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ECHO Researchers Investigate Association Between Maternal Inflammation Risk Factors and Dysregulation in Children

Posted on by Jodi Snare

Collaborative ECHO research led by Jean Frazier, MD, of the University of Massachusetts Chan Medical School and Mike O’Shea, MD, of the University of North Carolina at Chapel Hill investigated how factors linked with inflammation during pregnancy might be associated with dysregulation in children after birth. “Dysregulation” in this context refers to children’s attention, anxiety and depression, and aggression being measurably different from what is typically expected for children of their age.

Inflammation is a normal part of the body’s defense to injury or infection. The researchers found that several risk factors associated with inflammation, such as lower maternal educational attainment, pre-pregnancy obesity, prenatal infections, and prenatal tobacco use, were strongly correlated with dysregulation in offspring.

ECHO researchers collected data on maternal factors before and during pregnancy and then used the Child Behavior Checklist (CBCL) to identify children ages 6 to 18 with emotional, cognitive, and behavioral dysregulation. The assessments were collected between 2009 and 2021. The study involved 4,595 children and adolescents from 18 ECHO research sites across the United States.

About 13% of the children and adolescents studied were identified as having emotional and behavioral challenges. Children born to mothers with a prenatal infection had a higher risk for dysregulation later in childhood compared to children born to mothers without an infection. Lower maternal education levels, overweight before pregnancy, and smoking during pregnancy also were associated with a higher likelihood of childhood dysregulation. Children and adolescents who had a parent or sibling with a mental health disorder were more likely to experience dysregulation. Yet having a mother with gestational diabetes had no significant association with child dysregulation.

“Understanding how these factors can affect a child’s behavior can help guide interventions and support strategies to improve children’s well-being,” said Dr. Frazier.

The study highlights the importance of considering maternal inflammation risk factors when looking at children’s behavioral challenges. Future studies could explore the mechanisms linking maternal factors and childhood dysregulation, interventions for children guided by knowledge about inflammation experienced by their mother, and specific methods to prevent or mitigate the factors leading to maternal inflammation.

The research “Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence” was recently published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Read the research summary.

ECHO Researchers Reveal Link Between PFAS Exposure During Pregnancy and Childhood Obesity Risk

Posted on by Jodi Snare

Collaborative ECHO research led by Yun Liu, PhD and Joseph Braun, PhD of Brown University investigates the relationship between maternal exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and obesity risk among children and adolescents. The research team evaluated maternal PFAS levels during pregnancy and child body mass index (BMI) for 1,391 mother-child pairs across eight ECHO cohorts. The researchers found that higher levels of some PFAS during pregnancy were associated with higher BMIs and an increased risk of obesity in children. This research, titled “Associations of Gestational Perfluoroalkyl Substances Exposure with Early Childhood BMI Z-Scores and Risk of Overweight/Obesity: Results from the ECHO Cohorts,” is published in Environmental Health Perspectives.

This study included women who were pregnant between 1999-2019 in California, Illinois, Massachusetts, Colorado, New Hampshire, Georgia, and New York and their children who were evaluated between the ages of 2 and 5 years old. The researchers analyzed the levels of seven different PFAS in blood samples collected from mothers during pregnancy. They then used the children’s height and weight data to calculate their BMI, an approximate measure of body fat, while accounting for each child’s age and sex, as well as other factors related to PFAS exposure and body fat.

“There is growing interest in understanding the effects of PFAS exposure on children’s health,” said Dr. Braun. “Studies like this one will help researchers and policymakers better understand the risks of PFAS in order to take effective actions to protect vulnerable populations.”

Going forward, future studies will examine the associations between maternal PFAS exposure and obesity-related health outcomes in older children.

Read the research summary.

Prenatal Tobacco Exposure and Neurodevelopmental Outcomes in Middle Childhood

Posted on by Jodi Snare

A collaborative study led by ECHO researcher Liz Conradt, PhD of the University of Utah, examined the effects of simultaneous exposure to multiple substances—like tobacco, alcohol, and opioids—on outcomes in middle childhood. The team found that children ages 6 to 11 who were exposed prenatally to tobacco and multiple other substances were more likely to have below average verbal reasoning skills and higher levels of behavioral problems. Their research, titled “Prenatal Substance Exposure: Associations with Neurodevelopment in Middle Childhood,” is published in the American Journal of Perinatology.

