Studies have shown an association between self-reported maternal acetaminophen use during pregnancy and risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring; however, direct evidence of fetal acetaminophen exposure is absent in previous research. Here, the prospective association between cord plasma acetaminophen metabolites (direct evidence of fetal exposure) and childhood ADHD, ASD and other developmental disabilities (DD) was examined using data from mother-infant dyads from the Boston Birth Cohort who enrolled in the follow-up study (October 1, 1998-June 30, 2018) at birth. Dyads were included if 1) sufficient cord plasma (collected at birth) was available for metabolite analysis and 2) the child received a diagnosis of ADHD, ASD, other DD or neurotypical development (ND) during the follow-up period (n=996). ADHD and ASD groups had higher exposures of cord unchanged acetaminophen and its metabolites compared with the other DD and ND groups. Dose-response patterns emerged for cord unchanged acetaminophen and cord acetaminophen burden and the risk of ADHD diagnosis (p’s<0.001); cord unchanged acetaminophen, cord acetaminophen glucuronide and cord acetaminophen burden were also significantly associated with increased risk of ASD diagnosis (p=0.002) (Figure 1). Sensitivity analyses adjusting for a broad range of potential confounders (e.g., child’s sex, maternal alcohol use before or during pregnancy, breastfeeding) yielded comparable results (p’s<0.01). Findings from this study provide strong evidence that fetal exposure to acetaminophen is prospectively associated with significantly increased risk of childhood ADHD and ASD. Additional research is needed to determine specific safety parameters (e.g., dose, timing) regarding acetaminophen use during pregnancy.
Figure. Association between cord acetaminophen burden and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) diagnosis in childhood. A dose-response association was observed between cord acetaminophen burden and risk of ADHD diagnosis, compared to the ADHD reference group (refADHD). The highest cord acetaminophen burden was also associated with a greater risk of ASD diagnosis, compared to the ASD reference group (refASD). * p<0.001 compared to refADHD; † p=0.002 compared to refASD
Ji Y et al. JAMA Psychiatry 2020;77(2):180-9. Abstract
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