Obstetrics

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented Jan. 28 at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection,” Naima Joseph, MD, MPH, of Emory University, Atlanta, said in an interview.

“Our data demonstrate maternal capacity to mount an appropriate and robust immune response,” and maternal protective immunity lasted at least 28 days after infection, Dr. Joseph said. “Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates.”

The researchers analyzed the amount of IgG and IgM antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

“It’s reassuring that, so far, the physiological response is exactly what we expected it to be,” Judette Louis, MD, MPH, an associate professor of ob.gyn. and the ob.gyn. department chair at the University of South Florida, Tampa, said in an interview. “It’s what we would expect, but it’s always helpful to have more data to support that. Otherwise, you’re extrapolating from what you know from other conditions,” said Dr. Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants’ cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Dr. Joseph reported.

“Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1,” Dr. Joseph said in her presentation. Their data showed “suboptimal efficiency” at a ratio of 0.81.

The study’s small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.
 

Implications for maternal COVID-19 vaccination

Although the data are not yet available, Dr. Joseph said they have expanded their protocol to include vaccinated pregnant women.

“The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy,” Dr. Joseph told SMFM attendees. “I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust.”

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA “should not be withheld from pregnant individuals who choose to receive the vaccine.”

“One of the questions people ask is whether in pregnancy you’re going to mount a good response to the vaccine the way you would outside of pregnancy,” Dr. Louis said. “If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions.” Data such as those from Dr. Joseph’s study can also inform recommendations on timing of maternal vaccination.

“For instance, Dr. Joseph demonstrated that, 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies,” Dr. Louis said.
 

Consensus emerging from maternal antibodies data

The findings from Dr. Joseph’s study mirror those reported in a study published online Jan. 29 in JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children’s Hospital of Philadelphia, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Dr. Joseph’s study.

For their study, Dr. Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

About 6% of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers’ infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants’ cord blood did not, 5 had only IgM antibodies, and 6 had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

“However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother,” Dr. Munoz wrote.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, “maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn,” Dr. Munoz wrote. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Dr. Joseph’s study. Dr. Joseph and Dr. Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children’s Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Dr. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

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

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Peripartum maternal oxygen supplementation does not yield a clinically relevant improvement in umbilical artery gas pH or other neonatal outcomes, reported Nandini Raghuraman, MD, MS, of the Washington University School of Medicine, St. Louis, MO, and her associates.

In a meta-analysis of 16 studies identified between Feb. 18 and April 3, 2020, the investigators sought to determine whether maternal oxygen supplementation during delivery leads to improved measures in umbilical artery (UA) gas and neonatal outcomes. Using data from randomized clinical trials, they compared peripartum oxygen supplementation with room air and examined the link between oxygen delivery during regular labor or planned cesarean delivery (CD) with UA gas measures and other neonatal outcomes.

Altogether, 1,078 patients were randomized to the oxygen group or the room air group. UA pH remained similar between the two groups even after the researchers factored in risk of bias, use of low-flow devices, or FIO₂ below 60%, noted the authors. Oxygen supplementation also appeared to reduce rates of UA pH that were less than 7.2 and increase UA PaO₂ relative to room air during scheduled cesarean deliveries, they added.
 

Considerable interstudy heterogeneity was found

Although marginally lower one-minute Apgar scores were observed in infants whose mothers received oxygen during cesarean delivery, the mean difference between oxygen and room air was less than a point and there were no other statistically significant differences in any secondary outcomes, the authors said. Considerable interstudy heterogeneity was noted across most of the study outcomes.

It is important to note that results pooled from all the studies reviewed indicated an increase in UA PaO₂ but no notable differences in UA pH when oxygen was used. Citing multiple studies included in the review, the authors observed that UA PaO₂ is a “poor estimator of neonatal morbidity” because, when evaluated in cord blood gas, it represents dissolved oxygen and is not an accurate indication of how much oxygen is bound to hemoglobin. For this reason, dissolved oxygen content by itself is not an indication of hypoxia or subpar tissue oxygenation.

“Prolonged tissue hypoxia leads to anaerobic metabolism, resulting in decreased pH, which is why UA pH ultimately serves as a better marker for prediction of neonatal morbidity. An intervention that increases the PaO₂ without concomitantly increasing the pH has limited clinical benefit, particularly because hyperoxemia is associated with production of free radicals and oxidative cell damage in adults and neonates,” they explained.
 

With unproven benefits and potential for risk of harm, prolonged oxygen use should be limited

“A large, adequately powered trial is needed to investigate the effect of maternal oxygen supplementation in response to fetal heart rate tracings on short- and long-term neonatal morbidity,” the authors suggested. For the time being, they cautioned limiting prolonged oxygen use since the benefits are unproven and there is a potential risk of harm.

In a separate interview, Iris Krishna, MD, MPH, FACOG, Emory University, Atlanta, noted, “The use of maternal supplemental oxygen with the intent of improving fetal oxygenation is a common clinical practice. Previous studies on maternal oxygen supplementation during labor have yielded conflicting results; however, there is growing literature suggesting that maternal intrapartum supplemental oxygenation may not provide clinically significant benefit and there may even be potential harm to mother and baby.

