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 child neurodevelopment outcomes. A comprehensive overview of existing evidence is needed for firm conclusions to inform clinical guidelines. This umbrella review aims to synthesise high-quality evidence on prenatal analgesic drug exposure and risk of ASD and ADHD in children. Seven databases were searched from inception to May 2021 to identify relevant reviews of any design. The AMSTAR 2 and the GRADE quality assessments were used to evaluate risk of bias and heterogeneity. A narrative synthesis approach was used to summarise findings. Five systematic reviews and meta-analyses met the inclusion criteria. All reviews reported significant associations between maternal prenatal acetaminophen use and ADHD outcomes (risk ratio range: 1.08-1.34; no pooled incidence rate), with a potential dose-dependent relationship. Potential sources of heterogeneity included usage timing and dosage. Findings suggest minimisation of prenatal acetaminophen exposure due to risk for ADHD outcomes. Future studies should include assessing potentially interacting mechanisms associating acetaminophen use with future neurodevelopmental outcomes.