CHOP Researchers Build a Picture of Healthy Brain Development Through HBCD

Through the HBCD study, researchers are building a comprehensive, long-term picture of healthy neurodevelopment.

limjr [at] chop.edu (By Jillian Rose Lim)

From simple nutrition to a pregnant person's substance use, babies come into contact with a number of influences before and after birth. And while it's well-known that a child's early environment can influence their cognitive, behavioral, or social development, clinicians currently have no template by which to discern which factors pose great risk, which help confer resilience — and above all, what typical variability in brain development looks like.

Now, as part of the multi-site HEALthy Brain and Child Development Study (HBCD), Children's Hospital of Philadelphia researchers are building a comprehensive, long-term picture of healthy neurodevelopment through the power of big data collected in extraordinary detail.

Led by Hao Huang, PhD, and Sara DeMauro, MD, MSCE, principal investigators of the project, a multidisciplinary team including the Division of Neonatology, Department of Radiology, and collaborators at the University of Pennsylvania will collect a multimodal data set from hundreds of babies over the course of a decade in an unparalleled landmark study. CHOP received a $6 million dollar, five-year award in support of HBCD. HBCD is funded by 10 institutes and offices at the National Institutes of Health, as well as the Helping to End Addiction Long-term^SM Initiative, or NIH HEAL Initiative^SMand is led by the National Institute on Drug Abuse (NIDA).

"Though the grant is funded in part through the NIH HEAL Initiative, which is earmarked for understanding the downstream effects of the opioid epidemic, more broadly, this study also seeks to understand the effects of multiple exposures on the long-term development of a large cohort of babies," said Dr. DeMauro, who is an associate professor of Pediatrics at CHOP. "That's why HBCD is so big — we're interested in substances people may use during pregnancy, as well as environmental exposures that can happen during pregnancy and early childhood. It's a very broad look at many different things that could influence children over time."

"This national-level, fully-leveraged big data set will give more convincing and validated conclusions about many important questions in brain development," added Dr. Huang, professor of Radiology at CHOP.

Drs. DeMauro and Huang, alongside other investigators at CHOP, will recruit pregnant individuals primarily during their second trimester and follow them throughout the remainder of their pregnancies. The follow-up will continue during the mother's time of delivery and throughout the first several years of the child's life until the age 10. The data collected will include magnetic resonance imaging (MRI), electroencephalography, biospecimens, biosensors, developmental and behavioral assessments, and questionnaires regarding medical and family history.

For Dr. Huang, whose lab specializes in applying novel MR neuroimaging and analysis techniques to delineate human brain development, the study offers a rare opportunity to answer key questions.

"I have been studying typical brain development for decades, and I'm very interested in seeing how imaging measurements might deviate from what we observe as typical trajectories in this much larger cohort due to exposure from opioids or other substances and environments," Dr. Huang said. "We would like to understand whether there are important time points for early intervention to avoid more severe disorders from developing."

Meanwhile, Dr. DeMauro, an attending neonatologist whose research includes the rigorous longitudinal assessment of early childhood outcomes in high-risk neonates, anticipates the resulting data will help to inform clinical decisions.

"As a clinician who takes care of babies who have been exposed to all sorts of substances, one of the things we always struggle with is teasing out the effect of the substance itself from the effects of the environment into which the baby is born," Dr. DeMauro said. "This study is really designed to help us understand how those effects layer on one another, because there are some things that we as physicians can intervene on and some that we can't. If it turns out that the environment matters more than the exposure, that's hugely important for how we counsel these moms, how we take care of their babies, and how we help them take care of their babies after discharge."

CHOP researchers previously conducted studies on the impact of environmental influences and substance use, providing a solid backdrop for the current project. Dr. DeMauro specifically highlights work led by colleague Hallam Hurt, MD, an attending neonatologist and education director in the Neonatology Follow-Up Program at CHOP.

What's different, however, is the HBCD will allow the researchers to take Dr. Hurt's work even deeper: While the latter also conducted imaging of the infants growing up in adverse economic environments, the team can now also look at how environmental exposures affect babies in utero.

"We can put more of the pieces together," Dr. DeMauro said. "We are able to collect all of the exposure data, all of the imaging data, and all of the developmental data in the same group — a much bigger group — of babies across the country, at the same time. It's so much more powerful."

The team will begin the first five years of the HBCD study by focusing on significant data collection of the children in their first several years after birth. Alongside Drs. Huang and DeMauro, a number of CHOP investigators are involved in the project, including Heather Burris, MD, Erin Schwartz, MD, Scott Lorch, MD, Timothy Roberts, PhD, and Emily Kuschner, PhD. While CHOP researchers received the award as part of the HBCD study's second phase, Penn colleagues M. Dylan Tisdall, PhD, and Allyson Mackey, PhD, laid the framework for CHOP's involvement by participating in the study's first phase and will continue to provide their expertise during phase two.

Finally, while the scope of the study has broad and far-reaching implications, Drs. DeMauro and Huang each have their own parts of the project they are especially excited about.

"This is a very big longitudinal follow-up," Dr. Huang said. "It's very difficult to pull data from the second trimester in utero all the way to adolescence, while also including the mother's data. That longitudinal aspect is relatively rare, and so this gives us tremendous opportunity to study typical and atypical neurodevelopment."

"What I'm most interested in being able to accomplish as a scientist is to be able to test interventions that might modify atypical trajectories of early childhood development," Dr. DeMauro said. "HBCD is going to provide important insights into opportunities for interventions that might make a difference."