities, lateral displacement of the cervix, and cervical stenosis were observed in 47%, 28%, and 19% of the women, respectively.¹⁷ In this same study 22 women had none of these findings, but 8 had a complex ovarian mass consistent with endometriosis.

The possibility of endometriosis increases as the number of history and physical examination findings suggestive of endometriosis increase.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options

When transvaginal ultrasound can aid diagnosis

Most women with endometriosis have normal transvaginal ultrasonography (TVUS) results because ultrasound cannot detect small isolated peritoneal lesions of endometriosis present in Stage I disease, the most common stage of endometriosis. However, ultrasound is useful in detecting both ovarian endometriomas and nodules of deep infiltrating endometriosis (DIE).¹⁸ TVUS has excellent sensitivity (>90%) and specificity (>90%) for the detection of ovarian endometriomas because these cysts have characteristic, homogenous, low-level internal echoes.^19,20 For the diagnosis of DIE of the uterosacral ligaments and rectovaginal septum, TVUS has fair sensitivity (>50%) and excellent specificity (>90%).²¹ In most studies, magnetic resonance imaging performs no better than TVUS for imaging ovarian endometriomas and DIE. Hence, TVUS is the preferred imaging modality for detecting endometriosis.²²

This is a practice gap we can close

Clinicians take great pride in accurately solving patient problems in a timely and efficient manner. Substantial research indicates that we can improve the timeliness of our diagnosis of endometriosis. By acknowledging patients’ pain symptoms and recognizing the myriad symptoms and physical examination and imaging findings that are associated with endometriosis, we will close the gap and make this diagnosis with greater speed.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Endometriosis is a common gynecologic problem in adolescents and women. It often presents with pelvic pain, an ovarian endometrioma, and/or subfertility. In a prospective study of 116,678 nurses, the incidence of a new surgical diagnosis of endometriosis was greatest among women aged 25 to 29 years and lowest among women older than age 44.¹ Using the incidence data from this study, the calculated prevalence of endometriosis in this large cohort of women of reproductive age was approximately 8%.

Although endometriosis is known to be a very common gynecologic problem, many studies report that there can be long delays between onset of pelvic pain symptoms and the diagnosis of endometriosis (Figure 1).²⁻⁶ Combining the results from 5 studies, involving 1,187 women, the mean age of onset of pelvic pain symptoms was 22.1 years, and the mean age at the diagnosis of endometriosis was 30.7 years. This is a difference of 8.6 years between the age of symptom onset and age at diagnosis.²⁻⁶

What factors contribute to the diagnosis delay?

Both patient and physician factors contribute to the reported lengthy delay between symptom onset and endometriosis diagnosis.^7,8 Differentiating dysmenorrhea due to primary and secondary causes is difficult for both patients and physicians. Women may conceal the severity of menstrual pain to avoid both the embarrassment of drawing attention to themselves and being stigmatized as unable to cope. Most disappointing is that many women with endometriosis reported that they asked their clinician if endometriosis could be the cause of their severe dysmenorrhea and were told, “No.”^7,8

Of interest, the reported delay in the diagnosis of endometriosis is much shorter for women who pre-sent with infertility than for women who present with pelvic pain. In one study from the United States, the delay to diagnosis was 3.13 years for women who presented with infertility and 6.35 years for women who presented with severe pelvic pain.³ This suggests that clinicians and patients more rapidly pursue the diagnosis of endometriosis in women with infertility, but not pelvic pain.

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Initial treatment of pelvic pain with NSAIDs and estrogen—progestin contraceptives

Many women with undiagnosed endometriosis present with pelvic pain symptoms including moderate to severe dysmenorrhea. These women are often empirically treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and combination estrogen−progestin contraceptives in either a cyclic or continuous manner.^9,10 Since many women with endometriosis will have a reduction in their pelvic pain with NSAID and contraceptive treatment, diagnosis of their endometriosis may be delayed until their disease progresses years after their initial presentation. It is important to gently alert these women to the possibility that they have undiagnosed endometriosis as the cause of their pain symptoms and encourage them to report any worsening pain symptoms in a timely manner.

Sometimes women with pelvic pain are treated with NSAIDs and contraceptives but no significant reduction in pain symptoms occurs. For these women, speedy consideration should be given to offering a laparoscopy to determine the cause of their pain.

Related article:
Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain

Diagnosing endometriosis relies on identifying flags in the patient’s history

The gold standard for endometriosis diagnosis is surgical visualization of endometriosis lesions, most often with laparoscopy, plus histologic confirmation of endometriosis on a tissue biopsy.^9,10 A key to reducing the time between onset of symptoms and diagnosis of endometriosis is identifying adolescents and women who are at high risk for having the disease. These women should be offered a laparoscopy procedure. In women with moderate to severe pelvic pain of at least 6 months duration, medical history, physical examination, and imaging studies can be helpful in identifying those at increased risk for endometriosis.

