New ECHO Research Suggests Maternal Sleep During Second Trimester of Pregnancy May be Associated with ADHD Symptoms and Sleep Problems in Children

Collaborative ECHO research led by Claudia Lugo-Candelas, PhD, Tse Hwei, MPH, Seonjoo Lee, PhD, and Cristiane Duarte, MPH, PhD of the Columbia University Irving Medical Center and New York State Psychiatric Institutes investigates the effect of prenatal sleep on children’s health outcomes, including neurodevelopment disorders and sleep quality. This research, titled “Prenatal sleep health and risk of offspring ADHD symptomatology and associated phenotypes: A prospective analysis of timing and sex differences in the ECHO Cohort,” is published in The Lancet Regional Health – Americas.

Sleep difficulties are common in pregnancy. Poor prenatal sleep may relate to negative outcomes for both parent and child, including pregnancy complications and certain birth outcomes. The impact of poor prenatal sleep may also extend beyond pregnancy and birth and may increase the risk for neurodevelopment disorders in offspring, particularly attention-deficit/hyperactivity disorder (ADHD).

In this study, ECHO researchers aimed to study potential associations between poor prenatal sleep and an increased risk of ADHD symptoms and sleep problems in offspring. The research team used data from 794 mother-child pairs across five ECHO research sites and all enrolled pairs with available prenatal sleep and offspring ADHD assessments before age 7 were included. The pregnant participants reported on their sleep during pregnancy using self-report questionnaires and reported on children’s symptoms and behaviors when children were between 3 and 5 years old. The study assessed the children’s ADHD symptoms and associated characteristics using the Child Behavior Checklist Preschool Version, a widely used parent report that measures behavior problems in children.

The study found that prenatal sleep quality and duration, particularly in the second trimester, appeared related to children’s risk for ADHD, emotional reactivity, and sleep problems at age 4. Longer sleep duration in the second trimester was associated with fewer ADHD symptoms in children. Poorer sleep quality scores in the second trimester were associated with greater offspring ADHD symptomatology. Shorter duration and poorer quality of sleep during the second trimester were also associated with more sleep difficulties in children.

“This study extends prior work by examining the associations between self-reported prenatal maternal sleep health and offspring ADHD symptoms in early childhood in a large, socio-demographically diverse sample,” Dr. Lugo-Candelas said. “This study was also the first looking to understand if sleep at a particular time in pregnancy is specifically related to offspring outcomes. Our research suggests we need to better study the role of sleep in pregnancy on both the health of the pregnant woman and their offspring to understand these potential associations.”

Future studies are needed to replicate these findings, as well as investigate the possible mechanisms. Poor sleep may impact inflammation in pregnancy and offspring development, but studies have not examined that association.

Read the research summary.

ECHO Researchers Find Different Rhinoviruses Can Provide Limited Protection Against Each Other

Collaborative ECHO research led by Yury Bochkov, PhD and James Gern, PhD of the University of Wisconsin at Madison investigates similarities and differences in the immune responses to two types of rhinovirus—RV-A and RV-C. This research, titled “Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization,” is published in the Journal of Medical Virology.

Of the three species of rhinoviruses (A, B, and C) that can cause upper respiratory illnesses, RV-A and RV-C are more likely to cause wheezing illnesses in preschoolers and in children and adults who have asthma.  No specific vaccines for these viruses exist yet, in part because the large range of rhinovirus strains makes vaccine development difficult. The goal of this study was to test whether RV-C infections are more likely than RV-A infections to induce long-lasting antibodies that can protect against other RV-C strains.

Over 4,000 children ages 0 to 19 were enrolled in 14 independent studies across Australia, Finland, and the United States. The studies included healthy participants as well as those with asthma and RV illnesses of varying severity. Researchers found that while protective antibody responses to RV-C last for several years, they have only modest cross-species protection that is limited to genetically similar viruses.

“These findings suggest that vaccines against RV-C might need to include many of the most common RV-C types to offer broad protection,” Dr. Bochkov said.

