BACKGROUND AND AIMS: Recent decades have seen a rise in the number of pregnancies exposed to opioids. Whilst evidence of the impact of such exposure on pregnancy and infant outcomes is fairly robust, the impact of prenatal opioid exposure (POE) on longer-term outcomes for children and young people remains unclear. This systematic review aimed to examine comprehensively the evidence of the association between prenatal exposure to illicit opioids or medication for opioid use disorder (MOUD) and school-age health, social and educational outcomes.

METHODS: PubMed, Web of Science, Scopus and CINAHL were searched for papers published between 1 January 2015 and 13 February 2025, with a follow-up search conducted on 28 October 2025. Grey literature was searched through Google. Eligible studies could be quantitative or qualitative in nature, reporting empirical findings exploring POE (illicit opioids or MOUD) and health, educational or social outcomes at ages 5-18 years. Editorials, case reports, literature reviews, commentaries and conference abstracts, as well as non-English language papers, were excluded. Records were screened by two authors. Risk of bias was assessed using the Risk Of Bias In Non-randomised Studies - of Exposure (ROBINS-E) Tool. Due to heterogeneity within both exposures and outcomes, results were synthesised narratively.

RESULTS: Thirty-two papers comprising 16 studies were identified. Quality was mixed: 17/32 papers had high/very high risk of bias, primarily stemming from longitudinal attrition and lack of controlling for confounding. Five very high risk papers were excluded, leaving 27 included papers. Overall, 31 104 children exposed to opioids and 5 430 272 controls were included. Papers spanned 10 countries, primarily in North America, Australasia and Europe. Study designs included prospective birth cohort studies (n = 10), retrospective administrative data studies (n = 11), a combination of those two designs (n = 5) and one cross-sectional study. The most robust evidence of an association with POE was for poorer visual outcomes (e.g. general eye disorders, failure of standard visual assessments and specific impairments including strabismus and nystagmus) (4/4 studies indicating an association) and increased hyperactivity and attention difficulties (3/3 studies reporting an association). A majority of studies (n = 7/10) reported an association with increased cognitive difficulties across various measures. Results for physical health and brain structure/functioning were inconclusive. Evidence was based on few studies for each domain, often with low numbers of participants.

CONCLUSIONS: Prenatal opioid exposure through illicit opioids or medication for opioid use disorder is associated with visual outcomes, hyperactivity and inattention and cognitive functioning at 5-18 years. Almost all research focusses on 5-12 years, with little evidence available for adolescents.