Author: Jodi Snare

ECHO Researcher Publishes Review on Epigenetic and Environmental Influences on Generational Health

Posted on by Jodi Snare

Previous studies show that the environment may affect the health of multiple generations in one family. Environmental exposures and behaviors can change a person’s epigenetics, the markers and structural changes that direct how genes are read and understood. These markers and changes form a “molecular memory” can be passed down across generations. For example, if a pregnant woman is exposed to a chemical, her children’s and possibly grandchildren’s health may be impacted through epigenetic changes.

Carrie Breton, ScD

Knowing this, ECHO researcher Carrie Breton, ScD of the University of Southern California and her writing team gathered information from past studies to provide a review of existing epigenetic research and evaluate the potential role of epigenetics in the passing on of health risks to later generations. Breton served as lead author and was accompanied by other ECHO researchers, such as Rebecca Fry, PhD of the University of North Carolina at Chapel Hill; Alison Hipwell, PhD of the University of Pittsburgh; Cristiane Duarte, PhD of Columbia University; Linda Kahn, PhD of NYU Langone Health; Rachel Miller, MD of Icahn School of Medicine at Mount Sinai; and Joseph Braun, PhD of Brown University. Their research, titled “Exploring the evidence for epigenetic regulation of environmental influences on child health across generations” is now published in Communications Biology.

“While complex childhood disorders clearly have genetic components, it is increasingly clear that the environment can play a substantial role in affecting risk, even across generations. Our question was how much evidence exists to support epigenetic mechanisms as one route for conveying that risk,” said Breton.

To collect information, the writing team reviewed several studies on humans and animals investigating the role of epigenetics in multigenerational health. They used these studies to build a broad view of how environmental exposures and behaviors can have a lasting impact on the health and well-being of children for generations to come.

Research from this review found evidence in animals and humans that environmental exposures can affect health across multiple generations, potentially through altered epigenetics. One of the challenges of studying epigenetics in humans is untangling the complex interactions between epigenetic, genetic, and environmental factors associated with certain health outcomes. The scale of the ECHO Program makes it uniquely situated to address questions about environmental exposures across generations.

“By looking at many results together, scientists can find important patterns and form a better understanding of how the environment can affect the health of a mother, child, and grandchild,” said Fry.

Read the research summary.

Series Highlighting ECHO Program Now Available in Pediatric Research

Posted on by Jodi Snare

Pediatric Research recently published a series of articles highlighting the ECHO Program’s progress. In the introductory article, titled “The NIH ECHO Program: investigating how early environmental influences affect child health,” the NIH Program Office provides a broad overview of the program and its achievements to date. The second and third articles, written by members of the ECHO Coordinating Center (CC) and various ECHO investigators, focus on the program’s construction, challenges overcome during development, and the scientific opportunities that have already resulted from ECHO’s uniquely broad dataset.

The introductory article highlights the origins of the ECHO Program, dating back to September 2016. Authored by members of the NIH Program Office, this article details the breadth of the ECHO Program’s national network of cohorts, which includes 57,000 children and over 1,200 researchers participating through observational and interventional research. This piece also outlines program goals, including ECHO’s commitment “to enable high-impact research evidence that will inform clinical practices, policies, and programs for child health; and establish a national data platform and biorepository for the scientific community.”

Given its size and span, the program faced unique challenges. To tackle these head-on, governing committees facilitated the establishment of several specialized working groups to address challenges and direct the program in pursuing its goals. For example, the purpose of the Team Science Working Group was to “maximize ECHO’s scientific excellence and productivity by fostering team building and collaboration through effective communication.”

Another logistical challenge that ECHO faced from the beginning was the coordination of a dispersed set of established pediatric cohorts and the harmonization of their existing data to create a nationwide standardized dataset. As many of these individual cohorts had their own research focal points and routine sets of measurements, building a consistent dataset required ECHO to develop a unified set of required measurements and standard protocols. From this problem came the Protocol Working Group.

ECHO aims to enhance the health of children and adolescents through research that may help inform healthcare practices, programs, and policies. The third article details program strategies for fostering solution-oriented research that helps accomplish this goal, some of which include promoting ECHO research through publications and Opportunities and Infrastructure Fund (OIF) grants.

In the five years since its inception, the ECHO Program has made great strides in the development of a diverse, nationwide pediatric research framework with the power to inform children’s health policies and practices. Its large, varied population of participants, emphasis on multidisciplinary science, and capacity for pioneering innovative methods and technologies have shaped the program into an unprecedented resource in pediatric research.

“ECHO represents exciting new opportunities for pediatric research,” the third article concludes, “allowing for the investigation of scientific questions related to less common childhood outcomes and increasing inclusiveness of children participating in research in the United States.”

NIH ECHO Program Hosts Preconceptional Origins of Child Health Outcomes Workshop

Posted on by Jodi Snare

The National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Program hosted a free 2-day Preconceptional Orgins of Child Health Outcomes Webinar Thursday June 17, 2021 10:00AM – 4:15PM (EDT) and Friday June 18, 2021 10:00AM – 3:00PM (EDT).

Workshop Purpose

  1. To assess the state of the science, research gaps, and opportunities related to how preconception exposures may influence child health outcomes.
  2. To discuss how to overcome operational challenges in conducting preconception cohort studies.

The Workshop was composed of five themes. Each theme provides an opportunity for speakers and discussants to address theme-specific issues and for the audience to ask questions:

Thursday June 17, 2021

  • Theme 1: Lifestyle Factors/Obesity
  • Theme 2: Recruitment/Study Design
  • Theme 3: Fathers

Friday, June 18, 2021

  • Theme 4: Physical and Chemical Exposures
  • Theme 5: Psychosocial and Societal Influences

ECHO Researchers Create a Common Measure of Adult Depression

Posted on by Jodi Snare
Courtney K. Blackwell, PhD
Courtney K. Blackwell, PhD

More than 264 million people experience depression worldwide. In the United States alone, more than 17 million adults experience depression each year. And women, especially those who are currently or recently pregnant, are at higher risk for a depressive episode. As such, regular depression screenings for women during and after pregnancy is a recommended practice, and doctors may want to continue screening women throughout their lives. Consistent measurement of depression throughout a woman’s lifetime can be difficult because the measurement tools used around pregnancy are scored differently from the common measures of adult depression. Linking these measurement tools together will help doctors track the changes in depression across a woman’s lifetime.

To address this research gap, Courtney K. Blackwell, PhD, and her ECHO colleagues conducted a study aimed at linking the Edinburgh Postnatal Depression Scale (EPDS)—a measure of depression in women during or after pregnancy—with the Patient-Reported Outcomes Measurement Information System Depression (PROMIS-D), a general measure of adult depression.

This study included approximately 1,200 mothers from two ECHO sites in the Northern Plains of the US who each completed the EPDS and PROMIS-D surveys. All data were collected using an online survey. Most of the participants were white, but the sample also included American Indian/Alaska Natives. On average, the participants were 35 years old, and about half had a 4-year college degree or higher.

While the EPDS includes more specific measures of postpartum depression symptoms, the study found that the EPDS and PROMIS-D gave depression scores that were highly correlated for women around pregnancy. Both surveys asked questions about increased depressed mood and decreased interest and engagement in daily activities. The researchers were able to convert EPDS scores to PROMIS-D scores for consistent tracking of depression in women throughout adulthood. The converted scores held for different ages, ethnicities, races, and study sites.

“To know about someone’s depression across time, it is important to have a way to use data from different measures that may have been used at different timepoints,” said Blackwell. “This study provides a way to convert scores from a measure used during and after pregnancy to a measure that is used at any time in adulthood.”

The conversion table may also be useful to ECHO researchers who want to standardize depression measurements from multiple cohort sites. Additional studies may examine how different depression measures can be converted using similar methods.

The conversion table is available on prosettastone.org.

 

Access the research summary.

NIH Issues Request for Information to seek input about enhancing ECHO science

Posted on by Jodi Snare

The National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Program recently released a Request for Information (RFI) to seek input from the scientific community and the general public about enhancing ECHO science.

Through this RFI, the NIH asked for comments on any or all of but not limited to, the following topics:

I. General Topics

  • Approaches to promote scientific value while reducing burden on participants and staff in large consortia of parent-child cohort studies that involve primary data collection
  • Nimbleness to address public health emergencies in large collaborative consortia of longitudinal studies
  • Engagement strategies to enhance recruitment and retention of diverse study populations
  • Promotion of diversity of the scientific workforce related to child health

II. Preconceptional Origins of Child Health Outcomes:

  • Identifying solution-oriented (“so what”) scientific questions about preconceptional origins of child health outcomes, based on knowledge from pre-clinical, clinical work, and population research
  • Strategies for recruiting participants preconceptionally, and retaining through pregnancy into childhood
  • Measures and biospecimens from prospective mothers and fathers that cohorts should collect prior to or in early pregnancy
  • Ethical considerations regarding study participation of biological and non-biological fathers

The ECHO Program Office held a webinar on May 6, 2021 to discuss the RFI. If you were unable to attend the webinar or would like to view the recording, we are pleased to provide it here:

The ECHO Program Office released a Request for information (RFI) on April 22, 2021 titled “Request for information on enhancing the science for the Environmental influences on Child Health Outcomes program” under notice number NOT-OD-21-108 and extended under notice number NOT-OD-21-129. The purpose of the RFI was to gather input from stakeholders throughout the extramural scientific community and general public regarding the enhancement of ECHO science. The RFI closed on June 08, 2021 after being open for 47 days. ECHO received a total of 23 comments. The linked pdf below summarizes key information provided from the responses about how ECHO could enhance its science. Common themes among the RFI responses included the importance of the ECHO program; reducing burden on ECHO participants and staff; potential engagement strategies for recruiting and retaining diverse study populations; and whether to expand ECHO’s scientific focus to include the preconception period.

Compilation of RFI Responses

Review the RFI Response Summary

National Asthma and Allergy Awareness Month

Posted on by Jodi Snare

May is National Asthma and Allergy Awareness Month.

Nearly 5.5 million children in the U.S. are living with asthma, a respiratory disease that causes much suffering and loss of days at school and work.

ECHO investigators aim to fill gaps in research on conditions that affect kids’ airways by studying data from our pediatric cohorts and by testing interventions in our IDeA States Pediatric Clinical Trials Network. With its large sample size, diverse populations, and ongoing studies, the ECHO Program is well positioned to conduct studies that can help researchers and doctors better understand, prevent, and treat asthma in children.

I’m pleased that this month’s ECHO Connector includes some of ECHO’s latest research in our upper and lower airways outcome area. While many studies have focused on children who already have asthma, it’s also important to know who is at highest risk of getting asthma, so that researchers and doctors can better understand how to prevent it. In a paper by ECHO researchers published in JAMA Pediatrics this month, ECHO researchers share new findings about which groups of children are most likely to get an asthma diagnosis as they grow up.

In other news, the NIH ECHO Program Office recently released a Request for Information (RFI) to solicit input from the scientific community and the general public about enhancing ECHO science. I encourage you to provide input to this RFI, due to NIHKidsandEnironment@od.nih.gov  and sonia.arteaga@nih.gov by Tuesday, June 8, and share it with your networks and colleagues. Your input will be critical to enhancing ECHO research.

In addition, the ECHO Program is sponsoring a free workshop on preconception research this June 17-18, and I encourage you to register. This virtual workshop will feature presentations by NIH Director Dr. Francis Collins and other experts who will discuss the state of the science, research gaps, and opportunities related to how preconception exposures may influence child health outcomes.

ECHO Publication Examines the Relationship between Age, Race, and Childhood Asthma

Posted on by Jodi Snare

Asthma is a chronic (long-term) condition that affects the airways in the lungs. Asthma affects people of all ages and often starts during childhood.

Aruna Chandran, MD, MPH
Christine Cole Johnson, PhD, MPH

While many studies have focused on people that already have asthma, it’s also important to know who is at highest risk of getting asthma, so that researchers and doctors can better understand how to prevent it.

To shed light on this topic, ECHO researchers Chris Johnson, PhD, MPH of Henry Ford Health System and Aruna Chandran, MD, MPH of Johns Hopkins University Bloomberg School of Public Health and their team studied which children are at highest risk for getting asthma across the United States. Find their research in JAMA Pediatrics.

To conduct this research, the team gathered information from 24,635 children who were younger than 18 years old and taking part in 31 studies following children over time as part of the ECHO Program. Children shared the age at which they first learned from a doctor they had asthma, as well as their sex, race, and the state in which they lived. Researchers also collected information on their parents’ history of asthma.

“This research opened our eyes to information that was not known before about what groups of children were more likely to get a new asthma diagnosis as they grew up,” said Johnson.

The study found that children with at least one parent with a history of asthma had two to three times higher rates of asthma. This higher risk with family history of asthma mostly affected younger children through age 4. The rates for boys went down with age, but rates for girls stayed about the same. Black children were diagnosed with asthma more than white children during preschool years, but less than white children after age 9-10 years.

“This study adds to our understanding of new cases of asthma. We show that young black children with a parental history have the highest rates,” said Chandran. “Doctors and scientists can use this to focus on helping children at highest risk, working on programs for young children with a focus on Black children whose parents also have asthma.”

If you would like to learn more about asthma in children, please visit the Centers for Disease Control and Prevention’s website. You may also view this video on asthma from the National Heart Lung and Blood Institute (NHLBI).

Read the research summary.

Exploring Gaps in Factors that Affect Pre-Term Birth

Posted on by Jodi Snare

Although previous studies show the rates of pre-term birth (PTB) vary based on race and location, little is known about the origin of these differences. Therefore, ECHO researchers Anne Dunlop, MD, MPH, of Emory University, and Alicynne Glazier-Essalmi, of Michigan State University, sought to explore the link between the mother’s socioeconomic status (SES), race, location, and pre-term birth (PTB). Their research, titled “Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts,” is now published in PLoS One.

