Paracetamol (acetaminophen) use during pregnancy and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in children: a review of current evidence

This narrative review critically examines the potential association between paracetamol (acetaminophen) use during pregnancy and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children. Paracetamol remains the most widely used analgesic-antipyretic agent during pregnancy, used by approximately 60% of pregnant women. It is considered the first-line therapeutic option because non-steroidal anti-inflammatory drugs, particularly when used after 20 weeks of gestation, have been associated with adverse neonatal outcomes, including fetal renal dysfunction, oligohydramnios, and, rarely, neonatal renal failure, while their third-trimester use has also been linked to premature closure of the ductus arteriosus. In this context, unsubstantiated risk claims surrounding paracetamol create an important dilemma for clinicians and patients in clinical decision-making.The review evaluated large birth cohorts, sibling-controlled analyses, and meta-analyses from the literature, with a predominant focus on large-scale studies from Scandinavian countries (Norway, Denmark, Sweden). While several studies have reported small-to-moderate increases in risk between prenatal paracetamol exposure and ASD and ADHD, these associations lose significance in some sibling-controlled analyses, which are methodologically more rigorous.Current evidence suffers from substantial methodological limitations, including unmeasured confounding factors (particularly genetic susceptibility, familial characteristics, and maternal illnesses), validation problems in outcome measures, the absence of a demonstrable dose-response relationship, and confounding by indication. Furthermore, no valid, reproducible animal model specific to ASD exists.In conclusion, the available data do not support a causal relationship between paracetamol use during pregnancy and ASD or ADHD in offspring, and the reported associations remain questionable. Exaggerating unproven risks regarding medication use in pregnancy may unnecessarily amplify public concerns, discourage pregnant patients from receiving necessary treatment, and disrupt the balance between benefits and risks. Therefore, risk assessments should be conducted using an objective, evidence-based, cautious, and balanced approach.