Alterations in Metabolites Associated with Hypoxemia in Neonates and Infants with Congenital Heart Disease

(1) To measure the global shift in the metabolome in hypoxemic versus non-hypoxemic infants with congenital heart disease; (2) To identify metabolites and metabolic pathways that are altered in hypoxemia.

Analysis of serum samples obtained prior to cardiopulmonary bypass from 82 infants ≤120 days old with congenital heart disease requiring surgery at Children's Hospital Colorado. Infants were divided into groups based on pre-operative oxygen saturations: non-hypoxemic (>92%), mild hypoxemia (85-92%), and severe hypoxemia (<85%). Tandem mass spectrometry was used to analyze 165 targeted metabolites. Partial least squares discriminant analysis and t-tests were used to determine differences among metabolic profiles and individual metabolites respectively.

The broad metabolic fingerprint of neonates or older infants did not vary by degree of hypoxemia. There were 12 individual metabolites that differed between hypoxemic and non-hypoxemic neonates, including lower methylmalonic acid (p = 2.44 × 10^-4), glutamate (p = 0.001), and hypoxanthine (p = 0.003), and higher thymine (p = 8.67 × 10^-4) and myo-inositol (p = 0.014) seen in hypoxemic neonates. Individual metabolites did not vary significantly between older infants with or without hypoxemia.

We did not find evidence supporting global metabolic changes associated with cyanotic congenital heart disease in neonates or older infants. However, specific metabolites did discriminate between hypoxemic and non-hypoxemic neonates. These include methylmalonic acid, as well as several metabolites known to change in hypoxia-reoxygenation states (hypoxanthine) and chronic hypoxemic states (glutamate, thymine, myo-inositol) and may represent specific metabolic changes triggered by hypoxemia among neonates with cyanotic congenital heart disease.