Neonatal Medicine

The American Academy of Pediatrics now recommends against the routine administration of probiotics to preterm infants, particularly the most vulnerable (those whose birth weight is <1,000 g), for the treatment or prevention of necrotizing enterocolitis (NEC) and late-onset sepsis.

Although probiotics are increasingly given to preterm infants, the AAP notes that the data on their safety and efficacy are inconsistent. In addition, the supplements are not subject to approval by the Food and Drug Administration.

Therefore, the academy advises clinicians to use extreme caution in selecting preterm neonates to receive these microorganisms and recommends obtaining informed consent from parents after carefully discussing the risks. It also recommends that centers using probiotics conduct surveillance, inasmuch as probiotics can alter a center’s flora, potentially affecting all patients. Such centers should also carefully document outcomes, adverse events, and safety.

The AAP’s clinical report, published online May 24 in Pediatrics, highlights wide differences between commercially available formulations and a lack of regulatory standards in this country.

Absent FDA-approved drug labeling, these nutritional supplements cannot be marketed as treatment or prophylaxis, but that has scarcely stopped their use. “Despite lack of availability of a pharmaceutical-grade product, the number of preterm infants receiving probiotics in the United States and Canada is steadily increasing,” wrote Brenda Poindexter, MD, FAAP, chief of neonatology at Children’s Healthcare of Atlanta, and members of the AAP’s Committee on Fetus and Newborn.

Analyses of U.S. collaborative databases indicate that approximately 10% of neonates of extremely low gestational age receive a probiotic preparation in the neonatal intensive care unit (NICU). The use of these preparations varies widely across institutions.

“NEC is a devastating morbidity of prematurity, and it’s multifactorial. Some babies only given mother’s milk still get NEC, and the decision to use these products is a very nuanced one,” Dr. Poindexter said in an interview. “I suspect some people will disagree with the report, and we tried to give folks some wiggle room.”

Evidence from other countries suggests that probiotics can be protective against NEC, she added, “so not to have a reliable product in this country is very frustrating.”

Dr. Poindexter and colleagues pointed to a 2015 study that found that only 1 of 16 commercial products tested contained the exact organisms listed on their labels. One product contained none of the species listed on the label.

In light of increasing use, the AAP emphasizes the need for development of pharmaceutical-grade probiotics that would be rigorously evaluated for safety and efficacy.
 

The infant microbiome

Over the past decade, the gut microbiome has been increasingly recognized as a factor relevant to health and disease in preterm infants, the authors noted. Differences in the intestinal microbiota between full-term and preterm infants are substantial. The microbiome of preterm infants tends to include fewer bacterial species and greater proportions of potentially pathogenic strains.

Evidence of benefit from probiotics has been mixed. Some studies and pooled systematic analyses suggest a significant benefit. However, Dr. Poindexter and colleagues noted that some researchers express concerns about the study methods used, such as pooling results from trials that tested different probiotic strains or that had few infants in the highest risk category.

Whereas the potential for probiotic-related infection appears low, there does seem to be some risk for sepsis associated with colonization by a strain in a given product or from contamination with a pathogen during manufacturing, the report explains.

At least one trial found that a third of infants randomly assigned to receive placebo showed evidence of the probiotic strain.

“However, it may be difficult to distinguish the change in the infant from the change in the resident flora of the NICU,” the AAP panel wrote.

In addition, there have recently been several recalls of dietary supplement–grade probiotics for contamination, which have raised concerns. Pathogens include Salmonella, Rhizopus, and Penicillium species. Fatal gastrointestinal mucormycosis has also been reported in a preterm infant who received ABC Dophilus powder that was contaminated with the microfungus Rhizopus oryzae.

Other safety considerations, according to the authors, are the unknown longer-term effect of probiotics on preterm infants and the unknown impact of microorganisms on the microbiome over time.

Last year, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published a position paper with a conditional recommendation for selected probiotics to reduce NEC rates. “These guidelines would be applicable in the U.S. if we had products manufactured in a way that could guarantee that what’s on the label is in the bottle,” Dr. Poindexter said.

Asked for her perspective on the AAP clinical report, Erica Wymore, MD, assistant professor of neonatal and perinatal medicine at the University of Colorado at Denver, Aurora, called it “an excellent review of the current literature” that shows the inadequacy of data on the composition, dosage, timing, duration, and use of single-strain vs. multiple-strain probiotics to reduce NEC. Her clinical center, Children’s Hospital Colorado, does not administer probiotics to preterm babies.

Although guidelines can improve outcomes, said Dr. Wymore, who was not involved in the AAP report, improvement observed with probiotics results from more stringent care in centers that experience high NEC rates. “It’s hard to know if it’s due to the probiotics if they already have a high rate of NEC,” Dr. Wymore said.

She echoed the AAP’s position and stressed the need for extreme caution in giving these products to vulnerable infants with immature immune systems. Before that can be safely done, she said, “we need more FDA oversight of product composition [and] pharmaceutical-grade products, and more studies to determine efficacy.”

Added Dr. Poindexter: “Hopefully, this report will inform clinicians of the risks of using non–pharmaceutical-grade products and encourage industry to actually develop probiotics for neonates that we can feel comfortable using.”

The report received no external funding. Dr. Poindexter and Dr. Wymore have disclosed no relevant financial relationships.

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

The American Academy of Pediatrics now recommends against the routine administration of probiotics to preterm infants, particularly the most vulnerable (those whose birth weight is <1,000 g), for the treatment or prevention of necrotizing enterocolitis (NEC) and late-onset sepsis.

Although probiotics are increasingly given to preterm infants, the AAP notes that the data on their safety and efficacy are inconsistent. In addition, the supplements are not subject to approval by the Food and Drug Administration.

Therefore, the academy advises clinicians to use extreme caution in selecting preterm neonates to receive these microorganisms and recommends obtaining informed consent from parents after carefully discussing the risks. It also recommends that centers using probiotics conduct surveillance, inasmuch as probiotics can alter a center’s flora, potentially affecting all patients. Such centers should also carefully document outcomes, adverse events, and safety.

The AAP’s clinical report, published online May 24 in Pediatrics, highlights wide differences between commercially available formulations and a lack of regulatory standards in this country.

Absent FDA-approved drug labeling, these nutritional supplements cannot be marketed as treatment or prophylaxis, but that has scarcely stopped their use. “Despite lack of availability of a pharmaceutical-grade product, the number of preterm infants receiving probiotics in the United States and Canada is steadily increasing,” wrote Brenda Poindexter, MD, FAAP, chief of neonatology at Children’s Healthcare of Atlanta, and members of the AAP’s Committee on Fetus and Newborn.

Analyses of U.S. collaborative databases indicate that approximately 10% of neonates of extremely low gestational age receive a probiotic preparation in the neonatal intensive care unit (NICU). The use of these preparations varies widely across institutions.

“NEC is a devastating morbidity of prematurity, and it’s multifactorial. Some babies only given mother’s milk still get NEC, and the decision to use these products is a very nuanced one,” Dr. Poindexter said in an interview. “I suspect some people will disagree with the report, and we tried to give folks some wiggle room.”

Evidence from other countries suggests that probiotics can be protective against NEC, she added, “so not to have a reliable product in this country is very frustrating.”

Dr. Poindexter and colleagues pointed to a 2015 study that found that only 1 of 16 commercial products tested contained the exact organisms listed on their labels. One product contained none of the species listed on the label.

In light of increasing use, the AAP emphasizes the need for development of pharmaceutical-grade probiotics that would be rigorously evaluated for safety and efficacy.
 

The infant microbiome

Over the past decade, the gut microbiome has been increasingly recognized as a factor relevant to health and disease in preterm infants, the authors noted. Differences in the intestinal microbiota between full-term and preterm infants are substantial. The microbiome of preterm infants tends to include fewer bacterial species and greater proportions of potentially pathogenic strains.

Evidence of benefit from probiotics has been mixed. Some studies and pooled systematic analyses suggest a significant benefit. However, Dr. Poindexter and colleagues noted that some researchers express concerns about the study methods used, such as pooling results from trials that tested different probiotic strains or that had few infants in the highest risk category.

Whereas the potential for probiotic-related infection appears low, there does seem to be some risk for sepsis associated with colonization by a strain in a given product or from contamination with a pathogen during manufacturing, the report explains.

At least one trial found that a third of infants randomly assigned to receive placebo showed evidence of the probiotic strain.

“However, it may be difficult to distinguish the change in the infant from the change in the resident flora of the NICU,” the AAP panel wrote.

In addition, there have recently been several recalls of dietary supplement–grade probiotics for contamination, which have raised concerns. Pathogens include Salmonella, Rhizopus, and Penicillium species. Fatal gastrointestinal mucormycosis has also been reported in a preterm infant who received ABC Dophilus powder that was contaminated with the microfungus Rhizopus oryzae.

Other safety considerations, according to the authors, are the unknown longer-term effect of probiotics on preterm infants and the unknown impact of microorganisms on the microbiome over time.

Last year, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published a position paper with a conditional recommendation for selected probiotics to reduce NEC rates. “These guidelines would be applicable in the U.S. if we had products manufactured in a way that could guarantee that what’s on the label is in the bottle,” Dr. Poindexter said.

Asked for her perspective on the AAP clinical report, Erica Wymore, MD, assistant professor of neonatal and perinatal medicine at the University of Colorado at Denver, Aurora, called it “an excellent review of the current literature” that shows the inadequacy of data on the composition, dosage, timing, duration, and use of single-strain vs. multiple-strain probiotics to reduce NEC. Her clinical center, Children’s Hospital Colorado, does not administer probiotics to preterm babies.

