Women's Health

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

Researchers evaluating whether endometriosis is linked with preterm birth found no such association in a multicenter cohort study of more than 1300 women.

These new findings, which were published online in JAMA Network Open, suggest that changing monitoring strategies to prevent preterm birth for women with the disease may not be necessary.

The research team, led by Louis Marcellin, MD, PhD, with the department of obstetrics and gynecology at Université de Paris, also found that disease phenotype or whether the preterm birth was induced or spontaneous did not appear to alter the result.

Those results differ from previous research. Data on the phenotypes and their link with preterm birth have been scarce, but previous studies have shown the risk for preterm birth is more pronounced in women who have deep endometriosis than in women with ovarian endometriosis.

Dr. Marcellin said in an interview that “little is known about the impact of endometriosis on obstetric outcomes. In contrast to previous studies, we reported no differences in the risk for preterm delivery between women with endometriosis (34 of 470 [7.2%]) and those without endometriosis (53 of 881 [6.0%]), even when adjusted for multiple factors.”

The authors accounted for mother’s age, body mass index before pregnancy, birth country, number of times the woman had given birth, previous cesarean delivery, and history of preterm birth. After adjusting for potential confounders, endometriosis was not associated with preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.64-1.77).

The researchers found no differences among preterm births based on a mother’s endometriosis phenotype. Those phenotypes include Isolated superficial peritoneal endometriosis, ovarian endometrioma, and deep endometriosis.

“Monitoring pregnancy beyond the normal protocols or changing management strategies may not be warranted in cases of endometriosis,” Dr. Marcellin said.

More research on endometriosis’ potential link to birth outcomes is needed.

An expert not involved with the study said the new paper highlights important new avenues of research but should not be seen as the final word on the connection between endometriosis and preterm birth.

Of the 1,351 study participants (mean age, 32.9 years) who had a singleton delivery after 22 weeks’ gestation, 470 were assigned to the endometriosis group, and 881 were assigned to the control group.

The authors concluded that “pregnant women with endometriosis should not be considered to have an exceptionally high risk for preterm birth. However, further studies are needed to examine the potential for other adverse perinatal outcomes or specific but rare complications.”

Daniela Carusi, MD, said the difficulty with the study’s design is that “premature birth is not one problem or one disease.”

Many very different problems can all end with premature birth. Sometimes it’s an infection or inflammation or bleeding in the uterus or hypertension in the mother, for example, and all those things can lead to a preterm birth, she explained.

“This study inherently lumps all those things together,” said Dr. Carusi, who is director of surgical obstetrics and placental abnormalities in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston. “It’s quite possible endometriosis can have a big impact in one of those areas and no impact in the other areas, but the study design wouldn’t be able to pick that up.”
 

Editorialists: Results challenge findings of previous studies

In an accompanying commentary, Liisu Saavalainen, MD, PhD, and Oskari Heikinheimo, MD, PhD, both with the department of obstetrics and gynecology, Helsinki University Hospital, wrote that several previous studies have suggested that women with endometriosis have a slightly higher risk for preterm birth.

Those studies were mostly retrospective and differed in the way they classified endometriosis and the way they selected patients, the editorialists write. Also, most women in these studies typically had subfertility, they added.

The study by Dr. Marcellin and colleagues differs from previous related research in that was prospective and assessed the risk for preterm delivery in women both with endometriosis and those without endometriosis from several maternity centers in France. The women with endometriosis were classified according to the severity of their disease.

The editorialists wrote: “The novel results by Marcellin et al. challenge the findings of most previous studies on this topic. These results are valuable and comforting. However, they are also likely to trigger new studies on the pregnancy risks associated with different types of endometriosis. That is good news.”

Dr. Carusi said the study was well done and included a notably large size. Further complimenting the research, she said it’s important to talk about this little-discussed pregnancy complication. There’s been much more focus for women with endometriosis and their physicians on getting pregnant and on talking about the length of their term.

The study leaves some things unanswered.

The study was funded by research grants from the French Ministry of Health and was sponsored by the Département de la Recherche Clinique et du Développement de l’Assistance Publique–Hôpitaux de Paris. Dr. Carusi reported no relevant financial relationships. One study coauthor reported receiving personal fees from Bioserinity and Ferring outside the submitted work. No other disclosures were reported.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

Methylergonovine is often used to control severe bleeding immediately after cesarean deliveries. But a new study suggests that the ergot alkaloid agent could benefit these women if administered before delivery, researchers from the University of Iowa Hospitals, Iowa City, reported in the January edition of the American Journal of Obstetrics and Gynecology. The data were presented Feb. 4 at the 2022 virtual Pregnancy Meeting of the Society of Maternal-Fetal Medicine.

The findings have prompted the institution to begin administering prophylactic methylergonovine in addition to oxytocin at the time of cesarean deliveries, according to the researchers.

“The addition of prophylactic methylergonovine improved uterine tone, decreased the requirement of additional uterotonic agents, decreased the risk of postpartum hemorrhage, and decreased the need for blood transfusions,” lead author Nicole Masse, MD, assistant professor of maternal-fetal medicine at the University of Iowa, said in an interview.

Abnormal uterine tone is the leading cause of postpartum hemorrhage, Dr. Masse said. “Satisfactory uterine tone following delivery is essential. This study found a decreased need for blood transfusions in patients who received prophylactic methylergonovine. Given the risks of blood transfusions, which can include disease transmission and allergic reactions, transfusions should be avoided whenever possible.”