To gather these results, the team collected data on prenatal exposure to substances such as alcohol, tobacco, marijuana, and opioids. A total of 256 mother-child pairs participated from two ECHO cohorts with locations in Rhode Island, Minnesota, Washington, California, and New York. When the children were between six and 11 years old, their caregivers were asked to report on the absence or presence of problem behaviors, such as aggression and anxiety. The team also collected data on verbal and nonverbal reasoning and problem solving skills.

Using this information, the researchers identified two specific groups—Group 1 had average verbal reasoning skills, average spatial reasoning skills, and normal levels of problem behavior. Children in this group were exposed to fewer substances before birth. Group 2 had below average verbal reasoning skills, but average spatial reasoning skills, and higher levels of problem behavior. The researchers found that children exposed to multiple substances prenatally, especially including tobacco, were more likely to be in Group 2. The effects of tobacco exposure on problem behavior and reasoning skills were stronger than expected.

“This study shows that children with prenatal tobacco exposure may be at risk for having higher levels of problem behaviors and more challenges with verbal reasoning during middle childhood,” said Conradt. “This is an important risk for pediatricians to keep in mind when conducting yearly check-ups on these children.”

The practice of grouping children based on problem behavior and reasoning skills was a novel approach and can be used in future studies to identify subgroups of children at risk for these outcomes.

Visit The Center for Parenting and Opioids and National Institute on Drug Abuse sites for more information on substance exposures and outcomes.

Read the Research Summary.

Prenatal Substance Exposure Associated with Problem Behaviors in Middle Childhood

Posted on by Jodi Snare
Sarah Maylott, PhD

A collaborative research effort led by Sarah Maylott, PhD of Duke University, suggests that prenatal exposure to substances may increase a child’s risk for displaying problem behaviors in middle childhood. Specifically, children exposed to prenatal tobacco and alcohol were more likely to display rule-breaking or aggressive behaviors, while children exposed to illegal drugs, such as cocaine, methamphetamine, or heroin, were more likely to have higher rates of anxiety, depression, or withdrawn behaviors. However, not all children exposed to substances had behavioral problems, suggesting that some children may be more resilient than others.

This research, titled “Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes” is published in the Journal of Pediatrics.

The results outlined in Dr. Maylott’s work are particularly important, as approximately 1 in 5 women in the United States report use of legal or illegal substances while pregnant, varying from tobacco and alcohol to psychoactive drugs, such as opioids and cocaine. Previous studies have investigated how prenatal exposure to multiple substances may affect the health of young children, but less is understood about how polysubstance exposures may affect the neurodevelopment of older children.

Leveraging data from approximately 2,000 women from 10 ECHO cohorts across the country from 2000-2020, the research team used a statistical analysis technique to group women based on the types of substances used during pregnancy and compared these groups based on their child’s behaviors. On average, pregnant women were 28 years old when they gave birth, and child behaviors were assessed between ages 6 to 11 using the Child Behavior Checklist. The team hypothesized that children with prenatal polysubstance exposure would have more instances of problem behavior in middle childhood than those children with little to no prenatal substance exposure.

“Our work shows that it could be possible to identify children with certain behavioral challenges based on their mothers’ prenatal substance use profiles,” said Dr. Maylott. “With further research, clinicians and researchers may be able to use these results to identify and support children at higher risk for behavior problems.”

Subsequent large-scale studies are needed that look at how the quantity and timing of substance use during pregnancy affect children’s risk for behavioral problems and how the home environment may contribute to that risk. Researchers also need to find factors that may lead to resilient outcomes for children with prenatal substance exposure.

Read the research summary.

ECHO Researchers Examine Incidence Rates for Childhood Asthma With Recurrent Exacerbations and Suggest Possible Social and Environmental Risk Factors

Posted on by Jodi Snare

Collaborative ECHO research led by Rachel L. Miller, MD of Icahn School of Medicine at Mount Sinai and Christine C. Johnson, PhD, MPH of Henry Ford Health System investigates the factors that influence the rates of childhood asthma with recurrent exacerbations (ARE)—a subtype of asthma where children experience frequent, severe episodes of asthma. The researchers leveraged data from over 17,000 children born between 1990 and 2017 and found that children ages 2-4 years old, non-Hispanic Black and Hispanic Black children, and children who lived in the Northeast and Midwest had the highest incidence rates of ARE. Additionally, children with a parental history of asthma had ARE rates almost 3 times greater compared to those with no parental history. This research, titled “Incidence Rates of Childhood Asthma with Recurrent Exacerbations in the U.S. Environmental influences on Child Health Outcomes (ECHO) Program,” is published in The Journal of Allergy and Child Immunology.

