Nasal Nitric Oxide as a Novel Biomarker for Assessing Risk of Impaired Neurodevelopment in Infants and Newborns with Congenital Heart Disease.

Nasal nitric oxide (nNO) is a non-invasive marker for predicting the risk of neurodevelopmental delays. We investigated whether nNO in infants with CHD undergoing congenital cardiac surgery could serve as a biomarker for assessing the risk of impaired neurodevelopment. Retrospective cohort study. Single center in a tertiary care children's hospital. A retrospective study was conducted on 63 CHD patients, 0-12 months old, who had cardiac bypass surgery in the 1st year of life and for whom nNO levels had been collected before surgery using the chemiluminescent CLDsp88 NO analyzer. Neurodevelopmental assessments in patients older than 1 year were retained for analysis. NO levels were dichotomized as normal or low based on previously established age-stratified norms. Multivariable regression analysis was conducted to examine possible confounders. CHD patients with low nNO exhibited significant neurodevelopmental delays (P < 0.001), cognitive delays (P = 0.0021), language delays (P < 0.001), and a trend toward motor delays (P = 0.034). Multivariable regression analysis incorporating various confounders as covariates (stroke, cardiac arrest, arrhythmia, seizures, genetic anomalies) supports a significant association between low nNO and cognitive delay (P = 0.011), language delay (P = 0.001), and any delays (P = 0.001). Our findings show that low nNO in newborns with CHD is significantly associated with impaired neurodevelopmental outcomes. These findings suggest nNO may serve as a biomarker to identify newborns with CHD who are at increased risk for adverse neurodevelopment. This may create opportunities for early intervention targeting a common factor underlying both low NO and worse neurodevelopmental outcomes.