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Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability
- 1 Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
- 2 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
- 3 Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- 4 Department of Women’s Health, Division of Obstetrics, Karolinska University Hospital, Stockholm, Sweden
- 5 Department of Neonatology, Sachs’ Children and Youth Hospital, Stockholm, Sweden
- 6 Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
- 7 Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania
- 8 A.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania
Question Does acetaminophen use during pregnancy increase children’s risk of neurodevelopmental disorders?
Findings In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use.
Meaning Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding.
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.
Read More About
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
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