ECHO Researchers Evaluate an Adaptive, Short-form Questionnaire for Measuring Autism-related Traits in Children

Collaborative ECHO research led by Aaron Kaat, PhD of Northwestern University, and Kristen Lyall, ScD of the AJ Drexel Autism Institute evaluates two different versions of the full 65-question Social Responsiveness Scale (SRS) for measuring autism-related traits in preschool and school-age children. This study compared the questions used on each version and developed a comparable scoring method for both forms. Then, the researchers used computer-adaptive testing, where a computer program tailors the questionnaire in real-time to each participant, and found that a median of 14 questions was sufficient to reach a reliable score. This research, titled “Modifying the Social Responsiveness Scale for Adaptive Administration,” is published in Quality of Life Research.

Prior research has developed and examined shortened versions of the SRS questionnaire, but researchers haven’t been able to evaluate the reliability of these questionnaires for capturing broader traits in the general population or for preschool-age participants. This study included over 7,000 children ages 2.5-18 years old, most of whom did not have an autism diagnosis. The researchers conducted several analyses to assess a variety of factors that may affect how the full SRS and shortened versions of the SRS are scored. They were then able to use these data to simulate how computer-adaptive testing would score each individual after completing the minimum number of questions required to reach a comparable result.

“The results of this study suggest opportunities to reduce the amount of time participants need to spend completing questionnaires like the SRS,” said Dr. Lyall. “These results also suggest computer-adaptive questionnaires can be used to collect information in a way that is comparable to standard paper-based questionnaires, offering additional flexibility.”

The researchers are continuing to evaluate the computerized version of the SRS questionnaire developed in this study, comparing it to other versions of the questionnaire. Future research is needed to examine how these different questionnaires perform in different groups of people, and if results differ when captured according to self vs. parent report.

Read the research summary.

New ECHO Research Investigates the Effects of the COVID-19 Pandemic on Infant and Toddler Development

Collaborative ECHO research led by Sara Nozadi, PhD and Johnnye Lewis, PhD of the University of New Mexico, investigates whether the negative developmental effects observed in school-aged children over the course of the pandemic could also be seen in infants and toddlers. In this study, up to 15% of infants and toddlers who were developmentally on track prior to the COVID-19 pandemic showed signs of developmental delays during the pandemic. Male children showed more delays than female children, and language domain was the most affected developmental area. Additionally, families from minority communities and those with lower socioeconomic status were more likely to experience pandemic-related hardships. However, financial and social pandemic-related hardships were not associated with the individual changes observed in children’s developmental progress. This research, titled “Effects of COVID-19 financial and social hardships on infants’ and toddlers’ development in the ECHO program,” is published in International Journal of Environmental Research and Public Health.

This study included 684 children between the ages of 2 months and 4 years from eight ECHO cohort research sites across the United States. During this study, the researchers included children whose parents had filled out the Ages and Stages Questionnaire (ASQ), which uses parent-reported information to pinpoint a child’s developmental progress, within the 18-month periods before and after March 2020. Parents of participating children were also asked about financial hardship, defined as at least one parent experiencing job loss or change, or social hardships, defined as families’ quarantining from household members or extended family and friends, during the pandemic.

“This study highlights the importance of early developmental screening during times of adversity, such as pandemics, in order to identify delays and connect children to supportive services,” said Dr. Nozadi. “Previous studies have shown negative impacts of the pandemic on overall child development but have not looked at the effects of the pandemic on individual children’s development over time.”

In the future, we can follow the developmental progress of these children over time to determine whether COVID-19 hardships had an effect on children’s development over a longer period of time. Studies may also focus on pandemic-related stressors that could particularly effect infants and toddlers, such as family dynamics, parent-child interactions, and parental stress.

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ECHO Researchers Compare Thousands of Prenatal Vitamins to Help Pregnant Patients Get the Nutrients They Need

Collaborative ECHO research led by Katherine Sauder, PhD of the University of Colorado, Anschutz Medical Campus highlights six key nutrients essential for healthy pregnancies and identifies the best prenatal dietary supplements available in the United States to help pregnant women get the right amounts of these nutrients. Out of over 20,000 choices, the researchers found one prenatal dietary supplement that may potentially provide the right amounts of the most important nutrients needed during pregnancy: vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids. However, the supplement costs $200 per month and requires the patient to take seven pills a day, so the researchers identified other, more accessible vitamin supplement options that provide as close a match to the needed of amounts of nutrients as possible. This research, titled “Selecting a dietary supplement with appropriate dosing for six key nutrients in pregnancy," is published in The American Journal of Clinical Nutrition.

