ECHO Study Links Prenatal Tobacco Exposure to Autism Spectrum Disorder in Children

Through a collaborative research effort, Rashelle J. Musci, PhD of Johns Hopkins University and Irva Hertz-Picciotto, PhD of the University of California, Davis found that maternal tobacco use before or during pregnancy was associated with autism spectrum disorder (ASD) traits, such as symptoms of social impairment. Examples of social, communication, or other behaviors among individuals with ASD include little or no eye contact, difficulty with engaging in conversation, insistence on doing things the exact same way, repetitively, or having a narrow set of interests. Additionally, the researchers found that full-term babies whose mothers smoked before or during pregnancy had a 44% increased risk of receiving an ASD diagnosis later in childhood. Their research, titled “Maternal Tobacco Smoking and Offspring Autism Spectrum Disorder or Traits in ECHO Cohorts” is published in Autism Research.

“Previous studies provide varying results on how tobacco smoke exposure during pregnancy affects a child’s risk for autism,” said Dr. Hertz-Picciotto, highlighting the importance of this research.

To collect data, the research team gathered information from approximately 11,000 children in 13 cohorts across the United States. Each of the cohorts either collected diagnoses for ASD or administered the Social Responsiveness Scale to determine social impairments in the children, or both. The research team studied each cohort individually and combined these findings to come up with an overall result. It also collected data on the mothers’ prenatal smoking habits and other potential confounding variables.

“This study adds to existing evidence that suggests that by ceasing smoking before or during pregnancy, the mother benefits her child,” noted lead author Dr. Musci.

Future studies can help determine the specific prenatal period at which infants are most susceptible to cigarette smoke exposure and other factors, such as lifestyle habits or paternal smoking, that may influence the child’s development.

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New ECHO Research Investigates Relationship between Chronic Health Conditions and Children’s Positive Health

Julia Schuchard, PhD

Collaborative ECHO research led by Julia Schuchard, PhD of the Children’s Hospital of Philadelphia studied the association between chronic physical or mental health conditions and children’s assessment of their own well-being, also referred to as positive health. The findings show that many children and adolescents with chronic health conditions have similar levels of positive health as their peers without chronic conditions. The team’s research, titled “Influences of chronic physical and mental health conditions on child and adolescent positive health,” is published in Academic Pediatrics.

For this study, researchers gathered 1,764 children aged 8 to 17 from 13 ECHO cohorts across the U.S. and asked them about their physical, mental, and social health and life satisfaction. The children’s parents also provided information on their child’s chronic health conditions, including physical (e.g., asthma, chronic pain, motor problems), developmental (e.g., autism spectrum disorder, developmental delay, learning disabilities), and mental (e.g., depression, anxiety) health conditions. Around 54% of children participating in the study had some form of chronic health condition.

The results of this study suggest that mental health conditions such as depression in childhood may be a primary driver of decreased well-being and life satisfaction among children with chronic health conditions. “The symptoms of physical health conditions and developmental disorders may last for years or even a lifetime,” said Dr. Schuchard, “but it is possible that negative effects on life satisfaction could be minimized by preventing and treating mental health problems.”

More research is needed to identify the best mental health interventions for improving positive health outcomes among children with chronic health conditions. Effective interventions may include increasing the availability of mental health assessments and screening children and adolescents with chronic health conditions for depression more frequently.

“Examining the effects of interventions like these on positive health outcomes has the potential to shift perspectives around health” said Dr. Schuchard, “highlighting the importance of promoting children’s mental health and well-being.”

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ECHO Researchers Develop a Shorter Survey for Evaluating Sources of Stress in Adults

Phillip Sherlock, PhD

Through a collaborative effort led by Phillip Sherlock, PhD from Northwestern University, an ECHO research team developed a short-form version of the Crisis in Family Systems-Revised (CRISYS-R) questionnaire for evaluating the sources of stress that adults experience. The study found that the revised 24-question survey (CRISYS-SF) covered the same 11 areas of stress the 80-question CRISYS-R addressed and yielded very similar scores. The article, titled “A short form of the Crisis in Family Systems (CRISYS) in a racially diverse sample of pregnant women,” is published in Current Psychology.