Although guidelines can improve outcomes, said Dr. Wymore, who was not involved in the AAP report, improvement observed with probiotics results from more stringent care in centers that experience high NEC rates. “It’s hard to know if it’s due to the probiotics if they already have a high rate of NEC,” Dr. Wymore said.

She echoed the AAP’s position and stressed the need for extreme caution in giving these products to vulnerable infants with immature immune systems. Before that can be safely done, she said, “we need more FDA oversight of product composition [and] pharmaceutical-grade products, and more studies to determine efficacy.”

Added Dr. Poindexter: “Hopefully, this report will inform clinicians of the risks of using non–pharmaceutical-grade products and encourage industry to actually develop probiotics for neonates that we can feel comfortable using.”

The report received no external funding. Dr. Poindexter and Dr. Wymore have disclosed no relevant financial relationships.

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

The American Academy of Pediatrics now recommends against the routine administration of probiotics to preterm infants, particularly the most vulnerable (those whose birth weight is <1,000 g), for the treatment or prevention of necrotizing enterocolitis (NEC) and late-onset sepsis.

Although probiotics are increasingly given to preterm infants, the AAP notes that the data on their safety and efficacy are inconsistent. In addition, the supplements are not subject to approval by the Food and Drug Administration.

Therefore, the academy advises clinicians to use extreme caution in selecting preterm neonates to receive these microorganisms and recommends obtaining informed consent from parents after carefully discussing the risks. It also recommends that centers using probiotics conduct surveillance, inasmuch as probiotics can alter a center’s flora, potentially affecting all patients. Such centers should also carefully document outcomes, adverse events, and safety.

The AAP’s clinical report, published online May 24 in Pediatrics, highlights wide differences between commercially available formulations and a lack of regulatory standards in this country.

Absent FDA-approved drug labeling, these nutritional supplements cannot be marketed as treatment or prophylaxis, but that has scarcely stopped their use. “Despite lack of availability of a pharmaceutical-grade product, the number of preterm infants receiving probiotics in the United States and Canada is steadily increasing,” wrote Brenda Poindexter, MD, FAAP, chief of neonatology at Children’s Healthcare of Atlanta, and members of the AAP’s Committee on Fetus and Newborn.

Analyses of U.S. collaborative databases indicate that approximately 10% of neonates of extremely low gestational age receive a probiotic preparation in the neonatal intensive care unit (NICU). The use of these preparations varies widely across institutions.

“NEC is a devastating morbidity of prematurity, and it’s multifactorial. Some babies only given mother’s milk still get NEC, and the decision to use these products is a very nuanced one,” Dr. Poindexter said in an interview. “I suspect some people will disagree with the report, and we tried to give folks some wiggle room.”

Evidence from other countries suggests that probiotics can be protective against NEC, she added, “so not to have a reliable product in this country is very frustrating.”

Dr. Poindexter and colleagues pointed to a 2015 study that found that only 1 of 16 commercial products tested contained the exact organisms listed on their labels. One product contained none of the species listed on the label.

In light of increasing use, the AAP emphasizes the need for development of pharmaceutical-grade probiotics that would be rigorously evaluated for safety and efficacy.
 

The infant microbiome

Over the past decade, the gut microbiome has been increasingly recognized as a factor relevant to health and disease in preterm infants, the authors noted. Differences in the intestinal microbiota between full-term and preterm infants are substantial. The microbiome of preterm infants tends to include fewer bacterial species and greater proportions of potentially pathogenic strains.

Evidence of benefit from probiotics has been mixed. Some studies and pooled systematic analyses suggest a significant benefit. However, Dr. Poindexter and colleagues noted that some researchers express concerns about the study methods used, such as pooling results from trials that tested different probiotic strains or that had few infants in the highest risk category.

Whereas the potential for probiotic-related infection appears low, there does seem to be some risk for sepsis associated with colonization by a strain in a given product or from contamination with a pathogen during manufacturing, the report explains.

At least one trial found that a third of infants randomly assigned to receive placebo showed evidence of the probiotic strain.

“However, it may be difficult to distinguish the change in the infant from the change in the resident flora of the NICU,” the AAP panel wrote.

In addition, there have recently been several recalls of dietary supplement–grade probiotics for contamination, which have raised concerns. Pathogens include Salmonella, Rhizopus, and Penicillium species. Fatal gastrointestinal mucormycosis has also been reported in a preterm infant who received ABC Dophilus powder that was contaminated with the microfungus Rhizopus oryzae.

Other safety considerations, according to the authors, are the unknown longer-term effect of probiotics on preterm infants and the unknown impact of microorganisms on the microbiome over time.

Last year, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published a position paper with a conditional recommendation for selected probiotics to reduce NEC rates. “These guidelines would be applicable in the U.S. if we had products manufactured in a way that could guarantee that what’s on the label is in the bottle,” Dr. Poindexter said.

Asked for her perspective on the AAP clinical report, Erica Wymore, MD, assistant professor of neonatal and perinatal medicine at the University of Colorado at Denver, Aurora, called it “an excellent review of the current literature” that shows the inadequacy of data on the composition, dosage, timing, duration, and use of single-strain vs. multiple-strain probiotics to reduce NEC. Her clinical center, Children’s Hospital Colorado, does not administer probiotics to preterm babies.

Although guidelines can improve outcomes, said Dr. Wymore, who was not involved in the AAP report, improvement observed with probiotics results from more stringent care in centers that experience high NEC rates. “It’s hard to know if it’s due to the probiotics if they already have a high rate of NEC,” Dr. Wymore said.

She echoed the AAP’s position and stressed the need for extreme caution in giving these products to vulnerable infants with immature immune systems. Before that can be safely done, she said, “we need more FDA oversight of product composition [and] pharmaceutical-grade products, and more studies to determine efficacy.”

Added Dr. Poindexter: “Hopefully, this report will inform clinicians of the risks of using non–pharmaceutical-grade products and encourage industry to actually develop probiotics for neonates that we can feel comfortable using.”

The report received no external funding. Dr. Poindexter and Dr. Wymore have disclosed no relevant financial relationships.

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

Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.

“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.

The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.

In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.

During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.

Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.

No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.

The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
 

Study supports safety of rooming in

The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.

Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.

“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.

The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.

In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.

During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.

Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.

No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.

The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
 

Study supports safety of rooming in

The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.

Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.

“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.

The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.

In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.

During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.

Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.

No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.

The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
 

Study supports safety of rooming in

The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.

Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Postpartum depression (PPD) is a common and treatable problem affecting over 10% of all pregnant women. Without routine use of a screening questionnaire, many women go undiagnosed and without treatment. The risks of untreated PPD in a new mother are the risks of depression tripled: to her health and to the health of her new infant and their whole family. Although pediatricians treat children, they take care of the whole family. They appreciate their role in offering support and guidance to new parents, and in the case of PPD, they are in a unique position. The American Academy of Pediatrics recognized this when they issued their policy statement, “Incorporating Recognition and Management of Perinatal Depression into Pediatric Practice,” in January 2019. By screening, tracking, and connecting affected mothers to care and services, you can truly provide “two-generational care” for your youngest patients.

PPD affects an estimated one in seven women (13%) globally. In one large retrospective study that looked at the 39 weeks before and after delivery, 15.4% of mothers received a diagnosis of PPD and a second study indicated that 22% of new mothers had depressive symptoms that were persistent for 6 months.¹ The pathways to PPD include prior personal or family history of depression, stressors in the family (connected to social determinants of health), previous miscarriage or serious complications in a previous pregnancy, and sensitivity to hormonal changes. Indeed, PPD is the most common complication of childbirth.² Although as many as half of all women eventually diagnosed with PPD had symptoms during their pregnancy, the misperception that PPD is only post partum leads to it being mistaken for the normal process of adjustment to parenthood. PPD is particularly insidious as new mothers are likely to be silent if they feel shame for not enjoying what they have been told will be a special and happy time, and those around them may mistake symptoms for the normal “baby blues” that will resolve quickly and with routine supports.

Untreated PPD, creates risks for mother, infant, and family as she manages needless suffering during a critical period for her new baby. While depression may remit over months without treatment, suicide is a real risk, and accounts for 20% of postpartum deaths.³ Infants face serious developmental consequences when their mothers are withdrawn and disconnected from them during the first months of life, including impaired social development, physical growth, and cognitive development. This impairment persists. Exposure to maternal depression during infancy is associated with lower IQ, attentional problems, and special educational needs by elementary school,⁴ and is a risk factor for psychiatric illnesses in childhood and adolescence.^5,6 PPD has a broad range of severity, including psychosis that may include paranoia with the rare risk of infanticide. And maternal depression can add to the strains in a vulnerable caregiver relationship that can raise the risk for neglect or abuse of the mother, children, or both.

It is important to note that anxiety is often the presenting problem in perinatal mood disorders, with mothers experiencing intense morbid worries about their infant’s safety and health, and fear of inadequacy, criticism, and even infant removal. These fears may reinforce silence and isolation. But pediatricians are one group that these mothers are most likely to share their anxieties with as they look for reassurance. It can be challenging to distinguish PPD from obsessive-compulsive disorder or PTSD. The critical work of the pediatrician is not specific diagnosis and treatment. Instead, your task is to provide screening and support, to create a safe place to overcome silence and shame.

There are many reliable and valid screening instruments available for depression, but the Edinburgh Postnatal Depression Scale (EDPS) has been specially developed for and tested in this population. It is a 10-item scale that is easy to complete and to score. Scores range from 0 to 30 and a score of 10 is considered a cutoff for depression. It can be used to track symptoms and is free and widely available online and in multiple languages. Ideally, this scale can be administered as part of a previsit, automatically entered into an electronic medical record and given at regular intervals during the infant’s first year of primary care. Some new mothers, especially if they are suffering from depression, may feel anxious about filling this out. It is important that your staff tell them that you screen all new mothers in your practice, and that PPD is common and treatable and the pediatrician’s office is committed to the health of the whole family.

