Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature

Abstract

ObjectiveTo compare brain MRI biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). Study designWe examined 395 preterm infants (≤ 32 weeks gestational age[GA]) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III(BSID-III) at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. ResultsThe mean(SD) gestational age was 29.3(2.5) weeks; 35(8.9%) had POE and 20(5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs. 3.9%, respectively; p=0.002); findings remained significant with OR 4.16 (95% CI:1.26, 13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/GA (OR:0.93; 95% CI:0.78,1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95%CI: -11.8,-0.6) points on BSID-III Motor subscale compared with unexposed infants. ConclusionsPOE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.