Study identifies differences in brain development in newborns exposed to opioids - Children's National

A new study published in JAMA Network Open and led by researchers from the Developing Brain Institute at Children's National Hospital and multisite collaborators found that newborns exposed to opioids before birth showed measurable differences in the structure of their developing brains compared with newborns who were not exposed. The findings offer new insight into how prenatal opioid exposure may affect early brain maturation and could help researchers better understand the biological pathways that contribute to later cognitive, behavioral and developmental challenges.

The study is part of the Outcomes of Babies with Opioid Exposure (OBOE) Study, a large, ongoing national effort examining how prenatal opioid exposure influences infant brain development and long-term outcomes. Researchers analyzed brain MRI scans from 259 full-term newborns recruited across four U.S. sites, making it one of the largest neuroimaging studies of prenatal opioid exposure conducted to date.

"This study provides important new evidence that differences in brain development associated with prenatal opioid exposure are already detectable in the newborn period," said Yao Wu, PhD, research faculty in the Developing Brain Institute at Children's National and first author of the study. "By identifying these early structural changes, we can begin to better understand how prenatal exposures impact the developing brain and potentially identify opportunities for earlier intervention and support."

Dive deeper

Of the 259 infants included in the study, 164 had been exposed to opioids during pregnancy and 95 served as non-exposed controls. Using advanced neuroimaging techniques, researchers examined cortical folding, a process that allows the brain's surface to expand and organize into the complex networks responsible for cognition, language, memory, attention and behavior. The degree of cortical folding is considered an important marker of healthy brain maturation during late pregnancy and the newborn period.

Compared with non-exposed newborns, opioid-exposed infants demonstrated significant reductions in both cortical surface area and sulcal depth, suggesting differences in how the cerebral cortex develops before birth.

These differences were detectable shortly after birth, indicating that prenatal opioid exposure may alter brain development during a period of rapid growth that begins in the second trimester and accelerates during the final months of pregnancy. The findings build on previous work from the OBOE team that identified smaller global and regional brain volumes among opioid-exposed newborns. Together, the studies suggest that prenatal opioid exposure may affect multiple aspects of brain development, including both brain size and the organization of the cerebral cortex.

What this means

Researchers also found important differences based on the type of opioid exposure. Newborns exposed to methadone generally demonstrated larger reductions in cortical surface area than those exposed to buprenorphine, two medications commonly used to treat opioid use disorder during pregnancy. In addition, infants exposed to opioids alongside other substances showed more extensive changes than those exposed only to opioids, highlighting the potential compounding effects of multiple prenatal exposures on the developing brain.

While the study was not designed to determine whether these structural differences will lead to developmental challenges later in childhood, previous research has linked prenatal opioid exposure to increased risks of learning difficulties, attention challenges and behavioral concerns. The researchers emphasize that continued follow-up will be critical to understanding how these early brain maturational delays evolve over time and whether they can serve as biomarkers for future developmental outcomes.

What comes next

These findings underscore the importance of identifying brain-based markers of risk as early as possible. Ongoing studies are now tracking participating children with serial brain imaging and developmental assessments to better understand how early structural differences relate to later cognitive, behavioral and emotional development.

As communities across the country continue to address the impacts of the opioid epidemic, researchers say understanding how opioid exposure affects the developing brain is critical to creating more effective strategies for prevention, treatment and early intervention.

Additional authors from Children's National include Kushal Kapse, MS, Josepheen De Asis-Cruz, MD, and Catherine Limperopoulos, PhD. The study was conducted in collaboration with investigators from Cincinnati Children's Hospital Medical Center, University of Alabama at Birmingham, Children's Hospital of Philadelphia, Case Western Reserve University, RTI International, Tufts Medical Center, and Emory University.

Read the full study, "Antenatal Opioid Exposure and Cerebral Cortical Maturation in Newborns," published in JAMA Network Open.