Summary: In a definitive, long-term epidemiological study, researchers successfully settled the debate. By analyzing more than 700,000 mother-child pairs across more than two decades of data, researchers utilized a rigorous sibling-matched design, directly comparing brothers and sisters where one was exposed to paracetamol in the womb and the other was not.
The study conclusively proved that prenatal paracetamol exposure does not increase a child’s risk of developing autism or ADHD, providing massive global reassurance for obstetric and maternal health.
Key Facts
- The Sibling Control Breakthrough: Traditional studies on medication safety are frequently criticized because mothers who require pain relief may have underlying health differences from those who do not. By comparing siblings from the exact same mother, this study completely canceled out shared genetic and environmental background factors.
- Absolute Zero Association: The sibling-matched data revealed zero statistically significant correlation between a mother taking paracetamol during pregnancy and her offspring later developing ASD or ADHD.
- Consistency Across All Trimesters: The safety clearance remained completely unchanged regardless of the timing of the exposure. Taking the medication in the first, second, or third trimester yielded the exact same non-association profile.
- Dose and Pattern Neutrality: The study monitored multiple usage archetypes, tracking sporadic (one-off), intermittent (occasional), and persistent (long-term) use. The safety baseline held completely steady across all consumption volumes and frequencies.
- Overcoming Perinatal Pain Refusal: Lead author Dr. Shan Luo shared that she personally endured the severe, unmitigated neural pain of shingles (herpes zoster) during her own pregnancy due to mainstream media scaremongering. This study was explicitly designed to give future mothers the data-driven confidence to safely manage acute physical pain and maternal fevers.
- Global Data Infrastructure: The speed and precision of this study were made possible by a cross-continental strategic data alliance, leveraging Hong Kong’s comprehensive centralized electronic medical record infrastructure to track multi-decade pediatric development.
Source: Aston University
Researchers from the University of Hong Kong (HKUMed), along with Aston Pharmacy School’s Professor Ian Chi-Kei Wong, have shown that using paracetamol (acetaminophen) during pregnancy does not increase a child’s risk of developing autism spectrum disorder (ASD) or attention‑deficit hyperactivity disorder (ADHD).
Paracetamol is the most widely used medication for pain and fever during pregnancy. Yet, following statements from the US administration linking it with ASD, its safety became a subject of intense public and scientific debate. While the World Health Organization and other health bodies reaffirmed its safety profile, robust evidence was urgently needed, which this study provides.
To overcome the criticism that mothers taking paracetamol are different from those that do not, the study design compares siblings from the same mother, with at least one sibling exposed to paracetamol during pregnancy and the other unexposed. The research team analysed electronic medical records from 708,020 mother-child pairs in Hong Kong spanning over two decades, from 2000–2023.
Using a sibling-matched design that accounts for genetic and environmental factors, the study showed no association between prenatal paracetamol exposure and the risk of ASD or ADHD in offspring. Results remained consistent regardless of dosage, timing of exposure (i.e., first, second, or third trimester), or pattern of use (i.e., sporadic, intermittent, or persistent use).
The findings, published in JAMA Internal Medicine, provide timely reassurance for expectant mothers and clinicians in Hong Kong and globally.
Dr Shan Luo, research assistant professor, Department of Family Medicine and Primary Care, HKUMed, said:
“I had herpes zoster during my pregnancy, yet I did not take paracetamol for myself at that time because of the concerns in the news. As a researcher and mother, I share the deep-seated concerns that many women face. Our study provides the reassurance I wish I had and would have helped me with the pain I was experiencing.”
Professor Wong, Regius Chair in Pharmacy at Aston University, and a professor in the Department of Pharmacology and Pharmacy, HKUMed, said:
“Monitoring the long-term outcomes of children with in-utero drug exposure requires an incredibly robust data infrastructure. Aston Pharmacy School and HKUMed Department of Pharmacology and Pharmacy formed a strategic alliance with other international partners to address medication safety issues; consequently, we were able to rapidly address this urgent drug safety question with the necessary precision and scale.”
Key Questions Answered:
A: In normal medical studies, comparing a group of pregnant women who take paracetamol to a group who don’t is fundamentally flawed. The women taking the medication might be dealing with severe infections, high fevers, or systemic chronic stress, factors that could independently shape a baby’s development. A sibling-matched study outsmarts this problem by comparing a brother and sister born to the exact same mother, where one was exposed to paracetamol in the womb and the other wasn’t. Because the siblings share the exact same genetic pool, household environment, and maternal background, any hidden biases are completely wiped out, isolating the drug as the only true variable.
