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NIH Study Highlights Potential Disparities in Birthweight Outcomes Linked to Environmental Exposures in Vulnerable Populations

Posted on by Jodi Snare

A new study from the Environmental influences on Child Health Outcomes (ECHO) Program sheds light on how environmental exposures may have a larger impact on birth outcomes in vulnerable populations, particularly those defined by race, ethnicity, and maternal education. Researchers wanted to understand when the effect of these exposures becomes clinically significant and how different levels of exposure impact various groups differently.

To explore this, researchers used statistical models to simulate four potential scenarios in which average birthweights in a population could be reduced by varying amounts: 50g, 125g, 167g, and 250g. The study found that the percentage of children with low birthweight (LBW) (birthweight<2500g) varied by socioeconomic categories with the greatest percentage LBW seen in the most vulnerable socioeconomic groups. After analyzing the four scenarios, a clear trend was seen such that the greatest impact of an exposure was seen in the most vulnerable sub-populations. This trend was observed for all scenarios including the impact of a small environmental exposure. The most striking disparity among all scenarios was found in racial sub-populations.

This study showed how vulnerable groups, who already face higher risks of poor health, are more affected by small environmental exposures compared to the general population. Read a research summary here.

NIH Study Explores Pollution Exposure and Birth Outcomes in Pregnant Women Living in Historically Redlined Neighborhoods

Posted on by Jodi Snare

Residence in redlined census tracts during pregnancy was associated with higher exposure to PM2.5 and lower birth weight in a recent study funded by the Environmental influences on Child Health Outcomes (ECHO) Program. Redlining is the historical practice of designating certain neighborhoods, often where minority groups lived, as risky investments for lenders. Additionally, living in ungraded census tracts was linked to elevated PM2.5 exposure, lower birth weight, and increased odds of low birth weight. These findings underscore the complex nature of structural racism, suggesting that factors beyond redlining may contribute to ongoing inequalities in health outcomes. Further research is needed to explore these dynamics and their implications for maternal and infant health. Read the research summary here.

New ECHO Research Finds Children with Autism at Higher Risk for a Range of Health Outcomes

Posted on by Jodi Snare

Collaborative ECHO research led by Elizabeth Kaplan-Kahn, PhD, Kristen Lyall, ScD of the A.J. Drexel Autism Institute at Drexel University and Heather Volk, PhD, MPH of the Bloomberg School of Public Health at Johns Hopkins University investigates the factors that influence the overall health and well-being of people on the autism spectrum. This research, titled “Describing Multidomain Health Outcomes in Autistic Children in the ECHO Program,” is published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Approximately 3% of children in the United States have a diagnosis of autism spectrum disorder (or autism). A large proportion of autism research focuses on understanding the factors that influence the development of autistic traits. However, many people on the autism spectrum report that they would rather prioritize research into the factors that influence their overall health and well-being. This study addressed that priority by investigating the physical, emotional, and overall health outcomes of children on the autism spectrum.

The study included over 4,500 children and adolescents at 29 ECHO research sites across the United States, including 286 participants with autism, with participants varying in age from 5 to 20 years old. The research team conducted an initial analysis on the 4,511 participants by comparing data on their health outcomes and demographic characteristics. They then used a subsample of 1,809 participants, of which 116 were autistic, to group children with similar physical health, emotional health, and overall well-being outcomes into one of three categories, “positive health,” “poorer health,” and “mixed health.”

These profiles were categorized based on data from the research team’s primary outcome measures—multiple Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health scores, the Child Behavior Checklist (CBCL) Dysregulation score, the Social Responsiveness Scale, Second Edition (SRS-2), and standardized Body Mass Index (BMI). These measures evaluated participants’ peer relations, life satisfaction, behavior dysregulation, sleep disturbances, physical activity, etc. The three profiles of participants were then further analyzed to study differences in health outcomes between children on the autism spectrum to non-autistic children.