The researchers interviewed 884 pregnant women in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study from New York City and Boston. About 20% of these women spoke Spanish as their primary language, 20% had less than a high school education, and 60% reported having some degree of financial trouble. The participants answered all 80 of the CRISYS-R questions, and the researchers used statistical methods and expert input to identify which questions were the most useful for measuring stress.

Growing evidence suggests that exposure to stress can affect a patient’s overall health. The CRISYS-SF is a convenient method for doctors and researchers to more easily screen for participant stress, identify the sources of that stress, and plan effective interventions.

“Factors including questionnaire length contribute to participant burden,” said Dr. Sherlock, “and this burden can contribute to reduced response rate, incomplete data, and reduced data quality in clinical studies.” Future research into the effects of stress on specific health outcomes will benefit from the use of the CRISYS-SF questionnaire to gather reliable, high quality data on participant stress.

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ECHO Research Explores the Relationship between Early Life and Puberty

Izzuddin M. Aris, PhD
Izzuddin M. Aris, PhD

Collaborative ECHO research led by Izzuddin M. Aris, PhD of Harvard University found that children who grew more quickly than their peers in the first five years of life were more likely to start puberty earlier. The study examined the importance of early life factors in puberty development and found that male children who gained weight or grew faster than their peers in the first five years of life were associated with entering puberty at a younger age. The researchers found similar results in female children but only among those with faster weight gains during early childhood (two to five years of age). The article, titled “Analysis of early life growth and age at pubertal onset in US children,” is published in JAMA Network Open.

To obtain these findings, the researchers gathered height and weight data from nearly 7,500 children in 36 ECHO cohorts and examined the following markers of puberty:

  • Age at which the child reached maximum growth due to puberty
  • Age at first period (in female children only)
  • Pubertal development score
  • Onset of pubic hair development

The team studied how weight gain, height, and body mass index at ages 0–0.5, 0.5–2, and 2–5 years were related to puberty later in childhood.

“Puberty is a key stage during child development,” explained Dr. Aris. “Having a better understanding of the early life factors related to puberty is important to develop intervention strategies to prevent earlier pubertal onset.” Previous studies in the US have linked earlier puberty onset to diseases later in life, such as type 2 diabetes.

Dr. Aris says follow-up studies will aim to identify puberty’s role in explaining the relationship between early life factors and longer-term chronic diseases.

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ECHO Researchers Explore How Maternal Stress During Pregnancy Relates to Infant Suck Patterns

Collaborative ECHO research led by Emily Zimmerman, PhD, CCC-SLP from Northeastern University and Andréa Aguiar, PhD from the University of Illinois at Urbana-Champaign found that a mother’ s level of stress during pregnancy was linked to changes in the way her infant sucked on a pacifier.

Infants’ sucking patterns can be used to measure brain function soon after birth, and this research investigated how maternal stress during pregnancy related to infant suck patterns. Zimmerman, Aguiar, and team found that mothers who felt more stressed late in their pregnancy had infants who sucked on their pacifiers less frequently, but when they did suck on their pacifier, they did so for a longer period of time compared with infants of mothers who felt less stressed in late pregnancy.  It is important to note that the mother and infants participating in this study were from two different groups who had different maternal stress levels and infants’ sucking behaviors.  These differences in stress and infants’ sucking behaviors could be due to other differences between the two groups in their culture, ethnicity, geographical location, and income, and education levels. 

This research, titled “Examining the Association Between Prenatal Maternal Stress and Infant Non-Nutritive Suck,” was published in Pediatric Research.

