Research Horizons


In Utero Opioid Exposure Impacts Fetal Brain Size and Development

Radiology | Top Scientific Achievement
2023 Research Discoveries 38-year-old pregnant patient at 32 weeks 1 day of gestation who was not exposed to opioids during pregnancy. Patient underwent investigational fetal MRI. Sagittal T2-weighted SSFSE image of brain shows manual tracing of midline vermis area.

The opioid epidemic in the United States doesn’t discriminate—even infants are at risk.

Infants exposed to prenatal opioids are at increased risk of cognitive and behavioral problems during childhood. A case-control study led by first author Usha Nagaraj, MD, along with Stephanie Merhar, MD, MS, and others, looked at a series of fetal MRIs of subjects in the third trimester of pregnancy to determine the effects of opioid exposure.

Fetuses were classified as opioid exposed or unexposed in utero, and 14 two-dimensional biometric measurements of the fetal brain were manually assessed and used to derive four indexes. Adjusting for gestational age, fetal sex and nicotine exposure, the researchers discovered that seven measurements were smaller in the opioid-exposed fetal brains, indicating smaller brain size and larger frontal occipital index. These measurements include cerebral frontal occipital diameter, bone biparietal diameter, brain biparietal diameter, corpus callosum length, vermis height, anteroposterior pons measurement and transverse cerebellar diameter.

Additionally, while differences in fetal motion, cervical length and deepest vertical pocket of amniotic fluid were statistically insignificant between the two groups, opioid-exposed fetuses showed higher frequencies of both breech position and increased volume of amniotic fluid. Nagaraj explains that the increased incidence of breech presentation may reflect neuromuscular dysfunction in utero and that while the increased amniotic fluid volume is of unclear etiology, the finding suggests an underlying physiologic aberration.

“The findings suggest that opioids may have an impact on development even prior to birth,” says Nagaraj. “And while it is unclear at this time what the smaller brain sizes seen in the opioid-exposed fetuses mean in regard to postnatal development, future studies in larger cohorts may help shed light on this.”

Scatterplot showing cerebral fronto-occipital diameter on fetal MRI and gestational age, stratified by study group (opioid exposed fetuses or unexposed control fetuses).

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Publication Information
Original title: MRI Findings in Third-Trimester Opioid-Exposed Fetuses, With Focus on Brain Measurements: A Prospective Multicenter Case-Control Study
Published in: American Journal of Roentgenology
Publish date: Sept. 28, 2022
Read the study

Research By

Usha Nagaraj, MD
Usha Nagaraj, MD
Department of Radiology and Medical Imaging
Stephanie Merhar, MD, MS
Stephanie Merhar, MD, MS
Principal Investigator, Cincinnati site, NICHD Neonatal Research Network

Merhar serves as attending neonatologist at the Perinatal Institute at Cincinnati Children’s. Her research focuses on how the newborn brain can bounce back from insults including brain injury and substance exposure.