Tara Haelle

Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.

Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.

“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.

Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.

Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.

Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
 

Etiology of POI and associated conditions

A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.

Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.

Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.

Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.

“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.

To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:

• Menstrual irregularity for at least 3-4 months
• Test FSH and estradiol
• Test hCG, TSH, and prolactin
• If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.

However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
 

Long-term consequences of POI

Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.

“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
 

No interventions have been shown to increase ovarian activity

Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.

“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.

For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.

Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.

“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.

Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
 

Treatment of POI

Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.

The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.

Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.

Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”

Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.

Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.

Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.

“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.

Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.

Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.

Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
 

Etiology of POI and associated conditions

A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.

Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.

Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.

Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.

“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.

To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:

• Menstrual irregularity for at least 3-4 months
• Test FSH and estradiol
• Test hCG, TSH, and prolactin
• If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.

However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
 

Long-term consequences of POI

Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.

“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
 

No interventions have been shown to increase ovarian activity

Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.

“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.

For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.

Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.

“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.

Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
 

Treatment of POI

Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.

The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.

Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.

Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”

Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.

Primary ovarian insufficiency is not your mother’s early menopause, according to Laurie McKenzie, MD, a reproductive endocrinologist and associate professor of ob.gyn. at the University of Texas MD Anderson Cancer Center with a joint appointment at Baylor College of Medicine, both in Houston.

Known previously as primary ovarian failure, the syndrome of primary ovarian insufficiency (POI) no longer refers to a failure in part because of the term’s negative connotations but mostly because it’s not precisely accurate, Dr. McKenzie told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists on May 1.

“Many of these women, especially early on in diagnosis, may be experiencing some intermittent ovarian function, so it may not be a complete failure of the ovaries,” Dr. McKenzie said.

Although the condition is not common, affecting about 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this walk into their office, you really need to know how to address it because these women are understandably very distressed.” Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.

Women who develop POI lose ovarian activity before age 40, characterized by menstrual disturbance with raised gonadotropins and low estradiol. Symptoms include the hot flushes and night sweats characteristic of estrogen deficiency as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms can include sleep disturbance, mood changes, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido, and lack of energy.

Dr. McKenzie urged doctors to ask women about their symptoms if they present with amenorrhea because young women with primary amenorrhea rarely experience symptoms at presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” she said. Diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measurements of elevated follicle-stimulating hormone (FSH). Following this work-up, clinicians should seek the cause of the condition.
 

Etiology of POI and associated conditions

A wide range of conditions or genetic factors can cause POI or be more likely in patients with POI, Dr. McKenzie said. Many women diagnosed with POI have chromosomal abnormalities, and there is no cutoff for genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 anomalies. Autosomal gene mutations could also play a role in POI.

Although women with the full FMR1 mutation (Fragile X syndrome) do not have an increased risk of POI, those with the premutation (55-200 repeats) have a 13%-26% increased risk of developing POI, albeit no increased risk of intellectual disability. About 0.8%-7.5% of women with sporadic POI and up to 13% of women with a family history of POI have this genetic anomaly.

Autoimmune conditions may also develop or be related to POI, including hypothyroidism and adrenal insufficiency, Dr. McKenzie said. About 20% of adults with POI will develop hypothyroidism, so testing every 1-2 years is reasonable, though no formal screening guidelines exist. In women whose cause of POI is unknown or in whom you suspect an immune disorder, clinicians may consider screening for 21OH-Ab or adrenocortical antibodies. Patients with a positive 21OH-Ab or adrenocortical antibodies test should be referred to an endocrinologist to test adrenal function and rule out Addison disease.

Though diabetes mellitus has been linked to POI, not enough evidence exists to recommend screening women with POI for diabetes. There’s similarly no indication for infection screening, but infections can cause POI. Mumps oophoritis, for example, accounts for 3%-7% of POI cases. Cancer therapy, including radiotherapy and chemotherapy, and surgical treatment for cancer can result in POI.

“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated as influencing the age of menopause but are not readily diagnosable causes of POI,” Dr. McKenzie said. “Although not proven to cause POI, cigarette smoking is toxic to the ovaries and has been linked to an earlier age at menopause.” Then there are many women whose cause of POI is unknown.

To take all these possibilities into account, Dr. McKenzie described the complete diagnostic work-up recommended by ACOG:

• Menstrual irregularity for at least 3-4 months
• Test FSH and estradiol
• Test hCG, TSH, and prolactin
• If diagnosis is confirmed, test karyotype, FMR1 premutation, adrenal antibodies, and a pelvic sonogram.

However, she added during the Q&A after her talk, she is not sure why a sonogram is recommended or what additional information it might provide.
 

Long-term consequences of POI

Dr McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduced life expectancy linked to untreated POI is primarily caused by cardiovascular disease, she said. Women who undergo menopause aged between 35 and 40 years have a 50% greater risk of death related to ischemic heart disease than those ages 49-51, after adjusting for other comorbidities and confounders.

“Women with primary ovarian insufficiency should be advised on how to reduce cardiovascular risk factors by not smoking, taking regular exercise, and maintaining a healthy weight,” Dr McKenzie said.
 

No interventions have been shown to increase ovarian activity

Though fertility is substantially reduced in women with POI, it may not be completely gone. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic POI had some evidence of ovarian function. Clinicians should therefore recommend women with POI use contraception if they do not want to conceive. Egg donation is an option for preserving fertility in women with POI but only before POI is solidly established.

“No interventions have been reliably shown to increase ovarian activity and natural conception rates,” Dr. McKenzie said.

For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but risk of low birth weight is elevated in babies whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy have also been linked with cardiomyopathy and heart failure, so an echocardiogram prior to pregnancy is indicated in women with exposure to these or high-dose cyclophosphamide.

Abdominopelvic radiotherapy, however, has been linked to poor uterine function with a greater risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.

“Pregnancies in women with Turner syndrome are very high risk and may have a maternal mortality as high as 3.5%,” Dr. McKenzie said, so these pregnancies require involvement of a cardiologist.

Other sequelae of POI can include increased bone resorption, net loss of bone (2%-3% annually soon after menopause) and reduced bone mineral density. Women should be getting 1,000 mg/day of calcium and 800 IU/day of vitamin D, but bone screening remains controversial in the field. Finally, providers should not ignore psychosocial effects of POI, including grief, diminished self esteem, and sadness, even more so, potentially, among adolescents.
 

Treatment of POI

Managing POI involves a two-pronged strategy of providing enough estrogen (estradiol, ethinyl estradiol, or conjugated equine estrogens) to mimic normal physiology and enough progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.

The two primary options are hormone therapy and combination oral contraceptives. Hormone therapy might allow ovulation and pregnancy in some women, but combination oral contraceptive may feel less stigmatized in those who are still young, albeit with a potential risk for venous thromboembolism.

Continuous treatment tends to be easier and can involve breakthrough bleeding in younger patients; in postmenopausal women, breast cancer risk is higher but endometrial cancer risk is lower. Cyclic treatment mimics the endometrium’s normal function, resulting in bleeding that may help some women feel more “normal” and aids in knowing about a pregnancy. Those wanting to avoid bleeds and use contraception can use the levonorgestrel IUD off label.

Dr. Streicher said in an interview, “Not only is it critically important to recognize [long-term consequences] in this small group of women, but the lessons learned from young women who go though menopause can absolutely be extrapolated to women who go through menopause at an appropriate time.”

Dr. McKenzie had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceutical.

Sexual dysfunction is a common problem among breast cancer survivors, but it’s also an issue inadequately addressed by either ob.gyns. or hematologists and oncologists, according to Erin Keyser, MD, the program director of the San Antonio Uniformed Services Health Education Consortium. Dr. Keyser discussed management of sexual dysfunction and a variety of other issues frequently faced by women who have survived breast cancer at the at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician-gynecologists feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer,” Dr. Keyser quoted from a 2016 article in Obstetrics & Gynecology about the sexual health of women affected by cancer. As a breast cancer survivor herself, Dr. Keyser said hematologists and oncologists are even less equipped to discuss sexual health, “so oftentimes patients get punted between their hem-onc and their gyn,” with each telling the patient to ask the other specialist.

“There’s plenty of data in chronic health disease that maintaining sexual function for women is an indicator of the overall quality of life and that many women really don’t want to bring this up,” Dr. Keyser told attendees, so the onus is on the ob.gyn. to bring it up.

The effects of breast cancer treatment can impact women’s body image, fertility, menopause, sexual function, osteoporosis, and cardiovascular disease, but the bulk of Dr. Keyser’s talk focused on sexual health and bilateral salpingo-oophorectomy (BSO).

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, thought Dr. Keyser’s talk was useful for the general gynecologist but had some concerns about a few parts.

“She gave a very thoughtful analysis of whether someone should have their ovaries removed or not in a breast cancer diagnosis, ” Dr. Streicher said in an interview. “I would have liked to hear more about the consequences of an early menopause in women in terms of heart health, bone health, and cognitive function.”

Dr. Keyser noted that her talk pertained mostly to survivors of estrogen receptor (ER)–positive breast cancer since that population tends to struggle most with side effects of treatment. The most common medications used in this population are tamoxifen and aromatase inhibitors – such as anastrazole, letrozole, and exemestane – and these medications can affect management of different concerns.
 

Current guidance on ovarian removal

For women with a BRCA mutation, ACOG clinical guidance already exists regarding BSO. For other women, the complementary TEXT and SOFT trials changed the management of breast cancer treatment in premenopausal women, Dr. Keyser said.

Before these trials, postmenopausal hormone receptor–positive women began aromatase inhibitors and premenopausal HR-positive women began tamoxifen. These trials found that premenopausal women with HR-positive early breast cancer were less likely to experience recurrence when receiving adjuvant treatment with exemestane plus ovarian suppression compared to tamoxifen plus ovarian suppression. Ovarian suppression was achieved by either GnRH agonist injections, surgical removal of the ovaries, or radiation therapy to the ovaries.

The side effects of these treatments included hot flushes (92%), depression (87%), musculoskeletal symptoms (89%), vaginal dryness (52%), decreased libido (45%), dyspareunia (31%), osteoporosis (39%), insomnia (58%), and fatigue (61%). These are all quality of life concerns, Dr. Keyser said, and these findings raise questions about the consequences of long-term ovarian suppression. Findings from the Nurses’ Health Study showed that BSO before age 47.5 years resulted in lower mortality from ovarian cancer and breast cancer but was linked in women under 50 to increased all-cause mortality and mortality from coronary heart disease, lung cancer, and colorectal cancer, compared with ovarian conservation. Further, 74% of women who undergo risk-reducing BSO experience sexual dysfunction.

The bottom line, Dr. Keyser said, is that “premature removal of ovaries is not completely benign.” Her own recommendation is to follow ACOG guidance for women with BRCA mutations and, for women aged under 35 years, use ovarian suppression for 5-10 years, after which ovarian function may resume along with improved quality of life. In women aged over 40, remove ovaries since, after 5-10 years of treatment, there’s likely no benefit of retaining ovaries.
 

Addressing sexual health

Dyspareunia affects up to 45% of cancer survivors, Dr. Keyser said, and multiple treatment options exist for breast cancer survivors. The therapies she discussed included lubricants, moisturizers, local vaginal estrogen, DHEA, ospemifene, and CO₂ laser therapy.

Though Dr. Keyser briefly touched on vaginal lubricants and moisturizers, Dr. Streicher was disappointed that Dr. Keyser did not clearly define and differentiate between lubricants and moisturizers or mention hyaluronic acid products. Dr. Streicher also disagreed with the way Dr. Keyser represented the benefits of coconut oil as a lubricant. “Oils are not condom compatible and are known to potentially increase the risk of infection, and not just from poor handwashing,” Dr. Streicher said.

Small retrospective studies support the safety of topical vaginal estrogen in breast cancer survivors, Dr. Keyser said, and the 10-mcg Vagifem tablet and vaginal estradiol ring appear to have the lowest systemic absorption. ACOG guidance recommends that women taking aromatase inhibitors who don’t respond to nonhormonal approaches may benefit from switching temporarily to tamoxifen with vaginal estrogen and then returning to aromatase inhibitors. However, Dr. Keyser said there’s plenty of data to support using vaginal estrogen in patients taking aromatase inhibitors.

“I do feel that it’s safe for patients, whether they’re on tamoxifen or aromatase inhibitors, to take vaginal estrogen,” Dr. Keyser said. “I usually stick with the estradiol vaginal ring or the estradiol tablet, and I base that on a patient’s comfort with placing and removing a ring.” She also, instead of asking the patient’s hematologist-oncologist, simply notifies them of the treatment since most hematologist-oncologists are less familiar with the data.

Another effective option is vaginal DHEA/prasterone, which can significantly improve sexual desire, arousal, pain, and overall sexual function. Although breast cancer patients were included in early studies on DHEA, Intrarosa manufacturers excluded breast cancer patients in their Food and Drug Administration application, resulting in a package stating that “use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer” and that “Intrarosa has not been studied in women with a history of breast cancer.” While that’s true for Intrarosa specifically, DHEA has been studied in breast cancer patients, Dr. Keyser said, so she expects to see more research in this area.

Ospemifene is another option for improving vulvovaginal atrophy but cannot be taken at the same time as tamoxifen. It has similar chemopreventive effects as tamoxifen in rat studies, but it’s not as effective. It’s a reasonable option in women with refractory genitourinary syndrome of menopause (GSM) who have completed their 5-10 years of adjuvant therapy and have no history of venous thromboembolism.

Dr. Keyser said CO₂ laser therapy is still being studied for treating GSM, and current data have shown benefits for dyspareunia and vaginal dryness without documented harms. There have now been randomized, controlled trials; however, since it’s not FDA approved, it’s not covered by insurance and costs approximately $5,000 for three treatments.

Dr. Streicher was glad to see Dr. Keyser’s discussion of the safety and types of local vaginal estrogen, “although she neglected to mention the 4-mcg vaginal suppository, Imvexxy, which has the lowest systemic absorption,” Dr. Streicher said. Dr. Streicher also felt the inclusion of DHEA/prasterone and ospemifene were also important, especially since the latter is “underutilized in breast cancer patients.”

The information provided on CO₂ laser therapy, however, was problematic, Dr. Streicher said, given that long-term and randomized, controlled studies have now been published. Dr. Streicher also noted that two of the devices listed on the presentation slide, Thermiva and Voltiva, are radiofrequency, not laser devices.

Aside from these treatment options, the most consistent predictor of satisfying sexual experiences in women with breast cancer is the quality of their relationships, Dr. Keyser said, so couples counseling is recommended, and treatments in general are more effective with regularly sexual activity.

