by Justin Jackson , Medical Xpress

Credit: Pixabay/CC0 Public Domain

Maternal acetaminophen exposure during pregnancy is associated with a higher likelihood of childhood attention deficit hyperactivity disorder (ADHD), according to a study led by the University of Washington.

Researchers analyzed plasma biomarkers of acetaminophen (APAP) exposure in a cohort of 307 African American mother-child pairs. Detection of APAP in second-trimester maternal blood samples correlated with increased odds of ADHD diagnosis in children by age 8–10.

Acetaminophen (also called paracetamol) is widely used during pregnancy, with an estimated 41–70% of pregnant individuals in the United States, Europe, and Asia reporting its use. Despite its classification as a low-risk medication by regulatory agencies such as the U.S. Food and Drug Administration and the European Medicines Agency, accumulating evidence suggests a potential link between prenatal APAP exposure and adverse neurodevelopmental outcomes, including ADHD and autism spectrum disorder.

Most prior studies relied on self-reported APAP use, which may introduce recall bias and leave molecular mechanisms underlying these associations unclear.

In the study, “Associations of Maternal Blood Biomarkers of Prenatal APAP Exposure With Placental Gene Expression and Child Attention Deficit Hyperactivity Disorder,” researchers analyzed data from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort, a birth cohort based in Memphis, Tennessee.

The findings are published in the journal Nature Mental Health.

Researchers utilized untargeted metabolomics to identify APAP metabolites in second-trimester maternal plasma samples and examined their relationship with childhood ADHD diagnoses and placental gene expression.

APAP metabolites were detected in 20.2% of maternal plasma samples. Children whose mothers had APAP biomarkers present in their plasma had a 3.15 times higher likelihood of an ADHD diagnosis (95% confidence interval: 1.20 to 8.29) compared with those without detected exposure.

The association was stronger among females than males, with female children of APAP-exposed mothers showing a 6.16 times higher likelihood of ADHD (95% confidence interval: 1.58 to 24.05), while the association was weaker and nonsignificant in males.

Placental gene expression analysis of a subset of 174 participants indicated sex-specific transcriptional changes. In females, APAP exposure was associated with upregulation of immune-related pathways, including increased expression of immunoglobulin heavy constant gamma 1 (IGHG1).

Increased IGHG1 expression was statistically linked to ADHD diagnoses, with mediation analysis suggesting that APAP’s effect on ADHD was partly mediated through this gene’s placental expression.

Oxidative phosphorylation pathways were downregulated in both sexes, a pattern previously associated with neurodevelopmental impairment.

Findings align with prior epidemiological studies and experimental animal research linking prenatal APAP exposure to neurodevelopmental disruptions. The current study eliminated the bias concerns raised in previous studies where APAP use was self-reported by using objective biomarker measurements.

The comprehensive insights into potential molecular pathways underlying the observed associations offer avenues for additional studies to further elucidate the mechanisms involved.

More information: Brennan H. Baker et al, Associations of maternal blood biomarkers of prenatal APAP exposure with placental gene expression and child attention deficit hyperactivity disorder, Nature Mental Health (2025). DOI: 10.1038/s44220-025-00387-6

Journal information:Nature Mental Health

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