Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder defined by a combination of symptoms that are likely due to malfunctions in those areas of the brain that are associated with executive functions, including the prefrontal cortex,1 caudate nucleus,2 and cerebellar vermis.3 Over the years, multiple factors have been identified that probably contribute to its possible etiology. The most prominent has been genetics; ADHD is often identified by a high familial pattern with a high concordance in twin studies.4 However, no specific gene, gene pattern, or marker gene has been able to explain all but a small amount of the variance. In addition, environmental factors both pre- and postnatally (including prenatal alcohol5 and smoking exposure6 and postnatal head injuries7) have been found to increase the risk of its presence. There is also a great deal of variation in the presentation of the disorder, with 3 subtypes, and even within the subtypes, there are 9 described behaviors in each of the behavioral dimensions that also vary greatly in how they are expressed in any person with the condition. Although both medications and behavioral interventions have demonstrated strong evidence of efficacy, they also have varying effects on patients.
With so many factors contributing to the condition, it becomes difficult to further identify any additional contributing factors with any certainty. The techniques employed by Ystrom et al8 in their article “Prenatal exposure to acetaminophen and Risk of ADHD” demonstrate how it is possible to more specifically examine the possible association between prenatal exposure to acetaminophen and ADHD. They were able to use statistical techniques that required a large number of individuals with the condition. Obtaining such a large data set is expensive but easier to obtain through large health care systems in countries with central health care systems and in the United States in large academic centers or large health care organizations. The authors are careful to point out that their results from a relational study cannot establish a causal relationship between prenatal acetaminophen exposures and ADHD in the offspring, but they do suggest the possibility and raise the need for further study and more cautious consideration of acetaminophen use during pregnancy.
The possibility of a causal relationship brings to mind the association between aspirin and Reye syndrome. Establishing causal relationships ultimately led to a marked decrease in a syndrome that caused significant morbidity and mortality. Although the comparisons are far from perfect given the serious morbidity and risk of mortality associated with Reye syndrome, it does illustrate how finding associations between drug and disease can improve health outcomes. It is important to pursue further research on the possible drug associations with the development of ADHD, and that research will require longitudinal follow-up of large numbers of children with and without ADHD.
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
FUNDING: No external funding.
COMPANION PAPER: A companion to the article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2016-3840.
POTENTIAL CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The author has indicated he has no financial relationships relevant to this article to disclose.