In discussing nonhormonal options for treating vasomotor symptoms, Dr. Keyser recommended venlafaxine, gabapentin, and low-dose paroxetine (though SSRIs and tamoxifen are contraindicated since they may reduce tamoxifen’s efficacy).

These are all off label, Dr. Streicher said it was important to note, and she would have liked to have seen a mention of the development of KNdy neurokinin disrupters along with a more in-depth discussion about which lifestyle modifications and botanicals have been shown in randomized, controlled trials to mitigate vasomotor symptoms.

Dr. Keyser wrapped up with a few additional notes and takeaways:

• The only safe reversible long-term option for contraception in HR-positive breast cancer survivors is the Paraguard IUD.
• It’s important to discuss fertility with breast cancer patients and survivors since a majority report unmet needs in this area.
• Patients taking tamoxifen need to be sure to report any vaginal spotting or bleeding since it increases risk of endometrial cancer in postmenopausal women.
• Screen for depression and anxiety.
• Ask women about sexual health and hot flashes.
• Ensure that they’re getting bone screening.
• A recommended resource is Living Beyond Breast Cancer.

Dr. Keyser had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceuticals.

Sexual dysfunction is a common problem among breast cancer survivors, but it’s also an issue inadequately addressed by either ob.gyns. or hematologists and oncologists, according to Erin Keyser, MD, the program director of the San Antonio Uniformed Services Health Education Consortium. Dr. Keyser discussed management of sexual dysfunction and a variety of other issues frequently faced by women who have survived breast cancer at the at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician-gynecologists feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer,” Dr. Keyser quoted from a 2016 article in Obstetrics & Gynecology about the sexual health of women affected by cancer. As a breast cancer survivor herself, Dr. Keyser said hematologists and oncologists are even less equipped to discuss sexual health, “so oftentimes patients get punted between their hem-onc and their gyn,” with each telling the patient to ask the other specialist.

“There’s plenty of data in chronic health disease that maintaining sexual function for women is an indicator of the overall quality of life and that many women really don’t want to bring this up,” Dr. Keyser told attendees, so the onus is on the ob.gyn. to bring it up.

The effects of breast cancer treatment can impact women’s body image, fertility, menopause, sexual function, osteoporosis, and cardiovascular disease, but the bulk of Dr. Keyser’s talk focused on sexual health and bilateral salpingo-oophorectomy (BSO).

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, thought Dr. Keyser’s talk was useful for the general gynecologist but had some concerns about a few parts.

“She gave a very thoughtful analysis of whether someone should have their ovaries removed or not in a breast cancer diagnosis, ” Dr. Streicher said in an interview. “I would have liked to hear more about the consequences of an early menopause in women in terms of heart health, bone health, and cognitive function.”

Dr. Keyser noted that her talk pertained mostly to survivors of estrogen receptor (ER)–positive breast cancer since that population tends to struggle most with side effects of treatment. The most common medications used in this population are tamoxifen and aromatase inhibitors – such as anastrazole, letrozole, and exemestane – and these medications can affect management of different concerns.
 

Current guidance on ovarian removal

For women with a BRCA mutation, ACOG clinical guidance already exists regarding BSO. For other women, the complementary TEXT and SOFT trials changed the management of breast cancer treatment in premenopausal women, Dr. Keyser said.

Before these trials, postmenopausal hormone receptor–positive women began aromatase inhibitors and premenopausal HR-positive women began tamoxifen. These trials found that premenopausal women with HR-positive early breast cancer were less likely to experience recurrence when receiving adjuvant treatment with exemestane plus ovarian suppression compared to tamoxifen plus ovarian suppression. Ovarian suppression was achieved by either GnRH agonist injections, surgical removal of the ovaries, or radiation therapy to the ovaries.

The side effects of these treatments included hot flushes (92%), depression (87%), musculoskeletal symptoms (89%), vaginal dryness (52%), decreased libido (45%), dyspareunia (31%), osteoporosis (39%), insomnia (58%), and fatigue (61%). These are all quality of life concerns, Dr. Keyser said, and these findings raise questions about the consequences of long-term ovarian suppression. Findings from the Nurses’ Health Study showed that BSO before age 47.5 years resulted in lower mortality from ovarian cancer and breast cancer but was linked in women under 50 to increased all-cause mortality and mortality from coronary heart disease, lung cancer, and colorectal cancer, compared with ovarian conservation. Further, 74% of women who undergo risk-reducing BSO experience sexual dysfunction.

The bottom line, Dr. Keyser said, is that “premature removal of ovaries is not completely benign.” Her own recommendation is to follow ACOG guidance for women with BRCA mutations and, for women aged under 35 years, use ovarian suppression for 5-10 years, after which ovarian function may resume along with improved quality of life. In women aged over 40, remove ovaries since, after 5-10 years of treatment, there’s likely no benefit of retaining ovaries.
 

Addressing sexual health

Dyspareunia affects up to 45% of cancer survivors, Dr. Keyser said, and multiple treatment options exist for breast cancer survivors. The therapies she discussed included lubricants, moisturizers, local vaginal estrogen, DHEA, ospemifene, and CO₂ laser therapy.

Though Dr. Keyser briefly touched on vaginal lubricants and moisturizers, Dr. Streicher was disappointed that Dr. Keyser did not clearly define and differentiate between lubricants and moisturizers or mention hyaluronic acid products. Dr. Streicher also disagreed with the way Dr. Keyser represented the benefits of coconut oil as a lubricant. “Oils are not condom compatible and are known to potentially increase the risk of infection, and not just from poor handwashing,” Dr. Streicher said.

Small retrospective studies support the safety of topical vaginal estrogen in breast cancer survivors, Dr. Keyser said, and the 10-mcg Vagifem tablet and vaginal estradiol ring appear to have the lowest systemic absorption. ACOG guidance recommends that women taking aromatase inhibitors who don’t respond to nonhormonal approaches may benefit from switching temporarily to tamoxifen with vaginal estrogen and then returning to aromatase inhibitors. However, Dr. Keyser said there’s plenty of data to support using vaginal estrogen in patients taking aromatase inhibitors.

“I do feel that it’s safe for patients, whether they’re on tamoxifen or aromatase inhibitors, to take vaginal estrogen,” Dr. Keyser said. “I usually stick with the estradiol vaginal ring or the estradiol tablet, and I base that on a patient’s comfort with placing and removing a ring.” She also, instead of asking the patient’s hematologist-oncologist, simply notifies them of the treatment since most hematologist-oncologists are less familiar with the data.

Another effective option is vaginal DHEA/prasterone, which can significantly improve sexual desire, arousal, pain, and overall sexual function. Although breast cancer patients were included in early studies on DHEA, Intrarosa manufacturers excluded breast cancer patients in their Food and Drug Administration application, resulting in a package stating that “use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer” and that “Intrarosa has not been studied in women with a history of breast cancer.” While that’s true for Intrarosa specifically, DHEA has been studied in breast cancer patients, Dr. Keyser said, so she expects to see more research in this area.

Ospemifene is another option for improving vulvovaginal atrophy but cannot be taken at the same time as tamoxifen. It has similar chemopreventive effects as tamoxifen in rat studies, but it’s not as effective. It’s a reasonable option in women with refractory genitourinary syndrome of menopause (GSM) who have completed their 5-10 years of adjuvant therapy and have no history of venous thromboembolism.

Dr. Keyser said CO₂ laser therapy is still being studied for treating GSM, and current data have shown benefits for dyspareunia and vaginal dryness without documented harms. There have now been randomized, controlled trials; however, since it’s not FDA approved, it’s not covered by insurance and costs approximately $5,000 for three treatments.

Dr. Streicher was glad to see Dr. Keyser’s discussion of the safety and types of local vaginal estrogen, “although she neglected to mention the 4-mcg vaginal suppository, Imvexxy, which has the lowest systemic absorption,” Dr. Streicher said. Dr. Streicher also felt the inclusion of DHEA/prasterone and ospemifene were also important, especially since the latter is “underutilized in breast cancer patients.”

The information provided on CO₂ laser therapy, however, was problematic, Dr. Streicher said, given that long-term and randomized, controlled studies have now been published. Dr. Streicher also noted that two of the devices listed on the presentation slide, Thermiva and Voltiva, are radiofrequency, not laser devices.

Aside from these treatment options, the most consistent predictor of satisfying sexual experiences in women with breast cancer is the quality of their relationships, Dr. Keyser said, so couples counseling is recommended, and treatments in general are more effective with regularly sexual activity.

In discussing nonhormonal options for treating vasomotor symptoms, Dr. Keyser recommended venlafaxine, gabapentin, and low-dose paroxetine (though SSRIs and tamoxifen are contraindicated since they may reduce tamoxifen’s efficacy).

These are all off label, Dr. Streicher said it was important to note, and she would have liked to have seen a mention of the development of KNdy neurokinin disrupters along with a more in-depth discussion about which lifestyle modifications and botanicals have been shown in randomized, controlled trials to mitigate vasomotor symptoms.

Dr. Keyser wrapped up with a few additional notes and takeaways:

• The only safe reversible long-term option for contraception in HR-positive breast cancer survivors is the Paraguard IUD.
• It’s important to discuss fertility with breast cancer patients and survivors since a majority report unmet needs in this area.
• Patients taking tamoxifen need to be sure to report any vaginal spotting or bleeding since it increases risk of endometrial cancer in postmenopausal women.
• Screen for depression and anxiety.
• Ask women about sexual health and hot flashes.
• Ensure that they’re getting bone screening.
• A recommended resource is Living Beyond Breast Cancer.

Dr. Keyser had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceuticals.

Sexual dysfunction is a common problem among breast cancer survivors, but it’s also an issue inadequately addressed by either ob.gyns. or hematologists and oncologists, according to Erin Keyser, MD, the program director of the San Antonio Uniformed Services Health Education Consortium. Dr. Keyser discussed management of sexual dysfunction and a variety of other issues frequently faced by women who have survived breast cancer at the at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician-gynecologists feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer,” Dr. Keyser quoted from a 2016 article in Obstetrics & Gynecology about the sexual health of women affected by cancer. As a breast cancer survivor herself, Dr. Keyser said hematologists and oncologists are even less equipped to discuss sexual health, “so oftentimes patients get punted between their hem-onc and their gyn,” with each telling the patient to ask the other specialist.

“There’s plenty of data in chronic health disease that maintaining sexual function for women is an indicator of the overall quality of life and that many women really don’t want to bring this up,” Dr. Keyser told attendees, so the onus is on the ob.gyn. to bring it up.

The effects of breast cancer treatment can impact women’s body image, fertility, menopause, sexual function, osteoporosis, and cardiovascular disease, but the bulk of Dr. Keyser’s talk focused on sexual health and bilateral salpingo-oophorectomy (BSO).

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University, Chicago, thought Dr. Keyser’s talk was useful for the general gynecologist but had some concerns about a few parts.

“She gave a very thoughtful analysis of whether someone should have their ovaries removed or not in a breast cancer diagnosis, ” Dr. Streicher said in an interview. “I would have liked to hear more about the consequences of an early menopause in women in terms of heart health, bone health, and cognitive function.”

Dr. Keyser noted that her talk pertained mostly to survivors of estrogen receptor (ER)–positive breast cancer since that population tends to struggle most with side effects of treatment. The most common medications used in this population are tamoxifen and aromatase inhibitors – such as anastrazole, letrozole, and exemestane – and these medications can affect management of different concerns.
 

Current guidance on ovarian removal

For women with a BRCA mutation, ACOG clinical guidance already exists regarding BSO. For other women, the complementary TEXT and SOFT trials changed the management of breast cancer treatment in premenopausal women, Dr. Keyser said.

Before these trials, postmenopausal hormone receptor–positive women began aromatase inhibitors and premenopausal HR-positive women began tamoxifen. These trials found that premenopausal women with HR-positive early breast cancer were less likely to experience recurrence when receiving adjuvant treatment with exemestane plus ovarian suppression compared to tamoxifen plus ovarian suppression. Ovarian suppression was achieved by either GnRH agonist injections, surgical removal of the ovaries, or radiation therapy to the ovaries.

The side effects of these treatments included hot flushes (92%), depression (87%), musculoskeletal symptoms (89%), vaginal dryness (52%), decreased libido (45%), dyspareunia (31%), osteoporosis (39%), insomnia (58%), and fatigue (61%). These are all quality of life concerns, Dr. Keyser said, and these findings raise questions about the consequences of long-term ovarian suppression. Findings from the Nurses’ Health Study showed that BSO before age 47.5 years resulted in lower mortality from ovarian cancer and breast cancer but was linked in women under 50 to increased all-cause mortality and mortality from coronary heart disease, lung cancer, and colorectal cancer, compared with ovarian conservation. Further, 74% of women who undergo risk-reducing BSO experience sexual dysfunction.

The bottom line, Dr. Keyser said, is that “premature removal of ovaries is not completely benign.” Her own recommendation is to follow ACOG guidance for women with BRCA mutations and, for women aged under 35 years, use ovarian suppression for 5-10 years, after which ovarian function may resume along with improved quality of life. In women aged over 40, remove ovaries since, after 5-10 years of treatment, there’s likely no benefit of retaining ovaries.
 

Addressing sexual health

Dyspareunia affects up to 45% of cancer survivors, Dr. Keyser said, and multiple treatment options exist for breast cancer survivors. The therapies she discussed included lubricants, moisturizers, local vaginal estrogen, DHEA, ospemifene, and CO₂ laser therapy.

Though Dr. Keyser briefly touched on vaginal lubricants and moisturizers, Dr. Streicher was disappointed that Dr. Keyser did not clearly define and differentiate between lubricants and moisturizers or mention hyaluronic acid products. Dr. Streicher also disagreed with the way Dr. Keyser represented the benefits of coconut oil as a lubricant. “Oils are not condom compatible and are known to potentially increase the risk of infection, and not just from poor handwashing,” Dr. Streicher said.

Small retrospective studies support the safety of topical vaginal estrogen in breast cancer survivors, Dr. Keyser said, and the 10-mcg Vagifem tablet and vaginal estradiol ring appear to have the lowest systemic absorption. ACOG guidance recommends that women taking aromatase inhibitors who don’t respond to nonhormonal approaches may benefit from switching temporarily to tamoxifen with vaginal estrogen and then returning to aromatase inhibitors. However, Dr. Keyser said there’s plenty of data to support using vaginal estrogen in patients taking aromatase inhibitors.

