Friday, August 28, 2015

ADHD Diagnosis – What Risk is defined at birth?

By: Lydia Furman, MD,  Assistant Editor 
     How do prematurity and fetal growth impact risk of ADHD? Comprehensive epidemiological studies from countries such as Finland that have universal health care, national tracking registries and relatively homogeneous populations can provide unique insights into challenging questions like this one. Dr. Sucksdorff et al. (doi: 10.1542/peds.2015-1043) have conducted a careful and thoughtful study whose conclusions have both pragmatic practice implications, as well as potential to stimulate new research.
      The authors were able to use national registries to identify all 900,603 live singleton births between 1991 and 2001, and then to further select the study subpopulations of (a) all 10,321 children who were diagnosed with ADHD and (b) 38,355 matched healthy controls. Very few had missing information or exclusionary diagnoses, and the authors are able to cite prior work showing that 88% of children with an ADHD Registry diagnosis who were subsequently examined did meet the DSM-IV diagnostic criteria for ADHD. The exposures of interest were (1) gestational age by week, and (2) sex-specific fetal growth for gestational age by standard deviation category (please read the paper for relevant details); obviously the outcome of interest was the diagnosis of ADHD. The authors were able to include 9 key confounding variables in the analysis, for example maternal smoking and parental psychiatric diagnoses, with sufficient detail and documentation to provide meaningful information.
      The results of the logistic regression analyses are convincing. Readers familiar with multiple studies examining risk for ADHD will likely not be surprised by the results, but the magnitude of the association of gestational age with ADHD diagnosis is highly persuasive. Are late preterm, “early term” and even younger term infants impacted? The information is presented clearly in both the text and tables, and I hope you will enjoy the read. Previous work has suggested that small for gestational age status increases risk for ADHD, but Dr. Sucksdorff and colleagues are able to show a beautifully “fine-grained” view of the impact of being either larger or smaller for gestational age on risk for ADHD diagnosis. In both analyses (gestational age and weight for gestational age) there are interesting surprises, as well as implications for how we classify gestational maturity and appropriateness of fetal growth for gestational age. And the article may influence practicing pediatricians to think differently about risk for ADHD diagnosis in individual children.
      As the authors note, given the limited socioeconomic differences and disparities in perinatal health in Finland, it is unlikely that these results are hiding uncontrolled social factors. So although it can be difficult to generalize results from one country to another, in this case a study setting that essentially controls for the myriad of social and health disparities in the US provides a unique opportunity for researchers to think more clearly about the etiology of ADHD. These authors found a very minor impact of familial factors after adjustment for confounders. They point out that the processes underlying fetal neurodevelopment, including “synaptogenesis, brain folding and myelination,” along with factors related to the multiple possible mechanisms of preterm labor including inflammation, infection and ischemia, may play an etiologic role in susceptibility to ADHD, i.e. to the behaviors of inattention, hyperactivity and impulsiveness. And taking this one step further, since susceptibility or risk for ADHD is not ADHD diagnosis, what postnatal environmental factors might “tip the ship” and lead to or be associated with diagnosis? We will need to await another careful and thoughtful study to answer this question… 

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