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Weight gain during pregnancy may play role in child ADHD risk
Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.
Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.
Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.
However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).
“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.
The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).
Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.
Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”
Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.
The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”
The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”
Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.
The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”
Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”
Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”
This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.
This story was updated on 11/7/2022.
Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.
Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.
Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.
However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).
“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.
The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).
Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.
Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”
Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.
The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”
The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”
Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.
The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”
Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”
Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”
This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.
This story was updated on 11/7/2022.
Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.
Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.
Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66; 95% confidence interval: 1.07-2.60), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.
However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval: 1.14-4.01).
“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.
The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI: 0.78-2.36). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population. This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).
Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.
Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Dr. Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Dr. Perea said. ”This should be a priority in the current management of gestation.”
Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Dr. Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.
The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”
The current study does not say “anything new or novel,” Dr. Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”
Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Dr. Bornstein said in an interview.
The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”
Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Dr. Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”
Treating obesity prior to conception mitigates GDM risk, agreed Dr. Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”
This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Dr. Perea and study coauthors reporting have no conflicts of interest. Dr. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Dr. Bornstein reported having no conflicts of interest.
This story was updated on 11/7/2022.
The Journal of Clinical Endocrinology & Metabolism
Congenital cytomegalovirus declined in wake of COVID-19
Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.
A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.
“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.
The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).
Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.
Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).
Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.
The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.
The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.
However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.
Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.
The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.
Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.
Implications for other viruses
Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.
“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.
Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.
The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.
“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.
A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.
“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.
The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).
Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.
Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).
Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.
The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.
The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.
However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.
Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.
The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.
Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.
Implications for other viruses
Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.
“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.
Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.
The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.
“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
Congenital cytomegalovirus cases declined significantly during the COVID-19 pandemic, compared with a period before the pandemic, based on data from nearly 20,000 newborns.
A study originated to explore racial and ethnic differences in congenital cytomegalovirus (cCMV) began in 2016, but was halted in April 2020 because of the COVID-19 pandemic, wrote Mark R. Schleiss, MD, of the University of Minnesota, Minneapolis, and colleagues. The study resumed for a period from August 2020 to December 2021, and the researchers compared data on cCMV before and during the pandemic. The prepandemic period included data from April 2016 to March 2020.
“We have been screening for congenital CMV infection in Minnesota for 6 years as a part of a multicenter collaborative study that I lead as the primary investigator,” Dr. Schleiss said in an interview. “Our efforts have contributed to the decision, vetted through the Minnesota Legislature and signed into law in 2021 (the “Vivian Act”), to begin universal screening for all newborns in Minnesota in 2023. In the context of this ongoing screening/surveillance study, it was important and scientifically very interesting to examine the impact of the COVID-19 pandemic on the risk of congenital CMV infection,” he explained.
The findings were published in a research letter in JAMA Network Open. A total of 15,697 newborns were screened before the pandemic and 4,222 were screened during the pandemic period at six hospitals. The majority of the mothers participating during the prepandemic and pandemic periods were non-Hispanic White (71% and 60%, respectively).
Overall, the percentage screened prevalence for cCMV was 79% in the prepandemic period and 21% during the pandemic, with rates of 4.5 per 1,000 and 1.4 per 1,000, respectively.
Although the highest percentage of cCMV cases occurred in newborns of mothers aged 25 years and older (86%), the prevalence was highest among newborns of mothers aged 24 years and younger (6.0 per 1,000). The prevalence of cCMV overall was higher in infants of non-Hispanic Black mothers vs. non-Hispanic White mothers, but not significantly different (5.1 per 1,000 vs. 4.6 per 1,000) and among second newborns vs. first newborns (6.0 vs. 3.2 per 1,000, respectively).
Factors related to COVID-19, including reduced day care attendance, behavioral changes, and mitigation measures at childcare facilities such as smaller classes and increased hand hygiene and disinfection may have contributed to this decrease in cCMV in the pandemic period, the researchers wrote in their discussion.
The comparable prevalence in newborns of non-Hispanic Black and White mothers contrasts with previous studies showing a higher prevalence in children of non-Hispanic Black mothers, the researchers noted in their discussion.
The study was limited by several factors, including the variation in time points for enrollment at different sites and the exclusion of families in the newborn nursery with positive COVID-19 results during the pandemic, they wrote. More research is needed on the potential effects of behavioral interventions to reduce CMV risk during pregnancy, as well as future CMV vaccination for childbearing-aged women and young children, they concluded.
However, the researchers were surprised by the impact of COVID-19 on the prevalence of cCMV, Dr. Schleiss said in an interview. “We have had the knowledge for many years that CMV infections in young women are commonly acquired through interactions with their toddlers. These interactions – sharing food, wiping drool and nasal discharge from the toddler’s nose, changing diapers, kissing the child on the mouth – can transmit CMV,” he said. In addition, toddlers may acquire CMV from group day care; the child then sheds CMV and transmits the virus to their pregnant mother, who then transmits the virus across the placenta, leading to cCMV infection in the newborn, Dr. Schleiss explained.