“I do feel that it’s safe for patients, whether they’re on tamoxifen or aromatase inhibitors, to take vaginal estrogen,” Dr. Keyser said. “I usually stick with the estradiol vaginal ring or the estradiol tablet, and I base that on a patient’s comfort with placing and removing a ring.” She also, instead of asking the patient’s hematologist-oncologist, simply notifies them of the treatment since most hematologist-oncologists are less familiar with the data.

Another effective option is vaginal DHEA/prasterone, which can significantly improve sexual desire, arousal, pain, and overall sexual function. Although breast cancer patients were included in early studies on DHEA, Intrarosa manufacturers excluded breast cancer patients in their Food and Drug Administration application, resulting in a package stating that “use of exogenous estrogen is contraindicated in women with a known or suspected history of breast cancer” and that “Intrarosa has not been studied in women with a history of breast cancer.” While that’s true for Intrarosa specifically, DHEA has been studied in breast cancer patients, Dr. Keyser said, so she expects to see more research in this area.

Ospemifene is another option for improving vulvovaginal atrophy but cannot be taken at the same time as tamoxifen. It has similar chemopreventive effects as tamoxifen in rat studies, but it’s not as effective. It’s a reasonable option in women with refractory genitourinary syndrome of menopause (GSM) who have completed their 5-10 years of adjuvant therapy and have no history of venous thromboembolism.

Dr. Keyser said CO₂ laser therapy is still being studied for treating GSM, and current data have shown benefits for dyspareunia and vaginal dryness without documented harms. There have now been randomized, controlled trials; however, since it’s not FDA approved, it’s not covered by insurance and costs approximately $5,000 for three treatments.

Dr. Streicher was glad to see Dr. Keyser’s discussion of the safety and types of local vaginal estrogen, “although she neglected to mention the 4-mcg vaginal suppository, Imvexxy, which has the lowest systemic absorption,” Dr. Streicher said. Dr. Streicher also felt the inclusion of DHEA/prasterone and ospemifene were also important, especially since the latter is “underutilized in breast cancer patients.”

The information provided on CO₂ laser therapy, however, was problematic, Dr. Streicher said, given that long-term and randomized, controlled studies have now been published. Dr. Streicher also noted that two of the devices listed on the presentation slide, Thermiva and Voltiva, are radiofrequency, not laser devices.

Aside from these treatment options, the most consistent predictor of satisfying sexual experiences in women with breast cancer is the quality of their relationships, Dr. Keyser said, so couples counseling is recommended, and treatments in general are more effective with regularly sexual activity.

In discussing nonhormonal options for treating vasomotor symptoms, Dr. Keyser recommended venlafaxine, gabapentin, and low-dose paroxetine (though SSRIs and tamoxifen are contraindicated since they may reduce tamoxifen’s efficacy).

These are all off label, Dr. Streicher said it was important to note, and she would have liked to have seen a mention of the development of KNdy neurokinin disrupters along with a more in-depth discussion about which lifestyle modifications and botanicals have been shown in randomized, controlled trials to mitigate vasomotor symptoms.

Dr. Keyser wrapped up with a few additional notes and takeaways:

• The only safe reversible long-term option for contraception in HR-positive breast cancer survivors is the Paraguard IUD.
• It’s important to discuss fertility with breast cancer patients and survivors since a majority report unmet needs in this area.
• Patients taking tamoxifen need to be sure to report any vaginal spotting or bleeding since it increases risk of endometrial cancer in postmenopausal women.
• Screen for depression and anxiety.
• Ask women about sexual health and hot flashes.
• Ensure that they’re getting bone screening.
• A recommended resource is Living Beyond Breast Cancer.

Dr. Keyser had no disclosures. Dr. Streicher has consulted for Astellas Pharma and Church & Dwight, and she owns investments in InControl Medical and Sermonix Pharmaceuticals.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

The biggest factors that attract medical students to enter pediatric rheumatology are interest in disease pathology, the patient-physician relationship, and clinical exposure in residency, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

A shortage in pediatric rheumatology already exists and is expected to worsen to 61% by 2030, noted the authors. About one-third (32%) of current pediatric rheumatologists will retire in the next decade, and less than two-thirds of fellowship slots have filled in the past 5 years.

Katherine Schultz, MD, a clinical fellow in the division of rheumatology at Cincinnati Children’s Medical Center, led the study and said she was surprised that medical school exposure did not play a bigger role in attracting people to the field, but perhaps that’s because too few people received that early exposure.

“If we had earlier exposure, maybe that wouldn’t be definitive for saying, ‘yes, I want to do this subspecialty of pediatric rheumatology,’ but it would open the door, so when you hit residency, you can explore it further,” Dr. Schultz said in an interview.

Dr. Schultz and her colleagues conducted a survey using the CARRA registry during September-December 2020. Respondents included pediatric rheumatology clinical fellows, early-career pediatric rheumatology faculty with less than 7 years practice experience, and mid- to late-career pediatric rheumatology faculty – those with more than 7 years of practice. They are currently in the process of analyzing additional qualitative data.

Of the 428 clinicians recruited to complete the study, 92 did so, for a response rate of 21%. Most respondents were female and non-Hispanic White. A total of 40% were clinical fellows, 41% were early-career faculty, and 18% were mid- to late-career faculty.

Positive factors for choosing the field

More than 80% of respondents across all three experience levels cited disease pathology as a positive attribute of pediatric rheumatology, something that Dr. Schultz mentioned as well.

“The rewarding part of pediatric rheumatology is we take these complex diseases and we help give kids their life back,” she said.

Nearly all the clinical fellows who responded said the patient-physician relationship was important, which early- and mid- and late-career faculty mentioned as well, although to a slightly lesser extent.

Other factors following closely behind disease pathology, patient-physician relationship, and clinical exposure in residency were having a role model in the field – cited by more than three-quarters of clinical fellows and early-career faculty – and having mentorship during residency.

“One of the strengths of our field and one of the things I love about pediatric rheumatology is our community is so close-knit, so kind, and so welcoming,” Dr. Schultz said. “If students can have that exposure and they can see the kind of people who are in this field, that’s our greatest power to draw people to our field.”

Low compensation is a deterrent

The least frequently mentioned positive factors were research opportunities and income. In fact, income was by far the most commonly cited negative attribute of pediatric rheumatology, reported by nearly half of clinical fellows and more than a quarter of early- and mid- and late-career faculty.

“We are one of the lowest paid specialties in pediatrics. We often make [income] comparable to or less than a general pediatrician,” Dr. Schultz said. One reason for that is the difficulty of doing pediatric rheumatology in private practice. Most positions are at academic institutions, which will nearly always involve lower pay scales, she said. The field is also not a procedure-based one, which makes billing more difficult to quantify.

“If I spend an hour thinking about a patient’s diagnosis and interpreting their labs, how do we quantify that?” she asked. “Our field is so cognitive that it makes it hard to bill in the same manner” as fields who bill more procedures, she said.

The other specialties that respondents considered before choosing pediatric rheumatology varied by generation, but allergy and immunology and endocrinology were among the most cited by early-, mid-, and late-career faculty. Clinical fellows’ responses were more evenly distributed across a range of different subspecialties.

Early exposure is key

A large proportion of all three groups, including almost 90% of early-career faculty and clinical fellows, said they received exposure to pediatric rheumatology during residency. However, only a little more than two-thirds of clinical fellows had exposure to the field in medical school, and fewer than that reported medical school exposure among both faculty groups.

Both Dr. Correll and Dr. Schultz said that early exposure to pediatric rheumatology was key to bringing more people into the workforce.

“I believe that once a medical student or resident has an opportunity to work with a pediatric rheumatologist, they are able to see the many reasons for which this is a great career choice,” Dr. Correll said. “Pediatric rheumatologists are seen as positive role models. We love what we do, we have great patient-physician relationships, and we see interesting disease pathophysiology on a regular basis.”

Although earlier exposure to the field is primarily an institutional issue, clinicians can play a role as well.

“For the individual practitioners, the biggest way they can make an impact is to make themselves visible,” Dr. Schultz said. Although the subspecialty is stretched thin, she encouraged pediatric rheumatologists to do med school and resident lectures, volunteer to do feedback sessions, offer residents opportunities to rotate with them, and generally make themselves more visible. “It’s going to take the community to really make the change we need,” she said.

She and Dr. Correll both cited the American College of Rheumatology and CARRA pediatric residency programs as helpful, but there’s more to do. Other ways to increase exposure to the field include creating medical student rotations in pediatric rheumatology, working on case reports or small research projects with new learners, and requesting that pediatric rheumatology be a mandatory rotation in pediatrics training, Dr. Correll said.

“We absolutely have a responsibility to promote our field because if we don’t, the workforce supply issue will continue to worsen,” Dr. Correll said. “We already have a workforce shortage, and models show this shortage will only worsen if we don’t improve recruitment into the field, especially with many pediatric rheumatologists coming up on retirement. Once we are able to expose medical students and residents to the field, I think they easily see our passion and our love for the field, and it’s easy to recruit them.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. Dr. Schultz and Dr. Correll had no disclosures. 


The biggest factors that attract medical students to enter pediatric rheumatology are interest in disease pathology, the patient-physician relationship, and clinical exposure in residency, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

A shortage in pediatric rheumatology already exists and is expected to worsen to 61% by 2030, noted the authors. About one-third (32%) of current pediatric rheumatologists will retire in the next decade, and less than two-thirds of fellowship slots have filled in the past 5 years.

Katherine Schultz, MD, a clinical fellow in the division of rheumatology at Cincinnati Children’s Medical Center, led the study and said she was surprised that medical school exposure did not play a bigger role in attracting people to the field, but perhaps that’s because too few people received that early exposure.

“If we had earlier exposure, maybe that wouldn’t be definitive for saying, ‘yes, I want to do this subspecialty of pediatric rheumatology,’ but it would open the door, so when you hit residency, you can explore it further,” Dr. Schultz said in an interview.

Dr. Schultz and her colleagues conducted a survey using the CARRA registry during September-December 2020. Respondents included pediatric rheumatology clinical fellows, early-career pediatric rheumatology faculty with less than 7 years practice experience, and mid- to late-career pediatric rheumatology faculty – those with more than 7 years of practice. They are currently in the process of analyzing additional qualitative data.

Of the 428 clinicians recruited to complete the study, 92 did so, for a response rate of 21%. Most respondents were female and non-Hispanic White. A total of 40% were clinical fellows, 41% were early-career faculty, and 18% were mid- to late-career faculty.

Positive factors for choosing the field

More than 80% of respondents across all three experience levels cited disease pathology as a positive attribute of pediatric rheumatology, something that Dr. Schultz mentioned as well.

“The rewarding part of pediatric rheumatology is we take these complex diseases and we help give kids their life back,” she said.

Nearly all the clinical fellows who responded said the patient-physician relationship was important, which early- and mid- and late-career faculty mentioned as well, although to a slightly lesser extent.

Other factors following closely behind disease pathology, patient-physician relationship, and clinical exposure in residency were having a role model in the field – cited by more than three-quarters of clinical fellows and early-career faculty – and having mentorship during residency.

“One of the strengths of our field and one of the things I love about pediatric rheumatology is our community is so close-knit, so kind, and so welcoming,” Dr. Schultz said. “If students can have that exposure and they can see the kind of people who are in this field, that’s our greatest power to draw people to our field.”

Low compensation is a deterrent

The least frequently mentioned positive factors were research opportunities and income. In fact, income was by far the most commonly cited negative attribute of pediatric rheumatology, reported by nearly half of clinical fellows and more than a quarter of early- and mid- and late-career faculty.

“We are one of the lowest paid specialties in pediatrics. We often make [income] comparable to or less than a general pediatrician,” Dr. Schultz said. One reason for that is the difficulty of doing pediatric rheumatology in private practice. Most positions are at academic institutions, which will nearly always involve lower pay scales, she said. The field is also not a procedure-based one, which makes billing more difficult to quantify.

“If I spend an hour thinking about a patient’s diagnosis and interpreting their labs, how do we quantify that?” she asked. “Our field is so cognitive that it makes it hard to bill in the same manner” as fields who bill more procedures, she said.

The other specialties that respondents considered before choosing pediatric rheumatology varied by generation, but allergy and immunology and endocrinology were among the most cited by early-, mid-, and late-career faculty. Clinical fellows’ responses were more evenly distributed across a range of different subspecialties.

Early exposure is key

A large proportion of all three groups, including almost 90% of early-career faculty and clinical fellows, said they received exposure to pediatric rheumatology during residency. However, only a little more than two-thirds of clinical fellows had exposure to the field in medical school, and fewer than that reported medical school exposure among both faculty groups.

Both Dr. Correll and Dr. Schultz said that early exposure to pediatric rheumatology was key to bringing more people into the workforce.

“I believe that once a medical student or resident has an opportunity to work with a pediatric rheumatologist, they are able to see the many reasons for which this is a great career choice,” Dr. Correll said. “Pediatric rheumatologists are seen as positive role models. We love what we do, we have great patient-physician relationships, and we see interesting disease pathophysiology on a regular basis.”

Although earlier exposure to the field is primarily an institutional issue, clinicians can play a role as well.

“For the individual practitioners, the biggest way they can make an impact is to make themselves visible,” Dr. Schultz said. Although the subspecialty is stretched thin, she encouraged pediatric rheumatologists to do med school and resident lectures, volunteer to do feedback sessions, offer residents opportunities to rotate with them, and generally make themselves more visible. “It’s going to take the community to really make the change we need,” she said.

She and Dr. Correll both cited the American College of Rheumatology and CARRA pediatric residency programs as helpful, but there’s more to do. Other ways to increase exposure to the field include creating medical student rotations in pediatric rheumatology, working on case reports or small research projects with new learners, and requesting that pediatric rheumatology be a mandatory rotation in pediatrics training, Dr. Correll said.

“We absolutely have a responsibility to promote our field because if we don’t, the workforce supply issue will continue to worsen,” Dr. Correll said. “We already have a workforce shortage, and models show this shortage will only worsen if we don’t improve recruitment into the field, especially with many pediatric rheumatologists coming up on retirement. Once we are able to expose medical students and residents to the field, I think they easily see our passion and our love for the field, and it’s easy to recruit them.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. Dr. Schultz and Dr. Correll had no disclosures. 