“Unique to this meta-analysis is evaluation of maternal oxygen supplementation in the presence or absence of labor, hypothesizing that placental oxygen transfer may be affected by regular uterine contractions. The pooled results suggest that the use of maternal supplemental oxygenation does not result in clinically relevant fetal oxygenation in the presence or absence of labor when compared to room air. A limitation of this meta-analysis is that the use of oxygen in response to nonreassuring fetal tracing was not assessed, the most common clinical indication for maternal oxygen supplementation.

“This study further challenges the practice of maternal intrapartum supplemental oxygen and highlights that we have much to learn about the impact of this practice. More research is needed to assess optimal duration of oxygen supplementation, safety and efficacy of oxygen supplementation, appropriate clinical indications for oxygen supplementation, as well as the long-term neonatal outcomes of in utero hyperoxygenation.“

Dr. Raghuraman reported receiving multiple grants and acknowledged multiple funding sources. Her colleagues and Dr. Krishna had no conflicts of interest to report.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.

Birth rates for women who underwent assisted reproduction using fresh donor oocytes were significantly higher than for women who used cryopreserved-thawed embryos, based on data from more than 33,000 women.

Cryopreserved-thawed embryo transfers in donor oocyte cycles have gained in popularity in recent years for reasons including “convenience, elimination of the need for synchronization between donor and recipient cycles, and/or increasing utilization of preimplantation genetic testing for aneuploidy,” wrote Iris G. Insogna, MD, of Brigham and Women’s Hospital, Boston, and colleagues.“ However, to date, no comparison of pregnancy outcomes has been made between transfers of fresh embryos and cryopreserved-thawed embryos derived exclusively from fresh donor oocytes,” they said.

In a retrospective cohort study published in JAMA, the researchers identified 33,863 women who underwent IVF cycles using freshly retrieved oocytes with a total of 51,942 embryo transfer cycles; 15,308 fresh embryo transfer cycles, and 36,634 cryopreserved-thawed embryo transfer cycles.

Overall, the live birth rate was 56.6% for cycles involving fresh donor oocytes compared to 44.0% for cycles with cryopreserved-thawed embryos, with an adjusted relative risk of 1.42 after the researchers controlled for donor age, day of embryo transfer, use of gestational carrier, and assisted hatching. Demographics were similar between women who received fresh vs. cryopreserved-thawed embryos including median age (42 years for both), gravidity (1 for both), parity (0 vs. 1), and body mass index (24.5 vs. 24.4 kg/m²).

Clinical pregnancy rates for women with fresh vs. cryopreserved-thawed embryo transfers were 66.7% and 54.2%, respectively, and miscarriage rates were approximately 9% for both groups.

The average number of embryos transferred was similar between the groups, and blastocysts were transferred in 92.4% and 96.5% of fresh embryo and cryopreserved-thawed embryo transfer cycles, respectively.

The finding that, in cycles using fresh donor oocytes, fresh embryo transfer yielded higher birth rates than transfer of cryopreserved-thawed embryo transfer “was in contrast to previous investigations of cycles using autologous oocytes that demonstrated higher live birth rates following cryopreserved-thawed embryo transfers,” the researchers noted.

Live birth rates remained higher in cases of fresh embryo transfer when preimplantation genetic testing for aneuploidy (PGT-A) was performed, they added.

The study findings were limited by several factors, including the retrospective design and lack of data on potential confounding factors in the donor population, such as age, ethnicity, BMI, and smoking status, the researchers said. However, the results have implications for clinical practice by providing informed counseling information, given the significantly greater complexity of preparing a fresh transfer of an embryo from a fresh donor oocyte, the researchers noted. In addition, “given the considerable financial investment, these data may influence patient decision-making regarding transferring a fresh embryo derived from a fresh donor oocyte vs. cryopreserving all embryos a priori for convenience,” they said. More data on the cost-effectiveness of fresh vs. cryopreserved-thawed embryo transfer in the study population also would help guide clinical practice, they said.
 

Prospective studies needed to confirm potential

“For women who use autologous oocytes, there is increasing evidence for improved pregnancy rates by frozen embryo transfer (FET) rather than fresh, particularly in women with good ovarian response to gonadotropins,” Mark P. Trolice, MD, of the University of Central Florida, Orlando, said in an interview. The current study was important because it examined “whether the same concept applies with the use of embryos from donor oocytes,” he said.

Dr. Trolice, director of Fertility CARE: The IVF Center, in Orlando, said he was surprised by the study findings. The study “contradicts the experience in cycles using autologous oocytes,” he said. “Fresh embryo superiority remained after a subgroup analysis of first embryo transfers for fresh and frozen cycles as well as for embryos that underwent PGT-A (preimplantation genetic testing for aneuploidy, typically resulting in FET cycles, although a small percentage of cycles underwent fresh embryo transfer), yielding no difference to non-PGT-A fresh cycles. This reinforces the prior evidence for lack of improvement following PGT-A in women less than age 35 years,” he noted.

