CLINICAL QUESTION
Is prenatal exposure to acetaminophen (paracetamol) associated with autism or other neurodevelopmental disorders in children?
BOTTOM LINE
The meta-analysis of cohort studies failed to identify an association of prenatal exposure to acetaminophen with autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD), or intellectual disabilities in childhood. (Level of Evidence = 2a−)
SYNOPSIS
The authors conducted a meta-analysis of cohort studies to determine whether prenatal exposure to acetaminophen is associated with diagnosis of autism spectrum disorder, ADHD, or developmental delay in children compared with no exposure. They controlled for underlying maternal comorbidities and pharmacologic treatments before and during pregnancy. The authors allowed these disorders to be defined by the included studies, and they excluded studies that reported only unadjusted estimates. When possible, the authors stratified studies based on trimester of acetaminophen intake (ie, first, second, or third). They included 43 studies in the systematic review, 17 of which were included in the meta-analysis. The studies were heterogenous in how they reported acetaminophen exposure during pregnancy, timing and type of follow-up, and whether they stratified based on acetaminophen intake and dosage. For the subgroup of sibling comparison studies, acetaminophen exposure was not associated with a risk of autism spectrum disorder (odds ratio [OR] = 0.98; 95% CI, 0.93–1.03), ADHD (OR = 0.95; 95% CI, 0.86–1.05), or intellectual disability (OR = 0.93; 95% CI, 0.69–1.24). There were 11 studies classified as low risk of bias, and those showed a similar lack of difference in outcomes. The authors were unable to perform subgroup analysis based on trimester of intake or frequency of intake because few studies reported those data. This resulted in insufficient statistical power for reliable estimates.
Study Design: Meta-analysis (other)
Funding Source: Self-funded or unfunded
Setting: Various (meta-analysis)
Reference: D'Antonio F, Flacco ME, Della Valle L, et al. Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. Lancet Obstet Gynaecol Womens Health. 2026;2(3):e190-e198.