The study results indicate that autistic children are at higher risk than non-autistic children for poorer health outcomes indicated by lowest scores in Global Health and highest dysregulation scores (e.g. attention problems, aggressive behavior, and anxious-depressive symptoms). However, there is variability in health outcomes within autistic youth as shown by a group of autistic participants who showed high scores on positive health outcomes across domains. Additionally, compared to non-autistic children, more autistic children were born prematurely, had diagnoses of intellectual disability and ADHD, and had a sibling with autism.

“The results of this study offer a glimpse into the range of emotional, physical, and overall health outcomes for children on the autism spectrum,” Dr. Kaplan-Kahn said. “A deeper understanding of the range of health outcomes children with autism experience, and the factors that can affect these outcomes, may help families and practitioners identify and target areas for support or intervention.”

Future work may focus on understanding the factors that influence poor or positive health for children with autism and how those factors change over time. This work might identify opportunities to support these children and promote positive health outcomes.

Read the research summary.

Researchers Publish Overview of Existing Chemical Exposure Research using ECHO Cohort Data

Posted on by Jodi Snare

ECHO Research Spotlight — September 2024

ECHO researchers led by Emily Barrett, PhD, MA of the Rutgers University School of Public Health published a scoping review of existing ECHO research that evaluates the impact of chemical exposures on maternal and child health. A scoping review summarizes and provides an overview of the past and current research on a topic at a given point in time.

The review, titled “Advancing Understanding of Chemical Exposures and Maternal-child Health Through the U.S. Environmental influences on Child Health Outcomes (ECHO) Program: A Scoping Review,” was recently published in Current Environmental Health Reports.

While specific environmental chemical exposures have been proven to impact child well-being, exposure studies are often limited in size and variance, limiting the ability to draw generalizable conclusions from results. With data from more than 60,000 participants from 69 groups of pregnant participants, the ECHO program is the largest study of U.S. children’s health and a unique opportunity for more-representative research.

Barrett and her team analyzed the current landscape of chemical exposure research using ECHO Cohort data. The review was developed to understand how the program has made strides in understanding environmental contributors to maternal and child health.

“With several years of ECHO under our belts, including thousands of biospecimens analyzed for chemical exposures (by ECHO researchers), we thought it was time to check in on the progress that had been made and to highlight the new opportunities opening in Cycle 2 of ECHO,” she said.

Through December 31, 2023, 1,530 papers total were published acknowledging ECHO funding. As of early 2024, there were more than 200 single-cohort papers published on chemical exposures through support of ECHO. In addition, 10 collaborative multi-cohort papers have been published using harmonized ECHO Cohort data. These multi-cohort papers have examined prenatal exposure to per- and polyfluoroalkyl substances (PFAS), phthalates, phenols, parabens, organophosphate esters (OPEs), metals, melamine, aromatic amines, and emerging contaminants.

The NICHD’s Data and Specimen Hub (DASH) database houses extensive ECHO data including over 470,000 chemical assay results and complementary data on priority outcome areas (pre, peri-, and postnatal, airway, obesity, neurodevelopment, and positive health), making it a rich resource for future analyses.

The review points out that ECHO research has focused primarily on prenatal exposures as they relate to birth outcomes such as preterm birth or size at birth. Studies focused on later child health outcomes are anticipated in coming years as follow-up of participating children continues.

“As the ECHO Cohort matures, we’ll be better able to address later child health outcomes including asthma, neurodevelopmental disorders, and obesity,” Barrett said. “With many more ECHO-wide analyses of chemical exposures data ongoing, this is a really active area within ECHO. I would love to update this review five years from now, so we can see just how far we’ve come.”

Barrett also emphasized the value of ECHO research into new and emerging contaminants that may pose risks for children. “As older chemicals are phased out, often due to safety concerns, and newer replacements emerge, it’s imperative that we understand how they may be impacting children’s health and development,” she said.

BREATHE Study Achieves Recruitment Success for Infants with Bronchiolitis

Posted on by Jodi Snare

The BREATHE (Bronchiolitis Recovery and the Use of HEPA Filters) study successfully reached its recruitment goal ahead of schedule and has maintained high participant retention with a 94.5% survey completion rate.