“Coincidentally, the same findings were discovered using the same SART [Society for Assisted Reproductive Technology] database (from 2013 to 2015), namely fresh embryo transfer from donor oocytes was more likely to result in a live birth – 55.7% versus 39.5%,” said Dr. Trolice. “An abstract presented at the 2017 ASRM annual meeting also used the SART data base (from 2003 to 2014) and demonstrated live birth rates from fresh transfer of embryos using donor oocytes were 15%-20% higher than those from frozen embryo transfers,” he noted.

“In summary, the use of fresh embryos from donor oocytes consistently appears to have superior pregnancy outcomes compared with frozen embryos; a nearly 13% absolute difference in this recent study,” said Dr. Trolice. The strengths of the study included the primary outcome of live births and the heterogeneity, with cycles taken from all participating U.S. SART clinics, Dr. Trolice noted. Limitations included the “retrospective design with the inherent risk of selection bias and the lack of information on the embryo freezing method, i.e., the older ‘slow-freeze’ or the more advanced and popular method of vitrification,” he added. “Randomized, prospective studies are needed to more accurately address this important issue,” he emphasized.

The study received no outside funding. Lead author Dr. Insogna disclosed part-time work as an assistant physician for Teladoc Health. Dr. Trolice had no relevant financial conflicts to disclose.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Health care professionals miss an important opportunity if they do not use a holistic patient-centered approach in providing support to their postpartum patients, advised Alison M. Stuebe, MD, MSc, of the division of maternal-fetal medicine at the University of North Carolina at Chapel Hill, and colleagues.

Too often, the emphasis for health care professionals is on less common, highly morbid complications, while their patients’ needs are focused more on daily functioning.

More than half of maternal deaths occur not during delivery, but in the days, weeks, and months following birth. Many serious complications and management of less-emergent conditions such as flu-like symptoms go unnoticed or result in treatment delays. Routinely asking women who present for care whether they have been pregnant during the past year could go a long way in helping clinicians connect the dots for conditions they might not otherwise consider, suggested Dr. Stuebe and colleagues.

In response to what is becoming a growing burden of postpartum maternal morbidity and mortality in the United States, Dr. Stuebe and associates, in coordination with the Alliance of Innovation in Maternal Health, prepared a comprehensive consensus statement on postpartum care basics. The work came out of a day-long planning meeting of an interdisciplinary work group funded by AIMH to develop the maternal safety bundle, which established 28 goals across four phases – readiness, recognition and prevention, response, and reporting. Each phase is intended to occur as part of a coordinated effort between women experiencing pregnancy and their health care providers, with involvement from multiple clinical settings and health systems.
 

America needs to change the way it treats its new mothers

In a separate interview, Dr. Stuebe shared additional insights into the development of the consensus statement: “This article is part of a broader movement to change the way America treats new mothers. For too long, we’ve lavished attention on women in the weeks before birth and then left them alone to manage recovery, plunging hormones, sleepless nights, and new baby care. If the baby is the candy, and the mother is the wrapper, once the candy is out of the wrapper, we’ve tossed the wrapper aside. The goal of this article is to set out the ways that we can better support women in this critical transition period.

“We need to start during pregnancy, by working with women to plan for the fourth trimester and identify a care team that will support her and her baby. After birth, we need to adapt those plans and make sure she has the emotional and material support she needs to navigate the coming months. Many of these decisions are deeply personal, and we need to center the values and preferences of the woman and her family.”

Dr. Stuebe also spotlighted a new University of North Carolina–based program designed to support shared decision-making. Their Trimester Project team partnered with mothers to design NewMomHealth.com, the first national postpartum resource designed by and for new mothers, which is in the process of launching a culturally adapted Spanish-language site, saludmadre.com, in partnership with Urban Strategies.
 

Readiness prepares mothers, HCPs, and clinical settings for the fourth trimester

In the first phase, Readiness, there are three key parties involved: the woman experiencing pregnancy, the health care providers (HCPs) supporting her, and the clinical settings involved in her care. Each player has specific goals to achieve in this phase, women are responsible for four goals, health care providers have two goals, and clinical settings have five.

Prenatally, every woman should work with health care providers to develop a comprehensive, individualized postpartum care plan that designates a postpartum clinical “home” for addressing any care needed between birth and the “comprehensive postpartum visit.” The plan encourages the patient and her health care team give attention to social support, birth recovery, infant care and feeding plans, thoughts concerning future pregnancies, and specifically use of contraception, as well as any chronic health concerns and overall emotional well-being.

The plan should consist of a postpartum care team that includes friends and family and ensures that medical, material, and social support are available in the weeks following birth for both mother and baby.

The authors emphasized the importance for clinicians to develop a keen awareness of “reproductive justice,” which respects a woman’s right “to maintain personal bodily autonomy, have children, not have children, and parent the children we have in safe and sustainable communities.” They encouraged adopting a sensitivity to concerns deeply rooted in the history of family planning, which is perceived to have been “fraught by coercive tactics to incentivize sterilization and contraceptive implants among marginalized groups.” With this in mind, they urged clinicians to respectfully ask about the patient’s intentions before making any suggestions concerning future births and family planning preferences.

