<p><strong>Background: </strong>The small number of studies examining the association of prenatal acetaminophen with birth outcomes have all relied on maternal self-report. It remains unknown whether prenatal acetaminophen exposure measured in a biological specimen is associated with birth outcomes.</p>

<p><strong>Objectives: </strong>To investigate the association of acetaminophen measured in meconium with birthweight, gestational age, preterm birth, size for gestational age, gestational diabetes, preeclampsia, and high blood pressure.</p>

<p><strong>Methods: </strong>This birth cohort from Sherbrooke, QC, Canada, included 773 live births. Mothers with no thyroid disease enrolled at their first prenatal care visit or delivery. Acetaminophen was measured in meconium for 393 children at delivery. We tested associations of prenatal acetaminophen with birthweight, preterm birth, gestational age, small and large for gestational age, gestational diabetes, preeclampsia, and high blood pressure. We imputed missing data multiple imputation and used inverse probability weighting to account for confounding and selection bias.</p>

<p><strong>Results: </strong>Acetaminophen was detected in 222 meconium samples (56.5%). Prenatal acetaminophen exposure was associated with decreased birthweight by 136 g (β = -136; 95% CI [-229, -43]), 20% increased weekly hazard of delivery (hazard ratio = 1.20; 95% CI [1.00, 1.43]), and over 60% decreased odds of being born large for gestational age (odds ratio = 0.38; 95% CI [0.20, 0.75]). Prenatal acetaminophen was not associated with small for gestational age, preterm birth, or any pregnancy complications.</p>

<p><strong>Conclusion: </strong>Prenatal acetaminophen was associated with adverse birth outcomes. Although unobserved confounding and confounding by indication are possible, these results warrant further investigation into adverse perinatal effects of prenatal acetaminophen exposure.</p>

<p>Acetaminophen is the only over-the-counter pain reliever that is not contraindicated during pregnancy, but recent studies have questioned whether acetaminophen is safe for the fetus, particularly the developing brain. This prospective birth cohort study probed the previously observed association between in utero exposure to acetaminophen and neurodevelopment by using concentrations of acetaminophen measured in meconium, which more objectively captures exposure of the fetus than maternal report. Exposure, measured by liquid chromatography coupled with tandem mass spectrometry, was categorized into non-detection, low detection, and high detection levels. At age six to eight years, children completed a set of subtests from the Wechsler Intelligence Scale for Children, 4th edition. Additionally this study examined potential effect modification by child sex on the association between acetaminophen exposure and neurodevelopment. In fully adjusted models, in utero exposure to acetaminophen was not statistically significantly associated with decreased scores on any of the examined subtests in all children combined (n = 118). The effect of in utero acetaminophen exposure on the Coding subtest was marginally significantly different among boys and girls, with girls performing significantly better on the task with higher levels of acetaminophen compared to girls with undetectable levels of exposure [βgirls, low = 2.83 (0.97, 4.70), βgirls, high = 1.95 (-0.03, 3.93), βboys, low = 0.02 (-1.78, 1.81), βboys, high = -0.39 (-2.09, 1.31), pinteraction = 0.06]. Effect modification by child sex was not observed on other subtests. These results do not support prior reports of adverse neurodevelopmental effects of in utero exposure to acetaminophen.</p>