Conducted between June 2019 and February 2021, the single-center, randomized controlled trial of 160 women undergoing an intrapartum cesarean birth is the largest of its kind to date, Dr. Masse said. Women received either intravenous oxytocin at a dose of 300 mU per minute plus 1 mL of intramuscular normal saline (n = 80) or intravenous oxytocin at a dose of 300 mU per minute plus 0.2 mg (1 mL) of intramuscular methylergonovine (n = 80).

Women who received prophylactic methylergonovine required significantly less additional uterotonic agents than those who received oxytocin alone (20% vs. 55%; relative risk, 0.36; 95% confidence interval 0.22-0.59), according to the researchers. Those receiving methylergonovine were more likely to experience improved uterine tone (80% vs. 41.2%; RR, 1.94; 95% CI, 1.46-2.56), a lower incidence of postpartum hemorrhage (35% vs. 58.8%; RR, 0.6; 95% CI, 0.42-0.85), decreased need for a blood transfusion (5% vs. 22.5%; RR, 0.22; 95% CI, 0.08-0.63), and lower mean quantitative blood loss (996 mL vs. 1,315 mL; P = .004), they reported.      

“As the majority of postpartum hemorrhages are preventable, this study is clinically relevant and can serve to decrease the morbidity associated with postpartum hemorrhage,” Dr. Masse said.

Jennifer Choi, DO, clinical assistant professor of maternal-fetal medicine at Stony Brook University Hospital, New York, said the Iowa team’s results are contrary to prior studies showing no benefit with simultaneous use of oxytocin and ergot alkaloids.    

“It would be interesting to see long-term benefits across a diverse population,” she said. “But as methylergonovine is a known contraindication to hypertensive and cardiovascular disorders, including pre-eclampsia, patients would have to be carefully screened.”

Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the study “a novel idea, but more research and higher numbers are needed for a substantive conclusion.”

Additional studies should look at variables such as the number of prior cesarean deliveries, body mass index, presence of uterine myomas, presence of abnormal placentation (placenta accreta, increta, percreta), and presence of multiple gestation, said Dr. Gaither, who also is director of perinatal services at NYC Health + Hospitals/Lincoln.

“Methergine [methylergonovine] use is contraindicated in women with hypertension/pre-eclampsia spectrum, mitral valve prolapse, history of coronary artery disease, and liver pathology,” she noted.

The researchers reported no relevant financial conflicts of interest.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

A new study finding that samples from maternal urine and the meconium of their newborn babies frequently produce different results is raising more questions about drug testing of pregnant women.

The study found concerningly high rates of disagreement (or “discordance”) in biochemical testing between maternal urine in women with a documented history of or active drug use and the meconium in their newborns. In some cases, such discordance might be triggering the inappropriate intervention of childcare protective services, including the separation of infants from their mothers, according to the researchers, who presented their findings Feb. 4 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“There’s a very big debate right now in the obstetrics and perinatology communities about the utility of biochemical testing and the identification of high-risk women,” lead author Cassandra Heiselman, DO, MPH, clinical assistant professor in the department of obstetrics, gynecology and reproductive medicine at Stony Brook (N.Y.) University, said in an interview. “We know that each biochemical test has limitations, which can include basically the inability to detect all substances, especially synthetic opioids like fentanyl, [and] the possibility for false results.”

Inaccuracies in testing can potentially result in inappropriate separation of mother and baby. “Careful scrutiny of results is needed,” Dr. Heiselman said.

The Stony Brook team conducted a retrospective cohort study that identified women presenting for delivery from January 2017 to March 2021 with indications for drug testing, including a known history of or current substance use disorder/misuse, and late or no prenatal care. A standardized panel was used for testing maternal urine and newborn meconium.

Urine tests of 327 women resulted in 187 (57%) positive and 98 (30%) negative results, along with 42 (13%) samples with incomplete data, the researchers reported. In contrast, drug testing of newborn meconium was positive in 273 (83%) cases, negative in 42 (13%), and was not performed in 12 (4%) – for a rate of concordance of 41%.

Concordance of urine/meconium occurred more frequently in male newborns (65%), compared with females (35%). “It is unclear biologically why there is such a difference based on the sex of the infants’ test and is an area that needs further investigation,” Dr. Heiselman said.

Comparing urine and meconium tests for 11 substances resulted in 195/483 (40%) concordance, the researchers said; 18% were discordant with positive maternal urine, and 41% were discordant with newborn positive meconium.

Oxycodone and fentanyl were significantly discordant with positive maternal urine. Cannabis use was the most common factor associated with a positive test of meconium, according to the researchers.

“Some studies have shown cannabis use in the second trimester can show up in meconium testing even if the mother has stopped that behavior,” Dr. Heiselman said. “Then there is also cross-reactivity with other substances that can lead to higher false positive results, especially in the urine toxicology.”

The reasons for the discordant results are not clear and vary by substance, Dr. Heiselman said.

“Cannabis and methadone were the significant factors leading to discordance with positive newborn meconium, which may reflect prior use earlier in pregnancy without recent use before delivery,” she said in an interview. “Urine and meconium reflect potentially different timing in perinatal exposure and the potential differences in windows of detection for different substances. Therefore, we would expect some discordance in our comparisons, just not the extent that we saw.”

