A link between ADHD and acetaminophen?

A new study published in JAMA Pediatrics is raising concern about a potential association between use of acetaminophen in pregnancy and attention-deficit/hyperactivity disorder (ADHD) in offspring. But the Society for Maternal-Fetal Medicine (SMFM) is urging caution in interpretation and application of the findings, noting that the results relate to long-term use of acetaminophen, which is not typical in pregnancy, and association does not necessarily equal causation.

Researchers from the University of California – Los Angeles and the University of Aarhus, in Denmark, studied 64,322 live-born children and their mothers, who were enrolled in the Danish National Birth Cohort from 1996 to 2002. Use of acetaminophen was assessed by performing 3 computer-assisted telephone interviews during pregnancy and in the 6 months after delivery. Parental reports of behavioral problems in children aged 7 years were identified using the Strengths and Difficulties Questionnaire, hyperkinetic (HKD) diagnoses were identified using the Danish National Hospital Registry or the Danish Psychiatric Central registry prior to 2011, and prescriptions for ADHD medications such as methylphenidate, in children were identified using the Danish Prescription Registry. Hazard ratios were estimated for receiving a diagnosis of HKD or using an ADHD medication; risk ratios were estimated for behavioral problems in children after prenatal exposure to acetaminophen.

Over the course of their pregnancy, more than half of the mothers in the cohort used acetaminophen. The children of the acetaminophen users had a higher risk of having a hospital diagnosis of HKD (hazard ratio [HR] = 1.37; 95% confidence interval [CI], 1.19-1.59), use of ADHD medications (HR = 1.29; 95% CI, 1.15-1.44), or exhibiting ADHD-like behaviors at the age of 7 (risk ratio = 1.13; 95% CI, 1.01-1.27). The associations were stronger when acetaminophen was used in more than 1 trimester.  Exposure response trends had increasing frequency of acetaminophen use during gestation for all 3 outcomes (P< .001). The investigators found that the results were likely not confounded by maternal inflammation, infection during pregnancy, the mother’s mental health problems, and other evaluated cofounders.

Another study showing a possible link

SMFM, however, issued a response stating that the results need to be taken in context. “In fact, as the authors state, maternal infections or immunologic factors have been linked to childhood ADHD,” said Dr. Vincenzo Berghella, president of SMFM, in a press release. “These are the conditions for which acetaminophen is often used, so this is what is called ‘confounding,’ a finding which seems due to a factor, but is in fact due to another issue (e.g. infection) linked to both the exposure (e.g. acetaminophen) and outcome (e.g. ADHD).” He also pointed out that the strongest associations in the study were found with long-term acetaminophen use-sometimes for weeks or months-which is not a typical course of treatment in most pregnancies. 

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