Key Points Question Is prenatal opioid exposure associated with differences in childhood cognitive and motor development? Findings In this systematic review and meta-analysis of 26 studies including 1455 children exposed to prenatal opioids compared with unexposed children, prenatal opioid exposure was associated with lower cognitive scores. The largest difference was seen between ages 6 months and 6 years. Meaning The negative consequences of prenatal opioid exposure on neurocognitive and physical development appear to be present from 6 months and persist beyond school age.