Some test results might also have been false positives. Many commonly used medications, from cough syrups to proton pump inhibitors, have the potential to generate positive results for illicit drugs, Dr. Heiselman said.

“The issue of discordance is a complex one, where there are limitations of the tests being performed, possible cross-reactivity with false positives, and the difference in what test reflects as far as timing of prenatal exposure. Furthermore, a negative test does not rule out sporadic use, nor does a positive result diagnose substance use disorder or its severity,” she said.
 

Lack of standards

Dr. Heiselman said states and the federal government lack standards to biochemically evaluate women at risk for drug abuse and their newborns.

“My institution uses a risk-based protocol. Basically, we test cases where we have a known history of substance use disorder or active use, a history in the last 3 years of any kind of substance use, initiation of late prenatal care after 20 weeks, or no prenatal care at all,” she said. “And then the pediatricians on the other side will test neonates if the mother has any of that history or if the neonates themselves have unexplained complications or drug withdrawal symptoms.”

High rates of discordance can result in the inappropriate intervention by childcare protective service agencies when the mother may not have a substance use disorder, she noted.

Perinatologist Kecia Gaither, MD, MPH, associate professor of clinical obstetrics and gynecology at Weill Cornell Medicine, New York, called the findings “no surprise,” but added that negative findings in neonates “do not exclude the possibility of substance abuse by the mother. It is important to recognize the limitations inherent with screening tests for illicit substances in neonates from substance-abusing mothers.”

Dr. Heiselman added that understanding what maternal and infant drug tests truly reflect “can help us as clinicians in deciding when we test, whether it’s medically necessary, instead of just thinking biochemical tests are the best screening tool, because we know that we are screening. We must engage these women in empathetic and nonjudgmental discussions, which often will elucidate a substance use disorder history more so than just biochemical testing, negative or positive.”

The researchers disclosed no relevant financial relationships.

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

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Updated guidelines for the management and treatment of endometriosis reflect changes in clinical practice to guide clinician and patient decision-making, according to a statement from the European Society of Human Reproduction and Embryology, which issued the guidelines in February 2022.

Although the exact prevalence of endometriosis remains unclear, estimates suggest that approximately 190 million women and adolescent girls are affected by endometriosis during their reproductive years, and women continue to suffer beyond menopause, according to the authors. Endometriosis has a significant impact on society through both direct and indirect health care costs comparable to those of type 2 diabetes, rheumatoid arthritis, and Crohn’s disease, they noted.

The guidelines are the first update on the topic of endometriosis since 2014, and include more than 100 recommendations, according to the European Society of Human Reproduction and Embryology (ESHRE). The target audience, according to the authors, is secondary and tertiary health care providers who treat women with endometriosis. The recommendations were based on research papers published up to Dec. 1, 2020.

Although most of the recent studies confirm previous ESHRE recommendations, several topics reflect significant changes in clinical practice.

Notably, laparoscopy is no longer recommended as the diagnostic gold standard, and should be used only in patients with negative imaging for whom empirical treatment was unsuccessful.

For pain management, studies support the use of GnRH antagonists as a second-line treatment, while laparoscopic uterosacral nerve ablation and presacral neurectomy are no longer included in the recommendations.

The guidelines include new information on pregnancy and fertility preservation for women with endometriosis. The Endometriosis Fertility Index (EFI) was added to support joint decision-making for women seeking pregnancy after surgery. However, the extended use of GnRH antagonist prior to assisted reproductive technology treatments to improve live birth rate is not recommended.

Endometriosis in adolescent patients is included in the guidelines for the first time, and strong recommendations include taking a careful history and using ultrasound if appropriate, but the use of serum biomarkers is not recommended for diagnosis. Strong recommendations for treatment strategies for adolescents include hormonal contraceptives or progestins as a first-line therapy.

Recommendations for managing endometriosis in menopause are more extensive than in previous guidelines and the strongest update is against the use of estrogen-only treatment in these patients. However, the guidelines continue to recommend treating women with a history of endometriosis after surgical menopause with combined estrogen-progestogen therapy “at least up to the age of natural menopause.”

Expanded recommendations related to endometriosis and cancer begin with a strong recommendation for clinicians to advise women that endometriosis is not associated with a significantly higher risk of cancer overall. “Although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low,” the authors wrote. Other strong recommendations include reassuring women with endometriosis of the low risk of malignancy associated with hormonal contraceptive use, and performing cancer screening according to the existing population-based guidelines without additional screening. Epidemiologic data show that complete excision of visible endometriosis may reduce the risk of ovarian cancer, but the potential benefits must be weighed against the risks of surgery, including morbidity, pain, and ovarian reserve, the authors said.

The guidelines include recommendations related to asymptomatic endometriosis, extrapelvic endometriosis, and primary prevention of endometriosis, but without major changes to the 2014 guidelines.
 

Guidelines expand strategies, but research gaps remain

In 2021, an international working group of the American Association of Gynecologic Laparoscopists, the European Society for Gynecologic Endoscopy, ESHRE, and the World Endometriosis Society defined endometriosis as “a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process,” Mark P. Trolice, MD, director of The IVF Center, Orlando, Fla., and professor of obstetrics and gynecology at the University of Central Florida, said in an interview.