HCP readiness ensures that each woman “has a documented postpartum care plan and care team identified in the prenatal period.” HCPs are also responsible for developing and maintaining “a working knowledge of evidence-based evaluation and management of common issues facing the mother-infant dyad.”

Clinical setting readiness ensures that woman-centered postpartum care and education have been developed and optimized using adult learning principles whenever possible. Diversity of family structures, cultural traditions, and parenting practices are fully embraced. Dr. Stuebe and colleagues emphasized that traditional top-down teaching methods are ineffective and should be avoided.

Clinical setting readiness also ensures that systems are developed to pair families with community-based resources that provide medical follow-up as well as social and material support. Clinical protocols and reimbursement options should be available that give women easy access to preferred contraception. Systems should be in place that facilitate prompt, pertinent communication between in- and outpatient providers. Lastly, and perhaps most importantly, clinical setting readiness demands the development of protocols to screen and treat key postpartum concerns, such as depression, substance use disorders, family violence, and even incontinence in coordination with locally identified specialists.

Recognition and prevention promotes accountability and establishes key guidelines

Recognition and prevention require coordinated participation between women experiencing pregnancy and the clinical environments supporting their care. In this phase, women are responsible for three goals; clinical environments have four goals.

Women are to be identified and respected as the expert most knowledgeable of their own needs, cautioned the authors. They should also be empowered to trust their instincts, seeking care as early and as often as needed in the weeks after they give birth. Postpartum care needs to be viewed as an ongoing process, not just a singular encounter.

Women also need to take ownership for their postpartum care plan, reviewing and revising it as needed in coordination with their health care providers before maternity discharge is complete. Every plan should include a comprehensive list of warning signs and recommended action plans when faced with life-threatening complications, a list of resources for lactation support, and a “first-call” phone number that identifies the postpartum medical providers available to address breastfeeding issues and for postpartum care visits, including prescheduled dates and times.

Lastly, women are to take responsibility for attending their postpartum visit. Although new guidance suggests that the comprehensive visit take place no later than 12 weeks post partum, it also recognizes multiple visits may be required to address individual needs. All women should have contact with a maternal care provider within 3 weeks post partum, the American College of Obstetricians and Gynecologists recommends.

Responsibility for recognition and prevention in the clinical setting begins with determining guidelines for early postpartum visits, considering chronic conditions such as hypertension, diabetes, or substance abuse disorder and risk for postpartum conditions such as wound complications or postpartum depression, the authors wrote. Ongoing care between inpatient and outpatient settings as well as between maternal and infant care providers is coordinated to ensure health and well-being of both patients. Screening and treatment of common comorbidities such as mental health issues, smoking, and substance use as well as issues related to unstable housing and food insecurities are also addressed in the clinical environment. Lastly, clinicians are tasked with ensuring that every patient has selected a primary care provider for ongoing care.

Response ensures key parties and resources are connected at every step

In the response phase, clinical settings and health care providers are the key participants and they have two goals each.

Every clinical setting is tasked with implementing treatment protocols and providing needed care or facilitating referral in a timely fashion. The importance of a “warm hand-off” and “face-to-face introduction to the specialist to whom the patient is being referred” is encouraged. They are also responsible for keeping an updated inventory of community resources on hand for such unmet needs as 24-hour hotlines, food banks, diaper banks, lactation support groups, and home-visiting programs.

Every health care provider is tasked with developing strategies designed to reach women who do not attend their comprehensive postpartum visit. They are also responsible for assessing the severity of identified needs, and arranging immediate transportation to appropriate facilities in life-threatening circumstances. In nonacute cases, the woman and her care providers work with her to make appropriate decisions.

Reporting gives health systems the opportunity to assess and improve

Sole responsibility in the reporting phase falls to every health system. In this phase, they have a total of six goals.

Health systems are ideally organized to convene strategy-sharing sessions with inpatient as well as outpatient professionals to evaluate successes and opportunities for improvement. They are equally qualified to identify and monitor such quality measures as postpartum emergency department utilization and readmission rates. They are tasked with working toward quality metrics that compare postpartum outcomes and prenatal intentions, including patient receipt of preferred contraception or completion of planned breastfeeding duration.

Health systems are expected to conduct quality improvement measures designed to reduce postpartum morbidity when preventable. They are also the logical choice for maintaining a clearinghouse for resources, in collaboration with the community, that is designed to meet the postpartum needs of women.

Lastly, they play an important role in ensuring that reimbursement policies are structured such that they do not disincentivize postpartum visits.
 