The biggest factors that attract medical students to enter pediatric rheumatology are interest in disease pathology, the patient-physician relationship, and clinical exposure in residency, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

A shortage in pediatric rheumatology already exists and is expected to worsen to 61% by 2030, noted the authors. About one-third (32%) of current pediatric rheumatologists will retire in the next decade, and less than two-thirds of fellowship slots have filled in the past 5 years.

Katherine Schultz, MD, a clinical fellow in the division of rheumatology at Cincinnati Children’s Medical Center, led the study and said she was surprised that medical school exposure did not play a bigger role in attracting people to the field, but perhaps that’s because too few people received that early exposure.

“If we had earlier exposure, maybe that wouldn’t be definitive for saying, ‘yes, I want to do this subspecialty of pediatric rheumatology,’ but it would open the door, so when you hit residency, you can explore it further,” Dr. Schultz said in an interview.

Dr. Schultz and her colleagues conducted a survey using the CARRA registry during September-December 2020. Respondents included pediatric rheumatology clinical fellows, early-career pediatric rheumatology faculty with less than 7 years practice experience, and mid- to late-career pediatric rheumatology faculty – those with more than 7 years of practice. They are currently in the process of analyzing additional qualitative data.

Of the 428 clinicians recruited to complete the study, 92 did so, for a response rate of 21%. Most respondents were female and non-Hispanic White. A total of 40% were clinical fellows, 41% were early-career faculty, and 18% were mid- to late-career faculty.

Positive factors for choosing the field

More than 80% of respondents across all three experience levels cited disease pathology as a positive attribute of pediatric rheumatology, something that Dr. Schultz mentioned as well.

“The rewarding part of pediatric rheumatology is we take these complex diseases and we help give kids their life back,” she said.

Nearly all the clinical fellows who responded said the patient-physician relationship was important, which early- and mid- and late-career faculty mentioned as well, although to a slightly lesser extent.

Other factors following closely behind disease pathology, patient-physician relationship, and clinical exposure in residency were having a role model in the field – cited by more than three-quarters of clinical fellows and early-career faculty – and having mentorship during residency.

“One of the strengths of our field and one of the things I love about pediatric rheumatology is our community is so close-knit, so kind, and so welcoming,” Dr. Schultz said. “If students can have that exposure and they can see the kind of people who are in this field, that’s our greatest power to draw people to our field.”

Low compensation is a deterrent

The least frequently mentioned positive factors were research opportunities and income. In fact, income was by far the most commonly cited negative attribute of pediatric rheumatology, reported by nearly half of clinical fellows and more than a quarter of early- and mid- and late-career faculty.

“We are one of the lowest paid specialties in pediatrics. We often make [income] comparable to or less than a general pediatrician,” Dr. Schultz said. One reason for that is the difficulty of doing pediatric rheumatology in private practice. Most positions are at academic institutions, which will nearly always involve lower pay scales, she said. The field is also not a procedure-based one, which makes billing more difficult to quantify.

“If I spend an hour thinking about a patient’s diagnosis and interpreting their labs, how do we quantify that?” she asked. “Our field is so cognitive that it makes it hard to bill in the same manner” as fields who bill more procedures, she said.

The other specialties that respondents considered before choosing pediatric rheumatology varied by generation, but allergy and immunology and endocrinology were among the most cited by early-, mid-, and late-career faculty. Clinical fellows’ responses were more evenly distributed across a range of different subspecialties.

Early exposure is key

A large proportion of all three groups, including almost 90% of early-career faculty and clinical fellows, said they received exposure to pediatric rheumatology during residency. However, only a little more than two-thirds of clinical fellows had exposure to the field in medical school, and fewer than that reported medical school exposure among both faculty groups.

Both Dr. Correll and Dr. Schultz said that early exposure to pediatric rheumatology was key to bringing more people into the workforce.

“I believe that once a medical student or resident has an opportunity to work with a pediatric rheumatologist, they are able to see the many reasons for which this is a great career choice,” Dr. Correll said. “Pediatric rheumatologists are seen as positive role models. We love what we do, we have great patient-physician relationships, and we see interesting disease pathophysiology on a regular basis.”

Although earlier exposure to the field is primarily an institutional issue, clinicians can play a role as well.

“For the individual practitioners, the biggest way they can make an impact is to make themselves visible,” Dr. Schultz said. Although the subspecialty is stretched thin, she encouraged pediatric rheumatologists to do med school and resident lectures, volunteer to do feedback sessions, offer residents opportunities to rotate with them, and generally make themselves more visible. “It’s going to take the community to really make the change we need,” she said.

She and Dr. Correll both cited the American College of Rheumatology and CARRA pediatric residency programs as helpful, but there’s more to do. Other ways to increase exposure to the field include creating medical student rotations in pediatric rheumatology, working on case reports or small research projects with new learners, and requesting that pediatric rheumatology be a mandatory rotation in pediatrics training, Dr. Correll said.

“We absolutely have a responsibility to promote our field because if we don’t, the workforce supply issue will continue to worsen,” Dr. Correll said. “We already have a workforce shortage, and models show this shortage will only worsen if we don’t improve recruitment into the field, especially with many pediatric rheumatologists coming up on retirement. Once we are able to expose medical students and residents to the field, I think they easily see our passion and our love for the field, and it’s easy to recruit them.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. Dr. Schultz and Dr. Correll had no disclosures. 


Exposure to epidural analgesia during labor did not show a link to a later diagnosis of autism spectrum disorder (ASD) in a population-based cohort study published April 19 in JAMA Pediatrics.

Though the initial analysis showed an association, adjustment for a wide range of demographic, medical, and birth factors eliminated the link. The authors note that their findings contrast with those of a cohort study in California published in the same journal last year.

“It is possible that residual confounding explains this positive association because key perinatal variables, including induction of labor, labor dystocia, and fetal distress, were not included as confounders in that study,” write Elizabeth Wall-Wieler, PhD, of the University of Manitoba in Winnipeg and her colleagues. “To limit potential bias from unmeasured confounders, we included the aforementioned variables within a wide set of potential confounders.”

The researchers analyzed linked datasets from all singleton infants born in a hospital from 2005 to 2016 in Manitoba, Canada, to compare use of epidurals during birth with diagnoses of ASD before 18 months of age. The four data sources included the Statistics Canada, Manitoba Education, Manitoba Families, and Manitoba Health, Seniors and Active Living, which includes the Manitoba Health Insurance Registry, Medical Services, Hospital Abstracts, and Drug Program Information Network. The researchers excluded women with cesarean deliveries because it was not possible to differentiate between scheduled and unscheduled cesarean deliveries.

Among 123,175 children born to mothers with an average age of 28 years, 38.2% had been exposed to epidural analgesia during their labor. Autism diagnoses occurred among 2.1% of those exposed to epidurals and 1.7% of those not exposed to epidurals. After the researchers controlled for a range of potential confounders, the difference became nonsignificant (hazard ratio, 1.08).

The adjusted analysis accounted for mother’s age; high school degree; marital status; neighborhood socioeconomic status; receipt of public assistance during pregnancy; and presence of diabetes, hypertension, anxiety, or depression in the year before the birth. Other covariates included in the adjustment included the following pregnancy factors: “parity, gestational diabetes, gestational hypertension or preeclampsia, self-reported and diagnosed drug use, smoking, alcohol use, premature rupture of membranes, antepartum hemorrhage, infection of the amniotic sac and membrane, urogenital infection, antenatal mental health hospitalization, hypothyroidism, benzodiazepine use, antidepressant use, and antiepileptic use.” The researchers also included birth year, labor induction or augmentation, labor dystocia, fetal distress or macrosomia, gestational age at birth, the infant’s sex, and hospital type.

“There were substantial differences in maternal sociodemographic, preexisting, pregnancy-related, and birth-specific covariates between births who were exposed vs. nonexposed to epidural labor analgesia,” the authors report. “For example, births exposed to epidural labor analgesia were more likely to be nulliparous, have premature rupture of membranes, antepartum hemorrhage, induction of labor, augmentation of labor, and fetal distress.”

To take family history of ASD into account, the researchers also compared siblings who were and were not exposed to an epidural during labor: 80,459 children in the cohort had at least one sibling in it as well. The researchers still found no association between use of an epidural and a subsequent autism diagnosis (HR, 0.97). The authors conducted several sensitivity analyses for first-born children, those with two or more diagnostic codes for ASD on different days, and women with missing data on high school completion or marital status who delivered at 37 weeks of gestation or later; these results consistently showed no association between epidurals and ASD.

The findings are important but unsurprising, said Scott M. Myers, MD, a neurodevelopmental pediatrician and associate professor at the Geisinger Commonwealth School of Medicine’s Autism & Developmental Medicine Institute in Scranton, Pa. Dr. Myers, who was not involved in the study, said it was strengthened by the inclusion of a wide range of covariates and multiple sensitivity analyses.

“It confirms the suspicion of many experts who were skeptical of the association reported previously, that the small increase in ASD in offspring of mothers who had epidural labor analgesia was likely attributable to other factors that differed substantially between the exposed and unexposed groups,” Dr. Myers said in an interview. “The plausibility of exposure to epidural analgesia in labor having a large effect on ASD risk and accounting for changes in ASD prevalence over time is low.”

It’s possible to hypothesize about subgroups that are genetically susceptible to certain environmental risk factors, including epidurals, but such an association should show up in epidemiological research if the subgroup is large enough.

“For example, epidural labor analgesia can prolong labor, and if it were a significant risk factor for ASD, one might expect that longer labor would have been demonstrated to be associated with increased ASD risk, but this has been examined and is not the case,” he said. He also noted that other perinatal factors previously linked to ASD, such as cesarean delivery, may result from a shared factor that affects risk of both ASD and cesarean delivery.

“Although there haven’t been enough systematic postmortem brain studies to be certain that the findings are generalizable, the most consistent neuropathological findings associated with ASD clearly arise long before birth,”Dr. Myers said. “The information I would provide to a concerned pregnant mother is that the current weight of the evidence does not suggest an association between epidural analgesia in labor and increased likelihood of ASD in offspring, much less a causal association.”

Clay Jones, MD, a hospitalist specializing in neonatal-perinatal medicine at Newton (Mass.)–Wellesley Hospital, was not involved in the research and offered a similar assessment of the findings.

“Our understanding of autism is that it is more of a genetic condition which interferes with the organization of brain architecture, so the evidence for any environmental cause would need to be robust for it to change medical practice or our recommendations to the general public,” Dr. Jones said in an interview. Compared to the previous California study, “this new research is larger and better accounts for confounding variables that might increase the risk of a child eventually being diagnosed with autism,” he said.

While recognizing the value in conducting studies to uncover any potential environmental factors contributing to autism diagnoses, Dr. Jones also addressed science communication challenges related to this research.

“While many of these studies are valid early efforts at honing in on potential risk factors, they can be overhyped and lead to increased patient anxiety and potentially harmful changes in behavior,” Dr. Jones said. “There is already a significant amount of pressure for many women to avoid certain safe and effective pain reduction strategies during labor, such as epidural labor analgesia. This pressure is often based on misunderstandings of the risks, pseudoscientific beliefs regarding the benefits of so-called ‘natural childbirth,’ and blatant misogyny. I hope that this new study helps to reassure women that it is okay to request to be more comfortable during their labor experience with the help of epidural labor analgesia.”

The authors of the study also noted the benefits of epidural use during labor.

“It is recognized as the most effective method of providing labor analgesia,” they write. In addition, “the presence of an indwelling epidural catheter allows epidural anesthesia to be administered for an unplanned (intrapartum) cesarean delivery, thus secondarily avoiding any maternal complications or fetal exposure from general anesthesia.”

JAMA Pediatrics editor Dimitri A. Christakis, MD, MPH, wrote his second-ever Editor’s Note about this topic after the journal published two similar studies with different conclusions.

“Because there will never be experimental studies of environmental exposures, we are left with imperfect observational studies that are always at risk for residual confounding, especially when observed effect sizes are small,” Dr. Christakis writes. “Science is an imperfect and iterative process, and our responsibility as journal editors is to manage the process as best we can. Publishing two conflicting studies in such a short time frame serves as testament that we recognize the process for what it is.” His personal opinion is that any association has yet to be definitively established but that the journal will publish the study if a more definitive one is done.

In considering potentially contributing environmental risk factors to ASD, Gillian E. Hanley, PhD, of the University of British Columbia in Vancouver and two colleagues write that “meta-analyses have been unable to identify a single perinatal and neonatal factor associated with ASD risk, although some evidence suggested that exposure to a broad class of conditions such as fetal presentation, umbilical-cord complications, fetal distress, or multiple births, reflecting compromised neonatal health, may increase risk.”

Yet, they add, these studies are inconsistent in their effect size, likely because of differences in study methodology, comparison groups, sample size, diagnostic criteria, and exposure assessment.

“Thus, we continue to ask questions about whether biologically plausible associations exist or whether associations reflect residual confounding related to yet-to-be-determined maternal genetic or environmental factors,” Dr. Hanley and her colleagues write. They discuss precise differences between the California and Manitoba studies and the inevitability of selection bias since people who choose an epidural will differ in other ways from those who don’t.

“Epidural labor analgesia is an extremely effective approach to obstetric analgesia, and we have a collective responsibility to understand whether it is a safe option that sets a healthy developmental pathway well into childhood,” Dr. Hanley and her colleagues conclude. “Women have the right to make a truly informed choice about their pain relief during labor.”

The research was funded by the Canadian Institutes of Health. One author reported receiving personal fees or grants from Aetion, Alosa Foundation, Lilly, GSK, Pacira, and Takeda. No other authors had disclosures. Dr. Jones, Dr. Myers, and the editorial authors had no disclosures.

Exposure to epidural analgesia during labor did not show a link to a later diagnosis of autism spectrum disorder (ASD) in a population-based cohort study published April 19 in JAMA Pediatrics.

Though the initial analysis showed an association, adjustment for a wide range of demographic, medical, and birth factors eliminated the link. The authors note that their findings contrast with those of a cohort study in California published in the same journal last year.

“It is possible that residual confounding explains this positive association because key perinatal variables, including induction of labor, labor dystocia, and fetal distress, were not included as confounders in that study,” write Elizabeth Wall-Wieler, PhD, of the University of Manitoba in Winnipeg and her colleagues. “To limit potential bias from unmeasured confounders, we included the aforementioned variables within a wide set of potential confounders.”