While the prevalence of asthma has been reported widely in the United States and elsewhere, studies on childhood asthma incidence rates within specific populations and across various types of asthma and age ranges have been limited. “Describing the incidence rates of ARE across a large, diverse population of children is a critical first step for identifying potential risk factors and causes,” explained Dr. Johnson.

To conduct this research, the research team leveraged data from children enrolled in 60 ECHO cohorts across the U.S. and Puerto Rico. Child participants or their caregivers reported whether and when the child had an asthma diagnosis and any corticosteroids prescribed over time from their health care providers.  Recurrent exacerbations of asthma were based on reports of systemic (not inhaled) corticosteroid use. The researchers calculated incidence rates of ARE for the study population overall, along with rates for subsets of the population defined by the years the ARE were diagnosed, the decade children were born, their age and sex, their race and ethnicity, their residence at birth, and their parents’ history of asthma.

“While children with ARE are all different, these findings suggest that we should examine in the future key elements of the early environment, including viral respiratory tract infections, indoor allergens, environmental tobacco smoke, air pollution, stress, and socioeconomic status, which could contribute to ARE,” said Dr. Miller. “Understanding these causes will help researchers determine how to best prevent ARE and associated asthma outcomes.”

Read the research summary.­­

ECHO Researchers Investigate Associations Between Gestational Diabetes, Perinatal Maternal Depression, and Early Childhood Behavioral Problems

Posted on by Jodi Snare

Collaborative ECHO research led by Lauren C. Shuffrey, PhD of Columbia University investigates the effects of gestational diabetes, a type of diabetes that mothers develop during pregnancy, prenatal depression, and postpartum depression on early childhood behavior. This study found gestational diabetes, prenatal maternal depressive symptoms, and postnatal maternal depressive symptoms were each independently linked to higher levels of externalizing and internalizing behavior problems during early childhood. The study also found that gestational diabetes was only associated with autism-related behaviors when children were exposed to higher levels of perinatal maternal depressive symptoms. Finally, maternal gestational diabetes was only associated with child behavioral problems for male children.

This research, titled “Association of Gestational Diabetes Mellitus and Perinatal Maternal Depression with Early Childhood Behavioral Problems: An Environmental Influences on Child Health Outcomes (ECHO) Study” is published in Child Development.

Although previous research has shown associations between gestational diabetes and pre- and postnatal depression in mothers, prior studies have not determined if the combination of these conditions affect child behavioral outcomes.

This study included 2,379 children from ECHO cohorts located in Colorado, Massachusetts, New York, Pennsylvania, and Tennessee. More than half of child participants (52%) were male, and 216 participants were born to mothers with gestational diabetes during pregnancy.

More than half of maternal participants were from an underrepresented minority group with 32% self-identifying as Black, 23% as Hispanic, 15% as Mixed Race, and 4% as Asian.

In this study, ECHO researchers used the Preschool Child Behavior Checklist (CBCL) to examine the behavior of children ages 2 to 5 years old. The researchers also collected information from the mothers, including gestational diabetes diagnosis and self-assessments of depression symptoms during and after pregnancy. The study evaluated how gestational diabetes, prenatal depression, and postpartum depression affected children’s behavioral outcomes using the CBCL.

“Our findings suggest that children born to mothers who had both gestational diabetes and symptoms of depression during pregnancy could benefit from receiving additional monitoring for behavioral problems during early childhood,” said Dr. Shuffrey. “Future research should investigate potential biological mechanisms underlying associations between gestational diabetes, maternal depression, and early childhood behavioral outcomes.”

Read the research summary.

New ECHO Research Investigates Link Between Maternal Health, Newborn Metabolism, and Childhood BMI

Posted on by Jodi Snare

Collaborative ECHO research led by Britt Snyder, PhD, and Tina Hartert, MD, MPH, of Vanderbilt University Medical Center, and James Gern, MD, of the University of Wisconsin School of Medicine and Public Health, investigates the links between maternal health characteristics and the concentrations of various metabolites in newborns. In addition to identifying these links, the study also demonstrated that some metabolites were linked to childhood body mass index (BMI) at ages 1–3 years. The researchers collected data from 3,492 infants and their mothers and found that certain maternal health factors such as higher BMI before pregnancy or maternal age at delivery seemed to increase the levels of some key metabolites in newborns. This research, titled “The Associations of Maternal Health Characteristics, Newborn Metabolite Concentrations, and Child Body Mass Index among US Children in the ECHO Program,” is published in Metabolites.