This clinical trial, part of the ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN), focuses on airway health outcomes of infants hospitalized for bronchiolitis. The study, launched in November 2022 at 17 clinical sites across the country, aimed to recruit 230 children. In December 2023, study teams met their recruitment goal several months ahead of schedule and experienced successful retention over the past six months. ECHO ISPCTN anticipates sharing the primary results of this study in early 2025.

“Recruitment and retention successes are due to the hard work and dedication of each research study coordinator from the 17 sites,” said co-principal investigator Kelly Cowan, MD of the University of Vermont. “A big thank you goes out to these researchers as well as the families who agreed to participate, making a difference in children’s health outcomes.”

The goal of the BREATHE study is to determine whether using high-efficiency particulate air (HEPA) filters in the homes of infants under one year old, who were previously hospitalized for bronchiolitis, reduces symptom-free days from respiratory issues, such as cough or trouble breathing, in the six months after discharge.

Eligible families who consented to participate were randomly placed in an intervention or control group. The intervention group used HEPA units with active filters, and the control group used HEPA units with inactive filters. Caregivers agreed to place the HEPA units where the child slept and in a common space where the child spent a large amount of time. Small air pollution monitors were placed in those rooms to measure how the HEPA filters affected indoor air quality. At the conclusion of the study, all families were welcome to keep the HEPA unit(s) and were sent an individual report of their household’s indoor air quality during the study and a summary of the overall results.

Bronchiolitis, typically caused by a viral infection, is the most common cause of hospitalization in children younger than 2 years old in the U.S. Infants hospitalized for bronchiolitis face a higher risk of persistent respiratory symptoms and developing asthma. To date, no effective treatments have been identified.

Indoor air quality influences respiratory health and may be a promising target for intervention. Homes in rural and low-resourced communities often have greater exposure to sources of air pollution such as wood stoves and wildfires.

“If the intervention is successful, in-home HEPA air filtration would provide a strategy for improving breathing for many infants that will be relatively easy for families to implement,” explained co-principal investigator Erin Semmens, PhD of the University of Montana’s Center for Population Health Research.

Learn more about the BREATHE study.

New ECHO Cohort Research Suggests No Significant Association Between Prenatal Cannabis Exposure and Child Autism-Related Outcomes

Posted on by Jodi Snare

Collaborative ECHO research led by Chaela Nutor, MA and Patricia A. Brennan, PhD of Emory University investigates the association between prenatal cannabis exposure and autism spectrum disorder (ASD). The study looked at data from 11,570 school-aged children from across the United States and found no evidence that prenatal cannabis exposure increases the likelihood of ASD, regardless of the child’s sex or gestational age at birth. This research, titled “Examining the Association Between Prenatal Cannabis Exposure and Child Autism Traits: A Multi-cohort Investigation in the Environmental influences on Child Health Outcomes (ECHO) Program,” is published in Autism Research.

This study included children and their mothers from 34 ECHO cohorts across the United States. ECHO researchers gathered data on cannabis use during pregnancy directly from mothers and from their medical records. They also collected information on ASD diagnosis, as well as caregiver-reported data on the children’s autism traits when the children were 1 to 18 years. The researchers used these data and reports to test whether prenatal cannabis use might be associated with ASD.

“With the legalization of cannabis in some areas of the United States, there has been a decrease in the perception of risk and an increase in cannabis use among pregnant women,” said Chaela Nutor. “While fetal exposure to cannabis has been linked to poorer neonatal and cognitive outcomes, relatively few studies have tested the association between prenatal cannabis exposure and autism spectrum disorder.”

The results of this study supported the findings from previous studies showing that initial unadjusted associations between prenatal cannabis exposure and ASD behaviors in school-aged children are no longer significant when controlling for other factors, such as maternal use of other substances during pregnancy.

The researchers are planning another large national study to further investigate the relationship between prenatal cannabis exposure and autism-related behaviors. Future work could examine the role of continued exposure to cannabis after mothers are aware of pregnancy, and other studies could investigate combined exposure to tobacco and cannabis and associated risk for ASD.