To collect data, the researchers surveyed mothers from two ECHO cohorts—one from Urbana-Champaign, Illinois and the other from Manati, Puerto Rico—regarding their stress during late pregnancy using the Perceived Stress Scale. The researchers followed up with each mother within 8 weeks after giving birth and tested their baby’s sucking pattern on a pacifier connected to a pressure detector.

This research demonstrates that maternal mood and stress during pregnancy can affect infant behavior and development starting prenatally and through the first months of life. “This finding is important as it may allow for earlier awareness of stress exposure during pregnancy,” said Dr. Zimmerman, “and as a result, earlier treatment for stress-exposed infants.”

The next steps for this research include further investigation of the link between early infant sucking patterns and visual memory, attention, and speed processing in infants.

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How Does Maternal PFAS Exposure Affect Prenatal Development?

Per- and polyfluoroalkyl substances (PFAS) are long-lasting chemicals that can be found in many household materials, but not enough is known about pre- and perinatal negative health outcomes associated with PFAS exposure. Additionally, socioeconomically disadvantaged groups, such as African American women and children, may be at more risk for PFAS exposure, worsening health disparities. Previous studies have linked PFAS exposure with negative infant health outcomes, such as lower birth weight, but little is known about the specific biological mechanisms that PFAS exposures disrupt during prenatal development.

Che-Jung Chang, PhD (left) and Donghai Liang, PhD (right) served as first and corresponding authors for this publication.

To investigate these mechanisms, Che-Jung Chang, PhD, Donghai Liang, PhD, and their team of ECHO researchers at Emory University looked at pregnancy and exposure data from more than 300 African American women enrolled in the Atlanta ECHO cohort from 2014-2018. Their research, titled “Per- and polyfluoroalkyl substance (PFAS) exposure, maternal metabolomic perturbation, and fetal growth in African American women: A meet-in-the-middle approach,” is published in Environment International.

As part of this study, the researchers analyzed the levels of PFAS in the participants’ blood samples along with the levels of a variety of small molecules that are known to be essential to prenatal development. The researchers then used statistical methods to look at how these chemical differences affected birth weights. The analysis found that PFAS exposures were linked with lower birth weights in babies that African American women delivered. These lower birth weights may have been associated with changes in the levels of a variety of essential metabolites and molecules, including amino acids, lipid/fatty acid, bile acids, and sex hormones.

The results of this study reveal some of the key chemical mechanisms that may be responsible for the effects of PFAS exposure on prenatal development. “The molecular mechanisms and biomarkers presented in this study warrant future investigation in targeted studies,” said Dr. Liang. “These investigations may help develop early detection and intervention strategies in both public health and clinical settings.”

Going forward, the team will take a closer look at how PFAS exposures are reflected in the levels of key small molecules in newborn babies. Additionally, team members hope to expand their chemical analysis in order to get a more holistic view of how PFAS exposures affect prenatal development.

Access the brief flash talk from the authors in the following video:

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Recent ECHO Publication Uses New Tools to Explore the Impact of Chemical Exposures on Pregnancy

Chemical exposures from the environment can have a profound effect on health outcomes, especially for pregnant mothers and their babies. Prenatal development is a carefully controlled biological process that is sensitive to environmental chemicals and maternal health.

Brett Doherty
Brett Doherty, PhD, MSPH
Megan Romano
Megan Romano, PhD, MPH

In order to better understand the impact of chemical exposures on prenatal development, ECHO researchers Brett Doherty, PhD, MSPH, and Megan Romano, PhD, MPH of Dartmouth College used emerging technologies to investigate the link between chemical exposures and prenatal chemical processes. Their research, titled “Chemical co-exposures assessed via silicone wristbands and endogenous plasma metabolomics during pregnancy” is published in the Journal of Exposure Science and Environmental Epidemiology.

During this investigation, 177 pregnant women enrolled in the New Hampshire Birth Cohort Study (NHBCS) were given silicone wristbands to wear for a week in the early stages of their pregnancy. These wristbands captured snapshots of the chemical exposures the mothers experienced during pregnancy. Three months later, the researchers collected blood samples from the mothers for further analysis.