If a new mother screens positive, you might consider yourself to have three tasks: Reassure her that she is a wonderful mother and this is a treatable illness, not a cause for guilt, shame, or alarm; expand her support and decrease her isolation by helping her to communicate with her family; and identify treatment resources for her. Start by being curious about some of her specific worries or feelings, her energy level, feelings of isolation or trouble with sleep. Offer compassion and validation around the pain of these experiences in the midst of so much transition. Only after hearing a little detail about her experience, then you may offer that such feelings are common, but when they are persistent or severe, they often indicate PPD, and that her screening test suggests they do for her. Offer that this form of depression is very treatable, with both pharmacologic and psychotherapy interventions. And if she is resistant, gently offer that treatment will be very protective of her new infant’s physical, social, and cognitive growth and development. Hearing this from a pediatrician is powerful for a new mother, even if depressed. Finally, ask if you might help her bring other important adults in her family into an understanding of this. Could she tell her spouse? Her sister? Her best friend? Perhaps she could bring one of them to the next weekly visit, so you can all speak together. This intervention greatly improves the likelihood of her engaging in treatment, and strong interpersonal connections are therapeutic in and of themselves.

For treatment, the easier your office can make it, the more likely she is to follow up. Identify local resources, perhaps through connected community organizations such as Jewish Family and Children’s Services or through a public program like California’s First Five. Connect with the local obstetric practice, which may already have a referral process in place. If you can connect with her primary care provider, they may take on the referral process or may even have integrated capacity for treatment. Identify strategies that may support her restful sleep, including realistic daily exercise, sharing infant care, and being cautious with caffeine and screen time. Identify ways for her to meet other new mothers or reconnect with friends. Reassure her that easy attachment activities, such as reading a book or singing to her baby can be good for both of them without requiring much energy. This may sound like a daunting task, but the conversation will only take a few minutes. Helping an isolated new parent recognize that their feelings of fear, inadequacy, and guilt are not facts, offering some simple immediate strategies and facilitating a referral can be lifesaving.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com

References

1. Dietz PM et al. Am J Psychiatry. 2007;164(10):1515-20.

2. Hanusa BH et al. J Women’s Health (Larchmt) 2008;17(4):585-96.

3. Lindahl V et al. Arch Womens Ment Health. 2005;8(2):77-87.

4. Hay DF et al. J Child Psychol Psychiatry. 2001;42(7):871-89.

5. Tully EC et al. Am J Psychiatry. 2008:165(9):1148-54.

6. Maternal depression and child development. Paediatr. Child Health 2004;9(8):575-98.

Postpartum depression (PPD) is a common and treatable problem affecting over 10% of all pregnant women. Without routine use of a screening questionnaire, many women go undiagnosed and without treatment. The risks of untreated PPD in a new mother are the risks of depression tripled: to her health and to the health of her new infant and their whole family. Although pediatricians treat children, they take care of the whole family. They appreciate their role in offering support and guidance to new parents, and in the case of PPD, they are in a unique position. The American Academy of Pediatrics recognized this when they issued their policy statement, “Incorporating Recognition and Management of Perinatal Depression into Pediatric Practice,” in January 2019. By screening, tracking, and connecting affected mothers to care and services, you can truly provide “two-generational care” for your youngest patients.

PPD affects an estimated one in seven women (13%) globally. In one large retrospective study that looked at the 39 weeks before and after delivery, 15.4% of mothers received a diagnosis of PPD and a second study indicated that 22% of new mothers had depressive symptoms that were persistent for 6 months.¹ The pathways to PPD include prior personal or family history of depression, stressors in the family (connected to social determinants of health), previous miscarriage or serious complications in a previous pregnancy, and sensitivity to hormonal changes. Indeed, PPD is the most common complication of childbirth.² Although as many as half of all women eventually diagnosed with PPD had symptoms during their pregnancy, the misperception that PPD is only post partum leads to it being mistaken for the normal process of adjustment to parenthood. PPD is particularly insidious as new mothers are likely to be silent if they feel shame for not enjoying what they have been told will be a special and happy time, and those around them may mistake symptoms for the normal “baby blues” that will resolve quickly and with routine supports.

Untreated PPD, creates risks for mother, infant, and family as she manages needless suffering during a critical period for her new baby. While depression may remit over months without treatment, suicide is a real risk, and accounts for 20% of postpartum deaths.³ Infants face serious developmental consequences when their mothers are withdrawn and disconnected from them during the first months of life, including impaired social development, physical growth, and cognitive development. This impairment persists. Exposure to maternal depression during infancy is associated with lower IQ, attentional problems, and special educational needs by elementary school,⁴ and is a risk factor for psychiatric illnesses in childhood and adolescence.^5,6 PPD has a broad range of severity, including psychosis that may include paranoia with the rare risk of infanticide. And maternal depression can add to the strains in a vulnerable caregiver relationship that can raise the risk for neglect or abuse of the mother, children, or both.

It is important to note that anxiety is often the presenting problem in perinatal mood disorders, with mothers experiencing intense morbid worries about their infant’s safety and health, and fear of inadequacy, criticism, and even infant removal. These fears may reinforce silence and isolation. But pediatricians are one group that these mothers are most likely to share their anxieties with as they look for reassurance. It can be challenging to distinguish PPD from obsessive-compulsive disorder or PTSD. The critical work of the pediatrician is not specific diagnosis and treatment. Instead, your task is to provide screening and support, to create a safe place to overcome silence and shame.

There are many reliable and valid screening instruments available for depression, but the Edinburgh Postnatal Depression Scale (EDPS) has been specially developed for and tested in this population. It is a 10-item scale that is easy to complete and to score. Scores range from 0 to 30 and a score of 10 is considered a cutoff for depression. It can be used to track symptoms and is free and widely available online and in multiple languages. Ideally, this scale can be administered as part of a previsit, automatically entered into an electronic medical record and given at regular intervals during the infant’s first year of primary care. Some new mothers, especially if they are suffering from depression, may feel anxious about filling this out. It is important that your staff tell them that you screen all new mothers in your practice, and that PPD is common and treatable and the pediatrician’s office is committed to the health of the whole family.

If a new mother screens positive, you might consider yourself to have three tasks: Reassure her that she is a wonderful mother and this is a treatable illness, not a cause for guilt, shame, or alarm; expand her support and decrease her isolation by helping her to communicate with her family; and identify treatment resources for her. Start by being curious about some of her specific worries or feelings, her energy level, feelings of isolation or trouble with sleep. Offer compassion and validation around the pain of these experiences in the midst of so much transition. Only after hearing a little detail about her experience, then you may offer that such feelings are common, but when they are persistent or severe, they often indicate PPD, and that her screening test suggests they do for her. Offer that this form of depression is very treatable, with both pharmacologic and psychotherapy interventions. And if she is resistant, gently offer that treatment will be very protective of her new infant’s physical, social, and cognitive growth and development. Hearing this from a pediatrician is powerful for a new mother, even if depressed. Finally, ask if you might help her bring other important adults in her family into an understanding of this. Could she tell her spouse? Her sister? Her best friend? Perhaps she could bring one of them to the next weekly visit, so you can all speak together. This intervention greatly improves the likelihood of her engaging in treatment, and strong interpersonal connections are therapeutic in and of themselves.

For treatment, the easier your office can make it, the more likely she is to follow up. Identify local resources, perhaps through connected community organizations such as Jewish Family and Children’s Services or through a public program like California’s First Five. Connect with the local obstetric practice, which may already have a referral process in place. If you can connect with her primary care provider, they may take on the referral process or may even have integrated capacity for treatment. Identify strategies that may support her restful sleep, including realistic daily exercise, sharing infant care, and being cautious with caffeine and screen time. Identify ways for her to meet other new mothers or reconnect with friends. Reassure her that easy attachment activities, such as reading a book or singing to her baby can be good for both of them without requiring much energy. This may sound like a daunting task, but the conversation will only take a few minutes. Helping an isolated new parent recognize that their feelings of fear, inadequacy, and guilt are not facts, offering some simple immediate strategies and facilitating a referral can be lifesaving.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com

References

1. Dietz PM et al. Am J Psychiatry. 2007;164(10):1515-20.

2. Hanusa BH et al. J Women’s Health (Larchmt) 2008;17(4):585-96.

3. Lindahl V et al. Arch Womens Ment Health. 2005;8(2):77-87.

4. Hay DF et al. J Child Psychol Psychiatry. 2001;42(7):871-89.

5. Tully EC et al. Am J Psychiatry. 2008:165(9):1148-54.

6. Maternal depression and child development. Paediatr. Child Health 2004;9(8):575-98.

Postpartum depression (PPD) is a common and treatable problem affecting over 10% of all pregnant women. Without routine use of a screening questionnaire, many women go undiagnosed and without treatment. The risks of untreated PPD in a new mother are the risks of depression tripled: to her health and to the health of her new infant and their whole family. Although pediatricians treat children, they take care of the whole family. They appreciate their role in offering support and guidance to new parents, and in the case of PPD, they are in a unique position. The American Academy of Pediatrics recognized this when they issued their policy statement, “Incorporating Recognition and Management of Perinatal Depression into Pediatric Practice,” in January 2019. By screening, tracking, and connecting affected mothers to care and services, you can truly provide “two-generational care” for your youngest patients.