The researchers analyzed linked datasets from all singleton infants born in a hospital from 2005 to 2016 in Manitoba, Canada, to compare use of epidurals during birth with diagnoses of ASD before 18 months of age. The four data sources included the Statistics Canada, Manitoba Education, Manitoba Families, and Manitoba Health, Seniors and Active Living, which includes the Manitoba Health Insurance Registry, Medical Services, Hospital Abstracts, and Drug Program Information Network. The researchers excluded women with cesarean deliveries because it was not possible to differentiate between scheduled and unscheduled cesarean deliveries.

Among 123,175 children born to mothers with an average age of 28 years, 38.2% had been exposed to epidural analgesia during their labor. Autism diagnoses occurred among 2.1% of those exposed to epidurals and 1.7% of those not exposed to epidurals. After the researchers controlled for a range of potential confounders, the difference became nonsignificant (hazard ratio, 1.08).

The adjusted analysis accounted for mother’s age; high school degree; marital status; neighborhood socioeconomic status; receipt of public assistance during pregnancy; and presence of diabetes, hypertension, anxiety, or depression in the year before the birth. Other covariates included in the adjustment included the following pregnancy factors: “parity, gestational diabetes, gestational hypertension or preeclampsia, self-reported and diagnosed drug use, smoking, alcohol use, premature rupture of membranes, antepartum hemorrhage, infection of the amniotic sac and membrane, urogenital infection, antenatal mental health hospitalization, hypothyroidism, benzodiazepine use, antidepressant use, and antiepileptic use.” The researchers also included birth year, labor induction or augmentation, labor dystocia, fetal distress or macrosomia, gestational age at birth, the infant’s sex, and hospital type.

“There were substantial differences in maternal sociodemographic, preexisting, pregnancy-related, and birth-specific covariates between births who were exposed vs. nonexposed to epidural labor analgesia,” the authors report. “For example, births exposed to epidural labor analgesia were more likely to be nulliparous, have premature rupture of membranes, antepartum hemorrhage, induction of labor, augmentation of labor, and fetal distress.”

To take family history of ASD into account, the researchers also compared siblings who were and were not exposed to an epidural during labor: 80,459 children in the cohort had at least one sibling in it as well. The researchers still found no association between use of an epidural and a subsequent autism diagnosis (HR, 0.97). The authors conducted several sensitivity analyses for first-born children, those with two or more diagnostic codes for ASD on different days, and women with missing data on high school completion or marital status who delivered at 37 weeks of gestation or later; these results consistently showed no association between epidurals and ASD.

The findings are important but unsurprising, said Scott M. Myers, MD, a neurodevelopmental pediatrician and associate professor at the Geisinger Commonwealth School of Medicine’s Autism & Developmental Medicine Institute in Scranton, Pa. Dr. Myers, who was not involved in the study, said it was strengthened by the inclusion of a wide range of covariates and multiple sensitivity analyses.

“It confirms the suspicion of many experts who were skeptical of the association reported previously, that the small increase in ASD in offspring of mothers who had epidural labor analgesia was likely attributable to other factors that differed substantially between the exposed and unexposed groups,” Dr. Myers said in an interview. “The plausibility of exposure to epidural analgesia in labor having a large effect on ASD risk and accounting for changes in ASD prevalence over time is low.”

It’s possible to hypothesize about subgroups that are genetically susceptible to certain environmental risk factors, including epidurals, but such an association should show up in epidemiological research if the subgroup is large enough.

“For example, epidural labor analgesia can prolong labor, and if it were a significant risk factor for ASD, one might expect that longer labor would have been demonstrated to be associated with increased ASD risk, but this has been examined and is not the case,” he said. He also noted that other perinatal factors previously linked to ASD, such as cesarean delivery, may result from a shared factor that affects risk of both ASD and cesarean delivery.

“Although there haven’t been enough systematic postmortem brain studies to be certain that the findings are generalizable, the most consistent neuropathological findings associated with ASD clearly arise long before birth,”Dr. Myers said. “The information I would provide to a concerned pregnant mother is that the current weight of the evidence does not suggest an association between epidural analgesia in labor and increased likelihood of ASD in offspring, much less a causal association.”

Clay Jones, MD, a hospitalist specializing in neonatal-perinatal medicine at Newton (Mass.)–Wellesley Hospital, was not involved in the research and offered a similar assessment of the findings.

“Our understanding of autism is that it is more of a genetic condition which interferes with the organization of brain architecture, so the evidence for any environmental cause would need to be robust for it to change medical practice or our recommendations to the general public,” Dr. Jones said in an interview. Compared to the previous California study, “this new research is larger and better accounts for confounding variables that might increase the risk of a child eventually being diagnosed with autism,” he said.

While recognizing the value in conducting studies to uncover any potential environmental factors contributing to autism diagnoses, Dr. Jones also addressed science communication challenges related to this research.

“While many of these studies are valid early efforts at honing in on potential risk factors, they can be overhyped and lead to increased patient anxiety and potentially harmful changes in behavior,” Dr. Jones said. “There is already a significant amount of pressure for many women to avoid certain safe and effective pain reduction strategies during labor, such as epidural labor analgesia. This pressure is often based on misunderstandings of the risks, pseudoscientific beliefs regarding the benefits of so-called ‘natural childbirth,’ and blatant misogyny. I hope that this new study helps to reassure women that it is okay to request to be more comfortable during their labor experience with the help of epidural labor analgesia.”

The authors of the study also noted the benefits of epidural use during labor.

“It is recognized as the most effective method of providing labor analgesia,” they write. In addition, “the presence of an indwelling epidural catheter allows epidural anesthesia to be administered for an unplanned (intrapartum) cesarean delivery, thus secondarily avoiding any maternal complications or fetal exposure from general anesthesia.”

JAMA Pediatrics editor Dimitri A. Christakis, MD, MPH, wrote his second-ever Editor’s Note about this topic after the journal published two similar studies with different conclusions.

“Because there will never be experimental studies of environmental exposures, we are left with imperfect observational studies that are always at risk for residual confounding, especially when observed effect sizes are small,” Dr. Christakis writes. “Science is an imperfect and iterative process, and our responsibility as journal editors is to manage the process as best we can. Publishing two conflicting studies in such a short time frame serves as testament that we recognize the process for what it is.” His personal opinion is that any association has yet to be definitively established but that the journal will publish the study if a more definitive one is done.

In considering potentially contributing environmental risk factors to ASD, Gillian E. Hanley, PhD, of the University of British Columbia in Vancouver and two colleagues write that “meta-analyses have been unable to identify a single perinatal and neonatal factor associated with ASD risk, although some evidence suggested that exposure to a broad class of conditions such as fetal presentation, umbilical-cord complications, fetal distress, or multiple births, reflecting compromised neonatal health, may increase risk.”

Yet, they add, these studies are inconsistent in their effect size, likely because of differences in study methodology, comparison groups, sample size, diagnostic criteria, and exposure assessment.

“Thus, we continue to ask questions about whether biologically plausible associations exist or whether associations reflect residual confounding related to yet-to-be-determined maternal genetic or environmental factors,” Dr. Hanley and her colleagues write. They discuss precise differences between the California and Manitoba studies and the inevitability of selection bias since people who choose an epidural will differ in other ways from those who don’t.

“Epidural labor analgesia is an extremely effective approach to obstetric analgesia, and we have a collective responsibility to understand whether it is a safe option that sets a healthy developmental pathway well into childhood,” Dr. Hanley and her colleagues conclude. “Women have the right to make a truly informed choice about their pain relief during labor.”

The research was funded by the Canadian Institutes of Health. One author reported receiving personal fees or grants from Aetion, Alosa Foundation, Lilly, GSK, Pacira, and Takeda. No other authors had disclosures. Dr. Jones, Dr. Myers, and the editorial authors had no disclosures.

Exposure to epidural analgesia during labor did not show a link to a later diagnosis of autism spectrum disorder (ASD) in a population-based cohort study published April 19 in JAMA Pediatrics.

Though the initial analysis showed an association, adjustment for a wide range of demographic, medical, and birth factors eliminated the link. The authors note that their findings contrast with those of a cohort study in California published in the same journal last year.

“It is possible that residual confounding explains this positive association because key perinatal variables, including induction of labor, labor dystocia, and fetal distress, were not included as confounders in that study,” write Elizabeth Wall-Wieler, PhD, of the University of Manitoba in Winnipeg and her colleagues. “To limit potential bias from unmeasured confounders, we included the aforementioned variables within a wide set of potential confounders.”

The researchers analyzed linked datasets from all singleton infants born in a hospital from 2005 to 2016 in Manitoba, Canada, to compare use of epidurals during birth with diagnoses of ASD before 18 months of age. The four data sources included the Statistics Canada, Manitoba Education, Manitoba Families, and Manitoba Health, Seniors and Active Living, which includes the Manitoba Health Insurance Registry, Medical Services, Hospital Abstracts, and Drug Program Information Network. The researchers excluded women with cesarean deliveries because it was not possible to differentiate between scheduled and unscheduled cesarean deliveries.

Among 123,175 children born to mothers with an average age of 28 years, 38.2% had been exposed to epidural analgesia during their labor. Autism diagnoses occurred among 2.1% of those exposed to epidurals and 1.7% of those not exposed to epidurals. After the researchers controlled for a range of potential confounders, the difference became nonsignificant (hazard ratio, 1.08).

The adjusted analysis accounted for mother’s age; high school degree; marital status; neighborhood socioeconomic status; receipt of public assistance during pregnancy; and presence of diabetes, hypertension, anxiety, or depression in the year before the birth. Other covariates included in the adjustment included the following pregnancy factors: “parity, gestational diabetes, gestational hypertension or preeclampsia, self-reported and diagnosed drug use, smoking, alcohol use, premature rupture of membranes, antepartum hemorrhage, infection of the amniotic sac and membrane, urogenital infection, antenatal mental health hospitalization, hypothyroidism, benzodiazepine use, antidepressant use, and antiepileptic use.” The researchers also included birth year, labor induction or augmentation, labor dystocia, fetal distress or macrosomia, gestational age at birth, the infant’s sex, and hospital type.

“There were substantial differences in maternal sociodemographic, preexisting, pregnancy-related, and birth-specific covariates between births who were exposed vs. nonexposed to epidural labor analgesia,” the authors report. “For example, births exposed to epidural labor analgesia were more likely to be nulliparous, have premature rupture of membranes, antepartum hemorrhage, induction of labor, augmentation of labor, and fetal distress.”

To take family history of ASD into account, the researchers also compared siblings who were and were not exposed to an epidural during labor: 80,459 children in the cohort had at least one sibling in it as well. The researchers still found no association between use of an epidural and a subsequent autism diagnosis (HR, 0.97). The authors conducted several sensitivity analyses for first-born children, those with two or more diagnostic codes for ASD on different days, and women with missing data on high school completion or marital status who delivered at 37 weeks of gestation or later; these results consistently showed no association between epidurals and ASD.

The findings are important but unsurprising, said Scott M. Myers, MD, a neurodevelopmental pediatrician and associate professor at the Geisinger Commonwealth School of Medicine’s Autism & Developmental Medicine Institute in Scranton, Pa. Dr. Myers, who was not involved in the study, said it was strengthened by the inclusion of a wide range of covariates and multiple sensitivity analyses.

“It confirms the suspicion of many experts who were skeptical of the association reported previously, that the small increase in ASD in offspring of mothers who had epidural labor analgesia was likely attributable to other factors that differed substantially between the exposed and unexposed groups,” Dr. Myers said in an interview. “The plausibility of exposure to epidural analgesia in labor having a large effect on ASD risk and accounting for changes in ASD prevalence over time is low.”

It’s possible to hypothesize about subgroups that are genetically susceptible to certain environmental risk factors, including epidurals, but such an association should show up in epidemiological research if the subgroup is large enough.

“For example, epidural labor analgesia can prolong labor, and if it were a significant risk factor for ASD, one might expect that longer labor would have been demonstrated to be associated with increased ASD risk, but this has been examined and is not the case,” he said. He also noted that other perinatal factors previously linked to ASD, such as cesarean delivery, may result from a shared factor that affects risk of both ASD and cesarean delivery.

“Although there haven’t been enough systematic postmortem brain studies to be certain that the findings are generalizable, the most consistent neuropathological findings associated with ASD clearly arise long before birth,”Dr. Myers said. “The information I would provide to a concerned pregnant mother is that the current weight of the evidence does not suggest an association between epidural analgesia in labor and increased likelihood of ASD in offspring, much less a causal association.”

Clay Jones, MD, a hospitalist specializing in neonatal-perinatal medicine at Newton (Mass.)–Wellesley Hospital, was not involved in the research and offered a similar assessment of the findings.

“Our understanding of autism is that it is more of a genetic condition which interferes with the organization of brain architecture, so the evidence for any environmental cause would need to be robust for it to change medical practice or our recommendations to the general public,” Dr. Jones said in an interview. Compared to the previous California study, “this new research is larger and better accounts for confounding variables that might increase the risk of a child eventually being diagnosed with autism,” he said.

While recognizing the value in conducting studies to uncover any potential environmental factors contributing to autism diagnoses, Dr. Jones also addressed science communication challenges related to this research.

“While many of these studies are valid early efforts at honing in on potential risk factors, they can be overhyped and lead to increased patient anxiety and potentially harmful changes in behavior,” Dr. Jones said. “There is already a significant amount of pressure for many women to avoid certain safe and effective pain reduction strategies during labor, such as epidural labor analgesia. This pressure is often based on misunderstandings of the risks, pseudoscientific beliefs regarding the benefits of so-called ‘natural childbirth,’ and blatant misogyny. I hope that this new study helps to reassure women that it is okay to request to be more comfortable during their labor experience with the help of epidural labor analgesia.”

The authors of the study also noted the benefits of epidural use during labor.

“It is recognized as the most effective method of providing labor analgesia,” they write. In addition, “the presence of an indwelling epidural catheter allows epidural anesthesia to be administered for an unplanned (intrapartum) cesarean delivery, thus secondarily avoiding any maternal complications or fetal exposure from general anesthesia.”

JAMA Pediatrics editor Dimitri A. Christakis, MD, MPH, wrote his second-ever Editor’s Note about this topic after the journal published two similar studies with different conclusions.

“Because there will never be experimental studies of environmental exposures, we are left with imperfect observational studies that are always at risk for residual confounding, especially when observed effect sizes are small,” Dr. Christakis writes. “Science is an imperfect and iterative process, and our responsibility as journal editors is to manage the process as best we can. Publishing two conflicting studies in such a short time frame serves as testament that we recognize the process for what it is.” His personal opinion is that any association has yet to be definitively established but that the journal will publish the study if a more definitive one is done.

