Fertility Challenges May Be Associated With Slight Differences in Child Behavior and Autism-like Symptoms, ECHO Study Finds

Authors: Linda Kahn, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

More children are being conceived with the help of fertility treatments, and ECHO researchers wanted to assess whether these treatments or the fertility challenges that necessitate them might be linked to children’s behavior or autism-like symptoms. Fertility treatments include in vitro fertilization (IVF), where an egg is fertilized outside the body before being implanted in the uterus, as well as non-IVF treatments such as fertility medications or procedures like intrauterine insemination. Earlier studies investigating this association were often small, didn’t follow children for long, and couldn’t clearly distinguish the effects of treatment from the effects of infertility itself. They also did not consistently compare different types of fertility treatments. To address this gap, ECHO researchers used a large sample of study participants to compare children conceived with and without fertility treatment, including among families who experienced fertility challenges but conceived naturally, to better understand whether any differences in child behavior or autism-like symptoms are more likely related to treatment or to underlying fertility challenges.

What were the study results?

Trouble conceiving a pregnancy was associated with small differences in children’s behavior and autism-like symptoms. Children whose parents had fertility challenges had slightly higher behavior-problem scores, slightly more autism-like traits, and higher odds of an autism spectrum disorder (ASD) diagnosis, even when they were conceived without fertility treatment. The study also found that children conceived using non-IVF treatments had higher odds of ADHD compared with children conceived naturally (regardless of whether parents had reduced fertility). Researchers did not find clear evidence in this data that IVF itself was linked to brain development outcomes, and results did not meaningfully differ by the child’s sex or age group.

What was this study's impact?

These findings suggest that small increases in some behaviors such as aggression and rule-breaking or social communication problems in children conceived through fertility treatments may be related to the underlying fertility issues rather than the treatment itself. The possible link between non-IVF fertility treatments and ADHD needs more research, especially to understand whether the medical reasons for using these types of treatments rather than IVF explain the difference.

Who was involved?

The study included 15,382 mother-child pairs from 44 sites in the ECHO Cohort in the U.S. The analysis did not include adopted children or pregnancies using donor eggs or sperm. For twins or other multiples, the researchers included only one randomly selected child per pregnancy.

What happened during the study?

Researchers combined information from surveys and medical records to identify participants with a history of fertility challenges, including whether the parents had ever been told they had infertility, had infertility treatment, had two or more miscarriages, or had tried to conceive for 12 months without success. They also identified whether assisted conception involved IVF or non-IVF treatments (like fertility medications or intrauterine insemination). They then looked at the children’s development and diagnoses from ages 2–10, using parent-completed questionnaires and reports of clinician diagnoses of ASD and ADHD.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What happens next?

Future studies could help researchers better understand which specific fertility problems might be linked to outcomes like ADHD and help to identify the possible biological pathways behind these associations.

Where can I learn more?

Access the full journal article, titled “Associations of subfecundity and infertility treatment with child neurodevelopment in ECHO,” in JAMA Network Open.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published June 01, 2026

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Fertility Challenges May Be Associated With Slight Differences in Child Behavior and Autism-like Symptoms, ECHO Study Finds

Unusual Early Childhood Weight Patterns Associated with Higher Risk of Future Obesity

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Unusual Early Childhood Weight Patterns Associated with Higher Risk of Future Obesity

Authors: Chang Liu, Jody Ganiban, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

Childhood obesity is defined as having a body mass index (BMI) 0at or above the 95^th percentile for age and sex. Without early support or intervention, children who show patterns of high BMI during childhood are more likely to become overweight or obese as teenagers and adults. This increases their risk for long-term health issues, including diabetes and heart disease. To prevent these outcomes, it's important to understand how children's BMI changes over time and identify early-life factors—especially those that can be changed—that influence childhood growth patterns. This study aimed to identify unusual BMI patterns (sometimes called atypical BMI trajectories) in early childhood and understand which early-life factors may contribute to them.

What were the study results?