This study expanded on previous research investigating links between a variety of maternal characteristics and metabolite levels in newborns and also explored the link between these metabolites and child growth patterns. The researchers also investigated how maternal factors and related chemical changes in utero could possibly contribute to the link between newborn metabolism and childhood BMI. To address these questions, the researchers collected data on maternal health characteristics from self-reported questionnaires, birth certificates, and medical records. They then collected child BMI from medical records and study visits and used statistical tools to evaluate possible links between maternal health characteristics and newborn metabolism.

“These findings provide additional insights on potential in utero pathways through which maternal health characteristics may affect newborn metabolism and later child growth patterns,” said Dr. Snyder.

Future studies are needed to further explore these pathways and understand the relationship between maternal health characteristics and child health.

Read the Research Summary.

New Collaborative ECHO Research Demonstrates Effectiveness of “Eat, Sleep, Console” Approach in Caring for Newborns with Neonatal Opioid Withdrawal Syndrome

Posted on by Jodi Snare

A collaborative effort between the NIH’s Eunice Kennedy Shriver Institute of Child Health and Human Development (NICHD) Neonatal Research Network and the Environmental influences on Child Health Outcomes (ECHO) Program’s Institutional Development Award (IDeA) States Pediatric Clinical Trials Network (ISPCTN) found that the “Eat, Sleep, Console” (ESC) care approach is more effective for the treatment of newborns with neonatal opioid withdrawal syndrome (NOWS) than usual approaches to care. This research was led by ISPCTN investigators Leslie Young, MD of the University of Vermont; and Lori Devlin, DO, MHA, MS of the University of Louisville School of Medicine, Department of Pediatrics; along with Stephanie Merhar, MD, MS of Cincinnati Children’s Hospital and the NICHD Neonatal Research Network.

ESC prioritizes nonpharmacologic care, including holding, swaddling, and rocking in low-stimulus environments, as first-line treatment for neonatal opioid withdrawal symptoms. This research, funded through the NIH Helping to End Addiction Long-term® Initiative (HEAL), showed that infants cared for with ESC were medically ready for discharge after an average of 8.2 days, whereas infants cared for with usual approaches were medically ready for discharge after 14.9 days. That means that babies were, on average, able to go home 6.7 days sooner. Newborns cared for with ESC were also 63% less likely to receive medication as part of their treatment. Safety outcomes at three months of age were similar in both groups. This research, titled “Eat, sleep, console approach versus usual care for neonatal opioid withdrawal,” is published in the New England Journal of Medicine.

“The study included rural and medically underserved communities that have been hard hit by the opioid crisis,” said Matthew W. Gillman, MD, director of the ECHO program. “These findings promise to improve outcomes and address the long-term needs of opioid-exposed infants and their families.”

Newborns exposed to opioids before birth may develop symptoms of NOWS, including tremors, excessive crying and irritability, and problems with sleeping and feeding. In the United States, at least one newborn is diagnosed with NOWS every 24 minutes. There has not previously been strong evidence to support a standard approach to the care of babies with NOWS, and medical care for these babies has varied widely across hospitals.

Hospitals often use the Finnegan Neonatal Abstinence Scoring Tool (FNAST) to assess newborns with NOWS. The FNAST is an extensive scoring system that assesses signs of withdrawal in more than 20 areas. However, concerns have been raised about its subjectivity and overestimation of the need for opioid medication. The ESC care approach, developed about eight years ago, assesses an infant’s ability to eat, sleep, and be consoled without the introduction of medications. This approach keeps mother and baby together, empowering families to play a larger role in the care of their infants.

The study examined the hospital outcomes of a diverse group of 1,305 opioid-exposed infants from 26 hospitals across the U.S. that were randomized to transition from FNAST-based care to the ESC care approach at different times. These findings are based on three-month outcomes, and a two-year follow-up study of a subset of the infants is ongoing. This follow-up is critical to further inform the safety of the ESC care approach.