Researchers would also like to determine why RV-C infections occur so frequently, and why they are more likely to cause wheezing illnesses. The ultimate goal of these studies is to help researchers design a practical RV-C vaccine that could protect high-risk children.

Read the research summary.

New ECHO Research Reveals Communication, Collaboration, and Team Science Are Central to the Success of Large, Multi-Site Research Programs

Collaborative ECHO research led by Elissa Faro, PhD, of the University of Iowa, investigates what factors contribute to the success of large, multi-site research programs, like ECHO. The research team interviewed 24 ECHO investigators and staff, and found that communication and working as a team were important for successful collaboration. Most interviewees expressed a desire for more opportunities for direct connection, learning, and sharing with their colleagues. Overall, respondents felt the ECHO Program excels at conducting solution-oriented, high-impact child health research, but also that the Program has an opportunity to further improve communication, collaboration, and decision-making across its vast network of sites and components. This research, titled “A Mixed-Methods Analysis to Understand the Implementation of a Multi-stakeholder Research Consortium: Environmental influences on Child Health Outcomes (ECHO),” is published in the Journal of Clinical and Translational Science.

Large research collaboratives often have more success than single investigators conducting research alone. They produce more publications in journals with higher impact factors that result in more citations and continued research opportunities. As a result, funding agencies continue to increase their support for large, transdisciplinary research groups to address complex and challenging health problems. The National Institutes of Health’s (NIH) ECHO Program developed multi-site collaboration strategies to promote high-impact, collaborative, observational research on child health. Few studies have investigated the perspectives of researchers and staff of large research projects like ECHO, and many questions remain about what factors influence the success of team science. To address these questions, ECHO researchers sought to develop an in-depth understanding of the elements and conditions that influence the implementation of observational research in the ECHO Program.

In early 2022, researchers conducted 24 virtual interviews. The research team interviewed internal stakeholders from ECHO study sites and components, seeking broad representation of research and administrative roles across ECHO. Most interviewees were affiliated with an ECHO study site, but the research team was also able to gather the perspectives of all ECHO Program components except for the Human Health Exposure Analysis Resource (HHEAR)—the ECHO component responsible for testing samples from ECHO participants to help researchers assess the effects of chemical exposures—and the NIH.

The research team developed a semi-structured interview guide, and analyzed both the quantitative and qualitative data collected to understand how individual researcher’s experiences and perspectives reflect the overall implementation of the ECHO Program. As part of this analysis, the researchers tracked metrics organized around four central goals: (1) enrolling and retaining a large and diverse group of participants in ECHO to answer key scientific questions; (2) collecting high-quality data and making it available for analysis; (3) collecting, storing, and using biospecimen samples and data; and (4) publishing and disseminating high-quality, impactful science. These metrics provide complementary, quantitative assessment of ECHO implementation and progress toward key goals and priorities.

This study contributes insight on the implementation of large, multidisciplinary research consortium, and these lessons may be transferable to other large research consortia.

“ECHO researchers highly value team science, co-learning, and collaboration,” Dr. Faro said. “The range of experiences across the program suggests that best practices for large research ventures like ECHO may not be one-size-fits-all but may instead need to be tailored for different groups.”

Read the research summary.

New ECHO Research Identifies Best Epigenetic Tests to Use for Different Pediatric Tissue Samples

Collaborative ECHO research led by Fang Fang, PhD, of the Genomics and Translational Research Center of RTI International evaluates multiple epigenetic clocks to test their accuracy when used to predict the biological age of children. This research, titled “Evaluation of Pediatric Epigenetic Clocks Across Multiple Tissues,” is published in Clinical Epigenetics.

DNA methylation, or DNAm, is a molecular process that adds a tag to the DNA that can control gene expression. Certain well-studied DNAm have been associated with many age-related chronic diseases, including aging itself.