Although the current guidelines represent the second update since 2005, many unanswered questions remain, Dr. Trolice said. “There is a large diagnostic void between the onset of symptoms and the time to a reliable diagnosis averaging between 8 and 12 years,” he emphasized.

Dr. Trolice noted the change of the addition of an oral GnRH antagonist, “now FDA approved for the treatment of pain associated with endometriosis,” he said. However, “Extended GnRH agonist prior to ART is not recommended due to the lack of any clear benefit,” he noted.

Dr. Trolice noted the inclusion of the Endometriosis Fertility Index (EFI), published in 2010, “as a useful scoring system to predict postoperative non-IVF pregnancy rates (both by natural means and IUI [intrauterine insemination]) based on patient characteristics, revised ASRM staging, and ‘least function score of the adnexa.’ ” He agreed with the need for expanded information on the topics of endometriosis and adolescence and endometriosis and cancer.

The most important changes for clinical practice include reducing unnecessary laparoscopy and procedures without benefit, such as laparoscopic uterosacral nerve ablation and presacral neurectomy, and GnRH suppression using an oral antagonist, said Dr. Trolice. Other especially practical guidance includes the recommendation to discontinue advising patients that pregnancy will reduce symptoms of endometriosis, and to avoid prescribing estrogen-only treatment in menopause given the risk of malignant transformation of endometriosis, he said.

Another clinically useful recommendation, though not a significant update, is the need to identify extrapelvic endometriosis symptoms, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules that enlarge during menses, Dr. Trolice added.

Barriers to implementing the updated guidelines include lack of education of clinicians, including primary care providers, and the lack of definitive evidence for many areas, he noted.

As for additional research, more data are needed to explore the genetic, mutational, and epigenetic profile of endometriosis, and to identify biomarkers to noninvasively detect and provide a prognosis for endometriosis, and optimal methods for prevention and management, said Dr. Trolice. Other research gaps include “definitive medical and surgical treatment of endometriosis for improvement of fertility, quality of life, and reduction of pain,” he noted. From a fertility standpoint, more studies are needed on “the use of ovarian tissue or oocytes cryopreservation in adolescents and adults who undergo ovarian surgery for endometriomas, and the role of the EFI as a presurgical triage tool and to predict IUI outcomes,” said Dr. Trolice.

Overall, society recommendations such as these from ESHRE “serve as guides for physicians by providing evidence-based medicine and dispelling prior unproven practices so patients may receive the most effective care of endometriosis, throughout a woman’s life,” Dr. Trolice emphasized.

The current guideline will be considered for revision in 2025, and the full version is available on the ESHRE website.

Members of the ESHRE guideline development group received no payment for participating in the development process, although they were reimbursed for travel expenses related to guideline meetings.

Dr. Trolice had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn News.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

Exposure to opioid analgesics during the first trimester of pregnancy appears to increase the risk of congenital anomalies diagnosed in the first year of life, researchers report.

While the absolute risk of congenital anomalies was low, these findings add to an increasing body of evidence suggesting that prenatal exposure to opioids may confer harm to infants post partum.

“We undertook a population-based cohort study to estimate associations between opioid analgesic exposure during the first trimester and congenital anomalies using health administrative data capturing all narcotic prescriptions during pregnancy,” lead author Alexa C. Bowie, MPH, of Queen’s University in Kingston, Ont., and colleagues reported in CMAJ.

The researchers retrospectively reviewed administrative health data in a single-payer health care system from 2013 to 2018. They identified parent-infant pair records for all live births and stillbirths that occurred at more than 20 weeks’ gestation.

The exposure of interest was a prescription for any opioid analgesic with a fill date between the estimated date of conception and less than 14 weeks’ gestation. The referent group included any infant not exposed to an opioid analgesic during the index pregnancy period.
 

Results

The study cohort included a total of 599,579 gestational parent-infant pairs. Of these, 11,903 (2.0%) were exposed to opioid analgesics, and most were exposed during the first trimester only (75.8%).

Overall, 2.0% of these infants developed a congenital anomaly during the first year of life; the prevalence of congenital anomalies was 2.0% in unexposed infants and 2.8% in exposed infants.

Relative to unexposed infants, the researchers observed greater risks among infants who were exposed for some anomaly groups, including many specific anomalies, such as ankyloglossia (any opioid: adjusted risk ratio, 1.88; 95% confidence interval, 1.30-2.72; codeine: aRR, 2.14; 95% CI, 1.35-3.40), as well as gastrointestinal anomalies (any opioid: aRR, 1.46; 95% CI, 1.15-1.85; codeine: aRR, 1.53; 95% CI, 1.12-2.09; tramadol: aRR, 2.69; 95% CI 1.34-5.38).

After sensitivity analyses, which included exposure 4 weeks before conception or excluded individuals with exposure to opioid analgesics before pregnancy, the findings remained unchanged.

“Although the overall risk was low, we observed an increased risk of any congenital anomaly with tramadol, and a previously unreported risk with morphine,” the researchers wrote.

“Previous studies reported elevated risks of heart anomalies with first-trimester exposure to any opioid analgesic, codeine, and tramadol, but others reported no association with any opioid analgesic or codeine,” they explained.
 

Interpreting the results

Study author Susan Brogly, PhD, of Queen’s University said “Our population-based study confirms evidence of a small increased risk of birth defects from opioid analgesic exposure in the first trimester that was observed in a recent study of private insurance and Medicaid beneficiaries in the U.S. We further show that this small increased risk is not due to other risk factors for fetal harm in women who may take these medications.”

