Neonatal Medicine

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.

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.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.

Three genes that could predict susceptibility to congenital Zika virus (ZIKV) infection have been identified, Dr. Irene Rivero-Calle, MD, shared at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

ZIKV, an emerging flavivirus, is responsible for one the most critical pandemic emergencies of the last decade and has been associated with severe neonatal brain disabilities, declared Dr. Rivero-Calle, of the Hospital Clínico Universitario de Santiago de Compostela in Santiago de Compostela, Spain. “We think that understanding the genomic background could explain some of the most relevant symptoms of congenital Zika syndrome (CZS) and could be essential to better comprehend this disease.”

To achieve this understanding, Dr. Rivero-Calle and her colleagues conducted a study aiming to analyze any genetic factors that could explain the variation in phenotypes in newborns from mothers who had a Zika infection during their pregnancy. Additionally, they strove to “elucidate if the possible genetic association is specific to mothers or their newborns, and to check if this genomic background or any genomic ancestry pattern could be related with the phenotype,” she explained.

In their study, Dr. Rivero-Calle and her team analyzed 80 samples, comprising 40 samples from mothers who had been infected by ZIKV during their pregnancy and 40 from their newborns. Of those descendants, 20 were asymptomatic and 20 were symptomatic (13 had CZS, 3 had microcephaly, 2 had a pathologic MRI, 1 had hearing loss, and 1 was born preterm).

Population stratification, which Dr. Rivero-Calle explained “lets us know if the population is African, European, or Native American looking at the genes,” did not show any relation with the phenotype. We had a mixture of population genomics among all samples.”

Dr. Rivero-Calle and her team then performed three analyses: genotype analysis, an allelic test, and gene analysis. The allelic test and gene-collapsing method highlighted three genes (PANO1, PIDD1, and SLC25A22) as potential determinants of the varying phenotypes in the newborns from ZIKV-infected mothers. Overrepresentation analysis of gene ontology terms shows that PIDD1 and PANO1 are related to apoptosis and cell death, which is closely related to early infantile epilepsy. This could explain the most severe complications of CZS: seizures, brain damage, microcephaly, and detrimental neurodevelopmental growth. Regarding reactome and KEGG analysis, gene PIID1 is related with p53 pathway, which correlates with cell’s death and apoptosis, and with microcephaly, a typical phenotypic feature of CZS.

“So, in conclusion, we found three genes which could predict susceptibility to congenital Zika infection; we saw that the functionality of these genes seems to be deeply related with mechanisms which could explain the different phenotypes; and we saw that these three genes only appear in the children’s cohort, so there is no candidate gene in the mother’s genomic background which can help predict the phenotype of the newborn,” Dr. Rivero-Calle declared. “Finally, there is no ancestry pattern associated with disabilities caused by Zika infection.”

Dr. Rivero-Calle reported that this project (ZikAction) has received funding from the European Union’s Horizon 2020 research and innovation program, under grant agreement 734857.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

Nebulized delivery of surfactant reduced the need for intubation and liquid surfactant administration by half among newborns with signs of respiratory distress syndrome, according to results from a large randomized, multicenter trial.

Neonatologists have long sought alternatives to intubation for administering surfactant to newborns with respiratory distress syndrome (RDS). An effective noninvasive aerosolized treatment has remained elusive, with small clinical trials that have produced mixed results.

In research published in Pediatrics, James J. Cummings, MD, of Albany (N.Y.) Medical Center, and colleagues, randomized 457 infants (mean 33 weeks’ gestational age) with signs of RDS to either usual care or a nebulized bovine surfactant. Infants were recruited at 22 neonatal ICUs in the United States. Investigators were not blinded to treatment allocation and the decision to intubate was left up to the individual treating physician, because to do so, the authors wrote, would add “pragmatic strength” to the study, and “be ethically compliant with the infant’s best interest.”

Infants in the study received usual care or up to three treatments 4 or more hours apart of 35 mg/mL calfactant suspension, 210 mg phospholipid/kg body weight delivered into the mouth through a nebulizer modified with a pacifier. Dr. Cummings and colleagues found that intubation and liquid surfactant administration within the first 4 days after birth was 26% in the intervention group and 50% in the usual care group (P < .001).

