Acetaminophen is one of the most commonly used drugs during pregnancy globally. Recent studies have reported associations between prenatal exposure to acetaminophen and neurobehavioral problems in children, including attention-deficit hyperactivity disorders. Little research has investigated these associations in preschool-age children or the potential confounding effects of prenatal stress. The purpose of this study was to examine associations between prenatal acetaminophen exposure and offspring neurobehavioral problems at the age of 3 years, with a focus on the potentially confounding effects of prenatal stress.


We used data from the First Baby Study, a prospective cohort study conducted in Pennsylvania, USA, with 2,423 mother-child pairs. Women reported medication use and completed a prenatal stress inventory during their third trimester. Child behavioral problems were measured at the age of 3 years, using the 7 syndrome scale scores from the Child Behavior Checklist (CBCL) for ages 1 ½ to 5.


There were 1,011 women (41.7%) who reported using acetaminophen during pregnancy. Children who were exposed to acetaminophen during pregnancy scored significantly higher on 3 of the 7 CBCL syndrome scales: withdrawn, sleep problems and attention problems. Scores on all 7 of the CBCL syndrome scales were significantly associated with prenatal stress. After adjustment for prenatal stress and other confounders, 2 syndrome scales remained significantly higher in children exposed to acetaminophen: sleep problems (aOR = 1.23, 95% CI = 1.01–1.51) and attention problems (aOR = 1.21, 95% CI = 1.01–1.45).


These findings corroborate previous studies reporting associations between prenatal exposure to acetaminophen and attention problems in offspring and also show an association with sleep problems at age 3 years. Because use of acetaminophen during pregnancy is common, these results are of public health concern and suggest caution in the use of medications containing acetaminophen during pregnancy.

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Kristin K. Sznajder,Douglas M. Teti, Kristen H. Kjerulff
PLoS ONE September 28, 2022