PPD affects an estimated one in seven women (13%) globally. In one large retrospective study that looked at the 39 weeks before and after delivery, 15.4% of mothers received a diagnosis of PPD and a second study indicated that 22% of new mothers had depressive symptoms that were persistent for 6 months.¹ The pathways to PPD include prior personal or family history of depression, stressors in the family (connected to social determinants of health), previous miscarriage or serious complications in a previous pregnancy, and sensitivity to hormonal changes. Indeed, PPD is the most common complication of childbirth.² Although as many as half of all women eventually diagnosed with PPD had symptoms during their pregnancy, the misperception that PPD is only post partum leads to it being mistaken for the normal process of adjustment to parenthood. PPD is particularly insidious as new mothers are likely to be silent if they feel shame for not enjoying what they have been told will be a special and happy time, and those around them may mistake symptoms for the normal “baby blues” that will resolve quickly and with routine supports.

Untreated PPD, creates risks for mother, infant, and family as she manages needless suffering during a critical period for her new baby. While depression may remit over months without treatment, suicide is a real risk, and accounts for 20% of postpartum deaths.³ Infants face serious developmental consequences when their mothers are withdrawn and disconnected from them during the first months of life, including impaired social development, physical growth, and cognitive development. This impairment persists. Exposure to maternal depression during infancy is associated with lower IQ, attentional problems, and special educational needs by elementary school,⁴ and is a risk factor for psychiatric illnesses in childhood and adolescence.^5,6 PPD has a broad range of severity, including psychosis that may include paranoia with the rare risk of infanticide. And maternal depression can add to the strains in a vulnerable caregiver relationship that can raise the risk for neglect or abuse of the mother, children, or both.

It is important to note that anxiety is often the presenting problem in perinatal mood disorders, with mothers experiencing intense morbid worries about their infant’s safety and health, and fear of inadequacy, criticism, and even infant removal. These fears may reinforce silence and isolation. But pediatricians are one group that these mothers are most likely to share their anxieties with as they look for reassurance. It can be challenging to distinguish PPD from obsessive-compulsive disorder or PTSD. The critical work of the pediatrician is not specific diagnosis and treatment. Instead, your task is to provide screening and support, to create a safe place to overcome silence and shame.

There are many reliable and valid screening instruments available for depression, but the Edinburgh Postnatal Depression Scale (EDPS) has been specially developed for and tested in this population. It is a 10-item scale that is easy to complete and to score. Scores range from 0 to 30 and a score of 10 is considered a cutoff for depression. It can be used to track symptoms and is free and widely available online and in multiple languages. Ideally, this scale can be administered as part of a previsit, automatically entered into an electronic medical record and given at regular intervals during the infant’s first year of primary care. Some new mothers, especially if they are suffering from depression, may feel anxious about filling this out. It is important that your staff tell them that you screen all new mothers in your practice, and that PPD is common and treatable and the pediatrician’s office is committed to the health of the whole family.

If a new mother screens positive, you might consider yourself to have three tasks: Reassure her that she is a wonderful mother and this is a treatable illness, not a cause for guilt, shame, or alarm; expand her support and decrease her isolation by helping her to communicate with her family; and identify treatment resources for her. Start by being curious about some of her specific worries or feelings, her energy level, feelings of isolation or trouble with sleep. Offer compassion and validation around the pain of these experiences in the midst of so much transition. Only after hearing a little detail about her experience, then you may offer that such feelings are common, but when they are persistent or severe, they often indicate PPD, and that her screening test suggests they do for her. Offer that this form of depression is very treatable, with both pharmacologic and psychotherapy interventions. And if she is resistant, gently offer that treatment will be very protective of her new infant’s physical, social, and cognitive growth and development. Hearing this from a pediatrician is powerful for a new mother, even if depressed. Finally, ask if you might help her bring other important adults in her family into an understanding of this. Could she tell her spouse? Her sister? Her best friend? Perhaps she could bring one of them to the next weekly visit, so you can all speak together. This intervention greatly improves the likelihood of her engaging in treatment, and strong interpersonal connections are therapeutic in and of themselves.

For treatment, the easier your office can make it, the more likely she is to follow up. Identify local resources, perhaps through connected community organizations such as Jewish Family and Children’s Services or through a public program like California’s First Five. Connect with the local obstetric practice, which may already have a referral process in place. If you can connect with her primary care provider, they may take on the referral process or may even have integrated capacity for treatment. Identify strategies that may support her restful sleep, including realistic daily exercise, sharing infant care, and being cautious with caffeine and screen time. Identify ways for her to meet other new mothers or reconnect with friends. Reassure her that easy attachment activities, such as reading a book or singing to her baby can be good for both of them without requiring much energy. This may sound like a daunting task, but the conversation will only take a few minutes. Helping an isolated new parent recognize that their feelings of fear, inadequacy, and guilt are not facts, offering some simple immediate strategies and facilitating a referral can be lifesaving.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com

References

1. Dietz PM et al. Am J Psychiatry. 2007;164(10):1515-20.

2. Hanusa BH et al. J Women’s Health (Larchmt) 2008;17(4):585-96.

3. Lindahl V et al. Arch Womens Ment Health. 2005;8(2):77-87.

4. Hay DF et al. J Child Psychol Psychiatry. 2001;42(7):871-89.

5. Tully EC et al. Am J Psychiatry. 2008:165(9):1148-54.

6. Maternal depression and child development. Paediatr. Child Health 2004;9(8):575-98.

Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

For pregnant women, just half a cup of coffee a day may reduce neonatal birth size and body weight, according to a prospective study involving more than 2,500 women.

kjekol/thinkstock

That’s only 50 mg of a caffeine day, which falls below the upper threshold of 200 mg set by the American College of Obstetricians and Gynecologists, lead author Jessica Gleason, PhD, MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md, and colleagues reported.

“Systematic reviews and meta-analyses have reported that maternal caffeine consumption, even in doses lower than 200 mg, is associated with a higher risk for low birth weight, small for gestational age (SGA), and fetal growth restriction, suggesting there may be no safe amount of caffeine during pregnancy,” the investigators wrote in JAMA Network Open.

Findings to date have been inconsistent, with a 2014 meta-analysis reporting contrary or null results in four out of nine studies.

Dr. Gleason and colleagues suggested that such discrepancies may be caused by uncontrolled confounding factors in some of the studies, such as smoking, as well as the inadequacy of self-reporting, which fails to incorporate variations in caffeine content between beverages, or differences in rates of metabolism between individuals.

“To our knowledge, no studies have examined the association between caffeine intake and neonatal anthropometric measures beyond weight, length, and head circumference, and few have analyzed plasma concentrations of caffeine and its metabolites or genetic variations in the rate of metabolism associated with neonatal size,” the investigators wrote.

Dr. Gleason and colleagues set out to address this knowledge gap with a prospective cohort study, including 2,055 nonsmoking women with low risk of birth defects who presented at 12 centers between 2009 and 2013. Mean participant age was 28.3 years and mean body mass index was 23.6. Races and ethnicities were represented almost evenly even across four groups: Hispanic (28.2%), White (27.4%), Black (25.2%), and Asian/Pacific Islander (19.2%). Rate of caffeine metabolism was defined by the single-nucleotide variant rs762551 (CYP1A2*1F), according to which, slightly more women had slow metabolism (52.7%) than fast metabolism (47.3%).

Women were enrolled at 8-13 weeks’ gestational age, at which time they underwent interviews and blood draws, allowing for measurement of caffeine and paraxanthine plasma levels, as well as self-reported caffeine consumption during the preceding week.

Over the course of six visits, fetal growth was observed via ultrasound. Medical records were used to determine birth weights and neonatal anthropometric measures, including fat and skin fold mass, body length, and circumferences of the thigh, arm, abdomen, and head.

Neonatal measurements were compared with plasma levels of caffeine and paraxanthine, both continuously and as quartiles (Q1, ≤ 28.3 ng/mL; Q2, 28.4-157.1 ng/mL; Q3, 157.2-658.8 ng/mL; Q4, > 658.8 ng/mL). Comparisons were also made with self-reported caffeine intake.

Women who reported drinking 1-50 mg of caffeine per day had neonates with smaller subscapular skin folds (beta = –0.14 mm; 95% confidence interval, –0.27 to -–0.01 mm), while those who reported more than 50 mg per day had newborns with lower birth weight (beta = –66 g; 95% CI, –121 to –10 g), and smaller circumferences of mid-upper thigh (beta = –0.32 cm; 95% CI, –0.55 to –0.09 cm), anterior thigh skin fold (beta = –0.24 mm; 95% CI, –0.47 to -.01 mm), and mid-upper arm (beta = –0.17 cm; 95% CI, –0.31 to –0.02 cm).

Caffeine plasma concentrations supported these findings.

Compared with women who had caffeine plasma concentrations in the lowest quartile, those in the highest quartile gave birth to neonates with shorter length (beta = –0.44 cm; P = .04 for trend) and lower body weight (beta = –84.3 g; P = .04 for trend), as well as smaller mid-upper arm circumference (beta = -0.25 cm; P = .02 for trend), mid-upper thigh circumference (beta = –0.29 cm; P = .07 for trend), and head circumference (beta = –0.28 cm; P < .001 for trend). A comparison of lower and upper paraxanthine quartiles revealed the similar trends, as did analyses of continuous measures.

“Our results suggest that caffeine consumption during pregnancy, even at levels much lower than the recommended 200 mg per day of caffeine may be associated with decreased fetal growth,” the investigators concluded.

Sarah W. Prager, MD, of the University of Washington, Seattle, suggested that the findings “do not demonstrate that caffeine has a clinically meaningful negative clinical impact on newborn size and weight.”

She noted that there was no difference in the rate of SGA between plasma caffeine quartiles, and that most patients were thin, which may not accurately represent the U.S. population.

“Based on these new data, my take home message to patients would be that increasing amounts of caffeine can have a small but real impact on the size of their baby at birth, though it is unlikely to result in a diagnosis of SGA,” she said. “Pregnant patients may want to limit caffeine intake even more than the ACOG recommendation of 200 mg per day.”