It is important for pregnant women to get optimal amounts of the right nutrients. There are thousands of options for prenatal vitamins in the United States, so ECHO researchers designed this study to help pregnant women and doctors select the ones that contain optimal doses of key micronutrients to support a healthy pregnancy.

This study included 2,450 pregnant participants from six ECHO cohorts located across the United States. ECHO researchers first analyzed data about what participants ate and drank during their pregnancies. Then, they calculated how much of the six key nutrients (vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids) mothers were getting in their regular diet. The researchers compared the participants’ diets to nutrition recommendations for pregnancy to determine the amount of nutrients the participants would need from prenatal vitamins to supplement their diet.

“This research will inform pregnant patients and their doctors about key nutrients they may be missing in their diet and help them choose prenatal vitamins that can provide the nutrients they need,” said Dr. Sauder. “Dietary supplement manufacturers can also use these results to inform better dosing in their products.”

The results of this study highlight the ongoing need for prenatal vitamin options that are low cost and convenient, while still containing the optimal amounts of key nutrients. More research on nutrients in foods will also be needed to help pregnant patients get more of these key nutrients in their daily diets.

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New ECHO Research Suggests Differences in Placental Development for Male and Female Infants

Collaborative ECHO research led by Catherine Bulka, PhD, of the University of South Florida, and Rebecca Fry, PhD, of the University of North Carolina at Chapel Hill, investigates whether gene activity in the placenta might differ base on the infant’s sex. The results of this study suggest that the placentas of males and females might develop differently. This research, titled “Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis,” is published in Epigenetics.

This study included 774 infants (355 female and 419 male) from four ECHO research sites. One of the research sites enrolled infants born at less than 28 weeks, which provided samples from the earliest viable births. Research sites used placental tissue from male and female infants to investigate associations between gestational age (the amount of time the baby spent in-utero) and modifications of placental DNA. Researchers then located the modifications and identified the closest genes, allowing them to analyze the biological significance of the modifications.

The most prominent differences were linked to genes that play significant roles in immunity, inflammation, and pregnancy complications. These differences seen between male and female infants may be important when looking at sex-specific health and developmental outcomes.

“These findings highlight the importance of considering infant sex in studies of the placenta,” said Dr. Bulka. “Doing so may help identify the origins of sex disparities in health and disease that persist throughout life.”

Researchers are now using this data to estimate an infant’s “biological” rather than “chronological” gestational age based on the modification of placental DNA, and the findings of this study suggest that it may be important to consider the infant’s sex when calculating “biological’” gestational age.

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ECHO Researchers Investigate the Effect of Prenatal PFAS Exposure on Birthweight

In a study investigating how per- and polyfluoroalkyl substances (PFAS) exposures affected pregnant mothers and their babies, ECHO researchers Amy Padula, PhD, MSc, and Tracey Woodruff, PhD, MPH, from the University of California, San Francisco found that higher levels of prenatal exposure to PFAS are associated with lower birthweights. The PFAS were detected in all participating mothers, suggesting some level of PFAS exposure from the environment. PFAS are widely used, long lasting chemicals that break down very slowly over time and are found in drinking water, food, household products, personal care products, manufacturing facilities, and other sources.

This research, titled “Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental influences on Child Health Outcomes (ECHO) Program,” is published in Environmental Health Perspectives.

For this study, the researchers collected blood samples and pregnancy data from more than 3,000 pregnant women in 11 different ECHO cohorts. They then measured PFAS levels in the mothers’ blood samples and asked them about their stress levels during pregnancy. The team found that mothers who had higher levels of PFAS chemicals in their bodies were more likely to give birth to a baby of low birth weight than mothers with lower levels of PFAS. Additionally, previous studies have found that psychosocial stress may affect PFAS exposures and birthweight. However, the team did not find that stress played a role in the relationships between low birthweight and PFAS exposure.

This research suggests that PFAS exposures during pregnancy can affect infant birth weight, demonstrating the importance of efforts to reduce sources of environmental PFAS exposure. “Outside of research studies, pregnant women are not tested for PFAS and are uncertain of the potential harms PFAS cause,” said Dr. Padula. “We need to better understand where people are most likely to be exposed to these substances given the number of sources, from drinking water to consumer products.”

The next steps for this research include examining potential sources of PFAS exposure. Additional studies may examine how factors like body mass index and other health conditions in pregnancy might additionally affect the relationship between PFAS exposure and infant birthweight.

The US Environmental Protection Agency (EPA) has created a Roadmap to address PFAS as part of the Biden Administration plan to accelerate efforts to better protect Americans from PFAS exposure.