A: No danger whatsoever. The research team analyzed the data across every possible variation of use. They tracked mothers who took a single pill sporadically, those who used it intermittently, and those who required persistent, long-term doses. They also mapped the data across all three trimesters of pregnancy. The result was completely uniform: whether taken in the fragile first weeks of the first trimester or right before delivery in the third, and whether used once or continuously, paracetamol showed absolutely zero association with an increased risk of autism or ADHD.
A: Leaving a high fever untreated during pregnancy is actually incredibly dangerous; uncontrolled maternal hyperthermia (high body temperature) can directly cause severe birth defects and major fetal developmental issues. Because sensationalized news reports previously linked paracetamol to autism, many terrified mothers chose to suffer through excruciating pain or dangerous fevers completely unmedicated. Dr. Shan Luo notes that this massive study finally provides the definitive, rock-solid reassurance that mothers need to safely manage their health, ensuring they can protect themselves from pain and fever without worrying about their child’s future neurological development.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this ASD and ADHD research news
Author: Helen Tunnicliffe
Source: Aston University
Contact: Helen Tunnicliffe – Aston University
Image: The image is credited to 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, Esther Wai Yin Chan, Ian Chi Kei Wong, Jiayue Zhang, Linda Chan, Patrick Ip, Peter Tanuseputro, Qiaowa Gong, Shan Luo, William Chi Wai Wong, Yujie Ai. JAMA Internal Medicine
DOI:10.1001/jamainternmed.2026.2215
Abstract
Prenatal Acetaminophen (Paracetamol) Use and the Risk of Autism and/or Attention-Deficit/Hyperactivity Disorder Among Sibling-Matched Cohorts
Importance
Paracetamol (acetaminophen) is the first-line analgesic and antipyretic recommended globally during pregnancy. Observational studies have reported associations with increased risks of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring, raising public and clinical concern; however, these findings may be substantially confounded by unmeasured familial factors.
Objectives
To assess the association between prenatal paracetamol exposure and risk of ASD and ADHD in offspring using a sibling-matched study design to control for familial confounding.
Design, Setting, and Participants
This population-based cohort study, conducted from January 1, 2001, to December 31, 2023, in Hong Kong, used deidentified electronic health records within a triangulation framework. From an initial cohort of 708 020 mother-child pairs (approximately 43.3% with prenatally paracetamol exposure), sibling-matched cohorts were constructed of children from families with discordant prenatal paracetamol exposure and sufficient follow-up (≥2 years for ASD and ≥5 years for ADHD). Data analysis was conducted from October 2, 2025, to March 24, 2026.
Exposure
Prenatal paracetamol exposure, identified from electronic dispensing records (British National Formulary [BNF], section 4.7.1) with data on drug name, strength, dosage, and prescription dates.
Main Outcomes and Measures
Incident diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification, for ASD (code 299) or for ADHD (code 314) or a prescription for ADHD-specific medication licensed in Hong Kong (methylphenidate, atomoxetine, or lisdexamfetamine [BNF, section 4.4]).
Results
The final cohorts comprised 124 333 children for ASD analysis (mean [SD] age, 9.3 [4.7] years; 61 775 females [49.7%] and 62 558 males [50.3%]) and 97 285 for ADHD analysis (mean [SD] age, 7.6 [4.2] years; 48 455 females [49.8%], 48 830 [50.2%]). In the sibling-matched analyses, prenatal paracetamol exposure was not associated with the risk of 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 associations were consistent across exposure timing, cumulative dose, and usage patterns (sporadic, intermittent, persistent), and were robust in sensitivity analyses. However, positive associations were observed in conventional cohort analyses, and importantly, also in negative control analyses of prepregnancy exposure for ASD (HR, 1.12; 95% CI, 1.08-1.17) and ADHD (HR, 1.24; 95% CI, 1.20-1.28).
Conclusions and Relevance
In this population-based cohort study, a sibling-matched analysis found no evidence of an association between prenatal paracetamol exposure and the risk of ASD or ADHD in offspring. The positive signals observed in conventional studies are likely attributable to residual familial confounding. These findings provide important reassurance regarding the safety of indicated paracetamol use during pregnancy.