The results remained significant after investigators adjusted for gestational age, birth weight, age when randomized, sex, delivery mode, and antenatal steroids. Rates of intubation for surfactant administration were lower for infants in the intervention group in all gestational age brackets except the youngest (23-24 weeks); all of these infants needed intubation. Respiratory support at days 3, 7, and 28 did not differ between study groups.

“Our study is the first to reveal the efficacy of an aerosolized surfactant delivery system that does not require a respiratory circuit interface,” the investigators wrote.

In previous trials of aerosolized surfactants, they noted, treatment was delivered with nasal continuous positive airway pressure. “By using a separate, pacifier interface, both the aerosol delivery and [nasal continuous positive airway pressure] flow can be managed independently, which should allow for safer patient care.”

Dr. Cummings and colleagues also acknowledged several important limitations of their study, including its nonmasked, nonblinded design, and that it enrolled few infants with less than 28 weeks’ gestation. It takes 1-2 hours to deliver aerosolized calfactant, and “we did not want to delay definitive treatment.”

In an editorial comment accompanying the study, Kirsten Glaser, MD, of the University of Leipzig (Germany), and Clyde Wright, MD of the University of Colorado at Denver, Aurora, called the results promising. “Importantly, application of surfactant aerosols was well tolerated by using a modified nebulizer with a pacifier interface.”

The editorialists cautioned, however, of the study’s strong potential for selection bias. “Clinicians were aware that every infant randomly assigned to the nebulized surfactant arm received the intervention,” they wrote. “It is possible that clinicians delayed intubation and endotracheal surfactant instillation in this group, being biased by aerosolization and the hypothesis of lower risk of air leak and lung injury.”

Dr. Glaser and Dr. Wright further lamented that there were no formal criteria for administering surfactant therapy, and that the infants in the study might not be representative of those most in need of treatment. Today, bronchopulmonary dysplasia “primarily affects infants born at less than 28 weeks’ gestational age,” a minority of the infants recruited for this study, they wrote, urging further investigation in this patient group.

In an interview, neonatologist Roger F. Soll, MD, the H. Wallace Professor of Neonatology at the Larner College of Medicine at University of Vermont in Burlington, echoed the editorialists’ concerns that the study’s pragmatic design left a number of key questions unanswered. “It’s a promising study that laudably recruited on an order of magnitude more infants than any like it in the past,” Dr. Soll said. “And the kids who got the therapy seemed to do better, which is exciting. But with the broad entry criteria, the lack of formal diagnosis of RDS, and the outcome measures ultimately potentially biased by lack of blinding, it doesn’t give us the answers we need yet to consider aerosolized treatment.”

ONY Biotech, manufacturer of the study drug Infasurf, sponsored the trial. Dr. Cummings and one coauthor disclosed consulting arrangements with the sponsor, and another coauthor is an employee of the sponsor. The remaining investigators had no relevant financial disclosures. Dr. Glaser and Dr. Wright disclosed no conflicts of interest related to their editorial; Dr. Wright’s work was supported by the National Institutes of Health. Dr. Soll is president of the Vermont Oxford Network and coordinating editor of Cochrane Neonatal.
 

SOURCE: Cummings JJ et al. Pediatrics. 2020;146(5):e2020021576.

Nebulized delivery of surfactant reduced the need for intubation and liquid surfactant administration by half among newborns with signs of respiratory distress syndrome, according to results from a large randomized, multicenter trial.

Neonatologists have long sought alternatives to intubation for administering surfactant to newborns with respiratory distress syndrome (RDS). An effective noninvasive aerosolized treatment has remained elusive, with small clinical trials that have produced mixed results.

In research published in Pediatrics, James J. Cummings, MD, of Albany (N.Y.) Medical Center, and colleagues, randomized 457 infants (mean 33 weeks’ gestational age) with signs of RDS to either usual care or a nebulized bovine surfactant. Infants were recruited at 22 neonatal ICUs in the United States. Investigators were not blinded to treatment allocation and the decision to intubate was left up to the individual treating physician, because to do so, the authors wrote, would add “pragmatic strength” to the study, and “be ethically compliant with the infant’s best interest.”

Infants in the study received usual care or up to three treatments 4 or more hours apart of 35 mg/mL calfactant suspension, 210 mg phospholipid/kg body weight delivered into the mouth through a nebulizer modified with a pacifier. Dr. Cummings and colleagues found that intubation and liquid surfactant administration within the first 4 days after birth was 26% in the intervention group and 50% in the usual care group (P < .001).

