Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome.

Objectives The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in congenital heart disease (CHD) survivors. Methods Fetuses < 24 wks gestational age (GA) were enrolled in this prospective pilot study for serial Doppler assessment of the middle cerebral and umbilical artery. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalogram (EEG) and beta frequency (12–24Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18-months with the Bayley Scales of Infant Development III (BSID). Results 13 subjects were enrolled: 4 with hypoplastic left heart syndrome (HLHS), 4 with transposition of the great arteries (TGA), and 5 with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR<1(N=7) had lower mean BSID cognitive scores (91.4±4.8 vs. 99.2±3.8, p=.008). Fetal MCA PI z-score also correlated with BSID cognitive score (r=.589, p=0.044) as did neonatal EEG left frontal polar (r=.58, p=.037) and left frontal (r=.77,p=.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR<1 had lower left frontal polar (t=2.36, p=.038) and left frontal (t=2.85, p=.016) beta power as newborns compared with fetuses with normal CPR, and fetal MCA PI z-score correlated with neonatal EEG left frontal polar (r=.596, p=.04) and left frontal (r=.598, p=.04) beta power. Conclusions In CHD fetuses with HLHS, TGA, and TOF, abnormal cerebrovascular resistance predicted decreased neonatal EEG left frontal beta power and lower 18-mo cognitive development scores.