Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis

AIM: To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. METHOD: MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. RESULTS: Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. INTERPRETATION: Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome. WHAT THIS PAPER ADDS: Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment. Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children. Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence. Estimates of impairment may be biased by intermediate to poor quality evidence.