Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies

Acetaminophen is the analgesic and antipyretic most commonly used during pregnancy. Evidence of neurodisruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, Embase, and Cochrane databases for relevant studies up to January 2017. Data were independently extracted and assessed by 2 researchers. Seven eligible retrospective cohorts included 132,738 mother-child pairs, with follow-up periods ranging from 3 to 11 years. The pooled risk ratio for ADHD was 1.34 (95% confidence interval (CI): 1.21, 1.47; I2 = 72%); for ASD, the risk ratio was 1.19 (95% CI: 1.14, 1.25; I2 = 14%), and for hyperactivity symptoms, it was 1.24 (95% CI: 1.04, 1.43; I2 = 93%). In meta-regression analysis, the association between exposure and ADHD increased with the child's age upon follow-up (β = 0.03, 95% CI: 0.00, 0.07) and with the mean duration of exposure (β = 0.00, 95% CI: 0.00, 0.01). The available data is of observational nature only. Studies differed widely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD, and hyperactivity symptoms. These findings are concerning; however, results should be interpreted with caution given that the available evidence consists of observational studies and is susceptible to several potential sources of bias.