This study is part of the Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Collaborative.

Learn more about this clinical trial and the NIH Helping to End Addiction Long-term® Initiative on the NIH HEAL Initiative® website.

Read the research summary.

ECHO Researchers Examine Healthcare Use During the COVID-19 Pandemic for Children Born Preterm

Posted on by Jodi Snare

Collaborative research led by Elisabeth McGowan, MD and Barry Lester, PhD, of Brown University and Monica McGrath, ScD, and Andrew Law, ScM, of Johns Hopkins Bloomberg School of Public Health examined healthcare use during the COVID-19 pandemic by children and adolescents born preterm.

The research, titled “Healthcare Utilization During the COVID-19 Pandemic Among Individuals Born Preterm,” is published in JAMA Network Open.

This is one of the first studies to look at healthcare use during the COVID-19 pandemic by a high-risk population—children and adolescents who were born preterm (37 or fewer weeks after gestation). By looking for possible patterns of healthcare utilization, this study can help healthcare providers to improve care for patients in future pandemics or other public healthcare crises.

This study included data from 1,691 individuals ages 1–18 years, including 270 who were born preterm, 37 or fewer weeks of gestation. Among these participants, 159 were born at 28 or fewer weeks and were twice as likely to seek healthcare compared to those born at term.

Between April 2020 and August 2021, researchers collected caregiver- or self-reported questionnaires regarding the COVID-19 pandemic and healthcare use. The researchers studied healthcare use related to concerns about COVID-19 symptoms (like trouble breathing, fever, headache, muscle pain, fatigue, itchy eyes, nausea, diarrhea, vomiting, and loss of smell or taste) that resulted in overnight stays in hospitals, visits to urgent care centers or primary care offices, or virtual visits such as telehealth. Respiratory symptoms were the most common reason for seeking care for those children.

“Understanding the factors associated with both overall healthcare use and symptom-specific use may help healthcare providers identify the best strategies to provide targeted care,” said Dr. McGowan.

Further studies could evaluate the role socioeconomic factors may play in healthcare utilization.

Read the research summary.

ECHO Researchers Investigate the Effect of Family Hardships and Newborn Health Outcomes on the Behavior and Well-being of Young Children

Posted on by Jodi Snare

Collaborative ECHO research led by Julie Hofheimer, PhD of the University of North Carolina at Chapel Hill and Monica McGrath, ScD and Rashelle Musci, PhD, both of Johns Hopkins Bloomberg School of Public Health, investigates the link between family hardships, newborn health outcomes, and the behavior of young children. The researchers collected information on the behavior of 3,934 children between the ages of 18 and 72 months and used that data to identify early factors that increase a child’s risk for experiencing behavioral and emotional difficulties. The study found that children born preterm and those whose families had been exposed to more social, economic, or environmental hardships were more likely to experience continuous behavioral difficulties. This research, titled “Psychosocial and Neonatal Risk Factors Associated with Behavioral Dysregulation Trajectories Among Young Children from 18 through 72 Months of Age,” is published in JAMA Network Open.

Adverse conditions and family hardships have steadily increased over the past two decades, challenging the emotional and behavioral well-being of children and their families. To understand how health and environmental hardships affect a child’s risk for developing continuous behavioral problems, ECHO researchers collected early childhood behavior data from 20 ECHO cohorts from across the United States. About 20% of these children were born preterm (before 37 weeks of gestation).

The researchers collected caregiver self-reports, demographics, and medical and environmental data about the children and their mothers before and during pregnancy and from infancy through age six. Caregivers completed the Child Behavior Checklist at several study visits, and the researchers compared the children’s combined difficulty with anxiety, depression, attention, and aggression to their behavioral well-being across the first six years of life.

Some children who experienced less family adversity showed improved behavior over time. Importantly, some children were able to overcome hardships and improve their behavior. Through this study, the researchers were able identify early factors that increase a child’s risk for experiencing behavioral and emotional difficulties.

“Conditions during pregnancy and early infancy can identify toddlers who may benefit from early enriched services,” said Dr. Hofheimer. “Family support services tailored to the individual needs of children may prevent later behavioral problems and improve future outcomes for vulnerable children and their families.”

Future ECHO research may examine how childhood behavior continues to develop from six years onward, examining the link between early risk factors and behavioral patterns in middle school and adolescence.

Read the research summary.