Limbic System Microstructure in Neonates With Antenatal Opioid Exposure

By
María Guadalupe Mora Álvarez
Josepheen De Asis-Cruz
Kushal Kapse
Yao Wu
Stephanie L. Merhar
Carla M. Bann
Jamie E. Newman
Nicole Mack
Sara B. DeMauro
Namasivayam Ambalavanan
Scott A. Lorch
Deanne Wilson-Costello
Brenda B. Poindexter
Myriam Peralta-Carcelen
Jonathan M. Davis
Catherine Limperopoulos
July 2, 2026
0 min

Jama Network Open

Objective:

To compare brain microstructural organization in the limbic system in neonates who were opioid exposed and unexposed using a region of interest–based DTI approach.

Approach:

Study Design: A multisite, prospective, observational case-control study (ACT-NOW OBOE) was conducted with neonates born at 37 weeks’ gestation or later, comparing those with antenatal opioid exposure to unexposed controls.
Data Collection: Data were collected from maternal surveys and medical records, and exposure status was confirmed through toxicology reports.
Imaging Protocol: MRI scans were performed using a validated non-sedated neonatal protocol, acquiring 3D T2-weighted and DTI images on Siemens or Philips 3T scanners.

Key Findings:

Antenatal opioid exposure is associated with microstructural changes in the limbic system of neonates.
Previous studies indicated disrupted oligodendrocyte lineage and myelination processes in opioid-exposed animal models.
DTI studies in neonates have reported changes in white matter microstructure, including lower fractional anisotropy and higher mean diffusivity in various brain areas.

Interpretation:

Limitations:

Prior studies had small sample sizes and lacked matched controls, limiting their power.
Tract-based spatial statistics may not accurately represent anatomical changes in the developing brain.