According to Robert M. Silver, MD, of the University of Utah Health Sciences Center, Salt Lake City, “data from this study are of high quality, owing to the prospective cohort design, large numbers, assessment of biomarkers, and sophisticated analyses.”

Still, he urged a cautious interpretation from a clinical perspective.

“It is important to not overreact to these data,” he said. “The decrease in fetal growth associated with caffeine is small and may prove to be clinically meaningless. Accordingly, clinical recommendations regarding caffeine intake during pregnancy should not be modified solely based on this study.”

Dr. Silver suggested that the findings deserve additional investigation.

“These observations warrant further research about the effects of caffeine exposure during pregnancy,” he said. “Ideally, studies should assess the effect of caffeine exposure on fetal growth in various pregnancy epochs as well as on neonatal and childhood growth.”

The study was funded by the Intramural Research Program of the NICHD. Dr. Gerlanc is an employee of The Prospective Group, which was contracted to provide statistical support.

For pregnant women, just half a cup of coffee a day may reduce neonatal birth size and body weight, according to a prospective study involving more than 2,500 women.

kjekol/thinkstock

That’s only 50 mg of a caffeine day, which falls below the upper threshold of 200 mg set by the American College of Obstetricians and Gynecologists, lead author Jessica Gleason, PhD, MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md, and colleagues reported.

“Systematic reviews and meta-analyses have reported that maternal caffeine consumption, even in doses lower than 200 mg, is associated with a higher risk for low birth weight, small for gestational age (SGA), and fetal growth restriction, suggesting there may be no safe amount of caffeine during pregnancy,” the investigators wrote in JAMA Network Open.

Findings to date have been inconsistent, with a 2014 meta-analysis reporting contrary or null results in four out of nine studies.

Dr. Gleason and colleagues suggested that such discrepancies may be caused by uncontrolled confounding factors in some of the studies, such as smoking, as well as the inadequacy of self-reporting, which fails to incorporate variations in caffeine content between beverages, or differences in rates of metabolism between individuals.

“To our knowledge, no studies have examined the association between caffeine intake and neonatal anthropometric measures beyond weight, length, and head circumference, and few have analyzed plasma concentrations of caffeine and its metabolites or genetic variations in the rate of metabolism associated with neonatal size,” the investigators wrote.

Dr. Gleason and colleagues set out to address this knowledge gap with a prospective cohort study, including 2,055 nonsmoking women with low risk of birth defects who presented at 12 centers between 2009 and 2013. Mean participant age was 28.3 years and mean body mass index was 23.6. Races and ethnicities were represented almost evenly even across four groups: Hispanic (28.2%), White (27.4%), Black (25.2%), and Asian/Pacific Islander (19.2%). Rate of caffeine metabolism was defined by the single-nucleotide variant rs762551 (CYP1A2*1F), according to which, slightly more women had slow metabolism (52.7%) than fast metabolism (47.3%).

Women were enrolled at 8-13 weeks’ gestational age, at which time they underwent interviews and blood draws, allowing for measurement of caffeine and paraxanthine plasma levels, as well as self-reported caffeine consumption during the preceding week.

Over the course of six visits, fetal growth was observed via ultrasound. Medical records were used to determine birth weights and neonatal anthropometric measures, including fat and skin fold mass, body length, and circumferences of the thigh, arm, abdomen, and head.

Neonatal measurements were compared with plasma levels of caffeine and paraxanthine, both continuously and as quartiles (Q1, ≤ 28.3 ng/mL; Q2, 28.4-157.1 ng/mL; Q3, 157.2-658.8 ng/mL; Q4, > 658.8 ng/mL). Comparisons were also made with self-reported caffeine intake.

Women who reported drinking 1-50 mg of caffeine per day had neonates with smaller subscapular skin folds (beta = –0.14 mm; 95% confidence interval, –0.27 to -–0.01 mm), while those who reported more than 50 mg per day had newborns with lower birth weight (beta = –66 g; 95% CI, –121 to –10 g), and smaller circumferences of mid-upper thigh (beta = –0.32 cm; 95% CI, –0.55 to –0.09 cm), anterior thigh skin fold (beta = –0.24 mm; 95% CI, –0.47 to -.01 mm), and mid-upper arm (beta = –0.17 cm; 95% CI, –0.31 to –0.02 cm).

Caffeine plasma concentrations supported these findings.

Compared with women who had caffeine plasma concentrations in the lowest quartile, those in the highest quartile gave birth to neonates with shorter length (beta = –0.44 cm; P = .04 for trend) and lower body weight (beta = –84.3 g; P = .04 for trend), as well as smaller mid-upper arm circumference (beta = -0.25 cm; P = .02 for trend), mid-upper thigh circumference (beta = –0.29 cm; P = .07 for trend), and head circumference (beta = –0.28 cm; P < .001 for trend). A comparison of lower and upper paraxanthine quartiles revealed the similar trends, as did analyses of continuous measures.

“Our results suggest that caffeine consumption during pregnancy, even at levels much lower than the recommended 200 mg per day of caffeine may be associated with decreased fetal growth,” the investigators concluded.

Sarah W. Prager, MD, of the University of Washington, Seattle, suggested that the findings “do not demonstrate that caffeine has a clinically meaningful negative clinical impact on newborn size and weight.”

She noted that there was no difference in the rate of SGA between plasma caffeine quartiles, and that most patients were thin, which may not accurately represent the U.S. population.

“Based on these new data, my take home message to patients would be that increasing amounts of caffeine can have a small but real impact on the size of their baby at birth, though it is unlikely to result in a diagnosis of SGA,” she said. “Pregnant patients may want to limit caffeine intake even more than the ACOG recommendation of 200 mg per day.”

According to Robert M. Silver, MD, of the University of Utah Health Sciences Center, Salt Lake City, “data from this study are of high quality, owing to the prospective cohort design, large numbers, assessment of biomarkers, and sophisticated analyses.”

Still, he urged a cautious interpretation from a clinical perspective.

“It is important to not overreact to these data,” he said. “The decrease in fetal growth associated with caffeine is small and may prove to be clinically meaningless. Accordingly, clinical recommendations regarding caffeine intake during pregnancy should not be modified solely based on this study.”

Dr. Silver suggested that the findings deserve additional investigation.

“These observations warrant further research about the effects of caffeine exposure during pregnancy,” he said. “Ideally, studies should assess the effect of caffeine exposure on fetal growth in various pregnancy epochs as well as on neonatal and childhood growth.”

The study was funded by the Intramural Research Program of the NICHD. Dr. Gerlanc is an employee of The Prospective Group, which was contracted to provide statistical support.

For pregnant women, just half a cup of coffee a day may reduce neonatal birth size and body weight, according to a prospective study involving more than 2,500 women.

kjekol/thinkstock

That’s only 50 mg of a caffeine day, which falls below the upper threshold of 200 mg set by the American College of Obstetricians and Gynecologists, lead author Jessica Gleason, PhD, MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md, and colleagues reported.

“Systematic reviews and meta-analyses have reported that maternal caffeine consumption, even in doses lower than 200 mg, is associated with a higher risk for low birth weight, small for gestational age (SGA), and fetal growth restriction, suggesting there may be no safe amount of caffeine during pregnancy,” the investigators wrote in JAMA Network Open.

Findings to date have been inconsistent, with a 2014 meta-analysis reporting contrary or null results in four out of nine studies.

Dr. Gleason and colleagues suggested that such discrepancies may be caused by uncontrolled confounding factors in some of the studies, such as smoking, as well as the inadequacy of self-reporting, which fails to incorporate variations in caffeine content between beverages, or differences in rates of metabolism between individuals.

“To our knowledge, no studies have examined the association between caffeine intake and neonatal anthropometric measures beyond weight, length, and head circumference, and few have analyzed plasma concentrations of caffeine and its metabolites or genetic variations in the rate of metabolism associated with neonatal size,” the investigators wrote.

Dr. Gleason and colleagues set out to address this knowledge gap with a prospective cohort study, including 2,055 nonsmoking women with low risk of birth defects who presented at 12 centers between 2009 and 2013. Mean participant age was 28.3 years and mean body mass index was 23.6. Races and ethnicities were represented almost evenly even across four groups: Hispanic (28.2%), White (27.4%), Black (25.2%), and Asian/Pacific Islander (19.2%). Rate of caffeine metabolism was defined by the single-nucleotide variant rs762551 (CYP1A2*1F), according to which, slightly more women had slow metabolism (52.7%) than fast metabolism (47.3%).

Women were enrolled at 8-13 weeks’ gestational age, at which time they underwent interviews and blood draws, allowing for measurement of caffeine and paraxanthine plasma levels, as well as self-reported caffeine consumption during the preceding week.

Over the course of six visits, fetal growth was observed via ultrasound. Medical records were used to determine birth weights and neonatal anthropometric measures, including fat and skin fold mass, body length, and circumferences of the thigh, arm, abdomen, and head.

Neonatal measurements were compared with plasma levels of caffeine and paraxanthine, both continuously and as quartiles (Q1, ≤ 28.3 ng/mL; Q2, 28.4-157.1 ng/mL; Q3, 157.2-658.8 ng/mL; Q4, > 658.8 ng/mL). Comparisons were also made with self-reported caffeine intake.

Women who reported drinking 1-50 mg of caffeine per day had neonates with smaller subscapular skin folds (beta = –0.14 mm; 95% confidence interval, –0.27 to -–0.01 mm), while those who reported more than 50 mg per day had newborns with lower birth weight (beta = –66 g; 95% CI, –121 to –10 g), and smaller circumferences of mid-upper thigh (beta = –0.32 cm; 95% CI, –0.55 to –0.09 cm), anterior thigh skin fold (beta = –0.24 mm; 95% CI, –0.47 to -.01 mm), and mid-upper arm (beta = –0.17 cm; 95% CI, –0.31 to –0.02 cm).

