Null Link Confirmed: Prenatal Acetaminophen Autism Risk Study in Denmark

A major nationwide Danish cohort study has found no link between maternal acetaminophen use during pregnancy and autism in children. The new evidence on prenatal acetaminophen autism risk should reassure clinicians and expectant mothers, as both population-wide and sibling-controlled analyses showed adjusted hazard ratios near 1.0 with confidence intervals crossing the null.

No Dose-Response or Trimester Effect Detected

The absence of association held across every sensitivity analysis. Whether exposure was low, medium, or high, and regardless of whether it occurred in the first, second, or third trimester, hazard ratios remained consistently close to unity. Even after Denmark restricted over-the-counter sales in 2013, results were unchanged. These null findings persisted after extensive adjustment for maternal age, comorbidities, co-medications, healthcare use, and socioeconomic factors.

By comparing siblings discordant for prenatal acetaminophen autism exposure within the same family, the study effectively controlled for shared genetic and environmental confounders that likely explained earlier positive associations. The sibling-matched results were nearly identical to the full population analysis, markedly reducing the chance of residual confounding.

Massive Register-Based Cohort

Researchers analyzed all 1,506,155 singleton live births in Denmark from 1997 to 2022, linking national prescription, psychiatric, and birth registers. Acetaminophen exposure was captured prospectively via filled prescriptions, while autism diagnoses were drawn from validated psychiatric records with a 94% positive predictive value. Follow-up began at age one and continued until diagnosis, emigration, or July 2023.

Important Reassurance for Clinical Practice and Policy

These findings provide regulators, clinicians, and families with a clear upper bound: any true increase in autism risk from prenatal acetaminophen is unlikely to exceed 12%. The study aligns with a recent Swedish sibling-controlled analysis and an umbrella review that flagged confounding in earlier literature. It removes a previously hypothesized long-term neurodevelopmental risk that had complicated benefit-risk assessments and economic evaluations of pain management in pregnancy.