Items from the patient history that might raise the likelihood of endometriosis include:

• abdominopelvic pain, dysmenorrhea, menorrhagia, subfertility, dyspareunia and/or postcoital bleeding¹¹
• symptoms of dysmenorrhea and/or dyspareunia that are not responsive to NSAIDs or estrogen−progestin contraceptives¹²
• symptoms of dysmenorrhea and/or dyspareunia associated with absenteeism from school or work¹³
• multiple visits to the emergency department for severe dysmenorrhea
• endometriosis in the patient’s mother or sister
• subfertility with regular ovulation, patent fallopian tubes, and a partner with a normal semen analysis
• urinary frequency, urgency, and/or pain on urination
• diarrhea, constipation, nausea, dyschezia, bowel cramping, abdominal distention, and early satiety.

A daunting clinical challenge is that symptoms of endometriosis overlap with other gynecologic and nongynecologic problems including pelvic infection, adhesions, ovarian cysts, fibroids, irritable bowel syndrome, inflammatory bowel disease, interstitial cystitis, myofascial pain, depression, and history of sexual abuse.

Diagnosing endometriosis relies on identifying flags on physical exam

Physical examination findings that raise the likelihood that the patient has endometriosis include:

• fixed and retroverted uterus
• adnexal mass
• lesions of the cervix or posterior fornix that visually appear to be endometriosis
• uterosacral ligament abnormalities, including tenderness, thickening, and/or nodularity^14,15
• lateral displacement of the cervix (FIGURE 2)^16,17
• severe cervical stenosis.

Illustration: Marcia Hartsock for OBG Management

In one study of 57 women with a surgical diagnosis of endometriosis, uterosacral ligament abnormalities, lateral displacement of the cervix, and cervical stenosis were observed in 47%, 28%, and 19% of the women, respectively.¹⁷ In this same study 22 women had none of these findings, but 8 had a complex ovarian mass consistent with endometriosis.

The possibility of endometriosis increases as the number of history and physical examination findings suggestive of endometriosis increase.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options

When transvaginal ultrasound can aid diagnosis

Most women with endometriosis have normal transvaginal ultrasonography (TVUS) results because ultrasound cannot detect small isolated peritoneal lesions of endometriosis present in Stage I disease, the most common stage of endometriosis. However, ultrasound is useful in detecting both ovarian endometriomas and nodules of deep infiltrating endometriosis (DIE).¹⁸ TVUS has excellent sensitivity (>90%) and specificity (>90%) for the detection of ovarian endometriomas because these cysts have characteristic, homogenous, low-level internal echoes.^19,20 For the diagnosis of DIE of the uterosacral ligaments and rectovaginal septum, TVUS has fair sensitivity (>50%) and excellent specificity (>90%).²¹ In most studies, magnetic resonance imaging performs no better than TVUS for imaging ovarian endometriomas and DIE. Hence, TVUS is the preferred imaging modality for detecting endometriosis.²²

This is a practice gap we can close

Clinicians take great pride in accurately solving patient problems in a timely and efficient manner. Substantial research indicates that we can improve the timeliness of our diagnosis of endometriosis. By acknowledging patients’ pain symptoms and recognizing the myriad symptoms and physical examination and imaging findings that are associated with endometriosis, we will close the gap and make this diagnosis with greater speed.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Endometriosis is a common gynecologic problem in adolescents and women. It often presents with pelvic pain, an ovarian endometrioma, and/or subfertility. In a prospective study of 116,678 nurses, the incidence of a new surgical diagnosis of endometriosis was greatest among women aged 25 to 29 years and lowest among women older than age 44.¹ Using the incidence data from this study, the calculated prevalence of endometriosis in this large cohort of women of reproductive age was approximately 8%.

Although endometriosis is known to be a very common gynecologic problem, many studies report that there can be long delays between onset of pelvic pain symptoms and the diagnosis of endometriosis (Figure 1).²⁻⁶ Combining the results from 5 studies, involving 1,187 women, the mean age of onset of pelvic pain symptoms was 22.1 years, and the mean age at the diagnosis of endometriosis was 30.7 years. This is a difference of 8.6 years between the age of symptom onset and age at diagnosis.²⁻⁶

What factors contribute to the diagnosis delay?

Both patient and physician factors contribute to the reported lengthy delay between symptom onset and endometriosis diagnosis.^7,8 Differentiating dysmenorrhea due to primary and secondary causes is difficult for both patients and physicians. Women may conceal the severity of menstrual pain to avoid both the embarrassment of drawing attention to themselves and being stigmatized as unable to cope. Most disappointing is that many women with endometriosis reported that they asked their clinician if endometriosis could be the cause of their severe dysmenorrhea and were told, “No.”^7,8

Of interest, the reported delay in the diagnosis of endometriosis is much shorter for women who pre-sent with infertility than for women who present with pelvic pain. In one study from the United States, the delay to diagnosis was 3.13 years for women who presented with infertility and 6.35 years for women who presented with severe pelvic pain.³ This suggests that clinicians and patients more rapidly pursue the diagnosis of endometriosis in women with infertility, but not pelvic pain.