The participants involved in this study included women enrolled in the ECHO Program who delivered a baby, totaling more than 20,000 mother-infant pairs. These women provided all of the required information about themselves and their infant, including the mother’s age at delivery, education, physical address or region, alcohol use, prenatal care, and the child’s birth sex and gestational age. The research team then took this data and looked for patterns and connections between the given information and factors that affect PTB.

The study found race and ethnicity played a role in how early the child was born. Additionally, compared to non-Hispanic white women, women of all other races had a higher chance of PTB. “Education also played a role,” said Dunlop. “For women overall, a bachelor’s degree or above was linked to less chances of PTB, and a high school education or less led to higher chances of PTB.” This connection between education level and PTB was seen in women who lived in the South and Midwest regions of the United States. Lastly, non-Hispanic white women living in rural areas had a higher chance of PTB delivery compared to women living in urban areas.

“This study explored an important gap in the field of children’s health, as it gathered information on several factors that affect when and if a child is born prematurely,” said Glazier-Essalmi. “Given our findings on education, it is possible that higher education among women could decrease the chances of PTB in the county, especially in the South and Midwest regions.”

Because non-Hispanic Black women, Native American, and Alaskan Native women have the highest rates of PTB, future studies can help identify the causes for this difference and determine ways to prevent PTB in these populations.

Read the research summary here.

Can Multiple Studies Combine Their Results When Their Confounder Adjustment Sets Are Different?

Posted on by Jodi Snare
Ghassan Hamra, PhD

In research, directed acyclic graphs typically guide decisions on choosing confounders that need to be adjusted. These graphs also suggest how to get unconfounded, or unbiased, effect estimates, which are based on different statistical models and do not always provide the same actual numeric values. Therefore, Ghassan Hamra, PhD, of Johns Hopkins University Bloomberg School of Public Health, and his team from Wake Forest University and University of California Davis joined together to better understand when these values do and do not correspond.

Their study, “Combining Effect Estimates Across Cohorts and Sufficient Adjustment Sets for Collaborative Research: A Simulation Study” was recently published in the February issue of Epidemiology. To conduct this research, all study data were simulated, and Hamra built all of the models and analyzed all of the information. Ultimately, the team found the estimators showed similar numeric values of the estimates the majority of the time. The exception is when using a model known as logistic regression, which did not give similar estimates. Logistic regression provides an odds ratio, which is a non-collapsible quantity, or one that cannot be reliably combined.

“This study has a significant impact on the ECHO Program, as it allows researchers to understand and combine information across ECHO groups,” said Hamra. In the future, researchers can make additional models to explore other forms of bias that make combining information across studies difficult.

Read the research summary here.

ECHO ACT NOW Current Experience Manuscript Published in Pediatrics

Posted on by Jodi Snare

In December, the ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) published its first ACT NOW Current Experience manuscript, “Site-Level Variation in the Characteristics and Care of Infants with Neonatal Opioid Withdrawal,” in Pediatrics.

The ACT NOW (Advancing Clinical Trials in Neonatal Opioid Withdrawal) Current Experience Study is designed to describe variation in the care of infants with neonatal opioid withdrawal syndrome (NOWS). The data collected were used to inform two of the ACT NOW clinical trials which are currently enrolling and will shape policies, programs, and practices in the care of infants with NOWS.

This cross-sectional study of 1,377 infants with evidence of opioid exposure at 30 participating hospitals nationwide described variation in maternal-infant characteristics, infant management, and outcomes for infants with NOWS.

The study found that sites varied widely in the proportion of infants whose mothers received adequate prenatal care, medication-assisted treatment, and prenatal counseling. Sites also varied in the proportion of infants with toxicology screening and proportion of infants receiving pharmacologic therapy, secondary medications, and non-pharmacologic interventions, including fortified feeds and maternal breast milk. The mean length of stay varied across sites (from two to 29 days), as did the proportion of infants discharged with their parents.

The study concluded that the wide variation in characteristics and treatment makes it unlikely that all infants are receiving efficient and effective care for NOWS. The research suggests that this variation should be considered in future clinical trial development, practice implementation, and policy development.

“Understanding the current landscape of NOWS is critical for future research and the development of programs, policies, and practices to provide better care for these infants,” said Leslie Young, MD, of the University of Vermont. “The degree of variation among infants with NOWS observed in this study shows a significant opportunity to improve the care they receive.”

Also available is a commentary associated with the article, emphasizing the importance of ISPCTN’s work for the field.