The results remained significant after investigators adjusted for gestational age, birth weight, age when randomized, sex, delivery mode, and antenatal steroids. Rates of intubation for surfactant administration were lower for infants in the intervention group in all gestational age brackets except the youngest (23-24 weeks); all of these infants needed intubation. Respiratory support at days 3, 7, and 28 did not differ between study groups.

“Our study is the first to reveal the efficacy of an aerosolized surfactant delivery system that does not require a respiratory circuit interface,” the investigators wrote.

In previous trials of aerosolized surfactants, they noted, treatment was delivered with nasal continuous positive airway pressure. “By using a separate, pacifier interface, both the aerosol delivery and [nasal continuous positive airway pressure] flow can be managed independently, which should allow for safer patient care.”

Dr. Cummings and colleagues also acknowledged several important limitations of their study, including its nonmasked, nonblinded design, and that it enrolled few infants with less than 28 weeks’ gestation. It takes 1-2 hours to deliver aerosolized calfactant, and “we did not want to delay definitive treatment.”

In an editorial comment accompanying the study, Kirsten Glaser, MD, of the University of Leipzig (Germany), and Clyde Wright, MD of the University of Colorado at Denver, Aurora, called the results promising. “Importantly, application of surfactant aerosols was well tolerated by using a modified nebulizer with a pacifier interface.”

The editorialists cautioned, however, of the study’s strong potential for selection bias. “Clinicians were aware that every infant randomly assigned to the nebulized surfactant arm received the intervention,” they wrote. “It is possible that clinicians delayed intubation and endotracheal surfactant instillation in this group, being biased by aerosolization and the hypothesis of lower risk of air leak and lung injury.”

Dr. Glaser and Dr. Wright further lamented that there were no formal criteria for administering surfactant therapy, and that the infants in the study might not be representative of those most in need of treatment. Today, bronchopulmonary dysplasia “primarily affects infants born at less than 28 weeks’ gestational age,” a minority of the infants recruited for this study, they wrote, urging further investigation in this patient group.

In an interview, neonatologist Roger F. Soll, MD, the H. Wallace Professor of Neonatology at the Larner College of Medicine at University of Vermont in Burlington, echoed the editorialists’ concerns that the study’s pragmatic design left a number of key questions unanswered. “It’s a promising study that laudably recruited on an order of magnitude more infants than any like it in the past,” Dr. Soll said. “And the kids who got the therapy seemed to do better, which is exciting. But with the broad entry criteria, the lack of formal diagnosis of RDS, and the outcome measures ultimately potentially biased by lack of blinding, it doesn’t give us the answers we need yet to consider aerosolized treatment.”

ONY Biotech, manufacturer of the study drug Infasurf, sponsored the trial. Dr. Cummings and one coauthor disclosed consulting arrangements with the sponsor, and another coauthor is an employee of the sponsor. The remaining investigators had no relevant financial disclosures. Dr. Glaser and Dr. Wright disclosed no conflicts of interest related to their editorial; Dr. Wright’s work was supported by the National Institutes of Health. Dr. Soll is president of the Vermont Oxford Network and coordinating editor of Cochrane Neonatal.
 

SOURCE: Cummings JJ et al. Pediatrics. 2020;146(5):e2020021576.

Nebulized delivery of surfactant reduced the need for intubation and liquid surfactant administration by half among newborns with signs of respiratory distress syndrome, according to results from a large randomized, multicenter trial.

Neonatologists have long sought alternatives to intubation for administering surfactant to newborns with respiratory distress syndrome (RDS). An effective noninvasive aerosolized treatment has remained elusive, with small clinical trials that have produced mixed results.

In research published in Pediatrics, James J. Cummings, MD, of Albany (N.Y.) Medical Center, and colleagues, randomized 457 infants (mean 33 weeks’ gestational age) with signs of RDS to either usual care or a nebulized bovine surfactant. Infants were recruited at 22 neonatal ICUs in the United States. Investigators were not blinded to treatment allocation and the decision to intubate was left up to the individual treating physician, because to do so, the authors wrote, would add “pragmatic strength” to the study, and “be ethically compliant with the infant’s best interest.”

