Prenatal acetaminophen showed no neurodevelopmental harm

Sibling comparison found no association between prenatal acetaminophen use and later autism or attention-deficit/hyperactivity disorder.
*Population-based sibling-matched cohort study; Level 2b (OCEBM).

Citation

Luo S, Gong Q, Ai Y, et al. Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts. JAMA Internal Medicine. 2026;186(9):1102-1111. doi:10.1001/jamainternmed.2026.2215

Background

Acetaminophen is widely recommended for pain and fever during pregnancy, but prior observational studies raised concerns about child neurodevelopment. Because autism and attention-deficit/hyperactivity disorder run strongly in families, unmeasured family factors may distort conventional study results.

Patients

Hong Kong mother-child pairs with singleton live births from 2001 to 2023. Main sibling cohorts included 124,333 children for autism and 97,285 for attention-deficit/hyperactivity disorder. Exclusions included missing linkage or key data, multifetal pregnancy, nonlive birth, maternal age outside 15 to 50 years, and insufficient follow-up.

Intervention

Maternal acetaminophen dispensing during pregnancy, including timing, pattern, and dose.

Control

Unexposed siblings from the same mother.

Outcome

Autism diagnosis; attention-deficit/hyperactivity disorder diagnosis or medication treatment.

Follow-up Period

Median 10.2 years for autism; 11.3 years for attention-deficit/hyperactivity disorder.

Results

Analysis Autism Attention-deficit/hyperactivity disorder
Sibling-matched primary analysis NS NS
Conventional cohort analysis HR 1.17 (95% CI 1.13 to 1.20) HR 1.23 (95% CI 1.20 to 1.27)
Prepregnancy negative-control exposure HR 1.12 (95% CI 1.08 to 1.17) HR 1.24 (95% CI 1.20 to 1.28)

Null sibling-matched findings were consistent across trimester, cumulative dose, and use pattern. Positive findings before pregnancy suggest family-related confounding, not a drug effect.

Limitations

Prescription records missed over-the-counter and private use. Sibling matching reduces shared family confounding but may not remove pregnancy-specific differences. Results may not fully generalize beyond exposure-discordant sibling families.

Funding

Hong Kong public research funding; funders had no study role.

Clinical Application

Reassure pregnant patients: use acetaminophen when indicated, at the lowest effective dose for the shortest needed time.