The consensus bundle encourages change in the way America treats its new mothers

Angela Bianco, MD, maternal and fetal medicine specialist at Mount Sinai Hospital, New York, also interviewed separately, noted: “I think the fact that ACOG has created a postpartum bundle for providers to use for guidance is long overdue. The current prenatal care paradigm focuses on numerous/intensive prenatal visits but only a single postpartum visit. Many women report feeling ill-equipped to navigate the challenges that arise post delivery, including self-care, newborn care, and breastfeeding. In addition, most women experience the impact of dramatic hormonal fluctuations resulting in mood alterations. Add profound sleep deprivation to this and the result is often some degree of postpartum blues and/or depression. The importance of anticipatory guidance for our patients cannot be underestimated. Helping to facilitate potential social support structures be in place prior to the birth is optimal. Providers should reinforce the importance of access to a variety of tools, including digital apps, community support groups, and 24/7 web access services. Moving forward, it should be considered unconscionable to send a new mother home without ensuring the appropriate resources are in place. Postpartum care should be tailored to a woman’s needs and may require multiple visits and/or referrals.”

Dr. Stuebe and colleagues, as well as Dr. Bianco, disclosed receiving honoraria for various projects. Funding for the study was supported by the Alliance for Innovation on Maternal and Child Health, which is funded by a grant from the Health Resources and Services Administration.

Health care professionals miss an important opportunity if they do not use a holistic patient-centered approach in providing support to their postpartum patients, advised Alison M. Stuebe, MD, MSc, of the division of maternal-fetal medicine at the University of North Carolina at Chapel Hill, and colleagues.

Too often, the emphasis for health care professionals is on less common, highly morbid complications, while their patients’ needs are focused more on daily functioning.

More than half of maternal deaths occur not during delivery, but in the days, weeks, and months following birth. Many serious complications and management of less-emergent conditions such as flu-like symptoms go unnoticed or result in treatment delays. Routinely asking women who present for care whether they have been pregnant during the past year could go a long way in helping clinicians connect the dots for conditions they might not otherwise consider, suggested Dr. Stuebe and colleagues.

In response to what is becoming a growing burden of postpartum maternal morbidity and mortality in the United States, Dr. Stuebe and associates, in coordination with the Alliance of Innovation in Maternal Health, prepared a comprehensive consensus statement on postpartum care basics. The work came out of a day-long planning meeting of an interdisciplinary work group funded by AIMH to develop the maternal safety bundle, which established 28 goals across four phases – readiness, recognition and prevention, response, and reporting. Each phase is intended to occur as part of a coordinated effort between women experiencing pregnancy and their health care providers, with involvement from multiple clinical settings and health systems.
 

America needs to change the way it treats its new mothers

In a separate interview, Dr. Stuebe shared additional insights into the development of the consensus statement: “This article is part of a broader movement to change the way America treats new mothers. For too long, we’ve lavished attention on women in the weeks before birth and then left them alone to manage recovery, plunging hormones, sleepless nights, and new baby care. If the baby is the candy, and the mother is the wrapper, once the candy is out of the wrapper, we’ve tossed the wrapper aside. The goal of this article is to set out the ways that we can better support women in this critical transition period.

“We need to start during pregnancy, by working with women to plan for the fourth trimester and identify a care team that will support her and her baby. After birth, we need to adapt those plans and make sure she has the emotional and material support she needs to navigate the coming months. Many of these decisions are deeply personal, and we need to center the values and preferences of the woman and her family.”

Dr. Stuebe also spotlighted a new University of North Carolina–based program designed to support shared decision-making. Their Trimester Project team partnered with mothers to design NewMomHealth.com, the first national postpartum resource designed by and for new mothers, which is in the process of launching a culturally adapted Spanish-language site, saludmadre.com, in partnership with Urban Strategies.
 

Readiness prepares mothers, HCPs, and clinical settings for the fourth trimester

In the first phase, Readiness, there are three key parties involved: the woman experiencing pregnancy, the health care providers (HCPs) supporting her, and the clinical settings involved in her care. Each player has specific goals to achieve in this phase, women are responsible for four goals, health care providers have two goals, and clinical settings have five.

Prenatally, every woman should work with health care providers to develop a comprehensive, individualized postpartum care plan that designates a postpartum clinical “home” for addressing any care needed between birth and the “comprehensive postpartum visit.” The plan encourages the patient and her health care team give attention to social support, birth recovery, infant care and feeding plans, thoughts concerning future pregnancies, and specifically use of contraception, as well as any chronic health concerns and overall emotional well-being.

The plan should consist of a postpartum care team that includes friends and family and ensures that medical, material, and social support are available in the weeks following birth for both mother and baby.

The authors emphasized the importance for clinicians to develop a keen awareness of “reproductive justice,” which respects a woman’s right “to maintain personal bodily autonomy, have children, not have children, and parent the children we have in safe and sustainable communities.” They encouraged adopting a sensitivity to concerns deeply rooted in the history of family planning, which is perceived to have been “fraught by coercive tactics to incentivize sterilization and contraceptive implants among marginalized groups.” With this in mind, they urged clinicians to respectfully ask about the patient’s intentions before making any suggestions concerning future births and family planning preferences.

HCP readiness ensures that each woman “has a documented postpartum care plan and care team identified in the prenatal period.” HCPs are also responsible for developing and maintaining “a working knowledge of evidence-based evaluation and management of common issues facing the mother-infant dyad.”

