Prenatal acetaminophen use was associated with an increased risk of neurodevelopmental disorders in children, according to a systematic review of 46 human studies.
The review evaluated observational research on attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental outcomes. Twenty-seven studies reported positive associations, nine found no association, and four suggested protective effects. Higher-quality studies were more likely to report increased risks.
Large cohort studies showed modest increases in ADHD diagnoses among children exposed in utero, while biomarker-based studies using cord blood or meconium showed stronger associations. In one US cohort, prenatal exposure was linked to more than threefold higher odds of ADHD diagnosis and greater use of ADHD medications in childhood. Sibling-controlled studies found weaker effects, but overall patterns suggested elevated risk.
Eight studies investigated acetaminophen use and ASD, including a European cohort of nearly 74,000 participants that linked exposure to higher risks of both ADHD and ASD. Eighteen studies examined broader neurodevelopmental outcomes, including attention, executive function, and global development. Executive function refers to higher-order cognitive processes that allow children to plan, organize, remember instructions, regulate behavior, and shift between tasks. Deficits in executive function are often linked to difficulties in attention control, impulse regulation, and problem solving, and are considered core features in ADHD and related disorders.
A Danish cohort of more than 60,000 children found higher risks of hyperkinetic disorders and ADHD medication use when exposure occurred in all three trimesters. Other studies reported impairments in attention, executive functioning, and learning performance.
Researchers applied the Navigation Guide methodology, a structured framework for environmental health evidence. Studies were identified through PubMed and assessed for risk of bias, confounding, and study quality. Because of heterogeneity in exposure definitions and outcome measures, findings were synthesized qualitatively rather than through meta-analysis.
Limitations included potential confounding from maternal illness or fever, reliance on maternal recall, and possible overemphasis of minor flaws under the Navigation Guide scoring system. Variability in design and definitions also limited comparability.
Full disclosures can be found in the published study.
Source: Environmental Health