Open Access

ARTICLE

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

by Evan Pagano¹, Benjamin Frank¹, James Jaggers², Mark Twite³, Tracy T. Urban⁴, Jelena Klawitter^2,#, Jesse Davidson^1,#,*

1 University of Colorado, Department of Pediatrics, Aurora, CO 80045, USA
2 University of Colorado, Department of Surgery, Aurora, CO 80045, USA
3 University of Colorado, Department of Anesthesiology, Aurora, CO 80045, USA
4 Children’s Hospital Colorado Research Institute, Aurora, CO 80045, USA
# Dr. Klawitter and Dr. Davidson contributed equally to the senior authorship of this manuscript

* Corresponding Author: Jesse Davidson. Email:

Congenital Heart Disease 2020, 15(4), 251-265. https://doi.org/10.32604/CHD.2020.012219

Received 18 June 2020; Accepted 30 July 2020; Issue published 07 September 2020

Abstract

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 preoperative 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.

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