Researchers have developed biochemical models called epigenetic clocks that use DNAm to estimate an individual’s biological age. Scientists have studied these clocks in adult populations in whom accelerated biological age (DNAm-predicted age older than actual chronological age) seems strongly connected to age-related health complications. However, epigenetic clocks for pediatric populations have only recently been built. To understand how these clocks perform in different tissue types and developmental stages, researchers used data from 3,789 children from 20 ECHO research sites to conduct a comprehensive evaluation on seven of these epigenetic clocks—Horvath, Knight, Bohlin, Lee, Mayne, PedBE, and NeoAge—all of which researchers developed for different purposes and tissue types.

The study evaluated each clock to their corresponding tissues, and then compared them across different tissue samples. After comparing the suitability of various epigenetic clocks for each tissue type, researchers evaluated their performance across diverse populations. This evaluation included comparing epigenetic clocks between preterm and term infants within the same tissue type, across different self-reported racial groups, between males and females, and across different tissue types within the same set of participants.

The results of this study suggest that the best epigenetic clock to use depends on the type of sample being studied. For example, the Bohlin and Knight clocks were very similar when predicting gestational age from blood cell samples; the Lee clock outperformed the Mayne clock in predicting gestational age from placental samples; and the PedBE clock was more accurate than the Horvath clock at predicting chronological age from buccal cells. However, the Horvath clock was better at predicting chronological age when using blood cells samples.

The study results suggest the importance of researchers choosing the appropriate clock depending on the focus of their study, and provides practical recommendations for selecting the most appropriate epigenetic clock in different research contexts. The findings of this study may help scientists make better research tools, improving child health research.

“It is important for scientists to understand how these clocks perform in different tissue types and developmental stages throughout early life to ensure they are designing studies appropriately and then correctly interpreting the results of these studies,” Dr. Fang said.

Future studies may use the various epigenetic clocks as recommended to check the health of babies and children. However, researchers should interpret this data with caution as it pertains to conclusions about the performance of specific epigenetic clocks in pediatric populations with varied health backgrounds. In addition to practically applying the recommendations provided by this research, future studies may also examine the effects of genetics on the performance of different epigenetic clocks.

Read the research summary.

NIH Study Suggests Measurement Bias in Common Child Behavior Assessment Tool

FOR IMMEDIATE RELEASE

Researchers identify less biased questions that could reliably capture childhood behavior problems

Scores from a commonly used measure of behavior problems in young children may be skewed depending on the primary language, education, and sex of the caregiver who fills out the survey, as well as the child’s age and race, according to new research from the NIH’s Environmental influences on Child Health Outcomes (ECHO) Program.

ECHO Cohort researchers analyzed data from caregivers who filled out the widely used Child Behavior Checklist (CBCL) 1.5–5 on behalf of 9,087 young children ages 18 to 71 months from 26 ECHO research sites across the United States. The caregiver-reported survey evaluates a range of behavior problems in young children.

"Understanding children's behavior can help us identify potential issues in their development and mental health down the road,” said Shuting Zheng, PhD of the University of California, San Francisco. “To do this effectively, we need reliable ways to measure their behavior equivalently for children from diverse backgrounds."

The study found that how caregivers respond to the questions on the measure was biased the most by the language used to complete the survey, followed by factors such as the caregiver's education level and sex and the child's age and race. These biases persisted after accounting for mental health disparities between these groups. Researchers noted that some information could get lost in translation and people from different cultures could understand child behavior problems differently. The gender of the person answering the questions and their level of education also had an impact and researchers pointed to parents’ expectations about how children should develop as possible influences in how they answered the survey questions.

ECHO Cohort researchers were then able to identify some CBCL questions less affected by measurement biases introduced by sociodemographic factors but which still reliably captured childhood behavior problems. The subset of questions that showed little bias across survey-taker demographics still captures a wide range of behaviors across internalizing (e.g., emotionally reactive, withdrawn) and externalizing problems (aggressive behaviors and attention problems).

Going forward, ECHO Cohort researchers plan to apply these questions, evaluating their reliability in identifying children with clinically significant behavior problems.

