IMPORTANCE: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy.
OBJECTIVE: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.
DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study with sibling control analysis included a population-based sample of 2?480?797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021.
EXPOSURE: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records.
MAIN OUTCOMES AND MEASURES: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers.
RESULTS: In total, 185?909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively.
CONCLUSIONS AND RELEVANCE: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.
| Discipline Area | Score |
|---|---|
| Obstetrics |  |
| FM/GP/Mental Health | |
| FM/GP/Obstetrics |  |
| Internal Medicine | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
| Psychiatry |  |
Important piece of research to assure pregnant individuals that when acetominophnen is needed, they should feel they can take it without the risk for ASD, ADHD, or ID in their children.
Important and reassuring.
Recommending medications to patients who are pregnant is always tricky. This article is helpful in looking more carefully at possible risks of acetaminophen. I suspect many readers will not (as I was not) be aware of previous studies indicating a link between acetaminophen and autism, etc, (which this article dispels with matched sibling analysis), so this will probably not change any practice.
Obviously this is not a randomized trial, but the evidence is powerful for helping allay fears about using acetaminophen in pregnancy.
This is a great study and highlights the fallacies of the prior analyses that showed an association but were poorly designed.
An example of how an adequately performed trial can answer an important clinical issue for those providing care to pregnant patients.
Well conducted but of limited interest to the field.