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

OBJECTIVES: (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.

STUDY DESIGN: 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.

RESULTS: 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.

CONCLUSIONS: 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.