Although the researchers expected a decrease in CMV in the wake of closures of group day care, increased home schooling, decreased interactions among children, hygienic precautions, and social isolation, the decrease exceeded their expectations, said Dr. Schleiss. “Our previous work showed that in the 5-year period leading up to the pandemic, about one baby in every 200 births was born with CMV. Between August 2020 and December 2021, the number decreased to one baby in every 1,000 births,” a difference he and his team found striking.
The message from the study is that CMV can be prevented, said Dr. Schleiss. “Hygienic precautions during pregnancy had a big impact. Since congenital CMV infection is the most common congenital infection in the United States, and probably globally, that causes disabilities in children, the implications are highly significant,” he said. “The hygienic precautions we all have engaged in during the pandemic, such as masking, handwashing, and infection prevention behaviors, were almost certainly responsible for the reduction in CMV transmission, which in turn protected mothers and newborns from the potentially devastating effects of the CMV virus,” he noted.
Looking ahead, “Vaccines are moving forward in clinical trials that aim to confer immunity on young women of childbearing age to protect future pregnancies against transmission of CMV to the newborn infant; it would be very important to examine in future studies whether hygienic precautions would have the same impact as a potential vaccine,” Dr. Schleiss said. More research is needed to examine the effect of education of women about CMV transmission, he added. “We think it is very important to share this knowledge from our study with the pediatric community, since pediatricians can be important in counseling women about future pregnancies and the risks of CMV acquisition and transmission,” he noted.
Implications for other viruses
Although CMV poses minimal risk for healthy populations, irreversible complications for infants born with congenital CMV, especially hearing loss, are very concerning, said Catherine Haut, DNP, CPNP-AC/PC, a pediatric nurse practitioner in Rehoboth Beach, Del., in an interview.
“The study of viral transmission during a time of isolation, masking, and other mitigation procedures for COVID-19 assists in awareness that other viruses may also be limited with the use of these measures,” she said.
Dr. Haut was not surprised by the findings, given that CMV is transmitted primarily through direct contact with body fluids and that more than 50% of American adults have been infected by age 40, according to the Centers for Disease Control and Prevention, she said.
The take-home message for pediatricians, Dr. Haut said, is measures to prevent transmission of viral infection can yield significant positive health outcomes for the pediatric population; however, the effect of isolation, which has been associated with a higher rate of mental health problems, should not be ignored.
“Despite appropriate statistical analyses and presentation of findings in this study, the population sampled during the pandemic was less than 30% of the pre-COVID sampling, representing a study limitation,” and conducting research in a single state limits generalizability, Dr. Haut noted. “I agree with the authors that additional study is necessary to better understand prevention measures and apply these methods to reduce CMV transmission. Pursuit of CMV immunization opportunities is also needed,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Vaccine Program Office, the Minnesota Department of Health Newborn Screening Program, and the University of South Carolina Disability Research and Dissemination Center. Lead author Dr. Schleiss disclosed grants from the CDC, the National Institutes of Health, and the DRDC during the conduct of the study; he also disclosed receiving personal fees from Moderna, Sanofi, GlaxoSmithKline, and Merck unrelated to the study. Dr. Haut had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
FROM JAMA NETWORK OPEN
New study supports safety of COVID-19 boosters during pregnancy
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
WIC review finds broad benefits, knowledge gaps
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
In the rush to curtail abortion, states adopt a jumbled stew of definitions for human life
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Dolutegravir in pregnant patients with HIV showed more viral suppression at delivery vs. other treatments
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Exercise may counteract genetics for gestational diabetes
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
FROM JAMA NETWORK OPEN
Mother’s fat metabolism in early pregnancy linked to baby’s weight
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.
A baby’s weight and neurodevelopment in the first 2 years of life could be influenced by maternal fat metabolism in the early stages of pregnancy, according to a study.
Patterns of fetal abdominal growth were associated with maternal lipid metabolites that tracked newborn growth, adiposity, and development into childhood and could be identified as early as the 5th month of pregnancy, according to researchers at the University of Oxford, working with colleagues at the University of California.
These fetal growth patterns were also associated with blood flow and nutrient transfer by the placenta, demonstrating a complex interaction between maternal and fetal nutrition early in pregnancy, with implications for postnatal weight and health in later life, they suggested.
Stephen Kennedy, MD, professor of reproductive medicine at the University of Oxford, who co-led the investigation, said it had “provided valuable new insights into the biological origins of childhood obesity, which is one of the most pressing public health issues facing governments around the world.”
International study
The prospective observational study, published in The Lancet Diabetes and Endocrinology, involved 3,598 pregnant women from six countries – Brazil, Kenya, Pakistan, South Africa, Thailand, and the United Kingdom – aged 18 and older and with a BMI of less than 35 kg/m2. The women were monitored using regular fetal ultrasound scans and metabolomic analysis of early pregnancy maternal blood and umbilical cord venous blood at the time of birth.
Their infants, who were singletons, and conceived naturally, were then followed for 2 years to assess their growth and development.
Fetal abdominal circumference growth was found to accelerate or decelerate within “a crucial 20-25 week gestational age window” that followed 4 trajectories of faltering growth, early accelerating growth, late accelerating growth, or median growth. These traits were matched by fetus-placenta blood flow patterns throughout pregnancy and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood, researchers said.