In this study, researchers found two common patterns in how children’s BMI changes over time. Most children (89.4%) had a typical pattern where their BMI went down from ages 1 to 6, then slowly increased. A smaller group (10.6%) had an atypical pattern where their BMI stayed the same from ages 1 to 3.5, then showed rapid increases from ages 3.5 to 9. By age 9, these children were more likely to develop obesity, with an average BMI higher than the 99th percentile. Some factors that associated with the risk of a child developing obesity included high birthweight, maternal smoking during pregnancy, high maternal BMI before pregnancy, and greater maternal weight gain during pregnancy.

What was this study's impact?

The study highlights key prenatal risk factors and early childhood growth trajectories related to childhood obesity, offering opportunities for early prevention and intervention to help children stay on a healthy growth path and reduce their chances of becoming obese.

Who was involved?

The study included 9,483 children from diverse racial, geographical, and socioeconomic backgrounds from the ECHO Cohort.

What happened during the study?

Researchers looked at data collected over time about children’s weight and height from medical records, measurements taken by staff, reports from caregivers, or measurements taken at home. They tracked how children's BMI changed as they grew and looked for patterns.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What happens next?

Future studies could help researchers understand the biological mechanisms and social/environmental factors linked to childhood obesity, helping to develop targeted intervention programs that can redirect unhealthy BMI trajectories.

Where can I learn more?

Access the full journal article, titled “Early-Life Factors and Body Mass Index Trajectories Among U.S. Children in the ECHO Cohort,” in JAMA Network Open.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published May 22, 2025

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Unusual Early Childhood Weight Patterns Associated with Higher Risk of Future Obesity

Obesity, Diabetes, & High Blood Pressure Before and During Pregnancy are Associated with Higher Blood Pressure in Children

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Obesity, Diabetes, & High Blood Pressure Before and During Pregnancy are Associated with Higher Blood Pressure in Children

Authors: Zhongzheng Niu, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

High blood pressure in childhood is linked to a higher risk of experiencing high blood pressure and other heart-related complications later in life. Preventing high blood pressure during childhood could be a promising strategy to improve cardiovascular health into adulthood. Growing evidence suggests that maternal health during pregnancy may be a contributor. For this study, researchers wanted to look at how three common cardiometabolic risk factors— pre-pregnancy obesity, gestational diabetes, and high blood pressure (hypertension) during pregnancy—are related to blood pressure in their children between ages 2 and 18.

What were the study results?

A new finding from this study is that when mothers had more than one health issue during pregnancy—especially when high blood pressure occurred alongside gestational diabetes or pre-pregnancy obesity—their children’s blood pressure was higher than when the mother had only one of these conditions. Of the mothers included in this study, 44% had at least one cardiometabolic risk factor during pregnancy. The most common was pre-pregnancy obesity at 26%, followed by high blood pressure at 14% and gestational diabetes at 7.3%. Children whose mothers had any of these health issues during pregnancy had higher average blood pressure when compared to those born to mothers who did not. This was true for the top (systolic) and the bottom (diastolic) numbers in a blood pressure reading, even after accounting for the child’s age, sex, and height. These children also showed an increased rate of blood pressure change between ages 2 and 18. The association was stronger for diastolic blood pressure in female children and for systolic blood pressure in non-Hispanic Black children whose mothers had gestational diabetes or high blood pressure during pregnancy.

What was this study's impact?

This study can help researchers and clinicians better understand how a mother’s heart and metabolic health during pregnancy may influence a child’s long-term cardiovascular health. This highlights the potential value of early-life interventions aimed at monitoring and managing blood pressure in children with prenatal exposure to these maternal risk factors.

Who was involved?

The research included 12,480 mother-child pairs from study sites in the ECHO program. The mother's average age at pregnancy was 30 years, and 47% of participating mothers were non-White. At least one maternal cardiometabolic risk factor was present in 44% of the mothers.

What happened during the study?

Researchers gathered information about mothers’ heart and metabolic health from medical records or surveys. They also collected blood pressure readings from their children, either during study visits or from their medical records. They used statistical methods to look at how a mother’s health before and during pregnancy might be linked to her child’s blood pressure—both at the youngest age and as the child grew from age 2 to 18. They also looked at whether these links were different depending on the child’s sex or race and ethnicity.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What happens next?

