Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews.

This major review looked at studies examining whether taking paracetamol during pregnancy increases autism or ADHD risk in children. While some studies suggested a link, the research quality was poor. The most reliable studies compared siblings within the same family - these found no increased risk of autism or ADHD when mothers used paracetamol during pregnancy. Current evidence doesn't clearly show paracetamol causes autism or ADHD.

This umbrella review examined nine systematic reviews (40 studies) investigating maternal paracetamol use during pregnancy and autism/ADHD risk in offspring. While many reviews reported possible to strong associations, seven advised caution due to bias and confounding risks. Review quality was consistently low to critically low on AMSTAR 2 criteria. Critically, only two studies properly controlled for familial factors through sibling analyses.

In these higher-quality studies, the increased autism (HR 1.05) and ADHD (HR 1.07-2.02) risks observed in whole cohort analyses disappeared in sibling-controlled analyses (autism HR 0.98; ADHD HR 0.98-1.06). The authors conclude existing evidence does not clearly establish a causal link between maternal paracetamol use and neurodevelopmental outcomes.

Current evidence does not support avoiding paracetamol during pregnancy due to autism or ADHD concerns when medically indicated. The highest-quality studies using sibling controls found no causal relationship. Healthcare providers can counsel families that paracetamol use during pregnancy does not clearly increase neurodevelopmental risks in offspring.

High overlap between reviews (23% corrected covered area), consistently low to critically low review quality on AMSTAR 2 criteria, and only two studies appropriately controlled for familial confounding through sibling analyses. Most studies did not adequately address unmeasured confounders.

To assess the quality, biases, and validity of evidence on maternal paracetamol (acetaminophen) use during pregnancy and the risk of autism spectrum disorder (referred to as autism) and attention deficit/hyperactivity disorder (ADHD) in offspring. Umbrella review of systematic reviews. Medline, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews, along with grey literature, Epistemonikos, and the reference lists of included studies (inception to 30 September 2025). Systematic reviews of randomised trials and cohort, case-control, or cross sectional studies that reported maternal paracetamol use during pregnancy and the diagnosis of autism or ADHD in offspring.

Details of the primary studies included in the reviews are reported, including adjustments for key confounders (maternal characteristics, indication for paracetamol use, and familial factors) and unmeasured confounders and ascertainment of outcomes. Nine reviews (40 studies) reporting on autism (six studies) and ADHD (17 studies) in offspring were included. Four reviews undertook meta-analysis. The overlap of primary studies included in the reviews was very high (corrected covered area 23%).

The reviews reported a possible to strong association between maternal paracetamol intake and autism or ADHD or both in offspring. Seven of the nine reviews advised caution when interpreting the findings owing to the potential risk of bias and confounding in the included studies. Confidence in the findings of the reviews was low (two reviews) to critically low (seven reviews) based on the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) criteria. Only one review included studies (n=2) reporting autism and ADHD in offspring that appropriately adjusted for familial factors and unmeasured confounding through sibling controlled analyses.

In both studies, the increased risk of autism in offspring (one study, hazard ratio 1.05, 95% confidence interval 1.02 to 1.08) and ADHD (two studies, 1.07, 1.05 to 1.10 and 2.02, 1.17 to 3.25 ) observed in the whole cohort analyses did not persist in sibling controlled analyses for autism (0.98, 0.93 to 1.04) and ADHD (0.98, 0.94 to 1.02 and 1.06, 0.51 to 2.05). Existing evidence does not clearly link maternal paracetamol use during pregnancy with autism or ADHD in offspring. PROSPERO CRD420251154052.