In considering potentially contributing environmental risk factors to ASD, Gillian E. Hanley, PhD, of the University of British Columbia in Vancouver and two colleagues write that “meta-analyses have been unable to identify a single perinatal and neonatal factor associated with ASD risk, although some evidence suggested that exposure to a broad class of conditions such as fetal presentation, umbilical-cord complications, fetal distress, or multiple births, reflecting compromised neonatal health, may increase risk.”

Yet, they add, these studies are inconsistent in their effect size, likely because of differences in study methodology, comparison groups, sample size, diagnostic criteria, and exposure assessment.

“Thus, we continue to ask questions about whether biologically plausible associations exist or whether associations reflect residual confounding related to yet-to-be-determined maternal genetic or environmental factors,” Dr. Hanley and her colleagues write. They discuss precise differences between the California and Manitoba studies and the inevitability of selection bias since people who choose an epidural will differ in other ways from those who don’t.

“Epidural labor analgesia is an extremely effective approach to obstetric analgesia, and we have a collective responsibility to understand whether it is a safe option that sets a healthy developmental pathway well into childhood,” Dr. Hanley and her colleagues conclude. “Women have the right to make a truly informed choice about their pain relief during labor.”

The research was funded by the Canadian Institutes of Health. One author reported receiving personal fees or grants from Aetion, Alosa Foundation, Lilly, GSK, Pacira, and Takeda. No other authors had disclosures. Dr. Jones, Dr. Myers, and the editorial authors had no disclosures.

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

A quarter of children receiving treatment with rituximab developed hypogammaglobulinemia within 18 months of starting the drug, according to preliminary research shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance. The findings lend support to previous research identifying a risk of hypogammaglobulinemia in children and adolescents taking rituximab and the need for monitoring immunoglobulin levels in those prescribed it.

Marija Stepanovic/Getty Images Marija Stepanovic

“Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinemia and infections in pediatric patients with rheumatic conditions,” Mei-Sing Ong, PhD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute, both in Boston, and colleagues concluded. “Increased risks appeared to be mediated, at least in part, by exposure to glucocorticoids (hypogammaglobulinemia and serious infections) or cyclophosphamide (hypogammaglobulinemia) administered prior to rituximab.”

The observational study involved a cohort of 93 patients, aged 2-25 years, treated at Boston Children’s Hospital during 2009-2019. The patients received rituximab for a wide range of rheumatic diseases, including systemic lupus erythematosus, vasculitis, juvenile idiopathic arthritis, and juvenile dermatomyositis or other polymyositis. The researchers excluded patients who had previously had hypogammaglobulinemia before using rituximab.

In this cohort, 26.9% of patients developed hypogammaglobulinemia, and 20.4% of patients developed an infectious complication within 18 months of beginning rituximab treatment. The infection was serious enough to require inpatient treatment in more than half of those who developed infections (57.9%).

Risk of new-onset hypogammaglobulinemia increased with decreasing age (P = .004), and males were more than four times more likely to develop the condition (odds ratio, 4.55; P = .012). Risk of an infection was also more likely among younger patients (OR, 0.87; P = .039).

Patients with vasculitis were fivefold more likely to develop the hypogammaglobulinemia than were those with other rheumatic diseases after the researchers accounted for age, sex, underlying disease, and medication use (OR, 5.04; P = .017). Risk was also greater in patients with exposure to cyclophosphamide in the year before starting rituximab (OR, 3.76; P = .032), although the finding narrowly reached statistical significance after adjustment for those covariates (OR, 4.41; P = .048).

Glucocorticoid treatment in the month before rituximab was associated with an elevated risk of hypogammaglobulinemia before adjustment (OR, 4.53; P = .007) but lost significance after adjustment. Those taking glucocorticoids had a greater than eightfold increase in infection risk (OR, 8.5; P = .006) before adjustment, which dropped to a fivefold risk after accounting for age, sex, underlying disease, and medication use (OR, 5.4; P = .040).

Monitoring needed for relatively common side effect

The findings are consistent with those seen in a cohort study conducted at Lurie Children’s Hospital of Chicago and published in 2019, said Amer M. Khojah, MD, an attending physician in allergy, immunology, and rheumatology at Lurie and an assistant professor of pediatrics at Northwestern University, also in Chicago. He was not involved in the current study.

“The main takeaway from this study is that we need to be careful about this side effect because it’s relatively common,” Dr. Khojah said in an interview.

At his institution, all patients undergo baseline labs to measure IgG levels prior to initiating rituximab and then have labs drawn again at 3 months and 1 year after starting the drug. Transient hypogammaglobulinemia may not require treatment, he said, but if it persists or the patient develops an infection, treatment with intravenous immunoglobulin is indicated. Yet the drug is so commonly used across a wide range of specialties that there’s a great deal of variability in clinical practice in terms of monitoring and follow-up, Dr. Khojah said.

“The problem is, if you don’t measure it, the patient might be get hypogammaglobulinemia and you don’t know it,” potentially leading to infections that the physician may or may not hear about, he said. “If you are the one who gives them the rituximab, you need to make sure they don’t get the side effects” or that they receive treatment if they do, he said.

“These data are supportive of the necessity to follow patients closely for infection after rituximab, especially considering that many infections may be severe and require hospitalization,” Dr. McAtee said in an interview. “The period of immunosuppression and subsequent infection risk following rituximab, even after single courses, may last well beyond a year following a single course. This is particularly true in patients receiving concurrent immunosuppressive therapy.”

Dr. McAtee similarly published data this year finding frequent infections among young patients receiving rituximab. Hypogammaglobulinemia is already more likely in patients who require rituximab because of other immunosuppressive medication they often take, but the risk “jumped substantially following rituximab,” he said. In addition to patients with low levels of IgG, 41% of patients showed low levels of IgM in that study.

“Nearly a third of patients with normal baseline IgM had persistently low levels more than a year after rituximab, consistent with prolonged B-cell recovery,” Dr. McAtee said. “It is necessary to highlight the importance of IgM in these patients, as common strategies to treat hypogammaglobulinemia, specifically intravenous immunoglobulin, do not replete IgM.”

Neither Dr. Khojah nor Dr. McAtee saw the risk of hypogammaglobulinemia as a reason to avoid rituximab when indicated.

“It is often the best choice for patients whose diseases have not responded to first-line therapies,” Dr. McAtee said. “This and similar studies inform the risk-benefit decision that the medical team must make, as well as the medical surveillance to be considered for patients following a course of rituximab. Going forward, strategies to mitigate infection risk after rituximab, particularly in the first 3 months when they are most common, should be pursued.”

The research was funded by CARRA, which receives funding from the Arthritis Foundation. The authors did not note whether they had any disclosures. Dr. Khojah and Dr. McAtee had no disclosures.

Postpartum women with commercial health insurance use substantially more inpatient and outpatient care than nonpostpartum women, particularly in the first 2 months after giving birth, according to a retrospective cohort study published in the May 2021 issue of Obstetrics & Gynecology.

“These findings are consistent with previous studies that have documented elevated postpartum ED and hospitalization rates, and we contribute new evidence that indicates postpartum health care utilization rates are significantly higher than rates of health care utilization in the general population of reproductive aged women when they are not pregnant or postpartum,” Maria W. Steenland, ScD, of Brown University, Providence, R.I., and colleagues wrote. “Most notably, postpartum women were more than three times more likely to have an ED visit and eight times more likely to be hospitalized than nonpostpartum women in the early postpartum period.”

Approximately one-third of maternal deaths occur between 1 week and 1 year post partum, the authors noted in their background information. The overall U.S. maternal mortality rate was 17.4 per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention.

“This study underscores the importance of access to health care for women, in particular in the postpartum period,” Iris Krishna, MD, MPH, an assistant professor of maternal-fetal medicine at Emory University, Atlanta, said in an interview. “Maternal mortality is a public health crisis. The majority of maternal deaths are preventable and occur up to 1 year postpartum. Studies such as these are needed as the postpartum period is a critical time in the care of reproductive age women that is often overlooked.”

Using data from a large national commercial claims database, the researchers analyzed data from 149,563 women aged 18-44 years who gave birth in 2016 and from 2,048,831 women who were neither pregnant nor post partum during the same study period. In postpartum women, the researchers specifically looked at hospitalization, preventive visits, problem visits, and ED visits during three periods for postpartum women: early postpartum, defined as within 21 days of giving birth; postpartum, defined as 21-60 days after birth; and extended postpartum, defined as 61 days to 1 year after birth. These data were then compared with equivalent periods in nonpostpartum women.

“For the comparison group, we created a random start date of follow-up by generating a random variable between 0 and 365 and adding this integer to Jan. 1, 2016,” the authors explained. “These start dates correspond to the range of possible follow-up start dates among postpartum women who gave birth in 2016.”

The groups differed in age composition: 62% of the postpartum women were between 25 and 34 years old while the nonpostpartum women were more evenly distributed across the age range. A higher proportion of nonpostpartum women had a chronic disease, but median income and geographic region were similar between the groups. Just over a third of the postpartum women (36%) had a cesarean delivery, higher than the 2016 national average of 32%.

Nearly a quarter (23.7%) of postpartum women had a problem visit in the early postpartum period, compared with one in five (19.7%) nonpostpartum women in the equivalent period. This 4-point difference increased to an 4.8-point difference after adjustment for age group, chronic disease, geographic region, income, and month when follow-up began.

Postpartum women were also three times more likely to have an ED visit (3.2%) in the early postpartum period than nonpostpartum women (1%). Postpartum women’s problem visits and ED visits were most prevalent in the first 2 weeks after childbirth: 12.4% in the first week and 10.4% in the second. Complaints for these visits primarily included urinary tract infections and other genitourinary issues, hypertension, breast or breastfeeding issues, and respiratory issues, such as shortness of breath or chest pain. Hospitalization rates were also higher in the early postpartum period for postpartum women (0.8%) than nonpostpartum women (0.1%).

Problem visits showed a similar pattern during the postpartum period from 21 to 60 days after birth: 39.4% of postpartum women, compared with 30.2% of nonpostpartum women. Rate differences were narrower for ED visits (2% post partum vs. 1.9% non–post partum) and hospitalization (0.3% post partum vs. 0.2% non–post partum), but the differences remained significant, and ED visits were still 0.3 points higher after adjustment.

The biggest differences between the groups in the first 2 months occurred with preventive care. In the early postpartum period, 15% of postpartum women had a preventive visit, compared with 3.3% of nonpostpartum women. Similarly, the rates were 28.2% in postpartum women and 6.5% in nonpostpartum women in the postpartum period.

Differences between the groups evened out in the extended postpartum period, when postpartum women had slightly fewer preventive visits (42.5%) than nonpostpartum women (42.7%). ED rates (11.2% postpartum vs 11.1%) and hospitalization rates (1.4% postpartum vs. 1.6%) were similar, but postpartum women were significantly more likely to have problem visits (79.2%) in the year after childbirth than nonpostpartum women (72.8%).

“Compared with postpartum women overall, postpartum women with chronic disease, pregnancy complications, and cesarean births were more likely to receive health care of all types in the early postpartum period,” the researchers reported. “Of the three subgroups, health care use was highest among postpartum women with chronic disease, among whom 35% had at least one outpatient problem visit, 5% had an ED visit, and 1.3% were hospitalized within the first 20 days of childbirth.”

These findings as a whole point to an increased need for health care not only in the first 3 weeks after women give birth but “beyond the traditional 6-week postpartum period, which adds to the argument that the way we care for women in the postpartum period should be revised,” Dr. Krishna said.

The American College of Obstetricians and Gynecologists updated their postpartum recommendations in 2018 to advise that all postpartum women have a follow-up visit in the first 3 weeks after birth.

Dr. Krishna reiterated that postpartum patients should ideally have an initial follow-up within 3 weeks of giving birth, which the rapid expansion of telehealth has made more viable for both clinicians and mothers.

The authors similarly noted that telehealth and home visits “are promising options to promote early and consistent health care contact and reduce known barriers to postpartum care seeking such as fatigue, lack of transportation, and child care.” Predischarge guidance may also help meet postpartum patients’ health care needs.

“Health care professionals also may be able to reduce the escalation of common early postpartum problems identified in this study (e.g., respiratory problems, pain, urinary tract infections) with anticipatory postpartum counseling and care before hospital discharge such as ensuring that women have inhalers at home, developing a pain management plan, and screening for signs of urinary tract infection,” the authors wrote.

Dr. Krishna also pointed out the need to address racial inequalities in health care and material mortality.

“Black women have a maternal mortality rate two times the rate of non-Hispanic White women,” Dr. Krishna said. “One way to address health disparities between commercially insured and uninsured women is improving access to health care through Medicaid expansion for at least 1 year post partum. States that participated in the Affordable Care Acts Medicaid expansion have noted improvement in maternal mortality and a decrease in racial/ethnic inequities.”

The research was funded by the Robert Wood Johnson Foundation and the National Institutes of Health. Data was provided by Aetna, Humana, Kaiser Permanente and UnitedHealthcare. The authors and Dr. Krishna reported no disclosures.

Postpartum women with commercial health insurance use substantially more inpatient and outpatient care than nonpostpartum women, particularly in the first 2 months after giving birth, according to a retrospective cohort study published in the May 2021 issue of Obstetrics & Gynecology.

“These findings are consistent with previous studies that have documented elevated postpartum ED and hospitalization rates, and we contribute new evidence that indicates postpartum health care utilization rates are significantly higher than rates of health care utilization in the general population of reproductive aged women when they are not pregnant or postpartum,” Maria W. Steenland, ScD, of Brown University, Providence, R.I., and colleagues wrote. “Most notably, postpartum women were more than three times more likely to have an ED visit and eight times more likely to be hospitalized than nonpostpartum women in the early postpartum period.”

Approximately one-third of maternal deaths occur between 1 week and 1 year post partum, the authors noted in their background information. The overall U.S. maternal mortality rate was 17.4 per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention.

“This study underscores the importance of access to health care for women, in particular in the postpartum period,” Iris Krishna, MD, MPH, an assistant professor of maternal-fetal medicine at Emory University, Atlanta, said in an interview. “Maternal mortality is a public health crisis. The majority of maternal deaths are preventable and occur up to 1 year postpartum. Studies such as these are needed as the postpartum period is a critical time in the care of reproductive age women that is often overlooked.”

