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Fetal acetaminophen exposure may increase child's risk for ADHD, autism

Fetal acetaminophen exposure may increase a child’s risk for ADHD and autism spectrum disorder, according to results of a prospective cohort study published in JAMA Psychiatry.

“We identified a significant positive association between cord plasma acetaminophen metabolites and the risk for ADHD diagnosis and the risk for ASD in childhood,” Yuelong Ji, PhD, postdoctoral fellow at Johns Hopkins Bloomberg School of Public Health, and colleagues wrote. “The positive associations between cord acetaminophen and ADHD and the cord acetaminophen and ASD were observed across strata of pertinent covariates, including maternal fever during pregnancy, which is an indicator for acetaminophen use.”

According to the researchers, the present study was the first to investigate associations between several types of neurodevelopmental disabilities with adjustments for potential covariates and cord plasma metabolites of acetaminophen. They noted that limitations of previous studies were overcome by using cord plasma metabolites, which provide a direct measurement of fetal exposure before delivery rather than after delivery.

Ji and colleagues analyzed data for 996 mother-infant dyads, which were a subset of the Boston Birth Cohort, between October 1998 and June 2018. They measured three cord acetaminophen metabolites — unchanged acetaminophen, acetaminophen glucuronide and 3-[N-acetyl-_L-cystein-S-yl]-acetaminophen — in archived cord plasma samples collected at birth.

The final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other developmental disabilities and 327 (32.8%) who were neurotypical, according to the researchers. They detected unchanged acetaminophen levels in all cord plasma samples. They noted that being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (OR for second tertile = 2.26; 95% CI, 1.4-3.69; OR for third tertile = 2.86; 95% CI, 1.77-4.67), and ASD diagnosis (OR for second tertile = 2.14; 95% CI, 0.93-5.13; OR for third tertile = 3.62; 95% CI, 1.62-8.6). Using subgroup and sensitivity analyses, the researchers found consistent associations between acetaminophen burden and ADHD and acetaminophen burden and ASD. These associations persisted across strata of potential confounders, including child age and sex, preterm birth, substance use and maternal indication.

“Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations,” the researchers wrote. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.