“An opioid prescription dispensed in the first trimester would imply that there was an acute injury or chronic condition also present in the first trimester, which may also be associated with congenital abnormalities,” commented Elisabeth Poorman, MD, MPH, a clinical instructor and primary care physician at the University of Washington in Seattle.

“Opioid use disorder is often diagnosed incorrectly; since the researchers used diagnostic billing codes to exclude individuals with opioid use disorder, some women may have been missed,” Dr. Poorman explained.

Ms. Bowie and colleagues acknowledged that a key limitation of the study was the identification of cases using diagnostic billing codes. As a result, exposure-dependent recording bias could be present and limit the applicability of the findings.

“The diagnosis and documentation of minor anomalies and those with subtle medical significance could be vulnerable to exposure-dependent recording bias,” Ms. Bowie wrote.

Dr. Poorman recommended that these results should be interpreted with caution given these and other limitations. “Overall, results from this study may imply that there is limited evidence to suspect opioids are related to congenital abnormalities due to a very small difference observed in relatively unequal groups,” she concluded.

This study received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development and was also supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health. One author reported receiving honoraria from the National Institutes of Health and a grant from the Canadian Institute of Health Research, outside the submitted work. No other competing interests were declared.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

The potential effectiveness of using vaginal progesterone to prevent preterm birth in two different populations was the focus of a pair of studies with mixed results at the annual meeting sponsored by the Society for Maternal-Fetal Medicine on Feb. 3. One study found no benefit from vaginal progesterone in those with first trimester bleeding, while the other, in a head-to-head comparison with 17-alpha-hydroxyprogesterone caproate (17-OHPC), found vaginal progesterone performs similarly to 17-OHPC in singleton pregnancies with a history of preterm birth.

While the first study does not suggest any changes in clinical practice, the second one suggests that vaginal progesterone is an alternative to 17-OHPC, as the American College of Obstetricians and Gynecologists currently recommends. SMFM currently only includes 17-OHPC in its guidelines.

“In otherwise low-risk pregnancies with first trimester bleeding, progesterone should not be prescribed for the prevention of miscarriage or prematurity,” Haim A. Abenhaim, MD, MPH, of the Jewish General Hospital at McGill University, Montreal, told attendees in his presentation.

”Publishing the negative result is so important because this helps the overall body of literature reduce the amount of publication bias that exists in the literature,” Michael Richley, MD, an ob.gyn. and maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview. Dr. Richley was not involved in the research but attended the presentation.
 

Vaginal progesterone for first trimester bleeding

Most preterm birth occurs in pregnancies with no identifiable risk factors, but first-trimester bleeding may indicate subchorionic hemorrhage from placental detachment, which can increase the risk of preterm birth. Other risk factors where progesterone has previously shown effectiveness in reducing preterm birth risk include short cervix and a history of prior preterm birth.

The first study (PREEMPT) was a double-blind, randomized controlled trial conducted at six Canadian hospitals with 533 women. The participants all experienced bleeding within the first 14 weeks of pregnancy and a documented subchorionic hemorrhage. The trial excluded those who already required progesterone, had contraindications to progesterone or had an alternate cause of bleeding.

The intervention group included 264 women randomly assigned to use 200 mg of micronized progesterone administered with a vaginal suppository at bedtime, while the placebo group included 269 women who used a vaginal suppository with no medication, both administered until 34 weeks of pregnancy. The groups were not significantly different in age, race, or former pregnancies, live births, and miscarriages. They were also similar in clinical characteristics of bleeding and subchorionic hemorrhage.

The proportion of term births was similar between the progesterone (74.6%) and placebo (70.6%) groups (P =.3), as was the proportion of preterm births (10.2% progesterone vs. 12.3% placebo, P =.46). There were also no significant differences in the secondary outcomes of cramping, hospital admission, bed rest, or preventive measures, including pessary, cerclage, antibiotics, magnesium, and nifedipine. Newborns across both groups were statistically similar in average birth weight and distribution of birth weights and in incidence of neonatal ICU admission or respiratory distress syndrome. Adverse events were similar across both groups.

”The results are not surprising as several studies in the past have shown similar lack of efficacy,” Dr. said. “The pathophysiology of subchorionic hematoma is different from the multifactorial etiologies of spontaneous preterm birth, and given our lack of clear understanding of the actions of progesterone, the lack of efficacy in this subgroup with subchorionic hematoma is not surprising.”

Dr. Richley did note that having a low-risk population to start with may have affected the findings, which might be different in a high-risk population.

“I don’t believe this will change anything within clinical practice. At this time, progesterone is not used in any form in the setting of first trimester threatened abortion by maternal-fetal medicine specialists,” Dr. Richley said. “There may be other subgroups of clinicians who do prescribe progesterone in this setting, and these data should further encourage them to move away from this practice.”

Dr. Abenhaim noted a couple unexpected issues that occurred during the course of the study, such as underreporting of subchorionic hemorrhage with radiologic confirmation that resulted in a smaller population and a change in protocol to include patients with no identifiable secondary source of bleeding. The pandemic also halted enrollment, and the investigators halted the trial when recruitment could have continued since interim analysis showed no likely benefit.

Though first trimester bleeding is associated with a 25%-30% increased risk of miscarriage or preterm birth, the findings showed that progesterone did not prevent miscarriage or prematurity, or increase the live birth rate, in low-risk patients with first trimester bleeding.
 

Vaginal progesterone vs. 17-OHPC

Although a 2017 meta-analysis had found vaginal progesterone to be superior to 17-OHPC in preventing preterm birth, few studies were available, and they had wide confidence intervals. This open-label randomized controlled trial took place at five U.S. sites and included participants who had a singleton pregnancy less than 24 weeks along and a history of singleton preterm birth between 16 and 37 weeks. The trials excluded those with placenta previa or accreta, preterm labor, preterm premature rupture of the membranes, clinical chorioamnionitis, or a major fetal anomaly or chromosomal disorder.

Among 205 women initially randomized, 94 in each group completed the trial, either inserting 200 mg of micronized progesterone daily with a vaginal suppository or receiving 250 mg of weekly intramuscular injections of 17-OHPC from 16 to 36 weeks’ gestation. The only significant difference between the groups in demographics or clinical features was that the vaginal progesterone group had a higher proportion of multiple past preterm births (33%) compared with the 17-OHPC group (17%). Cervical length and use of cerclage were also similar between the groups.

Though 30.9% of the vaginal progesterone group delivered preterm before 37 weeks, compared with 38.3% in the 17-OHPC group, the difference was not significant (P =.28). There was a borderline statistical difference between gestational age at delivery: 37.4 weeks in the vaginal progesterone group versus 36.3 weeks in the 17-OHPC group (P =.047). Neonatal outcomes were clinically similar between the two groups. Therapy initiation did slightly differ between the groups, with an average start 1 gestational week earlier in the vaginal progesterone group (16.9 vs. 17.8, P =.001) and a higher proportion of patients in the 17-OHPC group initiating therapy after 20 weeks (16.5% vs. 2.2%, P =.001). Adherence was otherwise similar between the groups, and the groups reported similar rates and types of side effects.

The trial did not meet the primary endpoint of vaginal progesterone reducing risk of recurrent preterm birth by 50%, compared with 17-OHPC, but it may increase latency to delivery, Rupsa C. Boelig, MD, of Thomas Jefferson University, Philadelphia, told attendees. Though this was the largest trial to compare vaginal progesterone with 17-OHPC for preventing preterm birth, it was underpowered to detect a difference in efficacy, to conduct subgroup analyses, and to assess secondary outcomes, Dr. Boelig noted. “Baseline difference in preterm birth risk may affect apparent relative efficacy of vaginal progesterone.”

Nevertheless, the “totality of evidence appears to be greater for vaginal progesterone,” Dr. Boelig said, making vaginal progesterone an acceptable alternative to 17-OHPC. ACOG recommendations currently include offering either, but SMFM recommendations only mention 17-OHPC.

It’s worth noting, however, that the future of 17-OHPC, a synthetic compound, compared with naturally occurring micronized progesterone, continues to be uncertain following a 2020 study that found no evidence of its efficacy, leading the Food and Drug Administration to withdraw its approval for prevention of preterm birth. ”These findings are important especially in light of the controversy surrounding 17-OHP,” Jenny Mei, MD, a maternal-fetal medicine fellow at UCLA, said in an interview after attending the presentation. “It is also sometimes difficult for patients to commit to weekly 17-OHPC injections, which requires time and many doctors visits, as compared to vaginal progesterone, which patients can administer at home.” Since this study does not have a placebo group, “it does not address the question of the overall efficacy of either medication compared to a control,” Dr. Mei said. ”It is also a somewhat small patient population so the results may change with a larger population. The authors conclude it is worth readdressing the use of vaginal progesterone for these patients.”

Herman L. Hedriana, MD, professor and director of the division of maternal-fetal medicine and the maternal-fetal medicine fellowship program at the University of California, Davis, also pointed out notable differences between the two compounds.

“One has to remember that the formulation and mechanism of action are very different between 17-OHPC and the vaginal application of micronized progesterone. We do not have enough data to say one is superior versus the other,” said Dr. Hedriana, who was not involved in the research. “With 17-OHPC, the mechanism of action appears to be influenced by how the drug is metabolized based on race and ethnicity makeup, and may be influence by epigenetics,” while the mechanism for vaginal progesterone is probably local “given it is applied directly next to the cervix; hence, the results are it is effective in short cervices.” But those differing mechanisms don’t change the clinical significance of the findings. “One can use vaginal progesterone or 17-OHPC based on patient preference and availability,” Dr. Hedriana said.

The researchers of both studies reported no personal financial or industry disclosures, though Dr. Boelig disclosed that she had taken 17-OHPC and had cerclages during both her pregnancies, which resulted in healthy children today. The PREEMPT trial was funded by the Canadian Institutes of Health Research. The head-to-head trial was funded by the National Institute of Child Health and Development, the March of Dimes, the EW Thrasher Foundation, the PhRMA Foundation, and Covis Pharma, who manufactures the 17-OHPC drug Makena.

This story was updated on 2/8/2022.

