Acetaminophen Use During Pregnancy is Not Linked to a Child’s Risk of Autism or ADHD

Viktor H. Ahlqvist, PhD

Credit: Karolinska Institutet

Despite the belief taking acetaminophen (paracetamol) during pregnancy increases the child’s risk of autism, ADHD, or intellectual disability, a new study dispelled this myth, finding no link.¹ This was discovered through a sibling control analysis.

“Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions,” said investigator Brian Lee, PhD, from Drexel’s Dornsife School of Public Health, in a press release.²

Acetaminophen is the most widely used pain reliever taken during pregnancy—and is now believed to be safe.³ Since it is over the counter, it is easy to obtain. About 65% of women in the US report taking acetaminophen during pregnancy to relieve a headache or an aching back.

Back in 2021, a study noted evidence of acetaminophen interfering with fetal development, which could impact the effects on the brain, reproductive, and urinary systems, as well as genital development.2 However, the evidence came from animal and human observational studies—both of which cannot prove causality. A consensus statement by an international group of scientists and clinicians recommended pregnant women to stop taking acetaminophen unless it is “medically indicated.”

The new nationwide cohort study, led by Viktor H. Ahlqvist, PhD, from the Karolinska Institutet in Stockholm, Sweden, assessed the links between acetaminophen use during pregnancy with a child’s risk of autism, ADHD, and intellectual disability.¹ The team evaluated a population-based sample of 2,480,797 children born in 1995 to 2019 in Sweden, with a follow-up through December 31, 2021. To compare how acetaminophen use in a mother’s different pregnancies impacted the offspring’s development, investigators completed a sibling control analysis with 1,773,747 full siblings.

Investigators calculated the mean daily acetaminophen dose for each pregnancy and categorized it into no use, low daily use (< 166 mg 166mg/d; <25th percentile), medium daily use (<429mg/d; 25th to 75th percentile), and high daily use (≥430mg/d; 76th to 100th percentile). The team also collected data on a mother’s covariates, including a diagnosis of migraine, chronic pain, infection, fever, rheumatoid arthritis, and headaches from 1 year before pregnancy until the day of delivery.

Overall, 7.49% (n = 185,909) of children were exposed to acetaminophen during pregnancy. The crude absolute risk analysis showed 10-year-old children exposed to acetaminophen in the womb versus those not exposed had slightly greater risks of autism (1.53 vs. 1.33%), ADHD (2.87% vs. 2.46%), and intellectual disability (0.82% vs. 0.70%). Models without sibling control showed an increased risk of autism (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02 to 1.08), ADHD (HR, 1.07; 95% CI, 1.05 to 1.10), and intellectual disability (HR, 1.05; 95% CI, 1.00 to 1.10).

However, analyzing matched full sibling pairs, the sibling control analysis showed no evidence acetaminophen use during pregnancy was linked to autism (HR, 0.98; 95% CI, 0.93 to 1.04), ADHD (HR, 0.98; 95% CI, 0.94 to 1.02], or intellectual disability (HR, 1.01 [95% CI, 0.92 to 1.10). Furthermore, there was no evidence of a dose-response pattern in sibling control analyses. Children exposed to a low (< 25th percentile), medium (25th to 75th percentile), and high (> 75th percentile) daily acetaminophen had hazard ratios of 0.85, 0.96, 0.88, respectively, for autism, showing the amount of acetaminophen did not impact the autism risk.

Investigators highlighted 3 limitations, including not validating the ADHD and intellectual disability diagnoses, not having additional data on the dose including duration or time, and not having data on conditions that did not require inpatient or outpatient medical care. Mothers may have headaches, infections, fevers, and other pain, but it might not be severe enough to seek medical attention.

“This study’s findings may be welcome news for birthing people who use acetaminophen as a pain or fever management option since there are few safe alternatives for relief available,” said investigator Renee M. Gardner, PhD, from Karolinska Institutet.² “We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever.”

^References

1. ^{Ahlqvist, V, Sjöqvist, H, Dalman, C. 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}
2. ^{No Link Between Acetaminophen Use During Pregnancy and Children’s Risk Of Autism, ADHD, And Intellectual Disability Says Large Sibling Study From Drexel University And Sweden’s Karolinska Institutet. EurekAlert! April 9, 2024. https://www.eurekalert.org/news-releases/1040161?. Accessed April 9, 2024.}
3. ^{Bilodeau, K. Is A Common Pain Reliever Safe During Pregnancy? Harvard Health Publishing. October 29, 2021. https://www.health.harvard.edu/blog/is-a-common-pain-reliever-safe-during-pregnancy-202110292627. Accessed April 9, 2024.}