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ECHO Researchers Compare Methods of Placental Sample Preservation for Metabolite Analysis

Jennifer Straughen, PhD

Collaborative ECHO research led by Jennifer Straughen, PhD, of Henry Ford Health System compared two different methods of placental sample preservation for metabolite analysis: flash freezing versus room-temperature fixation in methanol. The results of this study demonstrated that the room-temperature collection method can produce similar metabolism data to the flash-freezing, the standard method. This research, titled “Comparison of methanol fixation versus cryopreservation of the placenta for metablomics analysis,” is published in Scientific Reports.

For this study, researchers collected placental samples from mothers following delivery at Henry Ford Health. The researchers then removed pea-sized pieces of placental tissue and preserved them using either flash-freezing or methanol fixation. Metabolite analysis of these samples revealed similar quality results for both methods—although a greater number of metabolites were typically detected in the methanol-fixed samples and methanol extract.

“The results presented in this paper allow for the collection of placental tissue samples for metabolite analysis at room temperature instead of by flash freezing,” said Dr. Straughen. “Room-temperature fixation in methanol requires less equipment than flash freezing and may be more feasible to perform in community-based hospitals.”

More work is needed in the future to describe the metabolic data collected during this study and compare it to data from previous studies. Researchers will also need to repeat this study with a larger sample size to confirm these findings.

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ECHO Researchers Investigate Link Between Mental Health and Pregnancy During the COVID-19 Pandemic

Collaborative ECHO research led by Alison Hipwell, PhD, ClinPsyD, of the University of Pittsburg, and Irene Tung, PhD, of California State University Dominguez Hills, found that being pregnant during the COVID-19 pandemic was associated with higher levels of stress and depression symptoms. The researchers found that participants who reported more emotional support and engaged in physical activity before and during the pandemic had less stress and fewer symptoms of depression. The results also showed that pregnancies during the pandemic were slightly shorter on average but there was no impact on infant birth weight. This study highlights the importance of providing access to emotional support and mental health care during pregnancy and identifying ways to promote physical activity to help improve maternal health and well-being, regardless of external conditions like the pandemic. This research, titled “Impact of Sedentary Behavior and Emotional Support on Prenatal Psychological Distress and Birth Outcomes During the COVID-19 Pandemic,” is published in Psychological Medicine.

The study included 501 pregnant participants who gave birth during the COVID-19 pandemic (between March 12, 2020 and May 30, 2021) and 501 pregnant participants who gave birth before the pandemic (prior to March 11, 2020). Participants were 31 years old on average and enrolled in one of 16 ECHO research sites across the United States. Participants answered questions about their experiences with stress and depression, reported on their physical activity and described the emotional support they received during pregnancy. The researchers also collected information on participants’ birth outcomes from medical records and maternal reports.

“More research is needed to understand how social support and physical activity may protect pregnant women during difficult times,” said Alison Hipwell, PhD, ClinPsyD, of the University of Pittsburgh. “Future research may look at what types of experiences during the pandemic had the most influence on pregnancy health and well-being.”

Read the research summary.

ECHO Researchers Examine Associations Between Mothers’ Demographic Characteristics and Health During Pregnancy and Their Newborns’ Behavior

Collaborative ECHO research led by Marie Camerota, PhD of the Warren Alpert Medical School of Brown University, investigates the link between newborns’ behavior patterns with their mothers’ demographic characteristics and health during pregnancy. The study looked at over 1,000 newborns and their mothers from across the U.S., and found that male babies, babies from younger mothers, and babies whose mothers were depressed or used tobacco during pregnancy were the most likely to have poorly regulated behavior shortly after birth. Babies with poorly regulated behavior were identified as hyper-aroused (i.e., too excitable) or hypo-aroused (i.e., slow to respond). This research, titled “Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program,” is published in Pediatric Research.

Previous studies have looked at mothers’ and babies’ characteristics that are associated with babies’ behavior shortly after birth, but these studies were conducted with smaller groups of babies who were very similar to one another—for example, studies with babies who were all born full term. There is a need for studies with a large, variable sample of mothers and their newborns, including babies who were born preterm and full term.

This study included mothers and their babies, born at gestational ages from 22 to 42 weeks, from 5 ECHO cohorts. The babies received a behavioral exam shortly after birth to assess their responses to objects and people, their reflexes, and their movement. Either mothers reported information about their own and their babies’ demographics and health information or it was collected from their medical records. ECHO researchers looked at how these characteristics were related to babies’ patterns of behavior.

ECHO researchers identified six groups of babies with different behavior patterns. Four of these groups included normal patterns of behavior and only two groups were characterized as poorly regulated (hyper- or hypo-aroused). Babies born at all different gestational ages were included in all groups.

“If these patterns of behavior are found in other large studies, this might mean that the patterns apply to all babies,” said Dr. Camerota. “This information could be used to identify babies at risk for poorly regulated behavior and inform practices to promote positive developmental outcomes starting at the very beginning of life.”