Infants in the study received usual care or up to three treatments 4 or more hours apart of 35 mg/mL calfactant suspension, 210 mg phospholipid/kg body weight delivered into the mouth through a nebulizer modified with a pacifier. Dr. Cummings and colleagues found that intubation and liquid surfactant administration within the first 4 days after birth was 26% in the intervention group and 50% in the usual care group (P < .001).

The results remained significant after investigators adjusted for gestational age, birth weight, age when randomized, sex, delivery mode, and antenatal steroids. Rates of intubation for surfactant administration were lower for infants in the intervention group in all gestational age brackets except the youngest (23-24 weeks); all of these infants needed intubation. Respiratory support at days 3, 7, and 28 did not differ between study groups.

“Our study is the first to reveal the efficacy of an aerosolized surfactant delivery system that does not require a respiratory circuit interface,” the investigators wrote.

In previous trials of aerosolized surfactants, they noted, treatment was delivered with nasal continuous positive airway pressure. “By using a separate, pacifier interface, both the aerosol delivery and [nasal continuous positive airway pressure] flow can be managed independently, which should allow for safer patient care.”

Dr. Cummings and colleagues also acknowledged several important limitations of their study, including its nonmasked, nonblinded design, and that it enrolled few infants with less than 28 weeks’ gestation. It takes 1-2 hours to deliver aerosolized calfactant, and “we did not want to delay definitive treatment.”

In an editorial comment accompanying the study, Kirsten Glaser, MD, of the University of Leipzig (Germany), and Clyde Wright, MD of the University of Colorado at Denver, Aurora, called the results promising. “Importantly, application of surfactant aerosols was well tolerated by using a modified nebulizer with a pacifier interface.”

The editorialists cautioned, however, of the study’s strong potential for selection bias. “Clinicians were aware that every infant randomly assigned to the nebulized surfactant arm received the intervention,” they wrote. “It is possible that clinicians delayed intubation and endotracheal surfactant instillation in this group, being biased by aerosolization and the hypothesis of lower risk of air leak and lung injury.”

Dr. Glaser and Dr. Wright further lamented that there were no formal criteria for administering surfactant therapy, and that the infants in the study might not be representative of those most in need of treatment. Today, bronchopulmonary dysplasia “primarily affects infants born at less than 28 weeks’ gestational age,” a minority of the infants recruited for this study, they wrote, urging further investigation in this patient group.

In an interview, neonatologist Roger F. Soll, MD, the H. Wallace Professor of Neonatology at the Larner College of Medicine at University of Vermont in Burlington, echoed the editorialists’ concerns that the study’s pragmatic design left a number of key questions unanswered. “It’s a promising study that laudably recruited on an order of magnitude more infants than any like it in the past,” Dr. Soll said. “And the kids who got the therapy seemed to do better, which is exciting. But with the broad entry criteria, the lack of formal diagnosis of RDS, and the outcome measures ultimately potentially biased by lack of blinding, it doesn’t give us the answers we need yet to consider aerosolized treatment.”

ONY Biotech, manufacturer of the study drug Infasurf, sponsored the trial. Dr. Cummings and one coauthor disclosed consulting arrangements with the sponsor, and another coauthor is an employee of the sponsor. The remaining investigators had no relevant financial disclosures. Dr. Glaser and Dr. Wright disclosed no conflicts of interest related to their editorial; Dr. Wright’s work was supported by the National Institutes of Health. Dr. Soll is president of the Vermont Oxford Network and coordinating editor of Cochrane Neonatal.
 

SOURCE: Cummings JJ et al. Pediatrics. 2020;146(5):e2020021576.

Black women living with HIV are a high-risk population for peripartum depressive symptoms, based on data from 143 women.

Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.

Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.

In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.

Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
 

Social factors show significant impact

In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.

The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.

The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
 

Quantitative studies needed

Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.

The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.

“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.

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

SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.

Black women living with HIV are a high-risk population for peripartum depressive symptoms, based on data from 143 women.

Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.

Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.

In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.

Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
 

Social factors show significant impact

In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.

The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.

The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
 

Quantitative studies needed

Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.

The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.

“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.

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

SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.

Black women living with HIV are a high-risk population for peripartum depressive symptoms, based on data from 143 women.

Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.

Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.

In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.

Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
 

Social factors show significant impact

In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.

The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.