Caffeine plasma concentrations supported these findings.

Compared with women who had caffeine plasma concentrations in the lowest quartile, those in the highest quartile gave birth to neonates with shorter length (beta = –0.44 cm; P = .04 for trend) and lower body weight (beta = –84.3 g; P = .04 for trend), as well as smaller mid-upper arm circumference (beta = -0.25 cm; P = .02 for trend), mid-upper thigh circumference (beta = –0.29 cm; P = .07 for trend), and head circumference (beta = –0.28 cm; P < .001 for trend). A comparison of lower and upper paraxanthine quartiles revealed the similar trends, as did analyses of continuous measures.

“Our results suggest that caffeine consumption during pregnancy, even at levels much lower than the recommended 200 mg per day of caffeine may be associated with decreased fetal growth,” the investigators concluded.

Sarah W. Prager, MD, of the University of Washington, Seattle, suggested that the findings “do not demonstrate that caffeine has a clinically meaningful negative clinical impact on newborn size and weight.”

She noted that there was no difference in the rate of SGA between plasma caffeine quartiles, and that most patients were thin, which may not accurately represent the U.S. population.

“Based on these new data, my take home message to patients would be that increasing amounts of caffeine can have a small but real impact on the size of their baby at birth, though it is unlikely to result in a diagnosis of SGA,” she said. “Pregnant patients may want to limit caffeine intake even more than the ACOG recommendation of 200 mg per day.”

According to Robert M. Silver, MD, of the University of Utah Health Sciences Center, Salt Lake City, “data from this study are of high quality, owing to the prospective cohort design, large numbers, assessment of biomarkers, and sophisticated analyses.”

Still, he urged a cautious interpretation from a clinical perspective.

“It is important to not overreact to these data,” he said. “The decrease in fetal growth associated with caffeine is small and may prove to be clinically meaningless. Accordingly, clinical recommendations regarding caffeine intake during pregnancy should not be modified solely based on this study.”

Dr. Silver suggested that the findings deserve additional investigation.

“These observations warrant further research about the effects of caffeine exposure during pregnancy,” he said. “Ideally, studies should assess the effect of caffeine exposure on fetal growth in various pregnancy epochs as well as on neonatal and childhood growth.”

The study was funded by the Intramural Research Program of the NICHD. Dr. Gerlanc is an employee of The Prospective Group, which was contracted to provide statistical support.

Although supine sleep positioning of preterm infants is becoming more common, racial disparities remain, according to a retrospective analysis involving more than 66,000 mothers.

monkeybusinessimages/iStock/Getty Images

Non-Hispanic Black preterm infants were 39%-56% less likely to sleep on their backs than were non-Hispanic White preterm infants, reported lead author Sunah S. Hwang, MD, MPH, of the University Colorado, Aurora, and colleagues.

According to the investigators, these findings may explain, in part, why the risk of sudden unexpected infant death (SUID) is more than twofold higher among non-Hispanic Black preterm infants than non-Hispanic White preterm infants.

“During the first year of life, one of the most effective and modifiable parental behaviors that may reduce the risk for SUID is adhering to safe infant sleep practices, including supine sleep positioning or back-sleeping,” wrote Dr. Hwang and colleagues. The report is in the Journal of Pediatrics. “For the healthy-term population, research on the racial/ethnic disparity in adherence to safe sleep practices is robust, but for preterm infants who are at much higher risk for SUID, less is known.”

To address this knowledge gap, the investigators conducted a retrospective study using data from the Pregnancy Risk Assessment Monitoring System (PRAMS), a population-based perinatal surveillance system. The final dataset involved 66,131 mothers who gave birth to preterm infants in 16 states between 2000 and 2015. The sample size was weighted to 1,020,986 mothers.

The investigators evaluated annual marginal prevalence of supine sleep positioning among two cohorts: early preterm infants (gestational age less than 34 weeks) and late preterm infants (gestational age 34-36 weeks). The primary outcome was rate of supine sleep positioning, a practice that must have been followed consistently, excluding other positions (i.e. prone or side). Mothers were grouped by race/ethnicity into four categories: non-Hispanic Black, non-Hispanic White, Hispanic, and other. Several other maternal and infant characteristics were recorded, including marital status, maternal age, education, insurance prior to birth, history of previous live birth, insurance, method of delivery, birth weight, and sex.

From 2000 to 2015, the overall adjusted odds of supine sleep positioning increased by 8.5% in the early preterm group and 5.2% in the late preterm group. This intergroup difference may be due to disparate levels of in-hospital education, the investigators suggested.

“Perhaps the longer NICU hospitalization for early preterm infants compared with late preterm infants affords greater opportunities for parental education and engagement about safe sleep practices,” they wrote.

Among early preterm infants, odds percentages increased by 7.3%, 7.7%, and 10.0% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers, respectively. For late preterm infants, respective rates increased by 5.9%, 4.8%, and 5.8% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers.

Despite these improvements, racial disparities were still observed. Non-Hispanic Black mothers reported lower rates of supine sleep positioning for both early preterm infants (odds ratio [OR], 0.61; P less than .0001) and late preterm infants (OR, 0.44; P less than .0001) compared with non-Hispanic White mothers.

These disparities seem “to be in line with racial/ethnic disparity trends in infant mortality and in SUID rates that have persisted for decades among infants,” the investigators wrote.

To a lesser degree, and lacking statistical significance, Hispanic mothers reported lower odds of supine sleep positioning than the odds of White mothers for both early preterm infants (OR, 0.80; P = .1670) and late preterm infants (OR, 0.81; P = .1054).

According to Dr. Hwang and colleagues, more specific demographic data are needed to accurately describe supine sleep positioning rates among Hispanic mothers, partly because of the heterogeneity of this cohort.

“A large body of literature has shown significant variability by immigrant status and country of origin in several infant health outcomes among the Hispanic population,” the investigators wrote. “This study was unable to stratify the Hispanic cohort by these characteristics and thus the distribution of supine sleep positioning prevalence across different Hispanic subgroups could not be demonstrated in this study.”

The investigators also suggested that interventional studies are needed.

“Additional efforts to understand the barriers and facilitators to SSP [supine sleep positioning] adherence among all preterm infant caregivers, particularly non-Hispanic Black and Hispanic parents, are needed so that novel interventions can then be developed,” they wrote.

According to Denice Cora-Bramble, MD, MBA, chief diversity officer at Children’s National Hospital and professor of pediatrics at George Washington University, Washington, the observed improvements in supine sleep positioning may predict lower rates of infant mortality, but more work in the area is needed.

“In spite of improvement in infants’ supine sleep positioning during the study period, racial/ethnic disparities persisted among non-Hispanic Blacks and Hispanics,” Dr. Cora-Bramble said. “That there was improvement among the populations included in the study is significant because of the associated and expected decrease in infant mortality. However, the study results need to be evaluated within the context of [the study’s] limitations, such as the inclusion of only sixteen states in the data analysis. More research is needed to understand and effectively address the disparities highlighted in the study.”

The investigators and Dr. Cora-Bramble reported no conflicts of interest.

Although supine sleep positioning of preterm infants is becoming more common, racial disparities remain, according to a retrospective analysis involving more than 66,000 mothers.

monkeybusinessimages/iStock/Getty Images

Non-Hispanic Black preterm infants were 39%-56% less likely to sleep on their backs than were non-Hispanic White preterm infants, reported lead author Sunah S. Hwang, MD, MPH, of the University Colorado, Aurora, and colleagues.

According to the investigators, these findings may explain, in part, why the risk of sudden unexpected infant death (SUID) is more than twofold higher among non-Hispanic Black preterm infants than non-Hispanic White preterm infants.

“During the first year of life, one of the most effective and modifiable parental behaviors that may reduce the risk for SUID is adhering to safe infant sleep practices, including supine sleep positioning or back-sleeping,” wrote Dr. Hwang and colleagues. The report is in the Journal of Pediatrics. “For the healthy-term population, research on the racial/ethnic disparity in adherence to safe sleep practices is robust, but for preterm infants who are at much higher risk for SUID, less is known.”

To address this knowledge gap, the investigators conducted a retrospective study using data from the Pregnancy Risk Assessment Monitoring System (PRAMS), a population-based perinatal surveillance system. The final dataset involved 66,131 mothers who gave birth to preterm infants in 16 states between 2000 and 2015. The sample size was weighted to 1,020,986 mothers.

The investigators evaluated annual marginal prevalence of supine sleep positioning among two cohorts: early preterm infants (gestational age less than 34 weeks) and late preterm infants (gestational age 34-36 weeks). The primary outcome was rate of supine sleep positioning, a practice that must have been followed consistently, excluding other positions (i.e. prone or side). Mothers were grouped by race/ethnicity into four categories: non-Hispanic Black, non-Hispanic White, Hispanic, and other. Several other maternal and infant characteristics were recorded, including marital status, maternal age, education, insurance prior to birth, history of previous live birth, insurance, method of delivery, birth weight, and sex.

From 2000 to 2015, the overall adjusted odds of supine sleep positioning increased by 8.5% in the early preterm group and 5.2% in the late preterm group. This intergroup difference may be due to disparate levels of in-hospital education, the investigators suggested.

“Perhaps the longer NICU hospitalization for early preterm infants compared with late preterm infants affords greater opportunities for parental education and engagement about safe sleep practices,” they wrote.

