Acetaminophen Use During Pregnancy Not Associated With ADHD, Other Neurodevelopmental Disorders
Acetaminophen use during pregnancy does not increase children’s risk of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and intellectual disability. Results from the population-based study were published in JAMA.
“Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses,” noted Viktor H. Ahlqvist, PhD, Karolinska Institutet, Stockholm, Sweden, and coauthors. “This suggests that associations observed in models without sibling control may have been attributable to confounding.”
While acetaminophen is considered to “pose minimal risk during pregnancy” by the US Food and Drug Administration as well as the European Medicines Agency, a 2021 consensus statement1 published in Nature Reviews Endocrinology suggested that pregnant people avoid the drug “unless its use is medically indicated” due to the potential risk of developmental disorders in offspring.
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The authors of the JAMA study designed a nationwide cohort study with sibling control analysis, with a population-based sample of 2,480,797 children born between 1995 and 2019 in Sweden, with follow-up continuing through December 2021. They analyzed the use of acetaminophen during pregnancy based on antenatal and prescription records in relation to rates of ADHD, autism, and intellectual disability as defined by codes in health registers based on the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision.
Overall, 185,909 (7.49%) were exposed to acetaminophen in utero. Initial analyses revealed that models without sibling controls exhibited slightly higher risks for 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%]) associated with acetaminophen use during pregnancy.
Matched full sibling pairs were then analyzed to account for unobserved confounding. 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%]). There was also no evidence of a dose-response pattern in sibling control analyses.
“The present results demonstrated a dose-response pattern that was attenuated with increasing covariate control and nullified in sibling control. Although the dose analysis suggested that even the highest level of acetaminophen use was not associated with increased risk, the results should not be interpreted as benchmarks for safety. Dose in this study only reflected dispensed prescriptions and not actual use of those dispensations or OTC use,” Ahlqvist et al concluded. Other study limitations included: no validation of ADHD and intellectual disability diagnoses, and imperfect exposure assessment.
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