The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
 

Quantitative studies needed

Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.

The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.

“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.

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

SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

The number of genes in humans seems inadequate to account for the diversity seen in people. While maternal and paternal factors do play a role in the development of offspring, increased attention is being paid to the forces that express these genes and the impact they have on the health of a person, including development of psychiatric conditions, according to Dolores Malaspina, MD.

Epigenetics, or changes that occur in a fetal phenotype that do not involve changes to the genotype, involve factors such as DNA methylation to control gene expression, histone modification or the wrapping of genes, or the silencing and activation of certain genes with noncoding RNA-associated factors, said Dr. Malaspina of the Icahn School of Medicine at Mount Sinai, New York.

When this occurs during pregnancy, “the fetus does not simply develop from a genetic blueprint of the genes from its father and mother. Instead, signals are received throughout the pregnancy as to the health of the mother and signals about the environment,” she said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

There is an evolutionary advantage to this so-called survival phenotype. “If, during the pregnancy, there’s a deficit of available nutrition, that may be a signal to the fetus that food will be scarce. In the setting of food scarcity, certain physiological adaptations during development can make the fetus more likely to survive to adulthood,” Dr. Malaspina said at the meeting, presented by Global Academy for Medical Education. But a fetus programmed to adapt to scarcity of food may also develop cardiovascular disease, metabolic disease, or mortality later in life if the prediction of scarce nutrition proved incorrect.

This approach to thinking about the developmental origins of health and disease, which examines how prenatal and perinatal exposure to environmental factors affect disease in adulthood, has also found a link between some exposures and psychiatric disorders. The most famous example, the Dutch Hunger Winter Families Study, found an increased risk of schizophrenia among children born during the height of the famine (Int J Epidemiol. 2007 Dec;36[6]:1196-204). During the Arab-Israeli war of 1967 (the Six-Day War), which took place in June, the fetuses of mothers who were pregnant during that month had a higher risk of schizophrenia if the fetus was in the second month (relative risk, 2.3; 95% confidence interval, 1.1-4.7) or third month (RR, 2.5; 95% CI, 1.2-5.2) of fetal life during June 1967, Dr. Malaspina and associates wrote (BMC Psychiatry. 2008 Aug 21;8:71).

“The key aspect is the ascertainment of individuals during a circumscribed period, the assessment and then the longitudinal follow-up,” she said. “Obviously, these are not easy studies to do, but enough of them have been done such that for the last decade at least, the general population should be aware of the developmental origins of health and disease.”

Maternal depression is another psychiatric condition that can serve as a prenatal exposure to adversity. A recent review found that children of women with untreated depression were 56% more likely to be born preterm and 96% more likely to have a low birth weight (Pediatr Res. 2019 Jan;85[2]:134-45). “Preterm birth and early birth along with low birth weight, these have ramifying effects throughout life, not only on neonatal and infant mortality, but on developmental disorders and lifetime morbidity,” she said. “These effects of maternal depression withstand all sorts of accounting for other correlated exposures, including maternal age and her medical complications or substance use.”

Maternal stress and depression can also harm neurocognitive development and effective functioning of the children, Dr. Malaspina noted. “The modulation of mood and affect can affect temperament and affect mental health. Studies exist linking maternal depression to autism, attention-deficit disorder, developmental delay, behavioral problems, sleep problems, externalizing behavior and depression, showing a very large effect of maternal depression on offspring well-being.”

To complicate matters, at least 15% of women will experience major depression during pregnancy, but of these, major depression is not being addressed in about half. Nonpharmacologic interventions can include cognitive-behavioral therapy and relaxation practices, but medication should be considered as well. “There’s an ongoing debate about whether antidepressant medications are harmful for the offspring,” she said. However, reviews conducted by Dr. Malaspina’s group have found low evidence of serious harm.

“My summary would be the depression itself holds much more evidence for disrupting offspring health and development than medications,” Dr. Malaspina said. “Most studies find no adverse birth effects when they properly controlled accounting for maternal age and the other conditions and other medications.”

Global Academy and this news organization are owned by the same parent company. Dr. Malaspina reported no relevant conflicts of interest.

The number of genes in humans seems inadequate to account for the diversity seen in people. While maternal and paternal factors do play a role in the development of offspring, increased attention is being paid to the forces that express these genes and the impact they have on the health of a person, including development of psychiatric conditions, according to Dolores Malaspina, MD.

