(874) nNO Is a Biomarker of Neurodevelopmental Impairment for Infants With Congenital Heart Defects

Introduction: Nasal nitric acid (nNO) is an intracellular messenger and neurotransmitter produced within the nasal mucosa that regulates ciliary motility. We previously reported that a low nNo level is associated with increased respiratory support after cardiopulmonary bypass and decreased right ventricular function. We analyzed the correlation between nNO level and neurodevelopmental outcomes in infants who underwent cardiac surgery within the first year of life to test the hypothesis that nNO can be utilized as a non-invasive biomarker for the neurodevelopmental outcomes of patients with congenital heart disease (CHD).

Methods: With IRB approval, we enrolled infants (ages 0-12 months) from the UPMC Children’s Hospital of Pittsburgh. With parental written informed consent, nNO values were acquired using a CLD 88sp NO analyzer (Eco Physics AG, Ann Arbor, Michigan) according to the manufacturer’s protocol. All values were obtained via a low continuous sampling suction at a rate of 0.3L/min from each naris during tidal breathing. The neurodevelopment assessements utilized were dependent on age and included Bayley Scales of Infant and Toddler Development III, Differential Ability Scales-II (DAS-II), or Wechsler Intelligence Scale for Children - Fourth and Fifth editions. Statistical analysis was performed using the R statistical software, version 4.1.0, to compare the neurodevelopmental outcomes with low or normal nNO levels.

Results: 64 individuals with CHD who required cardiac surgery within the first year of life were enrolled for the analysis. Patients above the age of 1 without CHD and/or without a neurodevelopmental assessment at or after 1 year of age were excluded. Low nNo level is associated with overall neurodevelopment delay (P=0.00014), cognitive delays (P=0.002), speech delays (P=0.0006), and had a trend to be associated with motor delays ( P= 0.04). For the confounding factors, cardiac arrest, ECMO support, strokes, and seizures before neurodevelopmental assessment are associated with motor delays (P=0.004, 0.02, 0.035, 0.006). Cardiac arrest, ECMO support, and seizure are associated with cognitive delays (P=0.03, 0.036, 0.005).

Conclusions: Low nNo level in infants with CHD is associated with poor neurodevelopmental outcomes.