Clinical setting readiness ensures that woman-centered postpartum care and education have been developed and optimized using adult learning principles whenever possible. Diversity of family structures, cultural traditions, and parenting practices are fully embraced. Dr. Stuebe and colleagues emphasized that traditional top-down teaching methods are ineffective and should be avoided.

Clinical setting readiness also ensures that systems are developed to pair families with community-based resources that provide medical follow-up as well as social and material support. Clinical protocols and reimbursement options should be available that give women easy access to preferred contraception. Systems should be in place that facilitate prompt, pertinent communication between in- and outpatient providers. Lastly, and perhaps most importantly, clinical setting readiness demands the development of protocols to screen and treat key postpartum concerns, such as depression, substance use disorders, family violence, and even incontinence in coordination with locally identified specialists.

Recognition and prevention promotes accountability and establishes key guidelines

Recognition and prevention require coordinated participation between women experiencing pregnancy and the clinical environments supporting their care. In this phase, women are responsible for three goals; clinical environments have four goals.

Women are to be identified and respected as the expert most knowledgeable of their own needs, cautioned the authors. They should also be empowered to trust their instincts, seeking care as early and as often as needed in the weeks after they give birth. Postpartum care needs to be viewed as an ongoing process, not just a singular encounter.

Women also need to take ownership for their postpartum care plan, reviewing and revising it as needed in coordination with their health care providers before maternity discharge is complete. Every plan should include a comprehensive list of warning signs and recommended action plans when faced with life-threatening complications, a list of resources for lactation support, and a “first-call” phone number that identifies the postpartum medical providers available to address breastfeeding issues and for postpartum care visits, including prescheduled dates and times.

Lastly, women are to take responsibility for attending their postpartum visit. Although new guidance suggests that the comprehensive visit take place no later than 12 weeks post partum, it also recognizes multiple visits may be required to address individual needs. All women should have contact with a maternal care provider within 3 weeks post partum, the American College of Obstetricians and Gynecologists recommends.

Responsibility for recognition and prevention in the clinical setting begins with determining guidelines for early postpartum visits, considering chronic conditions such as hypertension, diabetes, or substance abuse disorder and risk for postpartum conditions such as wound complications or postpartum depression, the authors wrote. Ongoing care between inpatient and outpatient settings as well as between maternal and infant care providers is coordinated to ensure health and well-being of both patients. Screening and treatment of common comorbidities such as mental health issues, smoking, and substance use as well as issues related to unstable housing and food insecurities are also addressed in the clinical environment. Lastly, clinicians are tasked with ensuring that every patient has selected a primary care provider for ongoing care.

Response ensures key parties and resources are connected at every step

In the response phase, clinical settings and health care providers are the key participants and they have two goals each.

Every clinical setting is tasked with implementing treatment protocols and providing needed care or facilitating referral in a timely fashion. The importance of a “warm hand-off” and “face-to-face introduction to the specialist to whom the patient is being referred” is encouraged. They are also responsible for keeping an updated inventory of community resources on hand for such unmet needs as 24-hour hotlines, food banks, diaper banks, lactation support groups, and home-visiting programs.

Every health care provider is tasked with developing strategies designed to reach women who do not attend their comprehensive postpartum visit. They are also responsible for assessing the severity of identified needs, and arranging immediate transportation to appropriate facilities in life-threatening circumstances. In nonacute cases, the woman and her care providers work with her to make appropriate decisions.

Reporting gives health systems the opportunity to assess and improve

Sole responsibility in the reporting phase falls to every health system. In this phase, they have a total of six goals.

Health systems are ideally organized to convene strategy-sharing sessions with inpatient as well as outpatient professionals to evaluate successes and opportunities for improvement. They are equally qualified to identify and monitor such quality measures as postpartum emergency department utilization and readmission rates. They are tasked with working toward quality metrics that compare postpartum outcomes and prenatal intentions, including patient receipt of preferred contraception or completion of planned breastfeeding duration.

Health systems are expected to conduct quality improvement measures designed to reduce postpartum morbidity when preventable. They are also the logical choice for maintaining a clearinghouse for resources, in collaboration with the community, that is designed to meet the postpartum needs of women.

Lastly, they play an important role in ensuring that reimbursement policies are structured such that they do not disincentivize postpartum visits.
 

The consensus bundle encourages change in the way America treats its new mothers

Angela Bianco, MD, maternal and fetal medicine specialist at Mount Sinai Hospital, New York, also interviewed separately, noted: “I think the fact that ACOG has created a postpartum bundle for providers to use for guidance is long overdue. The current prenatal care paradigm focuses on numerous/intensive prenatal visits but only a single postpartum visit. Many women report feeling ill-equipped to navigate the challenges that arise post delivery, including self-care, newborn care, and breastfeeding. In addition, most women experience the impact of dramatic hormonal fluctuations resulting in mood alterations. Add profound sleep deprivation to this and the result is often some degree of postpartum blues and/or depression. The importance of anticipatory guidance for our patients cannot be underestimated. Helping to facilitate potential social support structures be in place prior to the birth is optimal. Providers should reinforce the importance of access to a variety of tools, including digital apps, community support groups, and 24/7 web access services. Moving forward, it should be considered unconscionable to send a new mother home without ensuring the appropriate resources are in place. Postpartum care should be tailored to a woman’s needs and may require multiple visits and/or referrals.”

