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April 09, 2024
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Study refutes link between acetaminophen use in pregnancy and autism, ADHD

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Key takeaways:

  • Past studies have linked Tylenol use in pregnancy with neurodevelopmental disorders, perhaps because of familial confounding.
  • A new study of more than 185,000 children showed no association between the two.

A new study of more than 185,000 children showed no association between acetaminophen use in pregnancy and a risk for neurodevelopmental disorders in children, including autism and ADHD, according to results published in JAMA.

The findings conflict with previous research that suggested acetaminophen use in pregnancy raised the risk for neurodevelopmental disorders in children.

IDC0424Gardner_Graphic_01

One of the authors of the new study said the work began after a 2021 consensus statement in Nature Reviews Endocrinology recommended that pregnant people “minimize exposure (to acetaminophen) by using the lowest effective dose for the shortest possible time,” based on the findings that suggested prenatal exposure to the analgesic could increase the risk for neurodevelopmental and other conditions.

“There was a strong response to that statement, including a number of letters published in the same journal disputing the conclusions and pointing out that such ‘calls for action’ run the risk of adding to anxiety and guilt among pregnant women,” Renee M. Gardner, PhD, principal researcher in the department of global public health at Sweden’s Karolinska Institutet, told Healio.

One of Gardner’s doctoral students, Hugo Sjöqvist, MSC, had a pregnant relative who was “extremely concerned” about the statement, Gardner said.

“We knew that this fear and anxiety must also be affecting many expectant parents across the world,” Gardner said. “We also knew that there were some substantial limitations to the existing studies that examined the relationship between paracetamol” — the European name for acetaminophen — “and neurodevelopmental disorders.”

For example, some prior models that showed a link did not include sibling controls.

“We aimed to understand if those associations were also apparent in analyses when we controlled for different indications of acetaminophen use and when we compared full siblings,” Brian K. Lee, PhD, an associate professor at the Drexel Dornsife School of Public Health in Philadelphia and fellow at the A.J. Drexel Autism Institute, told Healio.

The researchers began the new study by pulling antenatal and prescription records from pregnancies in Sweden. They had access to clinical diagnoses of autism, ADHD and intellectual disability through a register of all specialist and inpatient care in Sweden.

“We compared children whose mothers had reported acetaminophen use during pregnancy or who obtained a prescription for use during pregnancy with children with no reported maternal use,” Lee said.

In a sample of more than 2.48 million children born in Sweden from 1995 to 2019 who received follow-up through the end of 2021, 7.49% were exposed to acetaminophen during pregnancy — a total of 185,909 children.

The researchers calculated the crude absolute risks for autism, ADHD and intellectual disability at age 10 years for children not exposed to acetaminophen during pregnancy vs. those who were exposed. Those results were:

  • 1.33% vs. 1.53% for autism
  • 2.46% vs. 2.87% for ADHD
  • 0.7% vs. 0.82% for intellectual disability.

However, in an analysis of matched full sibling pairs, the researchers found no increased risk for autism (HR = 0.98; 95% CI, 0.93-1.04), ADHD (HR = 0.98; 95% CI, 0.94-1.02), or intellectual disability (HR = 1.01; 95% CI, 0.92-1.1) — findings that Gardner said were not particularly surprising.

“Given the highly heritable nature of autism and other neurodevelopmental conditions and the fact that genetic variants that are associated with neurodevelopmental conditions have also been associated with migraine and pain, we felt that there was a very high risk that the associations that others had reported were due to confounding,” Gardner said.

While comparing pain relievers in the sibling analyses, the researchers found that aspirin use was associated with a lower risk for some of the outcomes, which Gardner said could be due to its use in treating women at risk for pre-eclampsia and its complications.

References:

Ahlqvist VH, et al. JAMA. 2024;doi:10.1001/jama.2024.3172.

Bauer AZ, et al. Nat Rev Endocrinol. 2021; doi:10.1038/s41574-021-00553-7.

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. https://www.eurekalert.org/news-releases/1040161?. Published Apr. 9, 2024. Accessed Apr. 9, 2024.