More research could help researchers understand how combinations of maternal cardiometabolic risk factors influence children’s blood pressure over time. Future studies could also examine how structural and social factors contribute to maternal health during pregnancy and shape long-term cardiovascular health in children.

Where can I learn more?

Access the full journal article, titled “Maternal cardiometabolic risk factors in pregnancy and offspring blood pressure at age 2-18 years,” in JAMA Network Open.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published May 08, 2025

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Obesity, Diabetes, & High Blood Pressure Before and During Pregnancy are Associated with Higher Blood Pressure in Children

No Significant Associations Observed Between Prenatal Antibiotic Use and Wheezing Symptoms in Infants

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No Significant Associations Observed Between Prenatal Antibiotic Use and Wheezing Symptoms in Infants

Authors: Rachel Greenberg, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

Wheezing symptoms occur in 20-40% of infants, contributing to a substantial impact on children’s quality of life and their use of healthcare. Multiple early exposures, such as prenatal exposure to cigarette smoking, have been associated with these wheezing symptoms.

Previous studies have suggested a possible link between antibiotic exposure during pregnancy and an increased risk of wheezing and cough in children, caused by an imbalance in the birthing parent’s microbiome due to antibiotic use. However, these studies had some limitations. Additional research was needed to include enough participants to produce reliable results and account for other factors that might have influenced outcomes. This study examined the association between prenatal antibiotic exposure and the development of wheezing during infancy using a large national sample of infants and birthing parents.

What were the study results?

In this study, 36% of pregnant participants used at least one antibiotic while pregnant, and about 26% of infants had a report of wheezing. Overall, the research team observed that exposure to antibiotics during pregnancy was not associated with infant wheezing during the first 18 months after birth. Note that most outcome data were based on birthing parent/caregivers’ self-reports.

Prenatal antibiotic exposure was also not associated with an increase in emergency room visits or hospitalizations for wheeze during infancy. However, prenatal antibiotic use was associated with higher odds of medication use for wheeze or dry cough during infancy, which could imply more severe symptoms and a medical provider’s diagnosis. It is important to note that the study team found an association between prenatal antibiotic exposure and medication use for wheeze or cough during infancy only among children born via vaginal delivery and thus exposed to the birthing parent's microbiota. This finding supports the theory that a change in the microbiome of the birthing parent and infant is related to this association.

The researchers also observed an association between prenatal antibiotic exposure and wheeze in research sites that recruited participants who had a family history of asthma, suggesting that a genetic or environmental risk within these families may increase the likelihood of wheeze.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

The results of this study raise the possibility of an association between prenatal use of prenatal antibiotics and medication use for wheezing in the 18 months after birth. It suggested that prenatal antibiotics may influence respiratory outcomes during infancy, but further studies are needed to understand how the timing and type of antibiotic use may influence these effects.

Who was involved?

This study included 4,721 pregnant participants and their 4,779 infants from 12 study sites in the ECHO Cohort Consortium. Most pregnant participants were between 25 and 35 years old, non-Hispanic White, and had a college degree or more. Overall, 36% of the pregnant participants used at least one antibiotic during their pregnancy.

What happened during the study?

The study team analyzed data collected using questionnaires, interviews, or medical records to analyze associations between prenatal antibiotic exposure and airway symptoms (e.g., wheeze, cough) during infancy. The study team confined the outcome of wheezing to infancy (prior to the age when asthma is typically diagnosed), and they evaluated antibiotic exposure throughout pregnancy.

What happens next?

Future research is needed to understand how the timing and type of antibiotic use during pregnancy influences infant wheeze outcomes. Additional studies are also needed to replicate these findings, which could then lead to clinical implications.

Where can I learn more?

Access the full journal article, titled “Association Between Prenatal Antibiotic Exposure and Infant Wheeze Outcomes,” in Acta Paediatrica.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Published February 27, 2025

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No Significant Associations Observed Between Prenatal Antibiotic Use and Wheezing Symptoms in Infants

Weight Gain During Infancy in Children Born Preterm Associated with Higher Risk of Obesity, According to New ECHO Research

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Weight Gain During Infancy in Children Born Preterm Associated with Higher Risk of Obesity, According to New ECHO Research

Authors: Michael O’Shea, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

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 can help inform evidence-based guidelines for managing infant nutrition and growth monitoring after infants born very preterm (prior to 32 weeks of gestation) are discharged from a neonatal intensive care unit (NICU), to support rates of growth less likely to contribute to childhood overweight and obesity.