Among early preterm infants, odds percentages increased by 7.3%, 7.7%, and 10.0% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers, respectively. For late preterm infants, respective rates increased by 5.9%, 4.8%, and 5.8% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers.

Despite these improvements, racial disparities were still observed. Non-Hispanic Black mothers reported lower rates of supine sleep positioning for both early preterm infants (odds ratio [OR], 0.61; P less than .0001) and late preterm infants (OR, 0.44; P less than .0001) compared with non-Hispanic White mothers.

These disparities seem “to be in line with racial/ethnic disparity trends in infant mortality and in SUID rates that have persisted for decades among infants,” the investigators wrote.

To a lesser degree, and lacking statistical significance, Hispanic mothers reported lower odds of supine sleep positioning than the odds of White mothers for both early preterm infants (OR, 0.80; P = .1670) and late preterm infants (OR, 0.81; P = .1054).

According to Dr. Hwang and colleagues, more specific demographic data are needed to accurately describe supine sleep positioning rates among Hispanic mothers, partly because of the heterogeneity of this cohort.

“A large body of literature has shown significant variability by immigrant status and country of origin in several infant health outcomes among the Hispanic population,” the investigators wrote. “This study was unable to stratify the Hispanic cohort by these characteristics and thus the distribution of supine sleep positioning prevalence across different Hispanic subgroups could not be demonstrated in this study.”

The investigators also suggested that interventional studies are needed.

“Additional efforts to understand the barriers and facilitators to SSP [supine sleep positioning] adherence among all preterm infant caregivers, particularly non-Hispanic Black and Hispanic parents, are needed so that novel interventions can then be developed,” they wrote.

According to Denice Cora-Bramble, MD, MBA, chief diversity officer at Children’s National Hospital and professor of pediatrics at George Washington University, Washington, the observed improvements in supine sleep positioning may predict lower rates of infant mortality, but more work in the area is needed.

“In spite of improvement in infants’ supine sleep positioning during the study period, racial/ethnic disparities persisted among non-Hispanic Blacks and Hispanics,” Dr. Cora-Bramble said. “That there was improvement among the populations included in the study is significant because of the associated and expected decrease in infant mortality. However, the study results need to be evaluated within the context of [the study’s] limitations, such as the inclusion of only sixteen states in the data analysis. More research is needed to understand and effectively address the disparities highlighted in the study.”

The investigators and Dr. Cora-Bramble reported no conflicts of interest.

Although supine sleep positioning of preterm infants is becoming more common, racial disparities remain, according to a retrospective analysis involving more than 66,000 mothers.

monkeybusinessimages/iStock/Getty Images

Non-Hispanic Black preterm infants were 39%-56% less likely to sleep on their backs than were non-Hispanic White preterm infants, reported lead author Sunah S. Hwang, MD, MPH, of the University Colorado, Aurora, and colleagues.

According to the investigators, these findings may explain, in part, why the risk of sudden unexpected infant death (SUID) is more than twofold higher among non-Hispanic Black preterm infants than non-Hispanic White preterm infants.

“During the first year of life, one of the most effective and modifiable parental behaviors that may reduce the risk for SUID is adhering to safe infant sleep practices, including supine sleep positioning or back-sleeping,” wrote Dr. Hwang and colleagues. The report is in the Journal of Pediatrics. “For the healthy-term population, research on the racial/ethnic disparity in adherence to safe sleep practices is robust, but for preterm infants who are at much higher risk for SUID, less is known.”

To address this knowledge gap, the investigators conducted a retrospective study using data from the Pregnancy Risk Assessment Monitoring System (PRAMS), a population-based perinatal surveillance system. The final dataset involved 66,131 mothers who gave birth to preterm infants in 16 states between 2000 and 2015. The sample size was weighted to 1,020,986 mothers.

The investigators evaluated annual marginal prevalence of supine sleep positioning among two cohorts: early preterm infants (gestational age less than 34 weeks) and late preterm infants (gestational age 34-36 weeks). The primary outcome was rate of supine sleep positioning, a practice that must have been followed consistently, excluding other positions (i.e. prone or side). Mothers were grouped by race/ethnicity into four categories: non-Hispanic Black, non-Hispanic White, Hispanic, and other. Several other maternal and infant characteristics were recorded, including marital status, maternal age, education, insurance prior to birth, history of previous live birth, insurance, method of delivery, birth weight, and sex.

From 2000 to 2015, the overall adjusted odds of supine sleep positioning increased by 8.5% in the early preterm group and 5.2% in the late preterm group. This intergroup difference may be due to disparate levels of in-hospital education, the investigators suggested.

“Perhaps the longer NICU hospitalization for early preterm infants compared with late preterm infants affords greater opportunities for parental education and engagement about safe sleep practices,” they wrote.

Among early preterm infants, odds percentages increased by 7.3%, 7.7%, and 10.0% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers, respectively. For late preterm infants, respective rates increased by 5.9%, 4.8%, and 5.8% for non-Hispanic Black, Hispanic, and non-Hispanic White mothers.

Despite these improvements, racial disparities were still observed. Non-Hispanic Black mothers reported lower rates of supine sleep positioning for both early preterm infants (odds ratio [OR], 0.61; P less than .0001) and late preterm infants (OR, 0.44; P less than .0001) compared with non-Hispanic White mothers.

These disparities seem “to be in line with racial/ethnic disparity trends in infant mortality and in SUID rates that have persisted for decades among infants,” the investigators wrote.

To a lesser degree, and lacking statistical significance, Hispanic mothers reported lower odds of supine sleep positioning than the odds of White mothers for both early preterm infants (OR, 0.80; P = .1670) and late preterm infants (OR, 0.81; P = .1054).

According to Dr. Hwang and colleagues, more specific demographic data are needed to accurately describe supine sleep positioning rates among Hispanic mothers, partly because of the heterogeneity of this cohort.

“A large body of literature has shown significant variability by immigrant status and country of origin in several infant health outcomes among the Hispanic population,” the investigators wrote. “This study was unable to stratify the Hispanic cohort by these characteristics and thus the distribution of supine sleep positioning prevalence across different Hispanic subgroups could not be demonstrated in this study.”

The investigators also suggested that interventional studies are needed.

“Additional efforts to understand the barriers and facilitators to SSP [supine sleep positioning] adherence among all preterm infant caregivers, particularly non-Hispanic Black and Hispanic parents, are needed so that novel interventions can then be developed,” they wrote.

According to Denice Cora-Bramble, MD, MBA, chief diversity officer at Children’s National Hospital and professor of pediatrics at George Washington University, Washington, the observed improvements in supine sleep positioning may predict lower rates of infant mortality, but more work in the area is needed.

“In spite of improvement in infants’ supine sleep positioning during the study period, racial/ethnic disparities persisted among non-Hispanic Blacks and Hispanics,” Dr. Cora-Bramble said. “That there was improvement among the populations included in the study is significant because of the associated and expected decrease in infant mortality. However, the study results need to be evaluated within the context of [the study’s] limitations, such as the inclusion of only sixteen states in the data analysis. More research is needed to understand and effectively address the disparities highlighted in the study.”

The investigators and Dr. Cora-Bramble reported no conflicts of interest.

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

Delta-9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, remains detectable in breast milk even after weeks of abstinence, new data show. The estimated half-life of THC in breast milk is 17 days, according to the study results, with a projected time to elimination of more than 6 weeks. The clinical importance of the remaining THC is up for debate, according to some experts.

“To limit THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and post partum,” Erica M. Wymore, MD, MPH, an assistant professor of pediatrics and neonatology at the University of Colorado at Denver, Aurora, and colleagues wrote. The group published their results online March 8, 2021, in JAMA Pediatrics.

And while the study was a pharmacokinetic analysis rather than a safety investigation, Dr. Wymore said in an interview that the detectable levels of THC suggest any use is of concern and no safety thresholds have been established. “We wish we had more data on the potential effects on the neurocognitive development of children, but for now we must discourage any use in prepregnancy, pregnancy, and breastfeeding, as our national guidelines recommend.”

Therefore, the findings support current guidelines discouraging any cannabis use in mothers-to-be and breast-feeding mothers issued by national organizations, including those from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the Academy of Breastfeeding Medicine.

Furthermore, the difficulties many mothers face in abstaining from marijuana, a commonly used drug in pregnancy, and the persistence of THC in maternal milk led the authors to question the feasibility of having women who use marijuana simply discard their breast milk until THC is cleared.

“We report challenges in abstention and prolonged excretion of THC in breast milk greater than 6 weeks among women with prenatal marijuana use,” they wrote. “These findings make the recommendations for mothers to discard breast milk until THC is undetectable unrealistic for mothers committed to breastfeeding.”

However, not all experts are equally concerned about low THC concentrations in breast milk. Neonatal pharmacologist Thomas R. Hale, PhD, a professor of pediatrics at Texas Tech University, Lubbock, said a previous study by his group showed that THC levels in maternal milk peaked within 60 minutes of a moderate dose of inhaled marijuana and fell to quite low levels over the next 4 hours. The highest concentration in maternal milk occurred shortly after the peak in plasma.

“So you can see that, just because a mom is drug screen positive, the clinical dose transferred to the infant is probably exceedingly low,” he said in an interview.

Dr. Hale also stressed that judgments about drugs in this context should weigh the risk of the drug against the risk of not breastfeeding. “All of us caution women not to use cannabis when pregnant or breastfeeding,” Dr. Hale said. “But when the decision has to be made as to whether a mom breastfeeds or not if she is drug screen positive, a lot of other factors must be analyzed to make such a decision.”
 

Study cohort

For the study, Dr. Wymore and colleagues screened 394 women who gave birth between Nov. 1, 2016, and June 30, 2019. Of those, 25 women, with a median age of 26 years, were eligible and enrolled. Inclusion criteria included known prenatal marijuana use, intention to breastfeed, and self-reported abstinence. Prenatal use primarily involved inhaling cannabis more than twice a week.

