Research team members, including Prof Peter Tanuseputro (back row, far right) and Dr April Luo (front row, second from the right)Prenatal paracetamol exposure is not associated with an increased risk of attention‑deficit/ hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), according to researchers from the University of Hong Kong (HKU).
“Paracetamol is the most frequently used medication for pain and fever during pregnancy,” wrote the researchers. “Observational studies have reported associations with increased risks of ASD and ADHD in offspring, raising public and clinical concern.”
“I had herpes zoster during pregnancy, but I did not take paracetamol at that time because of concerns raised in the media. As both a researcher and a mother, I deeply understand the anxiety many women face,” shared the study’s first author, Dr April Luo of the Department of Family Medicine and Primary Care, HKU.
As findings from observational studies may be substantially confounded by unmeasured familial factors, the researchers conducted a population-based cohort study using Hong Kong Hospital Authority’s electronic records from 708,020 mother-child pairs in Hong Kong from 2001 to 2023. The study triangulated evidence using a sibling-matched design, a conventional cohort analysis, and a negative control exposure analysis in the full cohort. [JAMA Intern Med 2026:e262215]
The final sibling-matched cohorts included 124,333 children for ASD analysis (mean age, 9.3 years; female, 49.7 percent) and 97,285 for ADHD analysis (mean age, 7.6 years; female, 49.8 percent). During the follow-up period (mean, 10.2 years for the ASD cohort, and 11.3 years for the ADHD cohort), 3,445 children (2.8 percent) were diagnosed with ASD and 5,168 (5.3 percent) were diagnosed with ADHD.
“Our primary sibling-matched analysis, which accounted for unmeasured familial confounding, found no association between prenatal paracetamol exposure and the risk of ASD [adjusted hazard ratio (aHR), 1.00; 95 percent confidence interval (CI), 0.91–1.11] or ADHD [aHR, 1.01; 95 percent CI, 0.93–1.08] in offspring,” reported the researchers.
The null finding was robust across exposure timing (across all trimesters), patterns of use (sporadic, intermittent or persistent), and doses for both outcomes. “The consistency of null findings from robust sibling-matched designs across different populations now provides strong evidence against a causal link,” noted the researchers.
However, positive associations were observed in conventional cohort analyses (ASD: HR, 1.17; 95 percent CI, 1.13–1.20; ADHD: HR, 1.23; 95 percent CI, 1.20–1.27) and, importantly, also in negative control analyses of prepregnancy exposure (ASD: HR, 1.12; 95 percent CI, 1.08–1.17; ADHD: HR, 1.24; 95 percent CI, 1.20–1.28).
The positive signal observed in both the conventional and negative control analyses likely reflects residual familial confounding rather than a true pharmacologic effect of prenatal paracetamol exposure.
“Previous conflicting studies generated doubt and unnecessary stress for expectant parents, leading many mothers to endure untreated pain or resort to other medications that may be less safe,” said Professor Peter Tanuseputro of the Department of Family Medicine and Primary Care, HKU.
“Our study provides the reassurance I wish I had, which would have helped me manage the pain I was experiencing,” added Luo.