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Limbic System Microstructure in Neonates With Antenatal Opioid Exposure.

María Guadalupe Mora Álvarez1, Josepheen De Asis-Cruz1, Kushal Kapse1

  • 1Developing Brain Institute, Children's National Hospital, Washington, District of Columbia.

JAMA Network Open
|July 2, 2026
PubMed
Summary

Neonatal brain scans reveal altered limbic system microstructure in infants exposed to opioids during pregnancy. These changes, particularly in the fornix, suggest potential long-term impacts requiring further clinical investigation.

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Area of Science:

  • Neuroscience
  • Neonatal Imaging
  • Developmental Pediatrics

Background:

  • Limited research exists on antenatal opioid exposure's impact on neonatal brain microstructure, especially within the limbic system.
  • Previous studies on white matter tracts were underpowered and lacked matched controls, highlighting the need for robust investigation.

Purpose of the Study:

  • To compare limbic system microstructure between neonates with and without antenatal opioid exposure.
  • To investigate potential differences in microstructure based on specific opioid exposure subgroups.

Main Methods:

  • A case-control study utilizing diffusion tensor imaging (DTI) on term neonates from the Outcomes of Babies With Opioid Exposure (OBOE) study.
  • DTI data acquired using harmonized protocols on 3T MRI scanners and analyzed using analysis of covariance.
  • Primary outcomes included comparisons of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity in the limbic system; False Discovery Rate (FDR) correction applied.

Main Results:

  • Opioid-exposed neonates exhibited significantly lower mean diffusivity and radial diffusivity in the fornix compared to unexposed controls.
  • Exploratory analyses indicated distinct limbic system microstructure patterns across different opioid exposure subgroups (buprenorphine, methadone, other opioids).
  • Specific findings included higher mean diffusivity in the parahippocampal gyrus for buprenorphine exposure and higher fractional anisotropy in the thalamus for other opioid exposures.

Conclusions:

  • Antenatal opioid exposure is associated with altered limbic system microstructure in neonates, particularly affecting the fornix.
  • Subgroup analyses reveal varied microstructural changes depending on the type of opioid exposure.
  • Further clinical correlation is warranted to understand the implications of these findings.