Dr. Stuebe and colleagues, as well as Dr. Bianco, disclosed receiving honoraria for various projects. Funding for the study was supported by the Alliance for Innovation on Maternal and Child Health, which is funded by a grant from the Health Resources and Services Administration.

Health care professionals miss an important opportunity if they do not use a holistic patient-centered approach in providing support to their postpartum patients, advised Alison M. Stuebe, MD, MSc, of the division of maternal-fetal medicine at the University of North Carolina at Chapel Hill, and colleagues.

Too often, the emphasis for health care professionals is on less common, highly morbid complications, while their patients’ needs are focused more on daily functioning.

More than half of maternal deaths occur not during delivery, but in the days, weeks, and months following birth. Many serious complications and management of less-emergent conditions such as flu-like symptoms go unnoticed or result in treatment delays. Routinely asking women who present for care whether they have been pregnant during the past year could go a long way in helping clinicians connect the dots for conditions they might not otherwise consider, suggested Dr. Stuebe and colleagues.

In response to what is becoming a growing burden of postpartum maternal morbidity and mortality in the United States, Dr. Stuebe and associates, in coordination with the Alliance of Innovation in Maternal Health, prepared a comprehensive consensus statement on postpartum care basics. The work came out of a day-long planning meeting of an interdisciplinary work group funded by AIMH to develop the maternal safety bundle, which established 28 goals across four phases – readiness, recognition and prevention, response, and reporting. Each phase is intended to occur as part of a coordinated effort between women experiencing pregnancy and their health care providers, with involvement from multiple clinical settings and health systems.
 

America needs to change the way it treats its new mothers

In a separate interview, Dr. Stuebe shared additional insights into the development of the consensus statement: “This article is part of a broader movement to change the way America treats new mothers. For too long, we’ve lavished attention on women in the weeks before birth and then left them alone to manage recovery, plunging hormones, sleepless nights, and new baby care. If the baby is the candy, and the mother is the wrapper, once the candy is out of the wrapper, we’ve tossed the wrapper aside. The goal of this article is to set out the ways that we can better support women in this critical transition period.

“We need to start during pregnancy, by working with women to plan for the fourth trimester and identify a care team that will support her and her baby. After birth, we need to adapt those plans and make sure she has the emotional and material support she needs to navigate the coming months. Many of these decisions are deeply personal, and we need to center the values and preferences of the woman and her family.”

Dr. Stuebe also spotlighted a new University of North Carolina–based program designed to support shared decision-making. Their Trimester Project team partnered with mothers to design NewMomHealth.com, the first national postpartum resource designed by and for new mothers, which is in the process of launching a culturally adapted Spanish-language site, saludmadre.com, in partnership with Urban Strategies.
 

Readiness prepares mothers, HCPs, and clinical settings for the fourth trimester

In the first phase, Readiness, there are three key parties involved: the woman experiencing pregnancy, the health care providers (HCPs) supporting her, and the clinical settings involved in her care. Each player has specific goals to achieve in this phase, women are responsible for four goals, health care providers have two goals, and clinical settings have five.

Prenatally, every woman should work with health care providers to develop a comprehensive, individualized postpartum care plan that designates a postpartum clinical “home” for addressing any care needed between birth and the “comprehensive postpartum visit.” The plan encourages the patient and her health care team give attention to social support, birth recovery, infant care and feeding plans, thoughts concerning future pregnancies, and specifically use of contraception, as well as any chronic health concerns and overall emotional well-being.

The plan should consist of a postpartum care team that includes friends and family and ensures that medical, material, and social support are available in the weeks following birth for both mother and baby.

The authors emphasized the importance for clinicians to develop a keen awareness of “reproductive justice,” which respects a woman’s right “to maintain personal bodily autonomy, have children, not have children, and parent the children we have in safe and sustainable communities.” They encouraged adopting a sensitivity to concerns deeply rooted in the history of family planning, which is perceived to have been “fraught by coercive tactics to incentivize sterilization and contraceptive implants among marginalized groups.” With this in mind, they urged clinicians to respectfully ask about the patient’s intentions before making any suggestions concerning future births and family planning preferences.

HCP readiness ensures that each woman “has a documented postpartum care plan and care team identified in the prenatal period.” HCPs are also responsible for developing and maintaining “a working knowledge of evidence-based evaluation and management of common issues facing the mother-infant dyad.”

Clinical setting readiness ensures that woman-centered postpartum care and education have been developed and optimized using adult learning principles whenever possible. Diversity of family structures, cultural traditions, and parenting practices are fully embraced. Dr. Stuebe and colleagues emphasized that traditional top-down teaching methods are ineffective and should be avoided.