Epigenetics, or changes that occur in a fetal phenotype that do not involve changes to the genotype, involve factors such as DNA methylation to control gene expression, histone modification or the wrapping of genes, or the silencing and activation of certain genes with noncoding RNA-associated factors, said Dr. Malaspina of the Icahn School of Medicine at Mount Sinai, New York.

When this occurs during pregnancy, “the fetus does not simply develop from a genetic blueprint of the genes from its father and mother. Instead, signals are received throughout the pregnancy as to the health of the mother and signals about the environment,” she said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

There is an evolutionary advantage to this so-called survival phenotype. “If, during the pregnancy, there’s a deficit of available nutrition, that may be a signal to the fetus that food will be scarce. In the setting of food scarcity, certain physiological adaptations during development can make the fetus more likely to survive to adulthood,” Dr. Malaspina said at the meeting, presented by Global Academy for Medical Education. But a fetus programmed to adapt to scarcity of food may also develop cardiovascular disease, metabolic disease, or mortality later in life if the prediction of scarce nutrition proved incorrect.

This approach to thinking about the developmental origins of health and disease, which examines how prenatal and perinatal exposure to environmental factors affect disease in adulthood, has also found a link between some exposures and psychiatric disorders. The most famous example, the Dutch Hunger Winter Families Study, found an increased risk of schizophrenia among children born during the height of the famine (Int J Epidemiol. 2007 Dec;36[6]:1196-204). During the Arab-Israeli war of 1967 (the Six-Day War), which took place in June, the fetuses of mothers who were pregnant during that month had a higher risk of schizophrenia if the fetus was in the second month (relative risk, 2.3; 95% confidence interval, 1.1-4.7) or third month (RR, 2.5; 95% CI, 1.2-5.2) of fetal life during June 1967, Dr. Malaspina and associates wrote (BMC Psychiatry. 2008 Aug 21;8:71).

“The key aspect is the ascertainment of individuals during a circumscribed period, the assessment and then the longitudinal follow-up,” she said. “Obviously, these are not easy studies to do, but enough of them have been done such that for the last decade at least, the general population should be aware of the developmental origins of health and disease.”

Maternal depression is another psychiatric condition that can serve as a prenatal exposure to adversity. A recent review found that children of women with untreated depression were 56% more likely to be born preterm and 96% more likely to have a low birth weight (Pediatr Res. 2019 Jan;85[2]:134-45). “Preterm birth and early birth along with low birth weight, these have ramifying effects throughout life, not only on neonatal and infant mortality, but on developmental disorders and lifetime morbidity,” she said. “These effects of maternal depression withstand all sorts of accounting for other correlated exposures, including maternal age and her medical complications or substance use.”

Maternal stress and depression can also harm neurocognitive development and effective functioning of the children, Dr. Malaspina noted. “The modulation of mood and affect can affect temperament and affect mental health. Studies exist linking maternal depression to autism, attention-deficit disorder, developmental delay, behavioral problems, sleep problems, externalizing behavior and depression, showing a very large effect of maternal depression on offspring well-being.”

To complicate matters, at least 15% of women will experience major depression during pregnancy, but of these, major depression is not being addressed in about half. Nonpharmacologic interventions can include cognitive-behavioral therapy and relaxation practices, but medication should be considered as well. “There’s an ongoing debate about whether antidepressant medications are harmful for the offspring,” she said. However, reviews conducted by Dr. Malaspina’s group have found low evidence of serious harm.

“My summary would be the depression itself holds much more evidence for disrupting offspring health and development than medications,” Dr. Malaspina said. “Most studies find no adverse birth effects when they properly controlled accounting for maternal age and the other conditions and other medications.”

Global Academy and this news organization are owned by the same parent company. Dr. Malaspina reported no relevant conflicts of interest.

The number of genes in humans seems inadequate to account for the diversity seen in people. While maternal and paternal factors do play a role in the development of offspring, increased attention is being paid to the forces that express these genes and the impact they have on the health of a person, including development of psychiatric conditions, according to Dolores Malaspina, MD.

Epigenetics, or changes that occur in a fetal phenotype that do not involve changes to the genotype, involve factors such as DNA methylation to control gene expression, histone modification or the wrapping of genes, or the silencing and activation of certain genes with noncoding RNA-associated factors, said Dr. Malaspina of the Icahn School of Medicine at Mount Sinai, New York.

