Nicole R. Bush

Feb 6, 2025 | nature.com | Brennan H. Baker |Theo K. Bammler |Emily S. Barrett |Nicole R. Bush |Brent R. Collett |Daniel A. Enquobahrie | +10 more

Despite evidence linking prenatal acetaminophen (APAP) exposure and adverse neurodevelopment in humans and animals, over half of pregnant women in most populations use APAP. Prior studies could be biased by inaccurate self-reported APAP use, and the molecular mechanisms linking prenatal APAP with adverse neurodevelopment are unknown. Here we estimated associations between maternal plasma biomarkers of APAP exposure, child attention deficit hyperactivity disorder (ADHD) and placental gene expression in 307 African American mother–child pairs. Overall, detection of APAP in second trimester plasma was associated with higher odds for child ADHD diagnosis (odds ratio of 3.15 (95% confidence interval 1.20 to 8.29)). Prenatal APAP exposure and ADHD were associated with placental upregulation of immune system pathways in females and downregulation of oxidative phosphorylation in both sexes. In females only, prenatal APAP was associated with 5.22% higher odds (0.0456–13.1%) of ADHD statistically, mediated through increased immunoglobulin heavy constant gamma 1 (IGHG1) expression. These results highlight placental molecular mechanisms that may underlie developmental toxicity of prenatal APAP exposure. In this study, the authors report that maternal plasma biomarkers of acetaminophen exposure during pregnancy were associated with an increased risk of a diagnosis of child attention deficit hyperactivity disorder. The findings suggest that acetaminophen exposure impacts immune pathways and oxidative phosphorylation, potentially mediating neurodevelopmental risks.