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

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. (J Pediatr2025;284:114669). Trial registration Clinicaltrials.gov NCT04149509.