Opioids' imprint on the developing fetal brain

WASHINGTON – Thanks to its imaging expertise, Children’s National Hospital has been invited to participate in a groundbreaking, multi-million dollar study to determine how being exposed to opioids in the womb impacts newborns’ long-term brain development.

According to the National Institutes of Health (NIH), an estimated 10.3 million U.S. people aged 12 and older misused opioids like heroin in 2018. This component of the NIH’s massive Helping to End Addiction Long-Term Initiative (HEAL) will enroll pregnant women from four U.S. regions struck hard by the opioid crisis, following these women and their children for years to gauge opioids’ imprint on children’s brains.

Under the new federally funded grant, opioid-exposed children will be closely evaluated for the first two years of the infants’ lives through sophisticated brain images taken during the first month of life, at 6 months old and again at 2 years old. In addition to the opioid-exposed babies, the research teams will also examine brain development of normal babies of the same age to compare the progress of one group with the other. The Data Coordinating Center of the Neonatal Research Networks is the study’s principal investigator.

Children’s National will serve as the magnetic resonance image (MRI) coordinating center for the four-year Outcomes of babies with opioid exposure (OBOE) study. That means the Developing Brain Research Laboratory at Children’s National will oversee all aspects of how these babies’ detailed brain scans are acquired, processed and analyzed, says Catherine Limperopoulos, Ph.D.

“The power here is we will be able to perform serial measures so we can understand how the brain is maturing over the first two critical years of life,” explains Limperopoulos, director of MRI Research of the Developing Brain. “I anticipate we will be able to identify important, early biomarkers in those infants who will go on to experience neurological or behavioral dysfunction later in life.”

As pregnancy progresses, the fetal brain grows larger and more complex, forming the foundation on which infants are able to learn to walk, run and speak; how children master new lessons in school; and how teenagers are able to hold a job and become productive adults. The team is looking for early biological clues of brain development delay or dysfunction.

The image analyses done at Children’s National for this project won’t be the standard analyses that people get with a routine MRI, she adds. Her team leverages quantitative MRI analyses, which drill down to the micro-structure of the brain. It’s the kind of precision and consistency that lets one doctor compare a person’s blood pressure reading to another patient to gauge who is at risk for a heart attack - except the metrics they compare describe essential brain structures and predict later neurodevelopmental problems.

Because this study can define how specific brain regions are developing with precision, Limperopoulos explains, it should be able to determine at what point brain development of vulnerable infants exposed to opioids in the womb begin to veer off course. That knowledge could enable doctors to intervene earlier.

“We will be able to very carefully characterize the infants’ neurological and behavioral outcomes, describing neurodevelopmental consequences that are associated with prenatal exposure to opioids,” she says.

In addition to examining the types of social and economic challenges these women and their young infants continue to face after birth, the research teams will collect very detailed timing of when these infants were exposed the opioids, in the same way someone would characterize the “dose effect” of a legal, prescription drug.

Pregnant women will be enrolled at four clinical sites that are part of a broader neonatal research network and who have worked together collaboratively for years:

• Case Western Reserve University
• Children’s Hospital of Philadelphia
• Cincinnati Children’s Hospital Medical Center
• University of Alabama at Birmingham

Children’s National was recruited to participate because of its unparalleled expertise in performing serial imaging and its state-of-the-art evaluation of the developing fetal brain.

“I am so proud of my growing research team, because being selected to participate in this study is a testament to our dedication in mastering new and better techniques to tease out such findings as the impact of nutrition on white matter development, tracking blood flow and metabolite concentrations within the developing fetal brain, characterizing regional and global brain volume and tracing the path of neurons as they speed through the neural network,” Limperopoulos adds. “Ultimately, our goal is to improve care for opioid-exposed infants to reduce the chance they will suffer lifelong neurological injuries, and the knowledge we build through this project has the potential to help other vulnerable infants.”

Media contact: Diedtra Henderson | 443-610-9826 | 202-476-4500