Levels of acetaminophen were measured in the cord blood of 996 pregnant mothers at the time of the child's birth. Women were divided into 3 equal groups defined as low acetaminophen, medium acetaminophen, and high acetaminophen. Compared to being in the low acetaminophen group, women in the medium and high groups were more likely to have children identified later as having ADHD or autism. For example, the middle exposure group had a 2.26 times higher rate of ADHD and the high exposure group had a nearly 3-fold increase in ADHD. Autism was also higher. Children born to the middle acetaminophen group had a 2.14 times higher rate of autism and those born in the highest group had a 3.62 times greater risk of autism (compared to the lowest group). This study with a large number of children provides a strong dose-response curve, suggesting Tylenol type medications increase ADHD and autism.
ABSTRACT
Importance:
Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report.
Objective:
To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood.
Design, setting, and participants: This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018.
Exposures:
Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth.
Main outcomes and measures: Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records.
Results:
Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), 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 DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; 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, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen burden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD.