Tracking Effects on Brain Development

We know the developing brain is shaped by both genetics and the environment, but the details remain unclear. What happens to a child’s brain after pre- or postnatal exposure to substances like opioids, tobacco, or alcohol? Or if environmental contaminants like air pollution are breathed in?

A groundbreaking new research project plans to find out, toward a better understanding of child well-being and health. The HEALthy Brain and Child Development (HBCD) Study will begin recruiting approximately 7,500 pregnant women in their second trimester from 25 states across the country, many of which have been heavily affected by the nationwide opioid crisis. The research will follow these women and their children throughout early childhood.

Supported by the NIH HEAL Initiative^® and 10 NIH Institutes, Centers, and Offices, this study will help address the lack of understanding of how opioid exposure during pregnancy affects a child’s long-term development and health, including vulnerability to drug use and addiction later in life.

Tracking Effects on Brain Development

A person’s brain continues to grow throughout childhood and into the mid-20s. During this long period of development, the brain is very changeable, especially during the early years of rapid development. Such flexibility makes it possible for a child to adapt quickly to the world – learning to walk, talk, read, and think through problems.

The rapidly growing brain is exposed to various factors that build resilience and vulnerability, which collectively shape overall health. Access to good nutrition and strong family and social support systems contribute to healthier outcomes, while prenatal exposure to opioids or other substances and various environmental influences like pollution, poverty, and violence may increase risks for adverse outcomes.

Harmful effects on the brain can result in immediate health problems like low birth weight and neonatal withdrawal symptoms, but also increased susceptibility to behavioral problems in childhood and adolescence. These include difficulties with thinking and emotional control, attention-deficit/hyperactivity disorder, early drug use, and depression.

Scientists don’t yet know the impacts of all the factors that affect brain development and behavior individually and together, as well as whether they can be reversed. An important aim of this research is to identify factors that enhance resilience or risk for future substance use, mental disorders, and other behavioral and developmental problems. Knowing this information can guide development of interventions to help.

Data Collection Over Time

The HBCD research project is an observational study, meaning that the researchers are not testing any treatments or interventions, but rather collecting information over time. Data will be broadly shared on an annual basis and made available for researchers to analyze, as well as generate new ideas for research.

At several timepoints throughout childhood, HBCD researchers will document detailed medical and family histories; conduct cognitive and behavioral testing; collect limited maternal and child biospecimens (blood, saliva, and urine); and monitor each child’s exposures by interviewing caregivers. The scientists will also record electrical activity of the brain using electroencephalograms and brain imaging scans shortly after birth, once between 3 and 12 months, and every 2 years after that. Wearable devices known as biosensors will enable real-time collection of data from infants in their home environments.

The researchers will study not only the substances and experiences a child is exposed to, but also how much and how often they are exposed. For example, positive factors like supportive parents, food security, and frequent physical activity may have beneficial effects. Conversely, the effects of occasional substance use may be very different from frequent use – or from use of multiple substances, which is increasingly common in the United States.

“In addition to monitoring use of substances like opioids, tobacco, alcohol, and marijuana, we’ll also ask about prescription and over-the-counter medications, vitamin supplements, herbal products, vaccines, and so on,” explains Christina Chambers, Ph.D., M.P.H., of the University of California, San Diego, who is helping to coordinate the many researchers across the nation participating in HBCD.

Zero to Twenty

The HBCD Study is unique and important based on its size. Researchers can only examine the effects of multiple influences if data are collected from a very large group of research participants. It will provide complementary insights to the Adolescent Brain Cognitive Development (ABCD) Study launched in 2015 to follow brain development of more than 12,000 children for at least 10 years, starting at ages 9 to 10. Notably, the HBCD Study is designed to align with the ABCD study, thus enabling data collection spanning prenatal development through age 20.

“Is the die already cast before a baby is born?” is one question people wonder about children exposed to drugs during pregnancy, says HBCD scientist Sara DeMauro, M.D., of the Children's Hospital of Philadelphia.

The answer is "probably not," she says.

Past evidence suggests that interventions can reshape future events.

“If you can identify factors in a child’s environment that promote resilience, then you can start to think about how to recreate and deliver those factors to help children thrive,” DeMauro says.

In addition, recognizing that substance use may harm their baby, some pregnant women with a substance use disorder may take steps toward recovery, such as taking medications to treat opioid use disorder or other types of addiction. The long-term effects of these medications remain largely unknown.

Research Across America

As the researchers get started on this long-term research project, they are connecting with communities across America. Many welcome this research, says Julie Croff, Ph.D., of Oklahoma State University, who has partnered for years with Indigenous people in the Great Plains region of the United States.

“These communities are very well aware that the opioid crisis has adversely affected American Indians, and they want to make sure that if a fetus has been exposed during pregnancy that the child can realize his or her potential in the best possible way.”

Croff notes that Indigenous communities are very tightly knit and protective of their youth, in part due to the tragic history of having children removed from their birth families and placed with White families for foster care. As a result, many Tribal Nations have developed systems to connect children with the most appropriate caregivers when necessary, and HBCD researchers will be able to learn from these established systems to generate recommendations more broadly.

“In Oklahoma, our tribes are sovereign nations that are very adaptive, and they’re able to move science into practice quickly,” she adds, noting that her team predicts enthusiastic participation due to the community’s strong interest in helping the next generation.

DeMauro’s team in Philadelphia has also been encouraged at the level of interest from women who want to participate in HBCD research.

“People love to learn about their children,” she says, adding that there is a palpable sense of wanting to give back. While the COVID-19 pandemic has disrupted research and healthcare dramatically, DeMauro explains, it has also opened people’s eyes about how important it is for people to be part of the research process.

“People now understand what it means to be part of a big study that generates knowledge that helps us improve the way we take care of children and families who are like them in the future.”

Navigating Health and Research

Access to prenatal and pediatric healthcare remains a significant barrier for many women across the United States, such as in the deep South.

“Fewer than half of the counties in our state deliver babies,” says Lea Yerby, Ph.D., of the University of Alabama, explaining that rural areas often rely on community clinics that see patients from surrounding areas, sometimes hundreds of miles away.

For the millions of Americans who don’t have reliable transportation, health providers travel long distances to meet people in their home communities. In rural parts of Alabama, many women travel up to 100 miles for care, Yerby notes, and much further than that in sparsely populated frontier states. Some of these providers will be asked to be part of the HBCD research team, enabling the study to recruit women from isolated areas.

The HBCD Study has put a special focus on rural recruitment, including historically disenfranchised communities in the southern United States, to ensure that the research findings reflect the true diversity of the United States. That is one of the reasons why nearly 8,000 families will be asked to participate in this research.

“Many of the individuals we recruit to participate in this study may have transportation needs and other needs related to food insecurity, housing, and childcare,” says DeMauro, adding that some may also benefit from connections to treatment resources for substance use disorders.

Designated health navigators will work alongside each of the HBCD research teams to help women and their families meet basic needs such as offering connections to food resources or transportation vouchers, onsite care for siblings during study visits, and supplies such as diapers and formula.

Looking to the Future

The HBCD research program will be the most detailed study of early brain development ever conducted, and the team has been carefully preparing over the past year for this very large endeavor.

Preparations include addressing technological needs, such as designing MRI-friendly cribs, forming relationships with local community partners and potential research participants to ensure all participant needs and challenges are addressed, and coordinating communication among the 25 research teams carrying out this research in partnership with women and their families.

Over time, knowledge gained by the HBCD Study can be used by researchers, within and outside of the HBCD Study. A main study goal is to learn about protective factors that can chart development of interventions to promote resilience and recovery. By tracking positive influences on the developing brain, the results will also map a strategy for defining the roots of resilience and a healthy future for all children.