When this occurs during pregnancy, “the fetus does not simply develop from a genetic blueprint of the genes from its father and mother. Instead, signals are received throughout the pregnancy as to the health of the mother and signals about the environment,” she said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

There is an evolutionary advantage to this so-called survival phenotype. “If, during the pregnancy, there’s a deficit of available nutrition, that may be a signal to the fetus that food will be scarce. In the setting of food scarcity, certain physiological adaptations during development can make the fetus more likely to survive to adulthood,” Dr. Malaspina said at the meeting, presented by Global Academy for Medical Education. But a fetus programmed to adapt to scarcity of food may also develop cardiovascular disease, metabolic disease, or mortality later in life if the prediction of scarce nutrition proved incorrect.

This approach to thinking about the developmental origins of health and disease, which examines how prenatal and perinatal exposure to environmental factors affect disease in adulthood, has also found a link between some exposures and psychiatric disorders. The most famous example, the Dutch Hunger Winter Families Study, found an increased risk of schizophrenia among children born during the height of the famine (Int J Epidemiol. 2007 Dec;36[6]:1196-204). During the Arab-Israeli war of 1967 (the Six-Day War), which took place in June, the fetuses of mothers who were pregnant during that month had a higher risk of schizophrenia if the fetus was in the second month (relative risk, 2.3; 95% confidence interval, 1.1-4.7) or third month (RR, 2.5; 95% CI, 1.2-5.2) of fetal life during June 1967, Dr. Malaspina and associates wrote (BMC Psychiatry. 2008 Aug 21;8:71).

“The key aspect is the ascertainment of individuals during a circumscribed period, the assessment and then the longitudinal follow-up,” she said. “Obviously, these are not easy studies to do, but enough of them have been done such that for the last decade at least, the general population should be aware of the developmental origins of health and disease.”

Maternal depression is another psychiatric condition that can serve as a prenatal exposure to adversity. A recent review found that children of women with untreated depression were 56% more likely to be born preterm and 96% more likely to have a low birth weight (Pediatr Res. 2019 Jan;85[2]:134-45). “Preterm birth and early birth along with low birth weight, these have ramifying effects throughout life, not only on neonatal and infant mortality, but on developmental disorders and lifetime morbidity,” she said. “These effects of maternal depression withstand all sorts of accounting for other correlated exposures, including maternal age and her medical complications or substance use.”

Maternal stress and depression can also harm neurocognitive development and effective functioning of the children, Dr. Malaspina noted. “The modulation of mood and affect can affect temperament and affect mental health. Studies exist linking maternal depression to autism, attention-deficit disorder, developmental delay, behavioral problems, sleep problems, externalizing behavior and depression, showing a very large effect of maternal depression on offspring well-being.”

To complicate matters, at least 15% of women will experience major depression during pregnancy, but of these, major depression is not being addressed in about half. Nonpharmacologic interventions can include cognitive-behavioral therapy and relaxation practices, but medication should be considered as well. “There’s an ongoing debate about whether antidepressant medications are harmful for the offspring,” she said. However, reviews conducted by Dr. Malaspina’s group have found low evidence of serious harm.

“My summary would be the depression itself holds much more evidence for disrupting offspring health and development than medications,” Dr. Malaspina said. “Most studies find no adverse birth effects when they properly controlled accounting for maternal age and the other conditions and other medications.”

Global Academy and this news organization are owned by the same parent company. Dr. Malaspina reported no relevant conflicts of interest.

Infants born to Black teenage mothers are significantly more likely to die than infants born to White or Hispanic teens, according to a new analysis from the National Center for Health Statistics.

In 2017-2018, overall mortality rates were 12.5 per 100,000 live births for infants born to Black mothers aged 15-19 years, 8.4 per 100,000 for infants born to White teenagers, and 6.5 per 100,000 for those born to Hispanic teens, Ashley M. Woodall, MPH, and Anne K. Driscoll, PhD, of the NCHS said in a data brief.

Looking at the five leading causes of those deaths shows that deaths of Black infants were the highest by significant margins in four, although, when it comes to “disorders related to short gestation and low birth weight,” significant may be an understatement.

