Acetaminophen Implicated In Autism & ADHD Again

The study published in JAMA Psychiatry suggests that among 996 mother child pairs those with higher levels of acetaminophen (Tylenol) exposure, which was measured through biomarkers in cord blood at delivery, had a significantly greater chance of the offspring being diagnosed later in with ASD or ADHD, according to Xiaobin Wang, MD, MPH, of Johns Hopkins University Bloomberg School of Public Health.

The researchers calculated an odds ratio of 2.86 for ADHD diagnosis for those infants in the highest tertile of acetaminophen exposure, and the odds ratio for ASD diagnosis was similar at 3.62 for those infants in the highest tertile of acetaminophen exposure. 

"For a long time, acetaminophen was considered [one of] the few safe pain and fever relief medications during pregnancy," Wang writes. "However, previous studies based on maternal self-report and our study based on acetaminophen metabolite biomarkers showed consistent findings between prenatal acetaminophen exposure and increased risk of ADHD risk, and possibly, ASD as well."

This is not the first study to link fetal acetaminophen exposure to the development of behavioral problems in children, just as it is not the first study to link fetal acetaminophen exposure to ASD and ADHD. Rather than suggesting acetaminophen be avoided during pregnancy completely, these findings may imply that patients should weigh all risks versus the benefits of using over the counter medications during pregnancy when other safer options may be available, suggests Kimford J. Meador, MD, of Stanford University, who was not involved in the study.

This study involved participants in the Boston Birth Cohort which had sufficient cord plasma samples to conduct metabolite assays; acetaminophen exposure was measured through 2 metabolites: glucuronide and 3-N-acetyl-L-cysteine-S-yl-acetaminophen, as well as a composite measure of both in cord blood collected at birth. Offspring were evaluated at a mean age of 10: of which 25.8% were diagnosed with ADHD, 6.6% were diagnosed with ASD,  4.2% were diagnosed with both ADHD and ASD, and just over 30% were diagnosed with other developmental disorders while the remaining one third were neurotypical. 

Mothers and offspring differed between groups such as mothers with offspring diagnosed with ADHD or ASD were more likely to have higher BMIs, feel stressed during pregnancy, or report having smoked or drank before or during pregnancy. The offspring with ADHD or ASD were more likely to be male, born preterm, and to have lower birth weights. 

Those offspring in the highest tertile of cord unchanged acetaminophen were more likely to be diagnosed with both conditions, but there was no relationship found between other metabolites and the dual diagnosis. The association beween exposure and neruodevelopment outcomes were attenuated but remained the same after adjusting for sex, maternal race/ethnicity, preterm birth, breastfeeding, maternal fever, maternal tobacco, alocohol or illicy drug use, stress during pregnancy, child lead levels, and child age at last visit. 

Meador suggests that this data is limited by not being adjusted for family history of ASD and ADHD, as well as not being adjusted for genetic factors related to the risk of these conditions. Limitations were extended by not adjusted for other medications that may have been used during birth. Additionally exposure was only measured once at delivery, meaning the full extent and timing of exposure could not be evaluated, and acetaminophen sulfate was not measured as well which means that the composite burden on the newborns was incomplete. The authors noted that all mothers tested positive for unchanged acetaminophen in samples collected at birth, meaning that there was no non-exposed group for reference.

"The authors didn't look at exposure in pregnancy and particularly the third trimester, which is a particularly susceptible time," Meador explains, adding that animal studies have demonstrated that the fetal brain is most vulnerable during the third trimester to alcohol and anticonvulsant drugs, for example.