Clinical setting readiness also ensures that systems are developed to pair families with community-based resources that provide medical follow-up as well as social and material support. Clinical protocols and reimbursement options should be available that give women easy access to preferred contraception. Systems should be in place that facilitate prompt, pertinent communication between in- and outpatient providers. Lastly, and perhaps most importantly, clinical setting readiness demands the development of protocols to screen and treat key postpartum concerns, such as depression, substance use disorders, family violence, and even incontinence in coordination with locally identified specialists.

Recognition and prevention promotes accountability and establishes key guidelines

Recognition and prevention require coordinated participation between women experiencing pregnancy and the clinical environments supporting their care. In this phase, women are responsible for three goals; clinical environments have four goals.

Women are to be identified and respected as the expert most knowledgeable of their own needs, cautioned the authors. They should also be empowered to trust their instincts, seeking care as early and as often as needed in the weeks after they give birth. Postpartum care needs to be viewed as an ongoing process, not just a singular encounter.

Women also need to take ownership for their postpartum care plan, reviewing and revising it as needed in coordination with their health care providers before maternity discharge is complete. Every plan should include a comprehensive list of warning signs and recommended action plans when faced with life-threatening complications, a list of resources for lactation support, and a “first-call” phone number that identifies the postpartum medical providers available to address breastfeeding issues and for postpartum care visits, including prescheduled dates and times.

Lastly, women are to take responsibility for attending their postpartum visit. Although new guidance suggests that the comprehensive visit take place no later than 12 weeks post partum, it also recognizes multiple visits may be required to address individual needs. All women should have contact with a maternal care provider within 3 weeks post partum, the American College of Obstetricians and Gynecologists recommends.

Responsibility for recognition and prevention in the clinical setting begins with determining guidelines for early postpartum visits, considering chronic conditions such as hypertension, diabetes, or substance abuse disorder and risk for postpartum conditions such as wound complications or postpartum depression, the authors wrote. Ongoing care between inpatient and outpatient settings as well as between maternal and infant care providers is coordinated to ensure health and well-being of both patients. Screening and treatment of common comorbidities such as mental health issues, smoking, and substance use as well as issues related to unstable housing and food insecurities are also addressed in the clinical environment. Lastly, clinicians are tasked with ensuring that every patient has selected a primary care provider for ongoing care.

Response ensures key parties and resources are connected at every step

In the response phase, clinical settings and health care providers are the key participants and they have two goals each.

Every clinical setting is tasked with implementing treatment protocols and providing needed care or facilitating referral in a timely fashion. The importance of a “warm hand-off” and “face-to-face introduction to the specialist to whom the patient is being referred” is encouraged. They are also responsible for keeping an updated inventory of community resources on hand for such unmet needs as 24-hour hotlines, food banks, diaper banks, lactation support groups, and home-visiting programs.

Every health care provider is tasked with developing strategies designed to reach women who do not attend their comprehensive postpartum visit. They are also responsible for assessing the severity of identified needs, and arranging immediate transportation to appropriate facilities in life-threatening circumstances. In nonacute cases, the woman and her care providers work with her to make appropriate decisions.

Reporting gives health systems the opportunity to assess and improve

Sole responsibility in the reporting phase falls to every health system. In this phase, they have a total of six goals.

Health systems are ideally organized to convene strategy-sharing sessions with inpatient as well as outpatient professionals to evaluate successes and opportunities for improvement. They are equally qualified to identify and monitor such quality measures as postpartum emergency department utilization and readmission rates. They are tasked with working toward quality metrics that compare postpartum outcomes and prenatal intentions, including patient receipt of preferred contraception or completion of planned breastfeeding duration.

Health systems are expected to conduct quality improvement measures designed to reduce postpartum morbidity when preventable. They are also the logical choice for maintaining a clearinghouse for resources, in collaboration with the community, that is designed to meet the postpartum needs of women.

Lastly, they play an important role in ensuring that reimbursement policies are structured such that they do not disincentivize postpartum visits.
 

The consensus bundle encourages change in the way America treats its new mothers

Angela Bianco, MD, maternal and fetal medicine specialist at Mount Sinai Hospital, New York, also interviewed separately, noted: “I think the fact that ACOG has created a postpartum bundle for providers to use for guidance is long overdue. The current prenatal care paradigm focuses on numerous/intensive prenatal visits but only a single postpartum visit. Many women report feeling ill-equipped to navigate the challenges that arise post delivery, including self-care, newborn care, and breastfeeding. In addition, most women experience the impact of dramatic hormonal fluctuations resulting in mood alterations. Add profound sleep deprivation to this and the result is often some degree of postpartum blues and/or depression. The importance of anticipatory guidance for our patients cannot be underestimated. Helping to facilitate potential social support structures be in place prior to the birth is optimal. Providers should reinforce the importance of access to a variety of tools, including digital apps, community support groups, and 24/7 web access services. Moving forward, it should be considered unconscionable to send a new mother home without ensuring the appropriate resources are in place. Postpartum care should be tailored to a woman’s needs and may require multiple visits and/or referrals.”

Dr. Stuebe and colleagues, as well as Dr. Bianco, disclosed receiving honoraria for various projects. Funding for the study was supported by the Alliance for Innovation on Maternal and Child Health, which is funded by a grant from the Health Resources and Services Administration.