Brother-Sister Matching Design
The researchers then conducted a sibling-matched analysis, comparing cases of autism and ADHD between siblings, some of whom were exposed to acetaminophen in utero and some who were not. This study design helps to take into account familial factors that influence the likelihood of conditions, particularly genetics and shared environmental conditions. The autism analysis included more than 124,000 sibling-matched children, and the attention-deficit/hyperactivity disorder (ADHD) analysis included more than 97,000 sibling-matched children.
Researchers did not see any association between prenatal acetaminophen use and any conditions. It does not matter what dose of acetaminophen was taken, when it was taken during pregnancy (which trimester), how often it was taken, or how old the mother was at the time. There was no link between acetaminophen and autism or ADHD.
Interestingly, there was a link when the researchers removed the sibling-matched design and instead compared acetaminophen-exposed to unexposed children, a finding that has come up in other studies. But when researchers conducted a “negative control” analysis and compared children whose mothers took acetaminophen before becoming pregnant or after giving birth, compared to mothers who did not use the painkiller, they also saw an association – which is “biologically implausible.”
The researchers concluded, “Collectively, these findings suggest that the positive signals observed in both traditional and negative control analyzes reflect residual familial confounding rather than a true pharmacologic effect of prenatal paracetamol exposure.”
Large sibling-matched studies in Sweden in 2024 and Japan in 2025 found no association between acetaminophen use in pregnancy and neurodevelopmental conditions in children.
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