“Finding questions with less measurement bias across socio-demographic groups helps researchers and clinicians measure behavior problems in different groups of kids of varying ages and family backgrounds more accurately,” Dr. Zheng said.

Dr. Zheng and Somer Bishop, PhD of the University of California, San Francisco, and Maxwell Mansolf, PhD of Northwestern University led this collaborative research that was published in the Journal of Child Psychology & Psychiatry Advances.

Zheng, S. et al. Measurement Bias in Caregiver-Report of Early Childhood Behavior Problems across Demographic Factors in an ECHO-wide Diverse Sample. Journal of Child Psychology & Psychiatry Advances. DOI: 10.1002/jcv2.12198.

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About ECHO:

Launched in 2016, the Environmental influences on Child Health Outcomes (ECHO) Program is a research program in the Office of the Director at the NIH with the mission to enhance the health of children for generations to come. ECHO investigators study the effects of a broad range of early environmental influences on child health and development. For more information, visit echochildren.org.

About the NIH: NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information, visit.

Media Contacts

For information or to request an interview, contact Rebekah Yeager,  rebekah.yeager@nih.gov.

If you are not a member of the media, but have a general inquiry, please contact  NIHKidsandEnvironment@od.nih.gov.

Connect With Us

echo connectorCheck out the recent issues of our bi-monthly newsletter, the ECHO Connector, for program news and the latest research findings.

To receive the ECHO Connector through email, subscribe here.

Follow @ECHOChildHealth for the latest ECHO Program updates on Twitter.

New ECHO Cohort Suggests Bias in Child Behavior Assessment Tool

Collaborative ECHO Cohort research led by Shuting Zheng, PhD, of the University of California, San Francisco, Maxwell Mansolf, PhD, of Northwestern University, and Somer Bishop, PhD, of the University of California, San Francisco suggests that scores from a commonly used measure of behavior problems in young children may be skewed depending on the primary language, education, and sex of the caregiver who fills out the survey.  This research, titled “Measurement Bias in Caregiver-Report of Early Childhood Behavior Problems across Demographic Factors in an ECHO-wide Diverse Sample,” is published in the Journal of Child Psychology & Psychiatry Advances.

Behavior problems observed in a young child can provide information on that child’s risk for certain developmental conditions and later mental health issues. A valid and unbiased measure of childhood behavior can help researchers and clinicians answer questions about the development of behavior problems in children from different backgrounds.

The Child Behavior Checklist 1.5-5 (CBCL) is a commonly used, caregiver-reported measure of internalizing (e.g., anxious) and externalizing (e.g., aggressive) behavior problems in children ages 1.5 to 5 years. Researchers wanted to find out if scores from this test could be affected by demographic factors such as the child’s age or the caregiver’s sex, education level, and primary language, even after accounting for mental health disparities between these groups. The research team’s goal for this study was to identify factors contributing to measurement bias and identify a subset of questions on the CBCL that were less impacted by bias but still reliably captured childhood behavior problems.

The study included caregivers of over 9,000 children between the ages of 18 to 71 months from 26 ECHO study sites across the United States. The data collected was used to evaluate how the characteristics of the child and the caregiver influence the caregiver responses to the CBCL questions. Researchers found that caregiver or child demographic factors affected caregiver responses to many questions on the CBCL. The language (English vs. Spanish) the caregiver used to complete the survey contributed most to measurement bias, followed by their education level and sex. The child’s age and race also influenced caregiver responses to many CBCL questions.

Researchers then selected the CBCL questions that showed the least amount of bias and compared how well they worked to evaluate childhood behavior problems when compared to the full CBCL survey. The researchers also mapped the scores from the less biased question sets to the scores provided by the full item sets, allowing users to derive comparable scores to the original CBCL scale.

Read the research summary.

A New Cycle for the ECHO Cohort Consortium

I take great pleasure in sharing that the ECHO Cohort Consortium entered a new cycle at the beginning of September, which will allow the ECHO Program to extend and expand the ECHO Cohort to fulfill its mission of enhancing child health for generations to come. We look forward to continuing the high-impact research coming out of ECHO over the next seven years.

