Background Acetaminophen is the most commonly used analgesic and antipyretic medication during preg-nancy. Recent epidemiological studies have suggested a possible association between acetaminophen exposure in-utero and impaired paediatric neurological develop-ment, including hyperactive attention deficit (ADHD) and related disorders.

Methods We conducted a systematic-review and me-ta-analysis to evaluate the risk for ADHD in children of women exposed to acetaminophen during pregnancy. We searched MEDLINE and EMBASE up to January 2017. We used meta-regression analysis to evaluate factors that may moderate this association. Reports of cohorts were pooled using random-effects models.

Results Six cohort studies met our inclusion criteria. Among 76 146 mothers who reported acetaminophen use during pregnancy, acetaminophen was associated with an increased risk for ADHD (RR=1.33, 95% CI: 1.19–1.47, I2=77%), hyperactivity symptoms (RR=1.24, 95% CI: 1.02–1.46, I2=95%), and conduct disorders (RR=1.28; 95% CI, 1.05–1.52, I2=93%). Using meta-regression, we found that the association was greater and heterogeneity re-duced as child’s age at diagnosis increased (β=0.045, p=0.035, heterogeneity accounted for (R2)=65.98%).

Conclusion This meta-analysis suggests that maternal acetaminophen use during pregnancy is associated with a higher risk for ADHD or related disorders. However, there is evidence of significant heterogeneity in the observed effect, and many of the studies suffer from significant lim-itations. These findings, together with additional recent evidence on teratogenicity of acetaminophen, warrants further investigation and consideration of public health actions.

PROSPERO registry-CRD42017055827