maternal paracetamol (acetaminophen) use in relation to autism spectrum and attention-deficit and hyperactivity (ADHD) risk in offspring

Prenatal and postnatal exposure to paracetamol (acetaminophen) in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood (1,2,3)

• meta-analysis (n=73,881 mother-child pairs) showed that children prenatally exposed to paracetamol were 19% more likely to subsequently have autism spectrum conditions (OR 1.19, 95% CI 1.07-1.33) and 21% more likely to have ADHD symptoms (1.21; 1.07-1.36) vs. non-exposed children (1):
  • study authors concluded that "considering all evidences on acetaminophen use and neurodevelopment, we agree with previous recommendations indicating that while acetaminophen should not be suppressed in pregnant women or children, it should be used only when necessary..."
    
    
• Swedish study (185,909 children exposed to paracetamol during pregnancy from database of 2 480 797 births), using sibling control analysis, found no evidence of association with autism (HR 0.98, 95%CI 0.93-1.04), ADHD (0.98, 0.94-1.02) & intellectual disability (1.01, 0.92-1.10) (2):
  • was also no evidence of a dose-response pattern
  • authors state that associations observed in other models may have been attributable to familial confounding
    
    
• an umbrella review of systematic reviews found that existing evidence does not clearly link maternal paracetamol use during pregnancy with autism or ADHD in offspring (3):
  • systematic reviews of randomised trials and cohort, case-control, or cross sectional studies that reported maternal paracetamol use during pregnancy and the diagnosis of autism or ADHD in offspring
  • study results
    • nine reviews (40 studies) reporting on autism (six studies) and ADHD (17 studies) in offspring were included
      • four reviews undertook meta-analysis
      • overlap of primary studies included in the reviews was very high (corrected covered area 23%)
      • the reviews reported a possible to strong association between maternal paracetamol intake and autism or ADHD or both in offspring.
      • seven of the nine reviews advised caution when interpreting the findings owing to the potential risk of bias and confounding in the included studies
      • confidence in the findings of the reviews was low (two reviews) to critically low (seven reviews) based on the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) criteria
      • only one review included studies (n=2) reporting autism and ADHD in offspring that appropriately adjusted for familial factors and unmeasured confounding through sibling controlled analyses
        • in both studies, the increased risk of autism in offspring (one study, hazard ratio 1.05, 95% confidence interval 1.02 to 1.08) and ADHD (two studies, 1.07, 1.05 to 1.10 and 2.02, 1.17 to 3.25 ) observed in the whole cohort analyses did not persist in sibling controlled analyses for autism (0.98, 0.93 to 1.04) and ADHD (0.98, 0.94 to 1.02 and 1.06, 0.51 to 2.05)
  • study authors concluded:
    • existing evidence does not clearly link maternal paracetamol use during pregnancy with autism or ADHD in offspring

Reference:

1. Alemany S et al. Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts. Eur J Epidemiol (2021). https://doi.org/10.1007/s10654-021-00754-4
2. Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172
3. Sheikh J, Allotey J, Sobhy S, Plana M N, Martinez-Barros H, Naidu H et al. Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviewsBMJ 2025; 391 :e088141