National Childhood Obesity Awareness Month this month reminds us that ECHO investigators conduct important research on how nutrition influences child health across all five ECHO outcome areas, including obesity. You can learn more in this month’s Research Spotlight story about a recent ECHO Cohort study that found limiting access to sugary drinks in the home can reduce child consumption by up to 87%, offering a possible approach to reduce childhood obesity.

Finally, I want to remind you that we have two current funding opportunities. These Notices of Funding Opportunities (NOFOs)  for postdoctoral fellows and doctoral candidates, respectively, both provide a chance to study child health outcomes by performing analysis of the ECHO Cohort’s large longitudinal data set on the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) Data and Specimen Hub (DASH) The knowledge and experience generated by these two opportunities will help ECHO pursue its goal of providing a national resource.

NIH Study Identifies Food to Help Pregnant Women Optimize Intake of Key Nutrients

FOR IMMEDIATE RELEASE

Study can help doctors and pregnant patients shape a balanced diet and supplement strategy.

Most pregnant women in the U.S. are at risk of not getting enough of six nutrients important to a healthy pregnancy—vitamin A, vitamin D, folate, calcium, iron, and omega-3 fatty acids—from foods alone. Yet finding a combination of foods and supplements that delivers the right amounts of these nutrients without exceeding calorie recommendations or safety limits can be challenging.

In a new study published in The Journal of Nutrition, researchers from NIH’s Environmental influences on Child Health Outcomes (ECHO) Program wanted to find low-calorie, nutrient-rich foods that could boost nutrient intake, much like dietary supplements do. They calculated how much of the six nutrients participants were getting from their diets and compared that data to pregnancy nutrition recommendations to determine the amount of nutrients the participants would need from additional foods to make up for the gaps in their diet.

What they found was that no single food they evaluated gave enough of all six nutrients in a reasonable serving size to bring typical diets in line with recommendations for nutrient intake during pregnancy. One food—raw seaweed—contained five of the key nutrients—vitamin A, folate, calcium, iron, and omega-3 fatty acid—but required up to 7 cups a day to meet daily requirements. Twenty-one foods and beverages contained at least four key nutrients in reasonable serving sizes, including a 1.2-cup ready-to-drink nutritional shake. Researchers also found that few foods met the targets for vitamin D and iron, suggesting that dietary supplements may be necessary to fill the gaps for those particular nutrients.

"This study emphasizes the importance of a balanced and varied diet during pregnancy, along with considering appropriate supplementation, to ensure the well-being of both the mother and the developing baby," study author Katherine Sauder, PhD of the Wake Forest University School of Medicine said.

The research highlights a selection of healthy, low-calorie foods that pregnant women can add to their diets to help meet nutritional requirements during pregnancy. Some examples of readily available foods to choose from include:

  • 2 cups of raw carrots for vitamin A
  • 6 cups of reduced-fat milk for vitamin D
  • 4 cups of edamame could provide the optimal amount of folic acid
  • 1 cup of a nutritional drink or shake for calcium
  • 9 cups of multigrain cereal for iron
  • 1 cups of canned chicken for omega-3 fatty acids

What happened during the study

ECHO researchers examined more than 2,300 foods and drinks that people in the U.S. typically eat, focusing on those containing one or more of the six essential nutrients to be consumed during pregnancy. The foods and quantities evaluated contained the minimum amount of one or more of the nutrients without exceeding 340 calories or the maximum amount of any of the other nutrients. Then, they compared diets of 2,450 pregnant participants from six ECHO research sites across the U.S. to pregnancy nutrition recommendations to determine how participants could fill the gaps in their diets.

This collaborative research was led by Dr. Sauder and Catherine Cohen, PhD, RD of the University of Colorado Denver - Anschutz Medical Campus.

