  Citation: Esturau-Escofet, N.; Rodríguez de San Miguel, E.; Vela-Amieva, M.; García-Aguilera, M.E.; Hernández-Espino, C.C.; Macias-Kauffer, L.; López-Candiani, C.; Naveja, J.J.; Ibarra-González, I. A Longitudinal 1 H NMR-Based Metabolic Profile Analysis of Urine from Hospitalized Premature Newborns Receiving Enteral and Parenteral Nutrition. Metabolites 2022, 12, 255. https://doi.org/10.3390/ metabo12030255 Academic Editor: Dae Young Lee Received: 8 February 2022 Accepted: 10 March 2022 Published: 17 March 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). metabolites H OH OH Article A Longitudinal 1 H NMR-Based Metabolic Profile Analysis of Urine from Hospitalized Premature Newborns Receiving Enteral and Parenteral Nutrition Nuria Esturau-Escofet 1,† , Eduardo Rodríguez de San Miguel 2,† , Marcela Vela-Amieva 3,† , Martha E. García-Aguilera 1 , Circe C. Hernández-Espino 1 , Luis Macias-Kauffer 4 , Carlos López-Candiani 5 , José J. Naveja 1 and Isabel Ibarra-González 6, * 1 Instituto de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; esturau.nuria@gmail.com (N.E.-E.); q.martha.garcia@gmail.com (M.E.G.-A.); circas0310@gmail.com (C.C.H.-E.); navejaromero@gmail.com (J.J.N.) 2 Departamento de Química Analítica, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; erdsmg@unam.mx 3 Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico; mvelaa@pediatria.gob.mx 4 Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México/Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City 04809, Mexico; luisrmacias@gmail.com 5 Departamento de Neonatología, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico; clopezcandiani@gmail.com 6 Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico * Correspondence: icig@servidor.unam.mx † These authors contributed equally to this work. Abstract: Preterm newborns are extremely vulnerable to morbidities, complications, and death. Preterm birth is a global public health problem due to its socioeconomic burden. Nurturing preterm newborns is a critical medical issue because they have limited nutrient stores and it is difficult to establish enteral feeding, which leads to inadequate growth frequently associated with poor neurodevelopmental outcomes. Parenteral nutrition (PN) provides nutrients to preterm newborns, but its biochemical effects are not completely known. To study the effect of PN treatment on preterm newborns, an untargeted metabolomic 1 H nuclear magnetic resonance (NMR) assay was performed on 107 urine samples from 34 hospitalized patients. Multivariate data (Principal Component Analysis, PCA, Orthogonal partial least squares discriminant analysis OPLS-DA, parallel factor analysis PARAFAC-2) and univariate analyses were used to identify the association of specific spectral data with different nutritional types (NTs) and gestational ages. Our results revealed changes in the metabolic profile related to the NT, with the tricarboxylic acid cycle and galactose metabolic pathways being the most impacted pathways. Low citrate and succinate levels, despite higher glucose relative urinary concentrations, seem to constitute the metabolic profile found in the studied critically ill preterm newborns who received PN, indicating an energetic dysfunction that must be taken into account for better nutritional management. Keywords: prematurity; enteral feeding; parenteral nutrition; 1 H NMR-based metabolic profile; chemometric analysis 1. Introduction Preterm birth is defined as any birth before 37 completed weeks of gestation. Preterm infants are extremely vulnerable to a range of morbidities, complications, and death [1]. The World Health Organization (WHO) has estimated that preterm birth causes one million neonatal deaths annually [2], accounting for 75% of perinatal mortality and more than Metabolites 2022, 12, 255. https://doi.org/10.3390/metabo12030255 https://www.mdpi.com/journal/metabolites