Using data from a large national commercial claims database, the researchers analyzed data from 149,563 women aged 18-44 years who gave birth in 2016 and from 2,048,831 women who were neither pregnant nor post partum during the same study period. In postpartum women, the researchers specifically looked at hospitalization, preventive visits, problem visits, and ED visits during three periods for postpartum women: early postpartum, defined as within 21 days of giving birth; postpartum, defined as 21-60 days after birth; and extended postpartum, defined as 61 days to 1 year after birth. These data were then compared with equivalent periods in nonpostpartum women.

“For the comparison group, we created a random start date of follow-up by generating a random variable between 0 and 365 and adding this integer to Jan. 1, 2016,” the authors explained. “These start dates correspond to the range of possible follow-up start dates among postpartum women who gave birth in 2016.”

The groups differed in age composition: 62% of the postpartum women were between 25 and 34 years old while the nonpostpartum women were more evenly distributed across the age range. A higher proportion of nonpostpartum women had a chronic disease, but median income and geographic region were similar between the groups. Just over a third of the postpartum women (36%) had a cesarean delivery, higher than the 2016 national average of 32%.

Nearly a quarter (23.7%) of postpartum women had a problem visit in the early postpartum period, compared with one in five (19.7%) nonpostpartum women in the equivalent period. This 4-point difference increased to an 4.8-point difference after adjustment for age group, chronic disease, geographic region, income, and month when follow-up began.

Postpartum women were also three times more likely to have an ED visit (3.2%) in the early postpartum period than nonpostpartum women (1%). Postpartum women’s problem visits and ED visits were most prevalent in the first 2 weeks after childbirth: 12.4% in the first week and 10.4% in the second. Complaints for these visits primarily included urinary tract infections and other genitourinary issues, hypertension, breast or breastfeeding issues, and respiratory issues, such as shortness of breath or chest pain. Hospitalization rates were also higher in the early postpartum period for postpartum women (0.8%) than nonpostpartum women (0.1%).

Problem visits showed a similar pattern during the postpartum period from 21 to 60 days after birth: 39.4% of postpartum women, compared with 30.2% of nonpostpartum women. Rate differences were narrower for ED visits (2% post partum vs. 1.9% non–post partum) and hospitalization (0.3% post partum vs. 0.2% non–post partum), but the differences remained significant, and ED visits were still 0.3 points higher after adjustment.

The biggest differences between the groups in the first 2 months occurred with preventive care. In the early postpartum period, 15% of postpartum women had a preventive visit, compared with 3.3% of nonpostpartum women. Similarly, the rates were 28.2% in postpartum women and 6.5% in nonpostpartum women in the postpartum period.

Differences between the groups evened out in the extended postpartum period, when postpartum women had slightly fewer preventive visits (42.5%) than nonpostpartum women (42.7%). ED rates (11.2% postpartum vs 11.1%) and hospitalization rates (1.4% postpartum vs. 1.6%) were similar, but postpartum women were significantly more likely to have problem visits (79.2%) in the year after childbirth than nonpostpartum women (72.8%).

“Compared with postpartum women overall, postpartum women with chronic disease, pregnancy complications, and cesarean births were more likely to receive health care of all types in the early postpartum period,” the researchers reported. “Of the three subgroups, health care use was highest among postpartum women with chronic disease, among whom 35% had at least one outpatient problem visit, 5% had an ED visit, and 1.3% were hospitalized within the first 20 days of childbirth.”

These findings as a whole point to an increased need for health care not only in the first 3 weeks after women give birth but “beyond the traditional 6-week postpartum period, which adds to the argument that the way we care for women in the postpartum period should be revised,” Dr. Krishna said.

The American College of Obstetricians and Gynecologists updated their postpartum recommendations in 2018 to advise that all postpartum women have a follow-up visit in the first 3 weeks after birth.

Dr. Krishna reiterated that postpartum patients should ideally have an initial follow-up within 3 weeks of giving birth, which the rapid expansion of telehealth has made more viable for both clinicians and mothers.

The authors similarly noted that telehealth and home visits “are promising options to promote early and consistent health care contact and reduce known barriers to postpartum care seeking such as fatigue, lack of transportation, and child care.” Predischarge guidance may also help meet postpartum patients’ health care needs.

“Health care professionals also may be able to reduce the escalation of common early postpartum problems identified in this study (e.g., respiratory problems, pain, urinary tract infections) with anticipatory postpartum counseling and care before hospital discharge such as ensuring that women have inhalers at home, developing a pain management plan, and screening for signs of urinary tract infection,” the authors wrote.

Dr. Krishna also pointed out the need to address racial inequalities in health care and material mortality.

“Black women have a maternal mortality rate two times the rate of non-Hispanic White women,” Dr. Krishna said. “One way to address health disparities between commercially insured and uninsured women is improving access to health care through Medicaid expansion for at least 1 year post partum. States that participated in the Affordable Care Acts Medicaid expansion have noted improvement in maternal mortality and a decrease in racial/ethnic inequities.”

The research was funded by the Robert Wood Johnson Foundation and the National Institutes of Health. Data was provided by Aetna, Humana, Kaiser Permanente and UnitedHealthcare. The authors and Dr. Krishna reported no disclosures.

Postpartum women with commercial health insurance use substantially more inpatient and outpatient care than nonpostpartum women, particularly in the first 2 months after giving birth, according to a retrospective cohort study published in the May 2021 issue of Obstetrics & Gynecology.

“These findings are consistent with previous studies that have documented elevated postpartum ED and hospitalization rates, and we contribute new evidence that indicates postpartum health care utilization rates are significantly higher than rates of health care utilization in the general population of reproductive aged women when they are not pregnant or postpartum,” Maria W. Steenland, ScD, of Brown University, Providence, R.I., and colleagues wrote. “Most notably, postpartum women were more than three times more likely to have an ED visit and eight times more likely to be hospitalized than nonpostpartum women in the early postpartum period.”

Approximately one-third of maternal deaths occur between 1 week and 1 year post partum, the authors noted in their background information. The overall U.S. maternal mortality rate was 17.4 per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention.

“This study underscores the importance of access to health care for women, in particular in the postpartum period,” Iris Krishna, MD, MPH, an assistant professor of maternal-fetal medicine at Emory University, Atlanta, said in an interview. “Maternal mortality is a public health crisis. The majority of maternal deaths are preventable and occur up to 1 year postpartum. Studies such as these are needed as the postpartum period is a critical time in the care of reproductive age women that is often overlooked.”

Using data from a large national commercial claims database, the researchers analyzed data from 149,563 women aged 18-44 years who gave birth in 2016 and from 2,048,831 women who were neither pregnant nor post partum during the same study period. In postpartum women, the researchers specifically looked at hospitalization, preventive visits, problem visits, and ED visits during three periods for postpartum women: early postpartum, defined as within 21 days of giving birth; postpartum, defined as 21-60 days after birth; and extended postpartum, defined as 61 days to 1 year after birth. These data were then compared with equivalent periods in nonpostpartum women.

“For the comparison group, we created a random start date of follow-up by generating a random variable between 0 and 365 and adding this integer to Jan. 1, 2016,” the authors explained. “These start dates correspond to the range of possible follow-up start dates among postpartum women who gave birth in 2016.”

The groups differed in age composition: 62% of the postpartum women were between 25 and 34 years old while the nonpostpartum women were more evenly distributed across the age range. A higher proportion of nonpostpartum women had a chronic disease, but median income and geographic region were similar between the groups. Just over a third of the postpartum women (36%) had a cesarean delivery, higher than the 2016 national average of 32%.

Nearly a quarter (23.7%) of postpartum women had a problem visit in the early postpartum period, compared with one in five (19.7%) nonpostpartum women in the equivalent period. This 4-point difference increased to an 4.8-point difference after adjustment for age group, chronic disease, geographic region, income, and month when follow-up began.

Postpartum women were also three times more likely to have an ED visit (3.2%) in the early postpartum period than nonpostpartum women (1%). Postpartum women’s problem visits and ED visits were most prevalent in the first 2 weeks after childbirth: 12.4% in the first week and 10.4% in the second. Complaints for these visits primarily included urinary tract infections and other genitourinary issues, hypertension, breast or breastfeeding issues, and respiratory issues, such as shortness of breath or chest pain. Hospitalization rates were also higher in the early postpartum period for postpartum women (0.8%) than nonpostpartum women (0.1%).

Problem visits showed a similar pattern during the postpartum period from 21 to 60 days after birth: 39.4% of postpartum women, compared with 30.2% of nonpostpartum women. Rate differences were narrower for ED visits (2% post partum vs. 1.9% non–post partum) and hospitalization (0.3% post partum vs. 0.2% non–post partum), but the differences remained significant, and ED visits were still 0.3 points higher after adjustment.

The biggest differences between the groups in the first 2 months occurred with preventive care. In the early postpartum period, 15% of postpartum women had a preventive visit, compared with 3.3% of nonpostpartum women. Similarly, the rates were 28.2% in postpartum women and 6.5% in nonpostpartum women in the postpartum period.

Differences between the groups evened out in the extended postpartum period, when postpartum women had slightly fewer preventive visits (42.5%) than nonpostpartum women (42.7%). ED rates (11.2% postpartum vs 11.1%) and hospitalization rates (1.4% postpartum vs. 1.6%) were similar, but postpartum women were significantly more likely to have problem visits (79.2%) in the year after childbirth than nonpostpartum women (72.8%).

“Compared with postpartum women overall, postpartum women with chronic disease, pregnancy complications, and cesarean births were more likely to receive health care of all types in the early postpartum period,” the researchers reported. “Of the three subgroups, health care use was highest among postpartum women with chronic disease, among whom 35% had at least one outpatient problem visit, 5% had an ED visit, and 1.3% were hospitalized within the first 20 days of childbirth.”

These findings as a whole point to an increased need for health care not only in the first 3 weeks after women give birth but “beyond the traditional 6-week postpartum period, which adds to the argument that the way we care for women in the postpartum period should be revised,” Dr. Krishna said.

The American College of Obstetricians and Gynecologists updated their postpartum recommendations in 2018 to advise that all postpartum women have a follow-up visit in the first 3 weeks after birth.

Dr. Krishna reiterated that postpartum patients should ideally have an initial follow-up within 3 weeks of giving birth, which the rapid expansion of telehealth has made more viable for both clinicians and mothers.

The authors similarly noted that telehealth and home visits “are promising options to promote early and consistent health care contact and reduce known barriers to postpartum care seeking such as fatigue, lack of transportation, and child care.” Predischarge guidance may also help meet postpartum patients’ health care needs.

“Health care professionals also may be able to reduce the escalation of common early postpartum problems identified in this study (e.g., respiratory problems, pain, urinary tract infections) with anticipatory postpartum counseling and care before hospital discharge such as ensuring that women have inhalers at home, developing a pain management plan, and screening for signs of urinary tract infection,” the authors wrote.

Dr. Krishna also pointed out the need to address racial inequalities in health care and material mortality.

“Black women have a maternal mortality rate two times the rate of non-Hispanic White women,” Dr. Krishna said. “One way to address health disparities between commercially insured and uninsured women is improving access to health care through Medicaid expansion for at least 1 year post partum. States that participated in the Affordable Care Acts Medicaid expansion have noted improvement in maternal mortality and a decrease in racial/ethnic inequities.”

The research was funded by the Robert Wood Johnson Foundation and the National Institutes of Health. Data was provided by Aetna, Humana, Kaiser Permanente and UnitedHealthcare. The authors and Dr. Krishna reported no disclosures.

An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.

The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.

“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.

According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.

“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”

The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.

“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”

The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.

“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.

Another common reason is habit.

“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”

The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.

“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
 

Acute bronchitis with COPD exacerbations

Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.

Community-acquired pneumonia

The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.

Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
 

UTIs: Uncomplicated cystitis and pyelonephritis

For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.

This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
 

Cellulitis

MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.

This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
 

Continuing to get the message out

Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.

“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”

Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.

Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.

The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.

The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.

“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.

According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.

“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”

The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.

“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”

The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.

“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.

Another common reason is habit.

“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”

The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.

“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
 

Acute bronchitis with COPD exacerbations

Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.

Community-acquired pneumonia

The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.

Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
 

UTIs: Uncomplicated cystitis and pyelonephritis

For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.

This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
 

Cellulitis

MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.

This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
 

Continuing to get the message out

Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.

“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”

Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.

Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.

The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.

The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.

“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.

According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.

“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”

The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.

“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”

The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.

“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.

Another common reason is habit.

“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”

The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.

“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
 

Acute bronchitis with COPD exacerbations

Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.

Community-acquired pneumonia

The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.

Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
 

UTIs: Uncomplicated cystitis and pyelonephritis

For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.

This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
 

Cellulitis

MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.

This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
 

Continuing to get the message out

Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.

“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”

Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.

Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.

The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant and breastfeeding women who receive an mRNA COVID-19 vaccine develop a strong immune response and produce antibodies that can transfer to the fetus through the placenta and to newborns through breast milk, according to a prospective cohort study published March 25 in the American Journal of Obstetrics and Gynecology.

The findings revealed that the antibody response to vaccination in this cohort was greater than that from a COVID-19 infection during pregnancy. Though the researchers detected SARS-CoV-2 antibodies in umbilical cord blood and breast milk, it’s not yet known how much protection these antibodies might provide to newborns.

“The presence of neutralizing antibody transfer in nearly all cords, and improved transfer with increased time from vaccination, points to the promise of mRNA vaccine–induced delivery of immunity to neonates,” wrote Kathryn J. Gray, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital’s department of obstetrics and gynecology, and colleagues. “Transfer would perhaps be optimized if vaccination is administered earlier during gestation, though this needs to be directly examined in future studies.”

The researchers tracked 84 pregnant women, 31 lactating women, and 16 nonpregnant women who received the COVID-19 vaccine. The titers of IgG, IgA, and IgM antibodies against the SARS-CoV-2 spike, receptor binding domain (RBD), and S1 and S2 components of the spike were measured in the 131 participants’ blood and in the lactating women’s breast milk four times: at baseline, when they received their second vaccine dose, at 2-6 weeks after their second dose, and at delivery for the 13 women who delivered during the study period.

The study population included health care workers and was predominantly White and non-Hispanic. In addition, two pregnant women, two lactating women, and one nonpregnant woman in the study had a previous SARS-CoV-2 infection.

Most of the pregnant women received the vaccine in their second (46%) or third (40%) trimester. The women across all three groups – pregnant, lactating, and nonpregnant – experienced similar side effects from the each dose of the vaccine, including fever/chills in 32% of the pregnant women and half the nonpregnant women after the second dose.