Sauder, K. et al. Identifying Foods That Optimize Intake of Key Micronutrients During Pregnancy. Journal of Nutrition. DOI: 10.1016/j.tjnut.2023.08.012

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About ECHO:

Launched in 2016, the Environmental influences on Child Health Outcomes (ECHO) Program is a research program in the Office of the Director at the NIH with the mission to enhance the health of children for generations to come. ECHO investigators study the effects of a broad range of early environmental influences on child health and development. For more information, visit echochildren.org.

About the NIH: NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information, visit www.nih.gov.

Media Contacts

For information or to request an interview, contact Rebekah Yeager,  rebekah.yeager@nih.gov.

If you are not a member of the media, but have a general inquiry, please contact  NIHKidsandEnvironment@od.nih.gov.

Connect With Us

echo connectorCheck out the recent issues of our bi-monthly newsletter, the ECHO Connector, for program news and the latest research findings.

To receive the ECHO Connector through email, subscribe here.

Follow @ECHOChildHealth for the latest ECHO Program updates on Twitter.

New ECHO Research Identifies Energy-efficient Foods to Boost Prenatal Nutrient Intake

Katherine Sauder, PhD

Collaborative ECHO Cohort research led by Katherine Sauder, PhD and Catherine Cohen, PhD, RD of the University of Colorado Denver – Anschutz Medical Campus identified more than 2,300 energy-efficient foods that could help provide the right amounts of six key nutrients for a healthy pregnancy. This research, titled “Identifying Foods that Optimize Intake of Key Micronutrients During Pregnancy” is published in The Journal of Nutrition.

Most pregnant women in the U.S. are at risk of not getting enough of the nutrients vitamin A, vitamin D, folate, calcium, iron, and omega-3 fatty acids from foods alone. Previous ECHO Cohort research found that only one prenatal supplement available in the U.S. may give pregnant women the optimal amounts of each of these six nutrients. However, that supplement costs $200 per month and requires the patient to take seven pills a day.

Researchers in this study wanted to identify nutrient-rich foods to supplement a pregnant woman’s diet to meet nutrient targets, in the same way that supplements do. They identified more than 2,300 low-calorie foods with enough of at least one of the six nutrients important in pregnancy, including many with reasonable serving amounts to avoid excessive intake. However, no single food evaluated gave enough of each nutrient to fill all six nutrient gaps. One food—raw seaweed—contained five of the key nutrients—vitamin A, folate, calcium, iron, and omega-3 fatty acid—but required up to 7 cups a day to meet daily requirements. Twenty-one other foods and beverages (mainly fish, vegetables, and beverages) provided target amounts of four of the six key nutrients. Few foods met targets for vitamin D or iron, suggesting that dietary supplements may be necessary to meet those nutrient needs.  Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.

The study included 2,450 pregnant participants from six ECHO Cohort Study Sites across the U.S. ECHO researchers looked at foods and drinks that pregnant participants consumed during their pregnancies and then calculated how much of these six nutrients they were getting from their diet. The researchers compared the participants’ diets to nutrition recommendations for pregnancy to determine the amount of nutrients the participants would need from foods to make up for the gaps in their diet.

“Our analysis indicates that more substantial shifts in dietary intake are likely needed to meet nutrient intake targets, as well as improve prenatal intake more generally,” Dr. Sauder said. “Clinicians can encourage pregnant females to reduce intake of nutrient-poor, energy-dense foods so that more nutrient-rich foods can be consumed without inducing excess calorie intake.”

Read the research summary.

ECHO Awards More Than $157 Million for Observational Research Into Environmental Influences on Child Health

The Environmental influences on Child Health Outcomes (ECHO) Program in the Office of the Director of the National Institutes of Health has made 49 awards totaling over $157 million for the first year of the second seven-year cycle of the ECHO Cohort Consortium.

Forty-five ECHO Cohort Study Sites will recruit and continue to follow participants across the country. A Coordinating Center, Data Analysis Center, Laboratory Core, and Measurement Core will help facilitate the science. Together, as the ECHO Cohort Consortium, they will conduct observational research to further investigate the roles of a broad range of early exposures, including during the preconception period, on five key child health outcomes among diverse populations.

Learn more on the NIH ECHO website.