Neurodevelopmental outcomes of prenatal opioid exposure and neonatal opioid withdrawal syndrome: A systematic review from birth to early adulthood.

The rise in prenatal opioid exposure (POE) has led to an increase in neonatal opioid withdrawal syndrome (NOWS), yet the long-term neurodevelopmental outcomes secondary to POE and subsequent diagnosis of NOWS remains underexplored. A systematic search of PubMed, Embase, CINAHL, APA, and PsycINFO identified 14 studies published between 2000 and 2021, 12 human and 2 animal studies, with data independently extracted and synthesized using a Synthesis Without Meta-analysis (SWiM) approach due to study heterogeneity. In human studies, children exhibited cognitive, language, motor delays, risk for ADHD and behavioral disorders, and lower academic performance through adolescence. Neuroimaging revealed structural brain changes, including white matter disruptions. Animal studies demonstrated hyperactivity, motor impairments, reduced cortical neuronal density, and altered physiological markers. Findings suggest that POE leading to NOWS may exert lasting impacts on brain development, underscoring the additive effects of POE leading to NOWS and the need for targeted early interventions and long-term monitoring.