This analysis utilized metabolomics, a relatively new technology that involves the quantification of all the small molecule building blocks in a sample as a way to determine what chemical processes are occurring in the system.

“We used new tools to investigate how chemicals can affect important small molecules during pregnancy,” said Doherty, “which provided clues to the impacts of those chemicals on the health of the mother and the baby.”

The researchers found that several of the chemical exposures experienced by women in the study were associated with changes in the relative amounts of different important chemical building blocks. Specifically, many of the exposures, including exposures to the insecticide DEET, were associated with changes in the amounts of various amino acids that make up many of the proteins vital to prenatal development.

These results may provide a useful framework for further investigations into the effects of prenatal chemical exposures. “Future investigations may find it helpful to link the impacts we observed to related health processes and outcomes,” Romano noted.

Access the research summary.

ECHO Article Investigates the Link between Childhood Asthma and Obesity

Erika Garcia, PhD, MPH
Erika Garcia, PhD, MPH
Nikos Stratakis, PhD
Nikos Stratakis, PhD

Rates of childhood asthma and obesity have been on the rise in the past few decades. Doctors have observed that children diagnosed with asthma often have a higher body mass index (BMI) associated with obesity. These observations lead ECHO researchers Nikos Stratakis, PhD and Erika Garcia, PhD, MPH of the University of Southern California to investigate the co-occurrence of asthma and obesity in children and the role of asthma treatment in this relationship. The abstract for this research, titled “The Role of Childhood Asthma in Obesity Development: A Nationwide U.S. Multi-cohort Study,” is now available online. Full study results will be published in the January 2022 issue of Epidemiology.

The study tracked more than 8,000 children and teens from 18 different ECHO cohorts across the U.S. between the ages of 6 to 18.5 years, with an average follow up of five years. The researchers selected participants who were not affected by obesity at the beginning of the study and looked at whether they developed obesity—defined as having a BMI in the top 5% for their age and sex—over the course of the study. The researchers also collected information on whether the children had received a diagnosis of asthma and whether they were treated with asthma medication. During the study, around 26% of the children were diagnosed with asthma and 11% developed obesity.

The study found that children with asthma were 23% more likely to develop obesity compared to children without asthma. However, children with asthma who used asthma medication at a higher proportion had a 64% lower risk of developing obesity compared to children with asthma who used asthma medication at a lower proportion.

“This study showed us that children with asthma may be more likely to develop obesity as they get older,” said Stratakis, “and asthma medication may reduce this likelihood.”

In the future, researchers may want to look more closely at the factors mediating the link between asthma and obesity, like levels of physical activity and sleep quality. Also, more research needs to be done to investigate how asthma medication reduces obesity risk and whether it could be an effective obesity prevention strategy for children with asthma. “It’s possible that asthma medication use leads to higher physical activity in children with asthma,” said Garcia, “which then lowers the risk of obesity later in childhood.”

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Too Much or Too Little: Exploring Micronutrient Intake in Pregnant Women

Good nutrition during pregnancy is important for a baby’s health. Too few vitamins and minerals, such as folic acid and vitamin A, can result in neural tube defects and alterations in heart structure. On the other hand, excessive intake of certain micronutrients may increase chronic disease risk. Although previously associated with lower income countries, meta-analyses and nationally representative samples have shown that at least one in every three pregnant women in the US aged 20-40 were at risk for inadequate intake of various vitamins while nearly one third of pregnant women exceeded the upper intake level of certain micronutrients by up to 5-10 times their required amount.

Katherine Sauder, PhD

To explore the disparities in nutrient intake among pregnant women, Katherine Sauder of CU Anschutz and her writing team collected data from nearly 10,000 women in 15 ECHO cohorts across 14 states. Participants in all of these cohorts reported sociodemographic data, weight, age, race/ethnicity, education status, and pre-pregnancy body mass index. Participants were women aged 14-50 who provided either 24-hour dietary recalls or food frequency questionnaires during their pregnancy between 1999-2019.