The rate of preterm/low-birth-weight deaths for white infants in 2017-2018 was 119 per 100,000 live births; for Hispanic infants it was 94 per 100,000. Among infants born to Black teenagers, however, it was 284 deaths per 100,000, they reported based on data from the National Vital Statistics System’s linked birth/infant death file.

The numbers for congenital malformations and accidents were closer but still significantly different, and with each of the three most common causes, the rates for infants of Hispanic mothers also were significantly lower than those of White infants, the researchers said.

The situation changes for mortality-cause No. 4, sudden infant death syndrome, which was significantly more common among infants born to White teenagers, with a rate of 91 deaths per 100,000 live births, compared with either black (77) or Hispanic (44) infants, Ms. Woodall and Dr. Driscoll said.

Infants born to Black teens had the highest death rate again (68 per 100,000) for maternal complications of pregnancy, the fifth-leading cause of mortality, but for the first time Hispanic infants had a higher rate (36) than did those of White teenagers (29), they reported.

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Infants born to Black teenage mothers are significantly more likely to die than infants born to White or Hispanic teens, according to a new analysis from the National Center for Health Statistics.

In 2017-2018, overall mortality rates were 12.5 per 100,000 live births for infants born to Black mothers aged 15-19 years, 8.4 per 100,000 for infants born to White teenagers, and 6.5 per 100,000 for those born to Hispanic teens, Ashley M. Woodall, MPH, and Anne K. Driscoll, PhD, of the NCHS said in a data brief.

Looking at the five leading causes of those deaths shows that deaths of Black infants were the highest by significant margins in four, although, when it comes to “disorders related to short gestation and low birth weight,” significant may be an understatement.

The rate of preterm/low-birth-weight deaths for white infants in 2017-2018 was 119 per 100,000 live births; for Hispanic infants it was 94 per 100,000. Among infants born to Black teenagers, however, it was 284 deaths per 100,000, they reported based on data from the National Vital Statistics System’s linked birth/infant death file.

The numbers for congenital malformations and accidents were closer but still significantly different, and with each of the three most common causes, the rates for infants of Hispanic mothers also were significantly lower than those of White infants, the researchers said.

The situation changes for mortality-cause No. 4, sudden infant death syndrome, which was significantly more common among infants born to White teenagers, with a rate of 91 deaths per 100,000 live births, compared with either black (77) or Hispanic (44) infants, Ms. Woodall and Dr. Driscoll said.

Infants born to Black teens had the highest death rate again (68 per 100,000) for maternal complications of pregnancy, the fifth-leading cause of mortality, but for the first time Hispanic infants had a higher rate (36) than did those of White teenagers (29), they reported.

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Infants born to Black teenage mothers are significantly more likely to die than infants born to White or Hispanic teens, according to a new analysis from the National Center for Health Statistics.

In 2017-2018, overall mortality rates were 12.5 per 100,000 live births for infants born to Black mothers aged 15-19 years, 8.4 per 100,000 for infants born to White teenagers, and 6.5 per 100,000 for those born to Hispanic teens, Ashley M. Woodall, MPH, and Anne K. Driscoll, PhD, of the NCHS said in a data brief.

Looking at the five leading causes of those deaths shows that deaths of Black infants were the highest by significant margins in four, although, when it comes to “disorders related to short gestation and low birth weight,” significant may be an understatement.

The rate of preterm/low-birth-weight deaths for white infants in 2017-2018 was 119 per 100,000 live births; for Hispanic infants it was 94 per 100,000. Among infants born to Black teenagers, however, it was 284 deaths per 100,000, they reported based on data from the National Vital Statistics System’s linked birth/infant death file.

The numbers for congenital malformations and accidents were closer but still significantly different, and with each of the three most common causes, the rates for infants of Hispanic mothers also were significantly lower than those of White infants, the researchers said.

The situation changes for mortality-cause No. 4, sudden infant death syndrome, which was significantly more common among infants born to White teenagers, with a rate of 91 deaths per 100,000 live births, compared with either black (77) or Hispanic (44) infants, Ms. Woodall and Dr. Driscoll said.

Infants born to Black teens had the highest death rate again (68 per 100,000) for maternal complications of pregnancy, the fifth-leading cause of mortality, but for the first time Hispanic infants had a higher rate (36) than did those of White teenagers (29), they reported.

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