Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis

Background: Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children. Objective: We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. Data sources: PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies. Study selection: We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals. Data extraction and synthesis: Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed. Results: Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]). Conclusion: There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.