The team compared the intake of 19 micronutrients from food alone versus food plus dietary supplements to estimate the proportion of the micronutrients consumed above and below their recommended amounts among the different sociodemographic and physical subgroups.

The study found that more than one in five pregnant women did not eat enough of the vitamins D, E, K, and choline and the minerals magnesium and potassium, even when taking dietary supplements. The women most likely to not get enough of these vitamins and minerals were those aged 14-18 years, those who were Hispanic or Black, those who had less than a high school education, and those with obesity. Also, non-Hispanic women were most likely to eat too much folic acid, potentially putting their child at an increased risk for chronic illness.

“This study shows that the dietary supplements women use today do not help them get all the nutrients they need in the right amounts. Personalized approaches for dietary counseling and dietary supplement recommendations are needed. Reformulation of supplements would likely benefit pregnant women as well,” said Sauder. “Choosing a prenatal vitamin can be hard because there are so many products at the store. Ask your doctor to help you choose the best one for you.”

In the future, the team will study how much vitamins and minerals women are getting from foods and compare this value to the recommended amounts for pregnant women. This will help doctors identify which dietary supplements on the market will give women the vitamins and minerals they need.

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The Effect of Phthalate Exposure on Placental Function and Gene Expression

Phthalates are man-made chemicals that are commonly found in plastics, solvents, and personal care products like perfumes, nail polishes, soaps, and hair sprays. Because they are found in so many household products, people can be exposed to them often. Unfortunately, there is little research on how exposure to phthalates can affect a pregnant woman’s health and the health of the developing baby. Investigating how exposures to phthalates affect the placenta, an organ that delivers oxygen and nutrients to the baby, can reveal more about the relationship between these chemical exposures and infant health.

Alison Paquette, PhD
Alison Paquette, PhD

To explore this research gap, Alison Paquette, PhD of Seattle Children’s Research Institute and the ECHO Pathways research team examined the association between phthalate exposure in the second and third trimester and gene expression in the placenta. This information provides insight into how phthalates may affect different placental functions.

To conduct this research, the team gathered urine samples from 760 women enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study in Shelby County, TN. Their placentas were also collected after giving birth. Participants were between 16-40 years old, with relatively healthy pregnancies, and a majority were Black.

The team measured the levels of 16 different phthalates in each urine sample provided during the mother’s second and third trimesters and analyzed the levels of expression for every gene in the placenta after giving birth. Gene expression is a measure of how DNA is converted into proteins, which perform a variety of important cellular functions and play critical roles in development. For each gene, the researchers investigated the link between that gene’s expression and phthalate levels during pregnancy. The researchers used this information to analyze which biological pathways in the placenta are potentially affected by phthalate exposure.

The study found that several phthalates were associated with higher or lower placental gene expression for 38 genes. The team also identified some changes in gene expression that were only significant in male or female infants, indicating that phthalates may alter placental function differently for the different sexes. The team also found 27 specific biological pathways that may have been affected by phthalate exposure, including pathways essential to infant development. For example, the team found phthalate exposure was linked with decreased expression of the genes involved in the generation of fatty acids, which are essential building blocks for organ development. Changes in generating these fatty acids may impact how the fetus grows, particularly the brain, which may have a long-term impact on the child’s health.

“Placental gene expression is an important marker that can tell us if the placenta is performing all its normal jobs correctly. If the placenta is not functioning correctly, it may lead to pregnancy complications that threaten the health of both the mother and baby, or cause changes in fetal growth and development,” said Paquette. “By identifying how chemicals like phthalates alter placental function, it may help us understand the associations between phthalate exposure and some pregnancy complications.”

Moving forward, the research team will study how changes in the placenta are associated with other pregnancy complications, such as preterm birth, within the same population of women. Additional research, paired with new tools and technology, will also help them map out how phthalates may cause these changes in gene expression.

Read the research summary.