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Low-dose aspirin may increase risk of postpartum bleeding if patients don’t discontinue its use at least 7 days before delivery, but it’s otherwise unclear whether its use increases bleeding risk, according to research presented Feb. 5 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“These findings were a little surprising to me because we have generally been taught that aspirin is safe to continue up until delivery with minimal risk,” Jenny Mei, MD, a maternal-fetal medicine fellow at the University of California, Los Angeles, said in an interview after attending the presentation. “Theoretically it makes sense that it may increase bleeding risk, but multiple studies in the past analyzing its use with gynecological surgery show minimal risk, which was conferred to the obstetrical population as well.”

She noted, however, that patients prescribed low-dose aspirin already have risk factors that may increase their risk of postpartum bleeding, and the study’s finding of possible increased risk was not statistically significant after accounting for those confounders. “I wouldn’t change my practice management over it, but it does raise awareness that all interventions likely come with some risk,” Dr. Mei said.

Hypertensive disorders of pregnancy are responsible for 6.6% of U.S. pregnancy-related deaths. The SMFM currently recommends low-dose aspirin starting at 12 weeks’ gestation in patients at high risk for preeclampsia, which includes people with multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease, or a history of preeclampsia. However, previous research has shown mixed results on the safety of low-dose aspirin in terms of bleeding risk, Kelsey White, MD, a second-year maternal-fetal medicine fellow of the Yale University, New Haven, Conn., told attendees.

This retrospective study compared a bleeding composite endpoint among those who did and did not take low-dose aspirin between January 2018 and April 2021. The composite included an estimated blood loss of greater than 1,000 mL, postpartum hemorrhage based on ICD-9/10 code diagnosis, and red blood cell transfusion. The researchers also compared bleeding risk within the aspirin group based on discontinuation at greater or less than 7 days before delivery.

Among 16,980 patients, 11.3% were prescribed low-dose aspirin. The patients prescribed low-dose aspirin significantly differed from those not prescribed it in all demographic and clinical characteristics except placenta accreta spectrum. The average age of the aspirin group was 39 years, compared with 24 years in the nonaspirin group (P < .01). More of the aspirin group patients were Hispanic and Black, and 52.3% of patients taking aspirin had a body mass index greater than 30 kg/m², compared with 22.9% of the nonaspirin group. Rates of diabetes, lupus, fibroids, nonaspirin anticoagulation use, cesarean delivery, and preterm delivery were all greater in the aspirin group.

In addition, 43.9% of the patients in the aspirin group had a hypertensive disorder, including 20.2% with preeclampsia, compared with 17.1% with hypertensive disorders, including 6.2% with preeclampsia, in the group not taking aspirin (P < .0001). “This shows that a high-risk population was prescribed aspirin, which correlates to the recommended prescription guidelines,” Dr. White said.

The postpartum bleeding composite outcome occurred in 14.7% of patients in the low-dose aspirin group, compared with 9.2% of patients in the nonaspirin group, for an unadjusted 1.7 times greater risk of bleeding (95% confidence interval, 1.49-1.96). After adjustment for confounders, the risk declined and was no longer statistically significant (aOR = 1.15; 95% CI, 0.98-1.34).

Meanwhile, 15% of those who discontinued aspirin within 7 days of delivery had postpartum bleeding, compared with 9% of those who discontinued aspirin at 7 or more days before delivery (P = .03).

Therefore, while the study found only a possible, nonsignificant association between low-dose aspirin and postpartum bleeding, risk of bleeding was significantly greater among those who discontinued aspirin only in the last week before delivery.

”Our study is timely and supports a recent Swedish study [that] found an increased risk of intrapartum bleeding, postpartum hemorrhage, and postpartum hematoma,” Dr. White said. She also noted that the United States Preventive Services Task Force changed their recommendation in 2021 for low-dose aspirin prophylaxis for cardiovascular disease.

“They now recommend against the use of low-dose aspirin for prevention in adults without a history of cardiovascular disease,” Dr. White said. “The change in recommendations came after recent randomized control trials showed that low-dose aspirin had very little benefit and may increase the risk of bleeding.”

However, Dr. White added that they “do not believe this study should be used to make any clinical decisions.” While the study had a large sample size, it was limited by its retrospective reliance on EMR data, including the EMR medication list, and the researchers couldn’t assess patient compliance or patient use of over-the-counter aspirin not recorded in the EMR.

Deirdre Lyell, MD, a professor of maternal-fetal medicine at Stanford (Calif.) University, agreed that the findings should not impact clinical practice given its limitations.

“The investigators could not entirely identify who stopped low-dose aspirin and when. When they estimated timing of stoppage of low-dose aspirin, their data suggested a small benefit among those who discontinued it at least 7 days before delivery, though this should be interpreted with caution, given the potential inaccuracy in these data,” Dr. Lyell, who was not involved in the study, said in an interview. “Their study did not examine factors that should be used to confirm if there are real differences in blood loss, such as changes in blood counts before and after delivery, or more use of medications that we use to stop heavy bleeding.”

In fact, Dr. Lyell noted, other research at the SMFM meeting found ”that low-dose aspirin is not used frequently enough in patients who might benefit, such as those at high risk for preeclampsia,” she said. ”Low-dose aspirin among those at increased risk has been shown to reduce rates of preeclampsia, reducing the likelihood of risky situations for moms and babies.”

The authors had no disclosures. Dr. Lyell has consulted for Bloomlife, a uterine contraction and fetal monitor. Dr. White and Dr. Mei had no disclosures.
 

