Thursday, February 12, 2015

Does Oxytocin "Augment" ADHD?

By: Editorial Board Member Lydia Furman MD,  

    A study that is sufficiently powered to answer a question about risk for ADHD has arrived. Following a trail of suggestive evidence from smaller studies Henriksen et. al (doi:10.1542/peds.2014-1542) examined the possible relationship of oxytocin augmentation of labor to subsequent development of ADHD in offspring. I don’t want to spoil the fun of the read for you, but I will note that the study is extraordinarily well done. The authors have the great advantage of large and comprehensive national registers from their home country of Denmark, including a National Birth Registry that permits identification of all augmented labors, and a National Patient Registry, National Psychiatric Registry and Medical Products Registry that, respectively, allow identification of all admits and discharges, all ADHD-diagnosed children, and all ADHD medication prescribed. Researchers in the US can only dream of such population-wide, comprehensive data sources.
     The authors note that “ADHD” is an “American DSM diagnosis” based on the Diagnostic and Statistical Manual (DSM-V) criteria, so in this cohort ADHD was diagnosed by either the ICD-10 code for “Hyperkinetic Disorder” as used in Denmark, or by having received ADHD-specific medications, or both. The sample size is a phenomenal 546,146 births (2000 – 2008), of which 25.5% were medically augmented; 0.9% of all offspring were diagnosed with ADHD. The tables are easy to read and the analysis accounts for basic potential confounders, including birth weight, gestational age, maternal age, parity, income, education and cohabitation status.
     At first glance, when compared to US rates, the number of ADHD-diagnosed children in the Henriksen study (0.9%) looks like a misprint or decimal point error. Although the ICD-10 “Hyperkinetic Disorder” code differs from DSM coding and requires that a child have hyperactivity, impulsivity and inattention, the order of magnitude difference begs explanation. The number of children in the US who are diagnosed with Attention Deficit with Hyperactivity Disorder (ADHD) has continued to increase, “from 7.8% in 2003 to 9.5% in 2007 and to 11.0% in 2011” (source: ). The overall estimated prevalence of ADHD depends directly on the methodology used to identify cases, and in meta-analysis ranges from 4.0-13.3%, with a proposed “best estimate” of 5.9-7.1% (Wilcutt, Neurotherapeutics 2012), still lower than the CDC-documented rate of diagnosis.
     The meaning and cause of the extraordinary observed increase in diagnosed children is debated, with concern by some for under-treatment (Froehlich et al Arch Pediatr Adolesc Med 2007) and by others for over-diagnosis (Klein et al, Child Care Health Dev 2014 and Coon et al, Pediatr 2014). A proposed approach of “stepped care” and “stepped diagnosis” from colleagues in the Netherlands (Batstra et al Dev Med Child Neurol 2012 and Thomas et al BMJ 2013; 347) shows promise, particularly in light of recent work demonstrating low positive predictive values for the AAP-recommended Parent and Teacher Vanderbilt scales, of 0.19 and 0.32, respectively (Bard et al J Dev Behav Pediatr 2013; Wolraich et al J Dev Behav Pediatr 2013).
     No biological marker (serology, genetic test, neuroimaging study or neurocognitive test) defines or diagnoses ADHD, so numerous studies have sought to identify correlates of diagnosis and risk. Confusing correlation with causation, or misinterpreting risk factors as etiologic factors, are the prime hazards of such studies. Prenatal smoking, for example, has been effectively dethroned as a “cause” of ADHD as additional causality studies were completed (Nigg, JAMA Pediatr 2012); prenatal smoking may instead serve as a proxy for environmental factors that foster development of the symptoms of inattention and hyperactivity. The Henrickson study makes a meaningful contribution in this arena of study, and the authors are careful to describe their work as examining an association, rather than as defining causation.

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