Showing posts with label ADHD. Show all posts
Showing posts with label ADHD. Show all posts

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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Thursday, March 26, 2015

Inner-city children with ADHD symptoms- what helps?

By: Lydia Furman, MD Assistant Editor  

      The work of Silverstein et al, (doi:10.1542/peds.2014-3221) “Collaborative Care for children with ADHD symptoms: a randomized comparative effectiveness trial,” is highly intriguing for several reasons. The authors studied a low-income inner-city population of children (and parents) that presented with ADHD symptoms, and randomized them to Enhanced or Basic Collaborative Care.  Enhanced Care included a trained lay facilitator who met with the family up to 5 times to address barriers to treatment and parental mental health concerns, and to provide ways to reduce coercive parenting in response to difficult behaviors. 
        The title raises a very interesting question – does diagnosis of ADHD help clinicians manage symptoms of inattention and hyperactivity? The authors’ approach suggests that it may not, since they enrolled all eligible children who were being evaluated for “ADHD symptoms”, and included both those who were ultimately diagnosed with ADHD, as well as those who were not, in the clinical trial. This empiric research strategy encourages us to think more broadly about how to help children who present with symptoms of inattention, impulsivity and hyperactivity. The diagnosis of ADHD as described “was defined as meeting DSM-IV symptom criteria on both the parent and teacher Vanderbilt scales, in the absence of a plausible alternative explanation for the child’s symptoms- as determined from narrative clinical information.” Given this straightforward and pragmatic evaluation using an instrument with relatively low positive predictive value (PPV of 0.19 and 0.32, respectively; Bard et al J Dev Behav Pediatr 2013; Wolraich et al J Dev Behav Pediatr 2013), it is worth considering the possibility that the 63 “ADHD consistent presentation” subjects (40% of all subjects), as compared to the “ADHD inconsistent presentation” subjects, differed quantitatively not qualitatively from each other. In other words, did children in the former group simply have more symptoms than those in the latter group, rather than a unique disease state?
        The “ADHD consistent presentation” subjects, whose outcomes were analyzed secondarily since the study was powered to look at outcomes of all subjects, showed greater symptom improvement in the Enhanced Collaborative Care group (please read the paper to learn about the summary results for all children!). Given the study design, the authors could not determine which component of the Enhanced Care was the most helpful. However, since there was not a statistically significant difference in specialty behavior services or in medication treatment between groups (52% in basic care vs. 72% in Enhanced care, p=0.10), and there was a difference in receipt of Triple P (Positive Parenting Program with 0% in basic care vs. 47% in the Enhanced Care Group receiving the intervention, the authors speculate that this could explain the impact of the Enhanced Care. In deference to the authors, I note that they believe the clinically meaningful difference in medication use between groups likely was important also, but we know from multiple publications, including the very well monitored MTA study in which actual medication adherence was 53.5% (Pappadopulos et al Medication adherence in the MTA JAACAP 2009), that compliance with medication treatment may be surprisingly low.
        In an accompanying Perspective, Dr. Mark Wolraich,(doi:10.1542/peds.2015-0070) who is the lead author of the AAP ADHD Guidelines and of the Vanderbilt forms, notes that “while progress is being made,” no etiology has been identified for ADHD  in over a decade of research, and “therapy is likely to remain symptom based,”  which is indeed the approach that Silverstein et al take.  Dr. Wolraich also notes that long term outcomes are not yet acceptable, and that even the MTA study found no difference in intensively monitored groups 2 years after treatment ended. In fact at 24 and 36 months post formal intervention, children in the MTA who were taking medication, as compared to those who were not, showed significantly greater symptom deterioration from 24 to 36 months, as well as higher delinquency at both these time points (Jensen et al 3-Year Follow-up of NIMH MTA JAACAP August 2007), information that may be new to many clinicians. Perhaps an entirely new paradigm is needed.

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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.