Acetaminophen Use in Pregnancy Linked to ADHD

A new Norwegian study has found a link between prenatal exposure to acetaminophen and an increased risk of ADHD. While the research cannot claim a definitive link, it may lead to understanding an often-used medication during pregnancy.

Acetaminophen is the recommended drug for pregnant women with fever or pain. Other studies have shown that between 65% and 70% of pregnant women in the United States use it. However, other studies of prenatal acetaminophen exposure have found that acetaminophen exposure longer than 28 days was associated with poorer motor and communication skills.

The study examined nearly 113,000 children from the Norwegian Mother and Child Cohort Study, a large prospective population-based birth cohort study conducted by the Norwegian Institute of Public Health. Of those children, 2246 were diagnosed with ADHD. While the risks of acetaminophen exposure have been studied before, this study was the first to account for other factors, such as parental symptoms of ADHD and the effects of paternal and maternal acetaminophen use before pregnancy.

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Of the maternal population examined in the current study, 27% used acetaminophen in one trimester, 16% in two trimesters, and 3.3% in all three trimesters. The researchers found a negative association in offspring exposed for less than 7 days, while the risk increased for each day after 7 days of use. For exposures over 29 days, the risks more than doubled compared to those who did not use the drug. This risk increased regardless of the reason for using the drug.

To explain the link between maternal use and ADHD, the authors gave three hypotheses. The first is based on studies using acetaminophen in mice. Neonatal exposure to acetaminophen changes the levels of brain-derived neurotropic factor in mice, which results in behavioral changes. The second hypothesis is that acetaminophen could interfere with certain maternal hormones linked to fetal brain development. Finally, acetaminophen could interrupt brain development through oxidative stress, which leads to neuronal death.

Additionally, the link between paternal preconceptional acetaminophen use and ADHD was similar to the link between maternal use during pregnancy and ADHD. The authors said that explanations behind the link between paternal use and ADHD are unclear, but may be due to “male germ-line epigenetic effects as described in endocrine disruption effects of acetaminophen on the human testis.” Maternal preconceptional use made no difference.

The study was published online in Pediatrics.