Outcomes in offspring of interventions to treat substance use in pregnancy: protocol for an umbrella review

BACKGROUND: Substance use during pregnancy is linked to adverse neonatal and longer-term outcomes in offspring, yet evidence syntheses have primarily focused on maternal outcomes. An umbrella review is needed to consolidate and critically appraise findings from systematic reviews on how interventions to treat substance use in pregnancy affect outcomes in offspring of pregnant women and pregnant individuals. METHODS: We will conduct an umbrella review of systematic reviews (with or without meta-analysis) that include quantitative primary studies of pregnant women and pregnant individuals with substance use who receive pharmacological, psychosocial/behavioural, integrated care, or community-based interventions. Searches will cover MEDLINE (PubMed), Embase, Web of Science, Scopus, the Cochrane Database of Systematic Reviews and Epistemonikos from inception. Two independent reviewers will perform title/abstract screening, full-text screening, and data extraction at every stage; a third reviewer will arbitrate disagreements. Methodological quality of included systematic reviews will be assessed using AMSTAR 2; risk of bias of primary studies will be reported as appraised in the original systematic reviews. Overlap of primary studies will be quantified using the Corrected Covered Area (CCA), with attention to multi-arm studies and to whether overlapping primary studies actually answer the same PICO question. We will narratively synthesise findings (avoiding vote counting) and, where systematic reviews report pooled estimates, we will summarise these without conducting de novo meta-analyses of primary studies. Certainty of evidence will be reported using existing GRADE assessments, complemented by a structured umbrella-level appraisal that incorporates large effects and dose-response gradients when relevant. DISCUSSION: This umbrella review will clarify which interventions have the strongest evidence of benefit (or harm) for neonatal, congenital, neurodevelopmental, and behavioural/mental health outcomes in offspring, identify evidence gaps and methodological limitations, and inform clinical guidance and maternal-child health policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261321678.