Pre-surgery urine metabolomics may predict late neurodevelopmental outcome in children with congenital heart disease
Luca Vedovelli,
Paola Cogo,
Elisa Cainelli,
Agnese Suppiej,
Massimo Padalino,
Maria Tassini,
Manuela Simonato,
Giovanni Stellin,
Virgilio P. Carnielli,
Giuseppe Buonocore,
Mariangela Longini
Affiliations
Luca Vedovelli
PCare Laboratory, Fondazione Istituto di Ricerca Pediatrica “Città della Speranza”, Corso Stati Uniti 4F, Padova, 35127, Italy
Paola Cogo
Division of Pediatrics, Department of Medicine, University of Udine, Piazzale Kolbe 4, Udine, 33100, Italy
Elisa Cainelli
Department of Developmental Psychology and Socialization, University of Padova, via Venezia 8, Padova, 35133, Italy
Agnese Suppiej
Department of Medical Sciences, Pediatric Section, University of Ferrara, via Aldo Moro 8, Cona, Ferrara, 44124, Italy
Massimo Padalino
Pediatric and Congenital Cardiovascular Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padova University Hospital, Via Giustiniani 3, Padova, 35128, Italy
Maria Tassini
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro, 2, Siena, 53100, Italy
Manuela Simonato
PCare Laboratory, Fondazione Istituto di Ricerca Pediatrica “Città della Speranza”, Corso Stati Uniti 4F, Padova, 35127, Italy; Corresponding author.
Giovanni Stellin
Pediatric and Congenital Cardiovascular Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padova University Hospital, Via Giustiniani 3, Padova, 35128, Italy
Virgilio P. Carnielli
Division of Neonatology, Department of Clinical Sciences, Polytechnic University of Marche and Azienda Ospedaliero-Universitaria Ospedali Riuniti, Via F.Corridoni 11, Ancona, 60123, Italy
Giuseppe Buonocore
Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, Siena, 53100, Italy
Mariangela Longini
Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, Siena, 53100, Italy
Background: From fetal life until cardiac surgery, complex congenital heart diseases (CHD) exhibit different hemodynamic and oxygenation patterns that can lead to alteration of the metabolic profile. We used a metabolomic approach to identify urine metabolic markers before cardiac surgery, aiming to define the physiology of patients with complex CHD and to contribute to predict their neurodevelopmental outcome. Methods: In a prospective, observational, single-center study we enrolled 28 patients with complex biventricular and univentricular CHD aged less than 5 years, on stable hemodynamic conditions, and with no genetic anomalies. We analyzed urine samples, collected at the induction of anesthesia, by 1H NMR spectroscopy. Profiles of 1H NMR spectra were submitted to unsupervised (principal component) and supervised (partial least squares-discriminant) multivariate analysis. Neurodevelopment was assessed by neuropsychological and adaptive functioning testing. Results: Principal components analysis divided CHD patients metabolic profiles in two distinct clusters (RED and BLACK). Metabolic profiles belonging to the RED cluster showed higher levels of accumulation of citric acid cycle intermediates and glucose compared to the profiles in the BLACK cluster, indicating a possible switching to anaerobic metabolism. Patients belonging to the RED cluster were significantly more prone to show an adverse neurodevelopment pattern (p = 0.01). Conclusions: The application of metabolomic analysis to CHD children permitted a deeper insight on their metabolic status that could help to obtain a better understanding of the physiological implications and to predict long-term neurodevelopmental outcome.