Of the 25 enrolled mothers, 12 who self-reported marijuana abstinence were in fact found to be abstinent according to the results of plasma analysis. Those who continued to use the substance were younger than the overall sample, with a median age of 21, and were less likely to have attended college (23%) than abstainers (58%).

The researchers prospectively collected data on self-reported marijuana usage and paired maternal plasma and breast milk samples several times a week. All participants had detectable THC in breast milk throughout the study. Initial median THC concentrations were 3.2 ng/mL (interquartile range, 1.2-6.8) within the first week after delivery. These increased to 5.5 ng/mL (IQR, 4.4-16.0) at 2 weeks and declined to 1.9 ng/mL (IQR, 1.1-4.3) at 6 weeks. In terms of ratio, the milk:plasma partition coefficient for THC was approximately 6:1 (IQR, 3.8:1-8.1:1).

Dr. Hale noted that, although THC was detectable in milk, the levels were exceedingly low. “This is where the risk assessment comes in. There’s a lot of hysteria in the cannabis field right now, and we’re going to need time and a lot more studies to really be able to predict any untoward complications.”

Dr. Wymore, however, countered that THC levels were low only in those who abstained and that her concerns relate not just to postpartum breast milk levels but the health effects on children of mothers’ cannabis use over the course of prepregnancy, pregnancy, and lactation. “[Dr. Hale’s] message makes it difficult for clinicians to counsel mothers since it goes against national guidelines,” she said. “We need to be consistent.”

But Dr. Wymore and other experts acknowledge the dilemma faced in that breast milk clearly offers substantial benefits for infant and child health. “The risks of an infant’s exposure to marijuana versus the benefit of breast milk must be considered,” said Amy B. Hair, MD, assistant professor of pediatrics and neonatal medicine at Baylor College of Medicine, Houston, who was not involved in the Colorado study. “And it’s unrealistic, as the study suggests, for mothers to discard breast milk for 6 weeks.”

Nevertheless, calling the findings of THC persistence after abstinence “troublesome,” Dr. Hair said the legalization of marijuana in some states gives the public the impression it’s safe to use marijuana even during pregnancy and lactation. “Research studies, however, are concerning for potential detrimental effects on brain growth and development in infants whose mothers use marijuana during pregnancy and breastfeeding,” she added.

Dr. Wymore stressed that more U.S. cannabis dispensaries must engage in rigorous point-of-sale counseling to women on the potential harms during pregnancy. This is the case in Canada, she noted, where recreational and medicinal cannabis has been legal since 2018 and more than 90% of outlets (vs. two thirds of their U.S. counterparts) advise women not to use cannabis during pregnancy or lactation, even for nausea.

“This is where many women are getting their information on cannabis,” she said. “We learned the hard way with alcohol and we don’t want to make the same mistake with marijuana.”

The study was funded by the Colorado Department of Public Health and Environment, the Children’s Hospital Colorado Research Institute, the Colorado Fetal Care Center, the Colorado Perinatal Clinical and Translational Research Center, and the Children’s Colorado Research Institute. Two study coauthors disclosed relationships with the private sector outside the submitted work. Dr. Hale and Dr. Hair have disclosed no competing interests with regard to their comments.

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

A baby girl who was born 3 weeks after her mom got the first dose of the Moderna COVID-19 vaccine has antibodies against the coronavirus, according to a preprint paper published on the medRxiv server Feb. 5. The paper hasn’t yet been peer reviewed.

The mom, a health care worker in Florida, developed COVID-19 antibodies after she received the shot. Testing showed that the antibodies passed through the placenta to the baby.

“Maternal vaccination for influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies,” Paul Gilbert, MD, and Chad Rudnick, MD, pediatricians and researchers at Florida Atlantic University, wrote in the paper.

Previous research has indicated that moms who have recovered from COVID-19 can deliver babies with antibodies, according to Insider, but this may be the first report that shows how vaccination during pregnancy can provide antibodies as well.

Dr. Gilbert and Dr. Rudnick said they were fortunate to connect with the mom in Boca Raton. She hadn’t contracted COVID-19 and was able to get the vaccine at the end of her pregnancy in January. When the baby was born, they were able to test the cord blood to look for antibodies specifically from the vaccine.

“We were very excited to see, once the test result came back, that the antibodies from the mom’s vaccine did in fact pass through the placenta to the newborn,” Dr. Rudnick told WPTV, an NBC affiliate in West Palm Beach.

“We knew that we were going to be potentially one of the first in the world to report it, and that opportunity probably only comes once in a career,” Dr. Gilbert told WPTV.

In the preprint, Dr. Gilbert and Dr. Rudnick said a “vigorous, healthy, full-term” baby was born, and the mom received the second dose of the Moderna vaccine during the postpartum period. The newborn received a normal “well-infant” evaluation and was breastfeeding.

The two doctors called for a “significant and urgent need” to research the safety and efficacy of COVID-19 vaccines during pregnancy. They also encouraged other researchers to create pregnancy and breastfeeding registries to study COVID-19 vaccines in pregnant and breastfeeding moms and newborns.

Dr. Gilbert and Dr. Rudnick are now preparing their research for publication and hope future studies will investigate the amount and length of antibody response in newborns.

“Total antibody measurements may be used to determine how long protection is expected, which may help to determine when the best time would be to begin vaccination,” they wrote.

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

A baby girl who was born 3 weeks after her mom got the first dose of the Moderna COVID-19 vaccine has antibodies against the coronavirus, according to a preprint paper published on the medRxiv server Feb. 5. The paper hasn’t yet been peer reviewed.

The mom, a health care worker in Florida, developed COVID-19 antibodies after she received the shot. Testing showed that the antibodies passed through the placenta to the baby.

“Maternal vaccination for influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies,” Paul Gilbert, MD, and Chad Rudnick, MD, pediatricians and researchers at Florida Atlantic University, wrote in the paper.

Previous research has indicated that moms who have recovered from COVID-19 can deliver babies with antibodies, according to Insider, but this may be the first report that shows how vaccination during pregnancy can provide antibodies as well.

Dr. Gilbert and Dr. Rudnick said they were fortunate to connect with the mom in Boca Raton. She hadn’t contracted COVID-19 and was able to get the vaccine at the end of her pregnancy in January. When the baby was born, they were able to test the cord blood to look for antibodies specifically from the vaccine.

“We were very excited to see, once the test result came back, that the antibodies from the mom’s vaccine did in fact pass through the placenta to the newborn,” Dr. Rudnick told WPTV, an NBC affiliate in West Palm Beach.

“We knew that we were going to be potentially one of the first in the world to report it, and that opportunity probably only comes once in a career,” Dr. Gilbert told WPTV.

In the preprint, Dr. Gilbert and Dr. Rudnick said a “vigorous, healthy, full-term” baby was born, and the mom received the second dose of the Moderna vaccine during the postpartum period. The newborn received a normal “well-infant” evaluation and was breastfeeding.

The two doctors called for a “significant and urgent need” to research the safety and efficacy of COVID-19 vaccines during pregnancy. They also encouraged other researchers to create pregnancy and breastfeeding registries to study COVID-19 vaccines in pregnant and breastfeeding moms and newborns.

Dr. Gilbert and Dr. Rudnick are now preparing their research for publication and hope future studies will investigate the amount and length of antibody response in newborns.

“Total antibody measurements may be used to determine how long protection is expected, which may help to determine when the best time would be to begin vaccination,” they wrote.

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

A baby girl who was born 3 weeks after her mom got the first dose of the Moderna COVID-19 vaccine has antibodies against the coronavirus, according to a preprint paper published on the medRxiv server Feb. 5. The paper hasn’t yet been peer reviewed.

The mom, a health care worker in Florida, developed COVID-19 antibodies after she received the shot. Testing showed that the antibodies passed through the placenta to the baby.

“Maternal vaccination for influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies,” Paul Gilbert, MD, and Chad Rudnick, MD, pediatricians and researchers at Florida Atlantic University, wrote in the paper.

Previous research has indicated that moms who have recovered from COVID-19 can deliver babies with antibodies, according to Insider, but this may be the first report that shows how vaccination during pregnancy can provide antibodies as well.

Dr. Gilbert and Dr. Rudnick said they were fortunate to connect with the mom in Boca Raton. She hadn’t contracted COVID-19 and was able to get the vaccine at the end of her pregnancy in January. When the baby was born, they were able to test the cord blood to look for antibodies specifically from the vaccine.

“We were very excited to see, once the test result came back, that the antibodies from the mom’s vaccine did in fact pass through the placenta to the newborn,” Dr. Rudnick told WPTV, an NBC affiliate in West Palm Beach.

“We knew that we were going to be potentially one of the first in the world to report it, and that opportunity probably only comes once in a career,” Dr. Gilbert told WPTV.

In the preprint, Dr. Gilbert and Dr. Rudnick said a “vigorous, healthy, full-term” baby was born, and the mom received the second dose of the Moderna vaccine during the postpartum period. The newborn received a normal “well-infant” evaluation and was breastfeeding.

The two doctors called for a “significant and urgent need” to research the safety and efficacy of COVID-19 vaccines during pregnancy. They also encouraged other researchers to create pregnancy and breastfeeding registries to study COVID-19 vaccines in pregnant and breastfeeding moms and newborns.

Dr. Gilbert and Dr. Rudnick are now preparing their research for publication and hope future studies will investigate the amount and length of antibody response in newborns.

“Total antibody measurements may be used to determine how long protection is expected, which may help to determine when the best time would be to begin vaccination,” they wrote.

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