Research Project
10409121
PROJECT SUMMARY/ABSTRACT Congenital heart disease (CHD) affects 40-50% of individuals with Down syndrome (DS), most commonly complete atrioventricular septal defect (CAVSD). Although the impact of perioperative risk factors during infant heart surgery are well studied in the general population, DS patients have been excluded from virtually all prospective studies on determinants of neurodevelopmental (ND) outcomes after infant heart surgery. Our overarching goal is to analyze the impact of CHD repaired in infancy on overall ND and behavioral outcomes in the DS population. Our proposed study is ancillary to the NHLBI-funded, prospective, Pediatric Heart Network (PHN) Residual Lesion Score (RLS) Study, which enrolled 207 DS patients with CAVSD. The parent RLS Study is evaluating the effect of technical adequacy of repair after infant heart surgery on early and mid-term outcomes, including perioperative morbidity and mortality, with follow-up through 12 months. Here, we will investigate determinants of ND and behavioral outcomes at 3-5 years of age in the RLS Study sample with DS who had CAVSD repair in the first year of life compared to an age-matched sample with DS without CHD from the same PHN sites. In Aim 1 (primary), we will compare ND and behavioral outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without CHD. Primary outcomes will be (i) verbal and non-verbal ratio IQs derived from the Mullen Scales of Early Learning and (ii) adaptive composite scores from the Vineland Adaptive Behavior Scales-3rd edition, and secondary outcomes will be (i) language scores derived from the Preschool Language Scales-5th edition, (ii) emotional and behavioral functioning scores on the Childhood Behavior Checklist, and (iii) attention and executive functioning scores on the Behavior Rating Inventory of Executive Functioning, Preschool Version. In Aim 2, we will investigate predictors of ND and behavior as measured in Aim 1 in children with DS with CAVSD repair and those without CHD, utilizing structural equation modeling to explore relationships and possible mediation among predictor variables. In Aim 3, we will establish a collection of biological material for future studies exploring genetic factors contributing to the wide spectrum of ND abilities seen in DS. We will incorporate a parent advisory group for research questions, design of study materials, and dissemination to the DS community. In addition to creating a large cohort of children with DS and CAVSD repair and an age-matched comparison group, this study addresses an important knowledge gap about whether CHD requiring infant heart surgery plays an important role in ND and behavioral outcomes in children with DS. If so, targeted interventions beginning in the early postoperative period could be designed for this vulnerable population. Positive or negative, this study will provide invaluable data for prenatal counseling on the impact of CAVSD on later ND. Finally, the biorepository will leverage the exquisite ND phenotyping of our study population by making samples available for future studies to identify molecular markers and genetic determinants of ND and behavior in children with DS.
