American Journal of Perinatology
Acetaminophen Use in Pregnancy: Evidence, Controversies, and Clinical Counseling
By Arielle J Higgs and Karl Edward Seif.
Abstract
Objective
To review the current evidence regarding acetaminophen use in pregnancy, evaluate reported associations with adverse neurodevelopmental and reproductive outcomes, and provide an evidence-based framework for clinical counseling and decision-making. Study Design: A narrative review of the literature was performed, emphasizing large observational cohort studies, sibling-comparison analyses, pharmacokinetic data, and recent systematic reviews evaluating prenatal acetaminophen exposure and maternal-fetal outcomes.
Results
Acetaminophen is the most commonly used analgesic and antipyretic in pregnancy, with 50–65% of pregnant individuals reporting use. Although observational studies have reported associations between prenatal acetaminophen exposure and adverse neurodevelopmental and reproductive outcomes, including attention-deficit/hyperactivity disorder, autism spectrum disorder, and cryptorchidism, these findings remain inconsistent and are subject to substantial confounding, particularly by indication. Large, methodologically rigorous studies incorporating sibling-controlled analyses have demonstrated attenuation or disappearance of these associations, suggesting that underlying maternal conditions may account for the observed risks. Pharmacokinetic studies demonstrate placental transfer of acetaminophen, although fetal metabolism differs because of limited glucuronidation capacity. Current pharmacologic evidence does not support a causal relationship between standard maternal acetaminophen use and premature fetal ductus arteriosus closure.