Prenatal exposure to acetaminophen increased ADHD-like behaviors, hyperkinetic disorders

Children whose mothers used acetaminophen while pregnant are at increased risk for attention-deficit/hyperactivity disorder-like behavioral problems and hyperkinetic disorders, according to recent study findings published in JAMA Pediatrics.

Zeyan Liew, MPH, a PhD student in the department of epidemiology at the School of Public Health, University of California, Los Angeles, and colleagues evaluated 64,322 children and their mothers enrolled in the Danish National Birth Cohort (1996-2002) to determine the effect of acetaminophen use during pregnancy.

More than half of the mothers reported using acetaminophen during pregnancy.

There was an increased risk for ADHD-like behaviors at age 7 years among children with prenatal exposure to acetaminophen (RR=1.13; 95% CI, 1.01-1.27). A higher Strengths and Difficulties Questionnaire score was associated with each additional week of prenatal acetaminophen use during pregnancy.

The risk for a hyperkinetic disorder diagnosis or ADHD medication was increased with prenatal exposure to acetaminophen. Twenty or more weeks of acetaminophen use during pregnancy nearly doubled the risk for a hyperkinetic disorder diagnosis (HR=1.84; 95% CI, 1.39-2.45) and increased the risk for ADHD medication by 50% (HR=1.53; 95% CI, 1.21-1.94).

“Using prospective data from a well-designed large cohort of pregnant women with a long duration of follow-up and registry-based outcome assessment, we found that prenatal exposures to acetaminophen may increase the risk in children of receiving a hospital diagnosis of [hyperkinetic disorders] or ADHD medication and of exhibiting ADHD-like behaviors, with higher use frequency increasing risk in an exposure-response manner,” the researchers wrote. “Because the exposure is frequent, these associations might explain some of the increasing incidence in [hyperkinetic disorder]/ADHD, but further studies are needed.”

In an accompanying editorial, Miriam Cooper, MRCPsych, MSc, of Cardiff University School of Medicine in Wales, and colleagues wrote that because causation cannot be inferred from the associations, it is appropriate that the study researchers recommend more studies.

“In summary, findings from this study should be interpreted cautiously and should not change practice,” they wrote. “However, they underline the importance of not taking a drug’s safety during pregnancy for granted, and they provide a platform from which to conduct further related analyses exploring a potential relationship between acetaminophen use and altered neurodevelopment.”

For more information:

Cooper M. JAMA Pediatr. 2014;doi:10.1001/jamapediatrics.2013.5292.

Liew Z. JAMA Pediatr. 2014;doi:10.1001/jamapediatrics.2013.4914.

Disclosure: One researcher reports financial ties with the University of Arizona, the Global Clinical Epidemiology, Drug Safety, and Epidemiology, Novartis Farmaceutica SA. The study was funded in part by the Danish Medical Research Council. The editorial was funded by the Medical Research Council.