Read the research summary.

New ECHO Research Investigates Association Between PFAS Exposure and Bioactive Lipids in Pregnant Participants

Posted on by Jodi Snare

Collaborative ECHO research led by Himal Suthar, MIDS and Max Aung, PhD of the University of Southern California, Los Angeles investigates the association between the concentration of per- and polyfluoroalkyl substances (PFAS) in the blood of pregnant participants with levels of bioactive lipids from three metabolic pathways. This research, titled “Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts,” is published in Environmental Science and Technology.

PFAS are a large, complex group of synthetic chemicals that have been used in consumer products around the world since about the 1950s. They are found in items such as non-stick cookware, stain-resistant fabrics, and firefighting foam. People are most likely exposed to these chemicals through contaminated water or food, using products containing PFAS, or breathing air with PFAS particles.

Because PFAS break down slowly, if at all, people and animals are repeatedly exposed to them, and blood levels of some PFAS can build up over time. Scientific studies have identified multiple health effects associated with PFAS exposure. Women exposed to PFAS during pregnancy are at increased risk for adverse birth outcomes and pregnancy complications.

Changes in bioactive lipids—metabolic and inflammation pathway indicators—have been linked to PFAS exposure and adverse pregnancy outcomes. Widespread evidence of human PFAS exposure and PFAS’ association with pregnancy outcomes warranted a detailed investigation into intermediate mechanisms of PFAS toxicity to inform risk assessment and develop potential interventions.

In this study, the research team estimated associations between 50 plasma bioactive lipids and 12 serum PFAS, in pairs and as a mixture, in 414 pregnant participants from three ECHO study sites. Serum PFAS was measured using liquid chromatography and tandem mass spectrometry. Plasma bioactive lipids were measured using mass spectrometry. Associations between prenatal PFAS exposure and bioactive lipids were quantified using various statistical analyses while controlling for several factors (e.g., maternal age, gestational age at sample collection, maternal education, pre-pregnancy BMI).

When researchers looked at data from different study sites, they found that higher levels of PFAS in blood were often linked with higher levels of certain bioactive lipids. The research team also noticed differences in the distribution of bioactive lipids between individual study sites, possibly driven by variations in the genetic makeup and sociodemographic characteristics of the populations or differences in environmental exposures due to diet.

Researchers found that the similar results from analyzing mixtures of and individual PFAS chemicals indicate that specific bioactive lipids could serve as useful biomarkers of PFAS exposure.

“Findings from our present study contextualize potential clinical care approaches proposed by the National Academies of Science, Engineering, and Medicine by providing details on specific prenatal lipid metabolite and PFAS exposure associations,” Suthar said. “While the bioactive lipids measured in this study have not yet been tested as routine biomarkers in clinical settings, these findings aid in advancing the future of healthcare as additional and more complex lipid biomarkers become measurable and are tested for clinical use.”

The researchers plan to measure associations between bioactive lipids and perinatal mental health outcomes including perinatal and postpartum depression. Future studies could also look at the influence of other variables on this relationship. For example, researchers could investigate the influence of diet, which has been linked to changes in both PFAS and bioactive lipid concentrations.

Read the research summary.

ECHO Cohort Researchers Investigate How Fish Consumption During Pregnancy Affects Child Health

Posted on by Jodi Snare

Fish is an important part of a healthy diet, especially during pregnancy. For example, the evidence-based Dietary Guidelines for Americans recommend that pregnant and breastfeeding women consume 8 to 12 ounces of fish per week.

However, relatively little information is available about how much fish people actually consume in pregnancy, and more research is needed on health outcomes related to consumption of fish, or the omega-3 fatty acids for which fish is a rich source, during pregnancy.

ECHO Cohort researchers addressed these gaps at a recent ECHO Discovery webinar on the science of fish consumption.

Kristen Lyall, ScD of the A.J. Drexel Autism Institute; Emily Oken, MD, MPH of Harvard Medical School and the Harvard Pilgrim Health Care Institute; and Margaret Karagas, PhD of the Geisel School of Medicine and Dartmouth College presented the latest science and discussed what ECHO researchers are hoping to contribute.

