Genetic Variation and Association with Post-Operative Outcomes for Neonates and Infants in the Cardiac Intensive Care...

Congenital heart defects (CHD) occur in 1% of live births, with an estimated at least 33% of affected infants having genetic defects. It has become standard to screen children with CHD for genetic findings that could aid clinical decision-making, yet modern testing yields large volumes of information without understanding clinical utility. Genome-wide studies have identified associations between large copy number variants and neurocognitive outcomes in patients with CHD. Still, little research exists on the prognostic power of screening tests such as microarrays. The goal of this study was to determine if abnormal microarray results in infants with CHD were associated with worse clinical outcomes in the cardiac intensive care unit (CICU).

This was a single-center retrospective cohort study. The Society of Thoracic Surgery (STS) and Pediatric Cardiac Critical Care (PCICU) registries (PC4) were queried for all surgical admissions of neonates and infants between 1 January 2014 and 31 December 2019. Patient demographics, surgical details, and post-operative outcomes were collected for surgical admissions related to the patient's index operation. A chart review was performed to ascertain microarray results, further genetic testing, and longitudinal outcomes. Patients without microarray results or long-term institutional follow-up were excluded. Wilcoxon rank-sum and chi-square tests were used to compare outcomes defined and collected in the PC4 registry between patients with normal and abnormal microarray results. Subgroup analysis was then performed using the same outcome measures to compare normal and abnormal microarray groups in children who required cardiac surgeries within 30 days of life and in children who presented with ventricular septal defect (VSD), atrioventricular septal defect (AVSD), aortic stenosis (AS), or Tetralogy of Fallot (TOF).

Of the 412 infants with surgical admissions to the CICU between 2014 and 2019, 43 infants had no longitudinal follow-up, and 65 infants had no microarray results. Three hundred and four infants were included in this study, of which 196 children had normal microarrays and 108 infants had abnormal microarrays. Both groups had similar distributions of gestational age and birth weight, but fundamental diagnoses and primary procedures differed significantly between groups (p < 0.005). STS score, deep hypothermic circulatory arrest (DHCA) time, and bypass time were each significantly lower in children with abnormal microarrays than in those with normal microarrays across the study. The patients with abnormal microarrays had a higher incidence of gastrostomy (G)-tube placement during their lifetime than infants with normal microarrays. On subgroup analysis, despite the differences in fundamental diagnoses and the fact that primary procedures differed significantly between normal and abnormal microarray groups that required cardiac surgery within 30 days of life, there were no detectable differences in the surgical and PCICU outcomes. DHCA time was once again significantly lower in the abnormal microarray subgroup in the second subgroup analysis.

Our data indicate that microarray results have limited value in predicting immediate post-operative outcomes, but children with copy number variants should be included in future CHD research.