What were the study results?

In comparison to infants with low weight gain after birth, infants with very high weight gain after NICU discharge, which was 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 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.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was this study's impact?

The study’s findings suggest possible benefits of close monitoring of post-NICU growth and healthier feeding practices to prevent obesity, which is associated with multiple adverse health outcomes. However, as single studies rarely provide sufficient evidence to change clinical practice, the authors note that the current study should not be the sole basis for such changes.

Who was involved?

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.

What happened during the study?

After birth, the participants were followed for 1 to 4 years, at which point their BMI and neurodevelopmental outcomes were assessed. Data about each of the participants were shared, with appropriate informed consent from a parent or guardian, with the ECHO Cohort Consortium. This allowed for analyses of relationships between weight gain following NICU discharge and neurodevelopmental outcomes and BMI at 1 to 4 years of age.

What happens next?

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.

Where can I learn more?

Access the full journal article, titled “Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental influences on Child Health Outcomes Cohort,” in the Journal of Pediatrics.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published August 2024

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Weight Gain During Infancy in Children Born Preterm Associated with Higher Risk of Obesity, According to New ECHO Research

ECHO Cohort Research Investigates Relationship Between Infant Gut Microbiome and Childhood Autism-related Traits

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ECHO Cohort Research Investigates Relationship Between Infant Gut Microbiome and Childhood Autism-related Traits

Authors: Vanja Klepac-Ceraj, Juliette C. Madan, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

The relationship between a person’s gut bacteria and the brain during early childhood, especially from birth to around age three years, helps the immune and nervous systems develop and function. The gut microbiome could be a promising area of research to understand the development of autism-related traits. Previous studies have found links between gut bacteria and social traits, but the results are not the same in different populations. To include a broader population of children in the U.S., researchers in this study sought to identify gut bacteria linked to social traits and brain development in two ECHO Cohort Study Sites.

What were the study results?

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.

Note: Results reported here are for a single study. Other or future studies may provide new information or different results. You should always consult with a qualified healthcare provider for diagnosis and for answers to your personal questions.

What was this study's impact?

Understanding the potential likelihood of autism-related traits through the lens of the gut-brain axis opens new avenues for targeted interventions in early life.

Who was involved?

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

What happened during the study?

The 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.

What happens next?

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 neurobehaviorial outcomes, such as anxiety and depression.

Where can I learn more?

Access the full journal article, titled “Prospective Association of the Infant Gut Microbiome with Social Behaviors in the ECHO Consortium,” in Molecular Autism.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published May 17, 2024

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ECHO Cohort Research Investigates Relationship Between Infant Gut Microbiome and Childhood Autism-related Traits

ECHO Study Analyzes Relationship Between Molecules During Pregnancy and Childhood BMI

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ECHO Study Analyzes Relationship Between Molecules During Pregnancy and Childhood BMI

Authors: Rachel Kelly, Nicole Prince, Donghai Liang, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was this study needed?

A child’s body mass index (BMI) can be associated with their future health. Some researchers seek to understand how factors during pregnancy may influence childhood BMI. Increasingly, researchers use molecular data to analyze the relationship between pregnancy and childhood health outcomes. Researchers sometimes combine molecular data from multiple study sites to increase the statistical power of these analyses. This study aimed to evaluate molecular data during pregnancy across multiple study sites while also using these data to test a framework for analyzing molecular data across multiple studies.

What were the study results?

ECHO researchers combined the results from multiple ECHO Cohort Study Sites including mothers and their children to determine whether a relationship existed between small molecules present in the mother’s blood during pregnancy and later childhood BMI. Altogether, 20 molecules showed up in all study sites, and 127 molecules showed up in at least two. The study found that the levels of only six small molecules, primarily related to maternal diet, were associated with BMI across all sites. However, statistical analysis across these study sites did not identify significant associations between these molecules and child BMI.