Overall, 709 maternal metabolites had a positive effect for the faltering growth phenotype, and 54 for the early accelerating growth phenotype, whilst 31 had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype.
The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was “highly abundant” in the early accelerating growth phenotype group.
‘A unique insight’
Aris Papageorghiou, professor of Fetal Medicine at the University of Oxford, who co-led the research, said: “This study provides evidence of distinct patterns of fetal abdominal growth and placental transfer and how they relate to longer term health. The finding of an association with maternal lipid metabolism early in pregnancy also provides unique insights into how the mother’s health and diet influence her child’s adiposity.”
First author José Villar, MD, professor of perinatal medicine at Oxford, said: “The study complements our previous work that identified fetal head growth trajectories associated with different developmental, behavioral, visual, and growth outcomes at 2 years of age.” Taken together, “the growth of babies’ bodies and brain[s] track separately and early – while still within the womb,” he said.
According to Dr. Kennedy, the latest results “could contribute to earlier identification of infants at risk of obesity” and urged policymakers to “take notice of these findings in their efforts to prevent the oncoming epidemic of obesity, with all its likely adverse social and economic consequences.”
Funding for the study was provided by the Bill and Melinda Gates Foundation.
A version of this article first appeared on Medscape UK.
Increased risk of dyspareunia following cesarean section
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
Use of antidotes in pregnancy and lactation
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].
The human pregnancy data reported for these 16 agents are very limited as only 8 of the drugs have this data. However, the 8 reports indicated that the use of these drugs was highly important for the mother and did not cause embryo/fetal harm.
- Acetylcysteine
The need for this antidote in a pregnant or lactating woman is most likely a rare requirement. However, the need for this agent does occur in women who have taken a potentially hepatic toxic dose of acetaminophen (e.g., Tylenol).
- Black widow spider antivenin
Only three reports of the use of this agent in a pregnant woman have been located. In each case, the symptoms from the spider bite did not respond to other therapies but did within 1 hour to the antivenin. There was no fetal harm in these cases.
- Deferasirox
This agent is an oral iron-chelating agent used for the treatment of chronic iron overload. Five case reports have described its use without causing any fetal harm.
- Deferoxamine
This agent has been used in more than 65 pregnancies for acute iron overdose or for transfusion-dependent thalassemia. No reports have observed adverse human developmental effects.
- Digoxin immune FAB (ovine)
Several reports have described the use of this agent in pregnancy. No fetal harm has been observed, but none of the reports involved exposure during organogenesis. However, in cases of digoxin overdose, the maternal benefits of therapy should take priority over the embryo/fetus.
- Dimercaprol
Although the limited animal data suggest low risk, there are no reports of the use of this drug in human organogenesis. The absence of data prevents an assessment of the embryo-fetal risk, but the maternal benefit and indirect embryo-fetal benefit appears to outweigh that risk.
- Edetate calcium disodium
This agent is used to treat acute or chronic lead poisoning. It is compatible in pregnancy because the maternal and possibly the embryo-fetal benefit appears to outweigh any unknown direct or indirect risks.
- Flumazenil
The use of this drug in the third trimester has been reported in two cases. Because the drug is indicated to reverse the effects of benzodiazepines on the central nervous system, the maternal benefit should far outweigh the unknown embryo-fetal risk.
- Glucagon
The embryo-fetal risks appear to be very low. Apparently, the drug does not cross the placenta.
- Glucarpidase
This drug is indicated for the treatment of methotrexate toxicity. There are no reports describing the use of this drug in pregnancy or during breastfeeding.
- Idarucizumab
This agent is a humanized monoclonal antibody fragment that is indicated for the reversal of the anticoagulant effects of dabigatran. No reports describing its use in human or animal pregnancy have been located. However, the maternal benefit appears to be high and probably outweighs the unknown risk to the embryo/fetus.
- Lanthanum carbonate
There are no human pregnancy or lactation data. It is used to reduce blood levels of phosphate in people with kidney disease.
- Pralidoxime
This agent relieves the paralysis of the muscles of respiration caused by an organophosphate pesticide or related compound. The human pregnancy experience is limited to two cases, one at 36 weeks and the other at 16 weeks, both of which delivered normal infants.
- Sapropterin
Four reports have described the use of sapropterin to lower blood phenylalanine levels in 31 pregnancies. There were no embryo-fetal adverse effects attributable to the drug.
- Sevelamer
Sevelamer is used to control high blood levels of phosphorus in people with chronic kidney disease who are on dialysis. There are no human pregnancy or breastfeeding data.
- Succimer
This drug is a heavy metal–chelating agent that is indicated for the treatment of lead poisoning in pediatric patients. The drug was teratogenic in rats and mice. Two reports described the use of the drug in two pregnant women for lead poisoning. It has also been used as an antidote for the treatment of arsenic, mercury, and cadmium poisoning in adults, but there have been no reports of this use in pregnant patients.
Mr. Briggs, now retired, was a clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].