Prenatal Opioid Exposure Is Associated with Punctate White Matter Lesions in Term Newborns

Stephanie L Merhar; Carla M Bann; Nicole Mack; Jamie E Newman; Catherine Limperopoulos; Namasivayam Ambalavanan; Jonathan M Davis; Sara B DeMauro; Scott A Lorch; Deanne E Wilson-Costello; Myriam Peralta-Carcelan; Lindsay M Parlberg; Brenda B Poindexter; Kushal Kapse; Beth M Kline-Fath; Jonathan G Murnick

doi:10.1016/j.jpeds.2025.114669

Prenatal Opioid Exposure Is Associated with Punctate White Matter Lesions in Term Newborns

J Pediatr. 2025 May 23:284:114669. doi: 10.1016/j.jpeds.2025.114669. Online ahead of print.

Authors

Stephanie L Merhar¹, Carla M Bann², Nicole Mack², Jamie E Newman², Catherine Limperopoulos³, Namasivayam Ambalavanan⁴, Jonathan M Davis⁵, Sara B DeMauro⁶, Scott A Lorch⁶, Deanne E Wilson-Costello⁷, Myriam Peralta-Carcelan⁴, Lindsay M Parlberg², Brenda B Poindexter⁸, Kushal Kapse³, Beth M Kline-Fath⁹, Jonathan G Murnick³

Affiliations

¹ Division of Neonatology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati, Cincinnati, OH. Electronic address: stephanie.merhar@cchmc.org.
² Analytics Division, RTI International, Research Triangle Park, NC.
³ Developing Brain Institute, Children's National Hospital, Washington, DC.
⁴ Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
⁵ Division of Newborn Medicine, Department of Pediatrics, Tufts University, Boston, MA.
⁶ Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
⁷ Division of Neonatology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
⁸ Division of Neonatology, Department of Pediatrics, Emory University, Atlanta, GA.
⁹ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

PMID: 40414418
DOI: 10.1016/j.jpeds.2025.114669

Abstract

Objective: To assess whether prenatal opioid exposure is associated with punctate white matter lesions (PWMLs) on brain magnetic resonance imaging (MRI) in a large prospective cohort of term newborns.

Study design: Newborns ≥37 weeks of gestation with prenatal opioid exposure and unexposed controls underwent brain MRI at 0-1 months of age in the prospective observational Outcomes of Babies with Opioid Exposure study. Exposure status was based on maternal self-report and maternal or neonatal toxicology screening. MRIs were scored by two pediatric neuroradiologists masked to exposure. Multinomial logistic regression was used to compute ORs for PWML by opioid exposure, adjusting for various confounders.

Results: Opioid-exposed newborns (n = 165) had lower birth weight and smaller head circumference and were more likely to have mothers who smoked, were positive for hepatitis C, and had limited education than unexposed neonates (n = 94); 27% of exposed newborns had 1 or more PWMLs compared with 13% of unexposed newborns (P = .031). After adjusting for covariates, opioid exposure was associated with higher odds of PWML (aOR: 2.68, 95% CI: 1.07-6.72, P = .04), with methadone exposure worse than buprenorphine and other opioids (aOR: 3.25, 95% CI: 1.21-8.75, P = .02).

Conclusions: Prenatal opioid exposure is associated with an increased risk of PWML in newborns, with methadone exposure significantly worse than buprenorphine. As PWML are associated with adverse neurologic outcomes in other populations, follow-up will evaluate if these lesions significantly impact neurodevelopmental outcomes.

Trial registration: Clinicaltrials.gov NCT04149509.

Keywords: brain MRI; neonatal opioid withdrawal syndrome; prenatal opioid exposure; white matter injury.

Associated data

ClinicalTrials.gov/NCT04149509