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Initial treatment of pelvic pain with NSAIDs and estrogen—progestin contraceptives

Many women with undiagnosed endometriosis present with pelvic pain symptoms including moderate to severe dysmenorrhea. These women are often empirically treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and combination estrogen−progestin contraceptives in either a cyclic or continuous manner.^9,10 Since many women with endometriosis will have a reduction in their pelvic pain with NSAID and contraceptive treatment, diagnosis of their endometriosis may be delayed until their disease progresses years after their initial presentation. It is important to gently alert these women to the possibility that they have undiagnosed endometriosis as the cause of their pain symptoms and encourage them to report any worsening pain symptoms in a timely manner.

Sometimes women with pelvic pain are treated with NSAIDs and contraceptives but no significant reduction in pain symptoms occurs. For these women, speedy consideration should be given to offering a laparoscopy to determine the cause of their pain.

Related article:
Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain

Diagnosing endometriosis relies on identifying flags in the patient’s history

The gold standard for endometriosis diagnosis is surgical visualization of endometriosis lesions, most often with laparoscopy, plus histologic confirmation of endometriosis on a tissue biopsy.^9,10 A key to reducing the time between onset of symptoms and diagnosis of endometriosis is identifying adolescents and women who are at high risk for having the disease. These women should be offered a laparoscopy procedure. In women with moderate to severe pelvic pain of at least 6 months duration, medical history, physical examination, and imaging studies can be helpful in identifying those at increased risk for endometriosis.

Items from the patient history that might raise the likelihood of endometriosis include:

• abdominopelvic pain, dysmenorrhea, menorrhagia, subfertility, dyspareunia and/or postcoital bleeding¹¹
• symptoms of dysmenorrhea and/or dyspareunia that are not responsive to NSAIDs or estrogen−progestin contraceptives¹²
• symptoms of dysmenorrhea and/or dyspareunia associated with absenteeism from school or work¹³
• multiple visits to the emergency department for severe dysmenorrhea
• endometriosis in the patient’s mother or sister
• subfertility with regular ovulation, patent fallopian tubes, and a partner with a normal semen analysis
• urinary frequency, urgency, and/or pain on urination
• diarrhea, constipation, nausea, dyschezia, bowel cramping, abdominal distention, and early satiety.

A daunting clinical challenge is that symptoms of endometriosis overlap with other gynecologic and nongynecologic problems including pelvic infection, adhesions, ovarian cysts, fibroids, irritable bowel syndrome, inflammatory bowel disease, interstitial cystitis, myofascial pain, depression, and history of sexual abuse.

Diagnosing endometriosis relies on identifying flags on physical exam

Physical examination findings that raise the likelihood that the patient has endometriosis include:

• fixed and retroverted uterus
• adnexal mass
• lesions of the cervix or posterior fornix that visually appear to be endometriosis
• uterosacral ligament abnormalities, including tenderness, thickening, and/or nodularity^14,15
• lateral displacement of the cervix (FIGURE 2)^16,17
• severe cervical stenosis.

Illustration: Marcia Hartsock for OBG Management

In one study of 57 women with a surgical diagnosis of endometriosis, uterosacral ligament abnormalities, lateral displacement of the cervix, and cervical stenosis were observed in 47%, 28%, and 19% of the women, respectively.¹⁷ In this same study 22 women had none of these findings, but 8 had a complex ovarian mass consistent with endometriosis.

The possibility of endometriosis increases as the number of history and physical examination findings suggestive of endometriosis increase.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options

When transvaginal ultrasound can aid diagnosis

Most women with endometriosis have normal transvaginal ultrasonography (TVUS) results because ultrasound cannot detect small isolated peritoneal lesions of endometriosis present in Stage I disease, the most common stage of endometriosis. However, ultrasound is useful in detecting both ovarian endometriomas and nodules of deep infiltrating endometriosis (DIE).¹⁸ TVUS has excellent sensitivity (>90%) and specificity (>90%) for the detection of ovarian endometriomas because these cysts have characteristic, homogenous, low-level internal echoes.^19,20 For the diagnosis of DIE of the uterosacral ligaments and rectovaginal septum, TVUS has fair sensitivity (>50%) and excellent specificity (>90%).²¹ In most studies, magnetic resonance imaging performs no better than TVUS for imaging ovarian endometriomas and DIE. Hence, TVUS is the preferred imaging modality for detecting endometriosis.²²

This is a practice gap we can close

Clinicians take great pride in accurately solving patient problems in a timely and efficient manner. Substantial research indicates that we can improve the timeliness of our diagnosis of endometriosis. By acknowledging patients’ pain symptoms and recognizing the myriad symptoms and physical examination and imaging findings that are associated with endometriosis, we will close the gap and make this diagnosis with greater speed.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.