More research is needed to determine which of the characteristics studied are stronger predictors of babies’ behavior patterns and development, and whether the impact of these factors changes among babies born at different gestational ages. Further research is also needed to learn more about how babies’ neurobehavior shortly after birth is related to their health and development later in childhood.

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ECHO Researchers Investigate Link Between Pregnancy Complications and Infant Development

Collaborative ECHO research led by Carrie Breton, ScD, MPH of the University of Southern California and Christine Ladd-Acosta, PhD of Johns Hopkins University found that preeclampsia and gestational diabetes may be linked to slower biological development in infants. The researchers found that newborns who were exposed to these pregnancy complications were biologically younger than those without exposure—an effect that was most noticeable in female infants. The results of this study provide an important clue about how biological mechanisms in offspring might be affected by common pregnancy complications and how these conditions could be linked to child health outcomes. This research, titled “Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns,” is published in JAMA Network Open.

The study included 1,801 children born between 1998 and 2008 from 12 ECHO cohorts across the United States. ECHO researchers calculated each infant’s epigenetic age—a measurement of their “biological age” based on molecular markers in their cells—using DNA samples collected at birth and compared their biological age to their actual age at birth (measured in pregnancy weeks). Then, the researchers compared the biological ages of newborn babies exposed to pregnancy complications to the biological ages of babies who were not exposed.

“In the future, we plan to continue our research with a larger sample of participants and investigate whether these biological changes detected at birth are linked to health outcomes later in childhood,” said Dr. Breton. “If so, doctors and researchers could use that knowledge to develop targeted interventions that can reduce the adverse effects of preeclampsia and gestational diabetes on children’s health.”

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New ECHO Research Investigates the Consequences of Maternal Exposure to Childhood Maltreatment on Their Children’s Health Outcomes

Collaborative ECHO research led by Claudia Buss, PhD of the University of California, Irvine and Charité – Universitätsmedizin Berlin and Nora K. Moog, PhD of Charité – Universitätsmedizin Berlin, suggests that maternal history of childhood maltreatment may increase the risk for multiple child health outcomes, including asthma, depressive symptoms, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). The results of this study also indicate that children of mothers who experienced neglect or abuse as children were more likely to develop several of these health outcomes simultaneously. This research, titled “Intergenerational transmission of the consequences of maternal exposure to childhood maltreatment – a United States nationwide observational study of multiple cohorts in the ECHO program,” is published in The Lancet Public Health.

Childhood maltreatment increases the risk for adverse health outcomes, and this risk can be transmitted from one generation to the next. Previous research has investigated single health outcomes in children of mothers exposed to childhood maltreatment. However, health problems are often interconnected and affected by the same factors, so this study investigated the association between maternal exposure to childhood abuse or neglect and children’s risk of experiencing more than one of six evaluated health outcomes simultaneously: ASD, ADHD, asthma, allergies, obesity, and internalizing behaviors (e.g., social withdrawal, trouble sleeping, symptoms of anxiety or depression).

The researchers evaluated data from 4,337 mothers and their children from 21 ECHO cohorts in the United States. Mothers self-reported on their childhood experiences, and researchers used this information to categorize them based on whether or not they were exposed to childhood neglect or abuse. About 44% of participating mothers reported experiencing some level of childhood maltreatment. The researchers then compared the rates of diagnosis for a number of physical and mental conditions between the children in the two groups.

Children of mothers exposed to childhood maltreatment had higher rates of asthma, ADHD, ASD, and internalizing problems compared with children of mothers without CM. Additionally, girls whose mothers experienced childhood neglect or abuse were more likely to develop obesity. Children of mothers who experienced childhood maltreatment were at higher risk of developing more than one of the evaluated health outcomes. Exposure to several different forms of maternal childhood maltreatment was associated with highest risk increases for most offspring health outcomes suggesting the more severe the maternal childhood experiences were, the higher the risk for adverse health outcomes in her child.

“Not all children of mothers with experiences of childhood maltreatment will develop health problems, but those who do are at risk of developing more than one condition,” said Dr. Buss. “Asking parents about their childhood experiences during prenatal and pediatric care, identifying parents with a history of childhood abuse or neglect, and offerin­­­­g counseling and support to those parents could help improve health outcomes for their children.”

Follow-up studies will further investigate the different pathways between maternal childhood maltreatment and child health outcomes. Future studies may also track the effects of other forms of negative childhood experiences in combination with childhood maltreatment on child health outcomes.

Read the research summary.

For more background, view this ECHO Discovery webinar about how a mother’s own adverse childhood experiences may affect her child’s health and well-being.