Analgesic drug use in pregnancy and neurodevelopment outcomes: An umbrella review

Emerging evidence from reviews suggests that analgesic drug exposure during pregnancy may contribute to childneurodevelopment outcomes. A comprehensive overview of existing evidence is needed for firm conclusions toinform clinical guidelines. This umbrella review aims to synthesise high-quality evidence on prenatal analgesicdrug exposure and risk of ASD and ADHD in children. Seven databases were searched from inception to May2021 to identify relevant reviews of any design. The AMSTAR 2 and the GRADE quality assessments were used toevaluate risk of bias and heterogeneity. A narrative synthesis approach was used to summarise findings. Fivesystematic reviews and meta-analyses met the inclusion criteria. All reviews reported significant associationsbetween maternal prenatal acetaminophen use and ADHD outcomes (risk ratio range: 1.08–1.34; no pooledincidence rate), with a potential dose-dependent relationship. Potential sources of heterogeneity included usagetiming and dosage. Findings suggest minimisation of prenatal acetaminophen exposure due to risk for ADHDoutcomes. Future studies should include assessing potentially interacting mechanisms associating acetaminophenuse with future neurodevelopmental outcomes.