What was this study's impact?

This study demonstrates some of the challenges that arise when harmonizing molecular data across diverse study sites and highlights important considerations for researchers trying to conduct similar analyses. Ensuring that all of the studies used in an analysis have the same standardized procedures for collecting samples, measuring molecules present in those samples, and collecting related data (e.g., BMI, diet) can improve the reliability and reproducibility of results.

Who was involved?

This study involved mothers and their children from multiple study sites: the Atlanta ECHO Cohort, the New Hampshire Birth Cohort, and the Vitamin D Antenatal Asthma Reduction Trial. The researchers included mothers in the second and third trimesters of pregnancy and measured their children’s BMI at the age of two years.

What happened during the study?

For this study, the authors combined existing results from multiple study sites. Pregnant participants provided blood samples, and researchers used those samples to measure a range of small molecules. These molecules provide information on each participant’s health, environment, and biological/genetic factors that could affect their pregnancy. The researchers continued to follow these participants and their children across pregnancy and early life to assess their ongoing health, height, and weight. Ultimately, in this analysis, the authors used data from these studies to evaluate the relationship between molecules measured during pregnancy and BMI at age two years, aiming to identify relationships that were consistent across all three studies.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What happens next?

Differences in how molecular data were collected and measured between the sites in this study made it difficult to draw strong conclusions on the relationship between small molecules during pregnancy and childhood BMI. Future analyses could involve larger, more standardized studies that all use the same methods for sample collection and measurement. Many ECHO Cohort Study Sites are now measuring small molecules in both mothers and children with a standardized approach under the ECHO Cohort Data Collection Protocol. ECHO researchers have an opportunity to use these data to power analyses that can explore the relationship between pregnancy health and child health outcomes.

Where can I learn more?

Access the full journal article, titled “Metabolomic Data Presents Challenges for Epidemiological Meta-Analysis: A Case Study of Childhood Body Mass Index from the ECHO Consortium,” in Metabolomics.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published January 24, 2024

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ECHO Study Analyzes Relationship Between Molecules During Pregnancy and Childhood BMI

ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples

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ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples

Authors: Fang Fang, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of The Director, National Institutes of Health supported this research.

Why was the study needed?

A molecular process called DNA methylation, or DNAm, 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, only epigenetic clocks for pediatric populations have only recently been built. Epigenetic clocks also allow scientists to evaluate the impact of various environmental exposures on early-life development and children’s health outcomes.

This study conducted 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. It is important for scientists to understand how these clocks perform in different tissue types and developmental stages throughout early life to ensure researchers are designing studies appropriately and then correctly interpreting the results of these studies.

What were the study results?

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.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study provides practical recommendations for selecting the most appropriate epigenetic clock in different research contexts, therefore leading to more accurate estimates of biological age. The findings of this study may help scientists make better research tools, improving child health research.

Who was involved?

Researchers used data from 3,789 children, who contributed a total of 4,555 samples, from 20 ECHO research sites. The sample set consisted of 2,273 male and 2,282 female samples.

What happened during the study?

The researchers evaluated seven different epigenetic clocks based on the DNAm data generated from the selected sample set. The study evaluated each clock in corresponding tissues based on previous study results, and then compared clocks 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.

What happens next?

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. Future studies may examine the effects of genetics on the performance of different epigenetic clocks.

Where can I learn more?

Access the full journal article, titled “Evaluation of Pediatric Epigenetic Clocks Across Multiple Tissues,” in Clinical Epigenetics.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published October 9, 2023

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ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples

ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

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ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

Authors: Marie Camerota, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was the study needed?

Birth outcomes for infants born very preterm have steadily improved over the past several decades. More children born at earlier gestational ages are surviving into childhood, however, it is unclear how being born very preterm may influence neurodevelopmental or behavioral problems.

Outcomes of children born at a gestational age of less than 33 weeks (“very pre-term”) vary significantly, with some children showing few neurodevelopmental concerns and others showing significant impairment. Most prior research has looked at single outcomes—for example, whether a child born preterm had a lower neurodevelopmental score or higher levels of behavior problems. Understanding how these different outcomes may group together can help researchers and healthcare providers provide more comprehensive treatment plans for children born very preterm.