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

Use of marijuana during pregnancy was associated with symptoms of nausea and vomiting and with use of prescribed antiemetics, according to a study presented Feb. 3 at the meeting sponsored by the Society for Maternal-Fetal Medicine. It’s unclear, however, whether the association suggests that pregnant individuals are using marijuana in an attempt to treat their symptoms or whether the marijuana use is contributing to nausea and vomiting – or neither, Torri D. Metz, MD, of the University of Utah Health in Salt Lake City, told attendees.

“Cannabis use has been increasing among pregnant individuals,” Dr. Metz said. “Reported reasons for use range from habit to perceived benefit for treatment of medical conditions, including nausea and vomiting.” She noted a previous study that found that dispensary employees in Colorado recommended cannabis to pregnant callers for treating of nausea despite no clinical evidence of it being an effective treatment.

”Anecdotally, I can say that many patients have told me that marijuana is the only thing that makes them feel better in the first trimester, but that could also be closely tied to marijuana alleviating their other symptoms, such as anxiety or sleep disturbances,” Ilina Pluym, MD, of the department of maternal-fetal medicine at the University of California, Los Angeles, said in an interview. ”In the brain, marijuana acts to alleviate nausea and vomiting, and it has been used successfully to treat nausea [caused by] chemotherapy,” said Dr. Pluym, who attended the abstract presentation but was not involved in the research. “But in the gut, with long-term marijuana use, it can have the opposite effect, which is what is seen in cannabinoid hyperemesis syndrome.”

Past research that has identified a link between cannabis use and nausea in pregnancy has typically relied on administrative data or self-reporting that are subject to recall and social desirability bias instead of a biomarker to assess cannabis use. This study therefore assessed marijuana use based on the presence of THC-COOH in urine samples and added the element of investigating antiemetic use in the population.

The study enrolled 10,038 nulliparous pregnant patients from eight U.S. centers from 2010 to 2013 who were an average 11 weeks pregnant. All participants completed the Pregnancy-Unique Quantification of Emesis (PUQE) tool at their first study visit and consented to testing of their previously frozen urine samples. The PUQE tool asks participants how often they have experienced nausea, vomiting, or retching or dry heaves within the previous 12 hours. A score of 1-6 is mild, a score of 7-12 is moderate, and a score of 13 or higher is severe.

Overall, 15.8% of participants reported moderate to severe nausea and 38.2% reported mild nausea. A total of 5.8% of participants tested positive for marijuana use based on THC levels in urine. Those with incrementally higher levels of THC, at least 500 ng/mg of creatinine, were 1.6 times more likely to report moderate to severe nausea after accounting for maternal age, body mass index, antiemetic drug use, and gestational age (adjusted odds ratio, 1.6; P < .001). An association did not exist, however, with any level of nausea overall. Those with higher creatinine levels were also 1.9 times more likely to report vomiting and 1.6 times more likely to report dry heaves or retching (P < .001).

About 1 in 10 participants (9.6%) overall had used a prescription antiemetic drug. Antiemetics were more common among those who had used marijuana: 18% of those with detectable THC had used antiemetics, compared with 12% of those without evidence of cannabis use (P < .001). However, most of those who used marijuana (83%) took only one antiemetic.

Among the study’s limitations were its lack of data on the reasons for cannabis use and the fact that it took place before widespread cannabidiol products became available, which meant most participants were using marijuana by smoking it.

Dr. Pluym also pointed out that the overall rate of marijuana use during pregnancy is likely higher today than it was in 2010-2013, before many states legalized its use. “But legalization shouldn’t equal normalization in pregnancy,” she added.

In addition, while the PUQE score assesses symptoms within the previous 12 hours, THC can remain in urine samples anywhere from several days to several weeks after marijuana is used.

”We’re unable to establish cause and effect,” Dr. Metz said, “but what we can conclude is that marijuana use was associated with early pregnancy nausea and vomiting.”

The findings emphasize the need for physicians to ask patients about their use of marijuana and seek to find out why they’re using it, Dr. Metz said. If it’s to treat nausea and vomiting of pregnancy, ob.gyns. should ensure patients are aware of the potential adverse effects of marijuana use in pregnancy and mention safe, effective alternatives. Research from the National Academy of Sciences has shown consistent evidence of decreased fetal growth with marijuana use in pregnancy, but there hasn’t been enough evidence to assess potential long-term neurological effects.

The research was funded by the National Institute on Drug Abuse and the National Institute of Child Health and Human Development. Dr. Metz and Dr. Pluym reported no disclosures.

The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.

As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.

The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.

“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”

Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.

Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.

Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”

According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
 

During maternity care

Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.

These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.

Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.

The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.

But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
 

Postpartum care

Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.

While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.

“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”

Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
 

Nonobstetric settings

Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.

Support materials

Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.

The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.

The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.

ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.

Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.

The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.

As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.

The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.

“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”

Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.

Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.

Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”

According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
 

During maternity care

Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.

These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.

Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.

The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.

But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
 

Postpartum care

Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.

While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.

“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”

Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
 

Nonobstetric settings

Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.

Support materials

Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.

The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.

The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.

ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.

Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.

The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.

As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.

The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.

“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”

Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.

Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.

Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”

According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
 

During maternity care

Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.

These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.

Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.

The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.

But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
 

Postpartum care

Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.

While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.

“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”

Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
 

Nonobstetric settings

Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.

Support materials

Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.

The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.

The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.

ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.

Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.