Summary: A large, long-term epidemiological study using robust sibling-matched methods has addressed concerns about the safety of paracetamol (acetaminophen) use during pregnancy. Researchers analyzed deidentified electronic health records for more than 700,000 mother–child pairs across over two decades and compared siblings within the same families where one pregnancy included paracetamol exposure and another did not.
The study found no evidence that prenatal paracetamol exposure increases the risk of autism spectrum disorder (ASD) or attention‑deficit/hyperactivity disorder (ADHD) in children, offering strong reassurance for clinicians and expectant parents about the indicated use of paracetamol during pregnancy.
Key facts
- Sibling-matched design: The study compared siblings born to the same mother where exposure to paracetamol differed between pregnancies. This design controls for shared genetic factors and many environmental influences that can confound traditional cohort studies.
- No association detected: In sibling-matched analyses, prenatal paracetamol exposure was not associated with an increased risk of ASD or ADHD.
- Consistency across trimesters: The null findings remained consistent regardless of the trimester in which paracetamol was taken.
- Dose and pattern examined: Researchers evaluated sporadic, intermittent, and persistent patterns of paracetamol use as well as cumulative dose; results showed no meaningful association with ASD or ADHD risk.
- Large, population-based data: The analysis drew on over two decades of centralized electronic medical records from Hong Kong, enabling precise, large-scale measurement of medication exposure and long-term child outcomes.
Source: Aston University
Overview
Researchers from the University of Hong Kong (HKUMed) and Aston Pharmacy School, including Professor Ian Chi‑Kei Wong, evaluated whether prenatal use of paracetamol is linked to later diagnoses of autism or ADHD. Paracetamol is widely recommended as a first-line medication for pain and fever during pregnancy, but past observational studies and media reports raised questions about a potential link to neurodevelopmental conditions. Major public health organizations continued to support its use, but higher-quality evidence was needed to address residual confounding and provide clearer guidance.
To reduce confounding from family-level factors, the team used a sibling-matched study design and analyzed deidentified records for an initial cohort of 708,020 mother–child pairs in Hong Kong, covering births from 2001 through 2023. From this population, sibling-matched cohorts were constructed including families with discordant prenatal paracetamol exposure and adequate follow-up time for outcome ascertainment.
In sibling-matched analyses, the study found no association between prenatal paracetamol exposure and the risk of ASD or ADHD. These results were robust across sensitivity analyses and consistent across timing of exposure, cumulative dose, and usage patterns.
The findings were published in JAMA Internal Medicine and provide relevant evidence for physicians and pregnant people weighing the benefits and risks of treating pain and fever during pregnancy.
Key quotes
Dr. Shan Luo, Research Assistant Professor, Department of Family Medicine and Primary Care, HKUMed, noted that fear stirred by earlier reports influenced personal choices during pregnancy. She said the study offers the kind of reassurance she would have welcomed while managing painful and potentially risky conditions such as febrile illness.
Professor Ian Chi‑Kei Wong highlighted that answering long-term safety questions required extensive, high-quality data and international collaboration. The alliance between Aston Pharmacy School and HKUMed, together with partner institutions, enabled rapid and precise assessment of this important drug-safety question.
Frequently asked questions
A: Comparing unrelated groups of women who did or did not take paracetamol can leave residual confounding because medication use may be linked to maternal illness, fever severity, chronic conditions, or other factors that independently influence child development. By comparing siblings born to the same mother with discordant prenatal exposure, the design reduces confounding from shared genetics and household environment, isolating the effect of the drug itself as much as possible in observational data.
A: No. Analyses that examined different frequencies of use (sporadic, intermittent, persistent) and exposure by trimester did not show an association between prenatal paracetamol and ASD or ADHD. The sibling-matched estimates were consistent across these stratified analyses.
A: High maternal body temperature and uncontrolled fever can pose risks to fetal development. Because paracetamol is an effective antipyretic and analgesic, demonstrating no association with ASD or ADHD in a rigorous sibling-matched study supports current guidance that indicated paracetamol use remains an appropriate option for treating pain and fever in pregnancy, under clinical advice.
Editorial notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff.
About this research
Author: Helen Tunnicliffe
Source: Aston University
Contact: Helen Tunnicliffe – Aston University
Image: Image credit: Neuroscience News
Original research (open access): “Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts” by Eric Yuk Fai Wan et al., JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2026.2215
Abstract (summary)
Importance: Paracetamol is the globally recommended first-line analgesic and antipyretic in pregnancy. Some observational studies reported links between prenatal paracetamol and increased risks of ASD and ADHD, but those findings may be confounded by family-level factors.
Objective: To evaluate the association between prenatal paracetamol exposure and risk of ASD and ADHD using a sibling-matched design that accounts for familial confounding.
Design, setting, and participants: Population-based cohort using deidentified electronic health records from Hong Kong, covering January 1, 2001, to December 31, 2023. The initial cohort included 708,020 mother–child pairs, of which approximately 43.3% had recorded prenatal paracetamol exposure. Sibling-matched cohorts were constructed from families with discordant exposure and adequate follow-up for outcome assessment.
Exposure: Prenatal paracetamol use identified from electronic dispensing records with information on drug name, strength, dosage, and prescription dates.
Main outcomes and measures: Incident ASD or ADHD diagnoses based on ICD-9-CM codes or prescription records for ADHD-specific medications licensed in Hong Kong (methylphenidate, atomoxetine, lisdexamfetamine).
Results: Final sibling-matched cohorts included 124,333 children for ASD analysis (mean age 9.3 years) and 97,285 for ADHD analysis (mean age 7.6 years). Sibling-matched analyses showed no association between prenatal paracetamol exposure and ASD (adjusted hazard ratio [aHR], 1.00; 95% CI, 0.91–1.11) or ADHD (aHR, 1.01; 95% CI, 0.93–1.08). Null results were consistent across timing of exposure, cumulative dose, and usage patterns and remained robust in sensitivity tests. Conventional cohort analyses and certain negative-control comparisons indicated positive associations, suggesting residual familial confounding in non–sibling-matched designs.
Conclusions and relevance: In this population-based cohort study, sibling-matched analyses found no evidence that prenatal paracetamol exposure increases the risk of ASD or ADHD in offspring. The findings suggest that previously reported positive associations likely reflect residual familial confounding and provide important reassurance regarding the safety of indicated paracetamol use during pregnancy.