What were the study results?

Researchers found evidence for four different neurobehavioral profiles based on different combinations of cognitive, motor, and behavioral outcomes of children at the age of two. These profiles range from few or no developmental concerns to severe impairment in one or more domains. The study placed most children (about 85%) into one of two groups with no/mild developmental delay and a low prevalence of behavioral problems. The remaining 15% fell into one of two profiles with more serious neurodevelopmental problems with (5%) or without (10%) co-occurring behavior problems.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study helps researchers better understand outcomes for children following a very pre-term birth. The different groups of children this study described might require different types of follow-up services or interventions.

Who was involved?

This study included more than 2,000 babies who were born at less than 33 weeks gestational age and were evaluated at the age of two years. Pre-term children from three ECHO research sites in the U.S. were included in this analysis.

What happened during the study?

Researchers recruited children born less than 33 weeks gestational age into the ECHO Program shortly after they were born. When these children reached age two years, researchers conducted a neurodevelopmental assessment and a motor exam; parents completed questionnaires about their children’s behavior. ECHO researchers looked for patterns in these data to understand whether there were groups of children with similar strengths and weaknesses.

What happens next?

More research is needed to understand why some preterm children develop neurodevelopmental and/or behavioral problems and others do not. To do this, future studies may study risk factors in pregnancy, the perinatal period, and in early infancy.

Where can I learn more?

Access the full journal article, titled “Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program,” in Pediatric Research.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published September 12, 2023

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ECHO Researchers Characterize Children Born Preterm into Four Neurobehavioral Profiles

“Accelerated” Biological Age at Birth Not Linked to Behavioral and Emotional Health Outcomes in Early Childhood

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“Accelerated” Biological Age at Birth Not Linked to Behavioral and Emotional Health Outcomes in Early Childhood

Authors: Christine Ladd-Acosta, Heather Volk, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health supported this research.

Why was the study needed?

Previous studies have shown that early identification and intervention in the development of emotional and behavioral health challenges in children seems connected to better long-term health outcomes. Recently, researchers have begun looking at how epigenetic factors affect children’s biological age and health outcomes.

A molecular process known as DNA methylation, or DNAm, adds a tag to DNA to control gene expression. Researchers measure DNAm to estimate a person’s biological age and compare it with their chronological age to better understand the factors that may influence their long-term health outcomes. In this study, ECHO researchers looked at the link between biological age at birth, the time between conception and birth (chronological gestational age), and emotional and behavioral health outcomes in children.

What were the study results?

Differences between biological age at birth and chronological gestational age did not appear linked to emotional and behavioral problems in childhood. This study did not find any difference between boys and girls in terms of the effect of “accelerated” biological age on behavioral and emotional outcomes.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should always consult with a qualified healthcare provider for diagnosis and for answers to your personal questions.

What was the study's impact?

These results highlight that because biological age at birth does not seem to predict emotional or behavioral health challenges in early childhood, research should investigate how other biological factors at birth may influence neurodevelopmental health outcomes in early childhood.

Who was involved?

The study included four ECHO research sites in the United States and a total of 592 children.

What happened during the study?

Researchers calculated each child’s “biological age” by analyzing DNA samples collected at birth, and they compared this age to the child’s chronological gestational age. They then tested whether newborns who showed increased biological age relative to their chronological age (“accelerated aging”) were more likely to have emotional and behavioral problems in early childhood.

What happens next?

Future research in a larger sample might confirm these findings. The relatively small sample size of this study may have made it difficult to observe differences in behavioral or emotional outcomes based on child sex. Future research with larger samples could help investigate potential differences in the results between boys and girls.

Where can I learn more?

Access the full journal article, titled “Accelerated epigenetic age at birth and child emotional and behavioral development in early childhood: a meta-analysis of four prospective cohort studies in ECHO,” in Epigenetics.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published September 10, 2023

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“Accelerated” Biological Age at Birth Not Linked to Behavioral and Emotional Health Outcomes in Early Childhood