Safety of acetaminophen use in pregnancy: review of existing evidence

Acetaminophen is the most widely used antipyretic and analgesic medication in pregnancy, but recent concerns have challenged its reproductive safety. Review articles and regulatory advisories have highlighted associations between prenatal acetaminophen exposure and adverse neurodevelopmental outcomes, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD); reproductive issues; and endocrine abnormalities. This review examines the biological plausibility, epidemiological evidence, and methodological limitations underlying observed associations. Systematic reviews and meta-analyses report small increased risks for ASD and ADHD that are minimal in sibling-controlled analyses. Evidence for male reproductive effects, including cryptorchidism and reduced anogenital distance, is inconsistent. Major biases in observational studies include confounding by indication, recall bias, and information bias. While existing data warrant ongoing scrutiny, the case for causality is weak, and the totality of evidence does not justify a change in practice. We support the current consensus from international regulatory and obstetrical bodies, which endorses judicious use of acetaminophen as a preferred analgesic and antipyretic in pregnancy. El resumen está disponible en Español al final del artículo.