Titers induced by the vaccine were similar across the pregnant, lactating, and nonpregnant women, and titers did not differ based on the trimester when women received the vaccine. The researchers then compared the titers from the vaccine recipients to titers of 37 pregnant women drawn 4-12 weeks after a natural SARS-CoV-2 infection. Vaccine-induced titers were significantly greater than those measured in the women who had a natural infection during pregnancy (P < .001).

The researchers identified IgG, IgA, and IgM antibodies in the breast milk samples, including a boost in IgG antibodies after the second vaccine dose from baseline. “However, whether these antibodies were transferred efficiently to infants remained unclear,” the authors noted.

The researchers found vaccine-induced antibodies in all 10 umbilical cord blood samples tested, all but one of which had been exposed to two doses of the vaccine.

“The cord with the lowest spike- and RBD-specific IgG belonged to a mother who delivered between the first and second vaccine doses and had received her first vaccine dose 17 days prior to delivery, suggesting that 2 doses may be essential to optimize humoral immune transfer to the neonate,” the authors wrote. “Based on what is known about other vaccines, the amount of maternal IgG transferred across the placenta to the cord is likely to differ by trimester of vaccination.”

Although umbilical cord sera had lower titers of neutralizing antibodies than found in maternal sera, the difference was not significant (median interquartile range 52.3 vs. 104.7, P = .05). The two cord blood samples without neutralizing antibodies came from a woman who had not had the second dose and a woman who received the second dose 1 week before delivery.

“These data provide a compelling argument that COVID-19 mRNA vaccines induce similar humoral immunity in pregnant and lactating women as in the nonpregnant population,” the authors wrote. “These data do not elucidate potential risks to the fetus.”

While the study provides evidence about the immune response induced by the COVID-19 mRNA vaccines during pregnant, it leaves other questions unanswered, said Kevin A. Ault, MD, professor of ob.gyn. at The University of Kansas Medical Center in Kansas City.

“The important thing about these findings is that the COVID vaccines are immunogenic in pregnant women. There may be a benefit to the newborns because antibodies are passed on through the placenta,” Dr. Ault said in an interview. “The main questions that remain are safety of the vaccine during pregnancy and effectiveness of the vaccine during pregnancy.”

He said he expects to see more studies on the safety and effectiveness of COVID-19 vaccines during pregnancy. Despite more than 73,600 infections and 80 deaths from COVID-19 in people who were pregnant, none of the initial COVID-19 vaccine trials included pregnant or lactating participants.

“This is an important initial study to confirm the antibody generation from mRNA vaccination in pregnant women, and the passage of antibody via cord blood and breast milk,” said Linda Eckert, MD, a professor of ob.gyn. at The University of Washington, Seattle, who specializes in maternal immunization. “Further studies are important to look at the timing of vaccination in pregnancy and whether it influences the level of antibody passed to the fetus.”

Though this study is not a safety study, it “does not show increased expected vaccine reactions, such as aches, pains, and fever, in pregnant versus nonpregnant patients,” Dr. Eckert said in an interview. “It is not able to evaluate pregnancy outcome data, but it does allow pregnant women being vaccinated with the mRNA vaccines to know that the vaccine is generating protection for them, and the protection is being passed to the fetus in utero via cordblood and to the infant via breast milk.”

The research was funded by the National Institutes of Health along with the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, the Ragon Institute of MGH and MIT, and Massachusetts General Hospital and Brigham and Women’s Hospital.

Lead author Dr. Gray has consulted for Illumina, BillionToOne, and Aetion, and three other authors have financial or scientific/medical advising connections to Alba Therapeutics, NextCure, Viome, Systems Seromyx, and Mirvie. Dr. Ault and Dr. Eckert had no disclosures.

Pregnant and breastfeeding women who receive an mRNA COVID-19 vaccine develop a strong immune response and produce antibodies that can transfer to the fetus through the placenta and to newborns through breast milk, according to a prospective cohort study published March 25 in the American Journal of Obstetrics and Gynecology.

The findings revealed that the antibody response to vaccination in this cohort was greater than that from a COVID-19 infection during pregnancy. Though the researchers detected SARS-CoV-2 antibodies in umbilical cord blood and breast milk, it’s not yet known how much protection these antibodies might provide to newborns.

“The presence of neutralizing antibody transfer in nearly all cords, and improved transfer with increased time from vaccination, points to the promise of mRNA vaccine–induced delivery of immunity to neonates,” wrote Kathryn J. Gray, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital’s department of obstetrics and gynecology, and colleagues. “Transfer would perhaps be optimized if vaccination is administered earlier during gestation, though this needs to be directly examined in future studies.”

The researchers tracked 84 pregnant women, 31 lactating women, and 16 nonpregnant women who received the COVID-19 vaccine. The titers of IgG, IgA, and IgM antibodies against the SARS-CoV-2 spike, receptor binding domain (RBD), and S1 and S2 components of the spike were measured in the 131 participants’ blood and in the lactating women’s breast milk four times: at baseline, when they received their second vaccine dose, at 2-6 weeks after their second dose, and at delivery for the 13 women who delivered during the study period.

The study population included health care workers and was predominantly White and non-Hispanic. In addition, two pregnant women, two lactating women, and one nonpregnant woman in the study had a previous SARS-CoV-2 infection.

Most of the pregnant women received the vaccine in their second (46%) or third (40%) trimester. The women across all three groups – pregnant, lactating, and nonpregnant – experienced similar side effects from the each dose of the vaccine, including fever/chills in 32% of the pregnant women and half the nonpregnant women after the second dose.

Titers induced by the vaccine were similar across the pregnant, lactating, and nonpregnant women, and titers did not differ based on the trimester when women received the vaccine. The researchers then compared the titers from the vaccine recipients to titers of 37 pregnant women drawn 4-12 weeks after a natural SARS-CoV-2 infection. Vaccine-induced titers were significantly greater than those measured in the women who had a natural infection during pregnancy (P < .001).

The researchers identified IgG, IgA, and IgM antibodies in the breast milk samples, including a boost in IgG antibodies after the second vaccine dose from baseline. “However, whether these antibodies were transferred efficiently to infants remained unclear,” the authors noted.

The researchers found vaccine-induced antibodies in all 10 umbilical cord blood samples tested, all but one of which had been exposed to two doses of the vaccine.

“The cord with the lowest spike- and RBD-specific IgG belonged to a mother who delivered between the first and second vaccine doses and had received her first vaccine dose 17 days prior to delivery, suggesting that 2 doses may be essential to optimize humoral immune transfer to the neonate,” the authors wrote. “Based on what is known about other vaccines, the amount of maternal IgG transferred across the placenta to the cord is likely to differ by trimester of vaccination.”

Although umbilical cord sera had lower titers of neutralizing antibodies than found in maternal sera, the difference was not significant (median interquartile range 52.3 vs. 104.7, P = .05). The two cord blood samples without neutralizing antibodies came from a woman who had not had the second dose and a woman who received the second dose 1 week before delivery.

“These data provide a compelling argument that COVID-19 mRNA vaccines induce similar humoral immunity in pregnant and lactating women as in the nonpregnant population,” the authors wrote. “These data do not elucidate potential risks to the fetus.”

While the study provides evidence about the immune response induced by the COVID-19 mRNA vaccines during pregnant, it leaves other questions unanswered, said Kevin A. Ault, MD, professor of ob.gyn. at The University of Kansas Medical Center in Kansas City.

“The important thing about these findings is that the COVID vaccines are immunogenic in pregnant women. There may be a benefit to the newborns because antibodies are passed on through the placenta,” Dr. Ault said in an interview. “The main questions that remain are safety of the vaccine during pregnancy and effectiveness of the vaccine during pregnancy.”

He said he expects to see more studies on the safety and effectiveness of COVID-19 vaccines during pregnancy. Despite more than 73,600 infections and 80 deaths from COVID-19 in people who were pregnant, none of the initial COVID-19 vaccine trials included pregnant or lactating participants.

“This is an important initial study to confirm the antibody generation from mRNA vaccination in pregnant women, and the passage of antibody via cord blood and breast milk,” said Linda Eckert, MD, a professor of ob.gyn. at The University of Washington, Seattle, who specializes in maternal immunization. “Further studies are important to look at the timing of vaccination in pregnancy and whether it influences the level of antibody passed to the fetus.”

Though this study is not a safety study, it “does not show increased expected vaccine reactions, such as aches, pains, and fever, in pregnant versus nonpregnant patients,” Dr. Eckert said in an interview. “It is not able to evaluate pregnancy outcome data, but it does allow pregnant women being vaccinated with the mRNA vaccines to know that the vaccine is generating protection for them, and the protection is being passed to the fetus in utero via cordblood and to the infant via breast milk.”

The research was funded by the National Institutes of Health along with the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, the Ragon Institute of MGH and MIT, and Massachusetts General Hospital and Brigham and Women’s Hospital.

Lead author Dr. Gray has consulted for Illumina, BillionToOne, and Aetion, and three other authors have financial or scientific/medical advising connections to Alba Therapeutics, NextCure, Viome, Systems Seromyx, and Mirvie. Dr. Ault and Dr. Eckert had no disclosures.

Pregnant and breastfeeding women who receive an mRNA COVID-19 vaccine develop a strong immune response and produce antibodies that can transfer to the fetus through the placenta and to newborns through breast milk, according to a prospective cohort study published March 25 in the American Journal of Obstetrics and Gynecology.

The findings revealed that the antibody response to vaccination in this cohort was greater than that from a COVID-19 infection during pregnancy. Though the researchers detected SARS-CoV-2 antibodies in umbilical cord blood and breast milk, it’s not yet known how much protection these antibodies might provide to newborns.

“The presence of neutralizing antibody transfer in nearly all cords, and improved transfer with increased time from vaccination, points to the promise of mRNA vaccine–induced delivery of immunity to neonates,” wrote Kathryn J. Gray, MD, PhD, of Harvard Medical School and Brigham and Women’s Hospital’s department of obstetrics and gynecology, and colleagues. “Transfer would perhaps be optimized if vaccination is administered earlier during gestation, though this needs to be directly examined in future studies.”

The researchers tracked 84 pregnant women, 31 lactating women, and 16 nonpregnant women who received the COVID-19 vaccine. The titers of IgG, IgA, and IgM antibodies against the SARS-CoV-2 spike, receptor binding domain (RBD), and S1 and S2 components of the spike were measured in the 131 participants’ blood and in the lactating women’s breast milk four times: at baseline, when they received their second vaccine dose, at 2-6 weeks after their second dose, and at delivery for the 13 women who delivered during the study period.

The study population included health care workers and was predominantly White and non-Hispanic. In addition, two pregnant women, two lactating women, and one nonpregnant woman in the study had a previous SARS-CoV-2 infection.

Most of the pregnant women received the vaccine in their second (46%) or third (40%) trimester. The women across all three groups – pregnant, lactating, and nonpregnant – experienced similar side effects from the each dose of the vaccine, including fever/chills in 32% of the pregnant women and half the nonpregnant women after the second dose.

Titers induced by the vaccine were similar across the pregnant, lactating, and nonpregnant women, and titers did not differ based on the trimester when women received the vaccine. The researchers then compared the titers from the vaccine recipients to titers of 37 pregnant women drawn 4-12 weeks after a natural SARS-CoV-2 infection. Vaccine-induced titers were significantly greater than those measured in the women who had a natural infection during pregnancy (P < .001).

The researchers identified IgG, IgA, and IgM antibodies in the breast milk samples, including a boost in IgG antibodies after the second vaccine dose from baseline. “However, whether these antibodies were transferred efficiently to infants remained unclear,” the authors noted.

The researchers found vaccine-induced antibodies in all 10 umbilical cord blood samples tested, all but one of which had been exposed to two doses of the vaccine.

“The cord with the lowest spike- and RBD-specific IgG belonged to a mother who delivered between the first and second vaccine doses and had received her first vaccine dose 17 days prior to delivery, suggesting that 2 doses may be essential to optimize humoral immune transfer to the neonate,” the authors wrote. “Based on what is known about other vaccines, the amount of maternal IgG transferred across the placenta to the cord is likely to differ by trimester of vaccination.”

Although umbilical cord sera had lower titers of neutralizing antibodies than found in maternal sera, the difference was not significant (median interquartile range 52.3 vs. 104.7, P = .05). The two cord blood samples without neutralizing antibodies came from a woman who had not had the second dose and a woman who received the second dose 1 week before delivery.

“These data provide a compelling argument that COVID-19 mRNA vaccines induce similar humoral immunity in pregnant and lactating women as in the nonpregnant population,” the authors wrote. “These data do not elucidate potential risks to the fetus.”

While the study provides evidence about the immune response induced by the COVID-19 mRNA vaccines during pregnant, it leaves other questions unanswered, said Kevin A. Ault, MD, professor of ob.gyn. at The University of Kansas Medical Center in Kansas City.

“The important thing about these findings is that the COVID vaccines are immunogenic in pregnant women. There may be a benefit to the newborns because antibodies are passed on through the placenta,” Dr. Ault said in an interview. “The main questions that remain are safety of the vaccine during pregnancy and effectiveness of the vaccine during pregnancy.”

He said he expects to see more studies on the safety and effectiveness of COVID-19 vaccines during pregnancy. Despite more than 73,600 infections and 80 deaths from COVID-19 in people who were pregnant, none of the initial COVID-19 vaccine trials included pregnant or lactating participants.

“This is an important initial study to confirm the antibody generation from mRNA vaccination in pregnant women, and the passage of antibody via cord blood and breast milk,” said Linda Eckert, MD, a professor of ob.gyn. at The University of Washington, Seattle, who specializes in maternal immunization. “Further studies are important to look at the timing of vaccination in pregnancy and whether it influences the level of antibody passed to the fetus.”

Though this study is not a safety study, it “does not show increased expected vaccine reactions, such as aches, pains, and fever, in pregnant versus nonpregnant patients,” Dr. Eckert said in an interview. “It is not able to evaluate pregnancy outcome data, but it does allow pregnant women being vaccinated with the mRNA vaccines to know that the vaccine is generating protection for them, and the protection is being passed to the fetus in utero via cordblood and to the infant via breast milk.”

The research was funded by the National Institutes of Health along with the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, the Ragon Institute of MGH and MIT, and Massachusetts General Hospital and Brigham and Women’s Hospital.

Lead author Dr. Gray has consulted for Illumina, BillionToOne, and Aetion, and three other authors have financial or scientific/medical advising connections to Alba Therapeutics, NextCure, Viome, Systems Seromyx, and Mirvie. Dr. Ault and Dr. Eckert had no disclosures.