These ECHO Cohort researchers described what is currently known about fish consumption during pregnancy and childhood and why the ECHO Program is uniquely positioned to further explore how fish can enhance the health of pregnant women and children.

Fish is rich in omega-3 fatty acids, essential nutrients for healthy fetal brain and eye development, Oken explained. Omega-3 fatty acid consumption during pregnancy also reduces the risk of preterm and early preterm birth, as summarized in a  2023 publication in the American Journal of Obstetrics & Gynecology.

The ECHO Program’s large, diverse participant population allows researchers to better understand the impact of fish consumption and omega-3 supplement intake among pregnant women in the U.S.

Because of the representative sample size, ECHO Cohort researchers are examining consumption of  fish intake and docosahexaenoic acid (DHA) supplements, an omega-3 fatty acid naturally found in seafood, during pregnancy.

Analysis of ECHO Cohort data found that around a quarter of the pregnant participants reported no fish intake during pregnancy. Even fewer participants reported taking omega-3 supplements. (Read the full analysis in the Journal of Public Health Nutrition.)

The data also show that people who did not consume enough fish also did not take DHA supplements. The people who ate enough fish took more supplements, Oken explained. She highlighted that in addition to a positive impact on brain and eye development, taking DHA supplements during pregnancy is associated with decreased preterm birth.

Prenatal fish consumption and autism spectrum disorder

In other recent work, ECHO investigators have examined how eating fish or taking DHA supplements affects childhood autism spectrum disorder (ASD) diagnoses and autism-related traits. (Read the full analysis in the American Journal of Clinical Nutrition.)

ECHO Cohort researchers are in a unique position to examine the relationship between fish intake and supplement use during pregnancy and childhood autism spectrum disorder (ASD) diagnosis and autism-related traits because of the large and representative study population.

A research article published July 1, 2024 in the American Journal of Clinical Nutrition provides an analysis of ECHO Cohort data to address this relationship. This analysis suggests that eating more fish, rather than taking supplements, may be associated with a lower likelihood of ASD diagnosis and, to a lesser extent, a lower likelihood of autism-related traits.

Fish consumption and child growth and development

Many questions remain regarding fish consumption in pregnancy.

The National Academies of Sciences, Engineering, and Medicine (NASEM) recently released a report on the role of maternal and child seafood consumption in child growth and development. Drs. Oken and Karagas served on the report committee, as did ECHO Cohort investigator Julie Herbstman, PhD, of Columbia Mailman School of Public Health; Dr. Herbstman also participated in the ECHO Discovery presentation.

Using data from the National Health and Nutrition Examination Survey (NHANES), the NASEM report found that children ages 1 to 2 years ate fewer than two seafood meals per month on average; only 6 percent of children ages 2 to 19 years reported eating two or more seafood meals per week.

In future work, ECHO Cohort researchers will continue to study how fish consumption impacts child growth and development.  ECHO’s ongoing follow-up, broad focus on health outcomes, and diverse participants allow the initiative to address the many research gaps surrounding the role of fish consumption on child health outcomes.

Reminder: Through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH), the ECHO Program provides de-identified data about ECHO participants so that the larger scientific community can discover new insights about pediatric health.

New ECHO Research Finds Association Between Weight Gain in Preterm Infants and Higher Obesity Risk in Children

Posted on by Jodi Snare

Collaborative ECHO research led by Michael O’Shea, MD, MPH of the University of North Carolina, Chapel Hill, School of Medicine investigates the effects of growth and weight gain during infancy on neurodevelopment and obesity in children born very preterm. This research, titled “Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental influences on Child Health Outcomes Cohort,” is published in the Journal of Pediatrics.

Infants born preterm typically have a period of poor growth in their first few months. After this stretch, they typically exhibit “catch-up” growth defined by an increase in weight z-score—a measure to classify a child’s nutritional status—during childhood and adolescence.

Prior research suggested that a “trade-off” may be associated with catch-up growth, such that individuals with more rapid weight gain during infancy have better neurodevelopmental outcomes than individuals with less weight gain. However, rapid catch-up growth during infancy has also been associated with a higher risk of becoming overweight or obese.

This study involved 1,400 children born before 32 weeks of gestation in hospitals in multiple states in the U.S. between 2002 and 2020. A majority of these children experienced neonatal complications—issues faced during the first 28 days of life—the most common of which was neonatal chronic lung disease. These children were followed for 1 to 4 years, at which point their BMI and neurodevelopmental outcomes were assessed. The data collected allowed for analyses of relationships between weight gain following NICU discharge and neurodevelopmental outcomes and BMI at 1 to 4 years of age.

The study team found that in comparison to infants with low weight gain after birth, infants with very high weight gain after NICU discharge, experienced by 13.6% of participants, had higher body mass index (BMI) scores and a higher risk of obesity at 12-48 months.

The study team also found no evidence that very high weight gain after NICU discharge was associated with better neurodevelopmental outcomes at 12 to 48 months of age. However, infants with very low weight gain after NICU discharge had lower scores on cognitive and language assessments. No significant differences were found between girls and boys.

These results suggest there are possible benefits of close monitoring of post-NICU growth and healthier feeding practices to prevent obesity, which is associated with multiple adverse health outcomes.

“Because this study suggests that very preterm infants who experienced a very high increase in body weight during the first four years after NICU discharge were more likely to have a high BMI with similar neurodevelopmental outcomes, avoiding high weight gain might be beneficial to very preterm infants’ health,” Dr. O’Shea said. “However, as single studies rarely provide sufficient evidence to change clinical practice, this study should not be the sole basis for such changes. If the findings of this ECHO study are replicated in other studies, changes in clinical practice might then be appropriate.”

Future studies are needed to evaluate the relationship between the pace of weight gain during early childhood, long-term developmental outcomes, and changes in children’s BMI. This study focused on weight gain among infants born very preterm after discharge from the NICU. Additional studies are needed to observe the effects of different rates of catch-up growth on infants born closer to term.

Read the research summary.

ECHO Cohort Study Finds Link Between Infant Gut Microbiome and Autism-Related Traits

Posted on by Jodi Snare

Collaborative ECHO research led by Vanja Klepac-Ceraj, PhD, of Wellesley College, and Juliette C. Madan, MD, MS, of Dartmouth Hitchcock Medical Center, investigates the relationship between the infant gut microbiome and childhood autism-related traits. This research, titled “Prospective Association of the Infant Gut Microbiome with Social Behaviors in the ECHO Consortium,” is published in Molecular Autism.

The study sought to identify gut bacteria linked to social traits and brain development in two ECHO Cohort Study Sites. Researchers found that certain features of the gut microbiome of infants were associated with higher scores on the Social Responsiveness Scale-2 (SRS-2), a questionnaire that measures autism-related traits. Specifically, certain bacteria and their functional genes, particularly those related to the production of short-chain fatty acids, were linked to autism-related traits. These associations varied between sex and age groups.

“The findings of this study help us understand the potential likelihood of autism-related traits through the gut-brain axis,” said Dr. Klepac-Ceraj. “This understanding could open up new avenues for targeted early interventions.”

Researchers studied 481 samples from 304 healthy child participants from ECHO Cohort study sites in New Hampshire and Rhode Island. The children were between 6 weeks and 2 years old when they provided stool samples and between 3 and 19 years old when social traits were assessed.

In this study, researchers compared groups of participants from two different study sites, focusing on their gut microbiomes when they were younger and social traits related to ASD at a later age. Both study sites contributing to this analysis had previously sequenced bacterial DNA from fecal samples collected from infants or toddlers. They calculated how common certain bacteria were in each sample and related that to the participant’s social behavior scores.

Future studies could explore interventions that could change the gut bacteria and potentially influence how the brain develops. Researchers also plan to investigate the influence of the developing gut microbiome on other neurobehavioral outcomes, such as anxiety and depression.

Read the research summary.