Longitudinal Assessment of Cerebrovascular Autoregulation (CA) and Associations to Neurodevelopmental Delays in Infants and Toddlers with and without Congenital Heart Disease (CHD)

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Significance Congenital heart disease (CHD) is one of the leading birth defects in the United States, affecting approximately 40,000 newborns annually.1,2 Despite efforts aimed at prevention and early detection of poor neurodevelopmental outcomes (NDO), many children with CHD will have neurologic deficits lasting into adulthood.4,5 Surgical factors explain only 20% of these poor NDOs,6,7 leading to the examination of factors intrinsic to CHD as the cause for poor outcomes. A hypothesis not extensively examined is whether impaired cerebrovascular autoregulation (CA) is responsible for poorer NDOs in infants with CHD.8 Career Development Goals My overall goal is to be an independent academic investigator creating strategies and interventions to reduce or prevent developmental delays in vulnerable pediatric populations, such as those with CHD, thereby improving their quality of life. This goal aligns with the National Institute of Nursing Research’s “Symptoms Science” strategic plan because it seeks to understand the mechanistic pathways underlying developmental delay in children with CHD. My career development plan is to: improve my knowledge of cardiovascular and brain physiology in CHD and healthy infants; learn how to analyze CA using correlations of mean arterial blood pressures with Near-Infrared Spectroscopy measures; acquire familiarity of statistical analyses of complex, multilevel, time-dependent models; and enhance grant and manuscript writing skills. The environment at Children’s Hospital Los Angeles and the University of Southern California have the support and infrastructure necessary to complete my training and project. The mentoring and training plan of the K23 will help me discover the mechanism of injury and may lead to treatments that improve CA, which will prevent or attenuate developmental delays in high-risk children. Study Aims To assess CA in infants and toddlers with and without CHD, and to evaluate the association of CA with NDOs at birth, 6, 9, and 18-months of age time points. Aim #1: Compare CA between CHD infants and healthy controls through 4 developmental time points. Aim #2: Assess the association of CA with NDOs in CHD infants and whether the association of CA with NDOs varies across diagnostic groups (CHD vs controls). Methods This study is a prospective, longitudinal, 2-group cohort design. We will enroll 64 infants at birth [± 2 weeks] (32 with CHD and 32 age- and sex-matched healthy controls to yield 50 with complete data after ~20% attrition over the 18-month follow-up). CA will be measured using posture- induced changes in brain oxygenation. NDOs will be measured using standard age-appropriate tools, e.g., the Bayley Scales of Infant and Toddler Development IV. Impact If the hypotheses of this study are supported, impaired CA will be shown to be important determinants of poorer NDOs in CHD, and they will serve as new targets for future preventive interventions to improve developmental outcomes in these high-risk children. Both the knowledge of CHD infants at higher-risk for impaired CA and the early time points to intervene, will improve lifelong NDOs in this vulnerable population.