Interventions to reduce pharmacologic opioid exposure in neonatal opioid withdrawal syndrome: a systematic review and meta-analysis of randomized studies.

Background: Neonatal opioid withdrawal syndrome (NOWS) is increasingly prevalent and is frequently managed with pharmacologic opioid therapy, raising concerns regarding early-life opioid exposure and prolonged hospitalization. Interventions aimed at reducing pharmacologic exposure while maintaining safety have emerged, most notably care-model-based approaches. This study aims to systematically review the evidence evaluating interventions designed to reduce pharmacologic opioid exposure in neonates with NOWS compared with standard care. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed/MEDLINE, Cochrane CENTRAL, and Google Scholar were searched from inception through the final search date. Randomized controlled trials, comparative observational studies, and quality-improvement studies evaluating exposure-reduction strategies were included. Interventions of interest primarily comprised care-model approaches such as Eat-Sleep-Console (ESC). Outcomes included duration of opioid therapy, cumulative opioid exposure, length of hospital stay, and safety outcomes. Due to substantial heterogeneity across studies, findings were synthesized narratively. Results: Six studies met inclusion criteria, comprising three randomized studies and three observational or quality-improvement studies. Meta-analysis of randomized evidence showed ESC-based care significantly reduced hospital stay length (MD -6.50 days; 95% CI -9.63 to -3.36; Conclusions: Care-model interventions emphasizing functional assessment and nonpharmacologic support-particularly the ESC approach-are associated with reduced pharmacologic opioid exposure and shorter hospitalization for infants with NOWS without compromising short-term safety. These findings support evolving guideline recommendations favoring exposure-reduction strategies in NOWS management.