http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2014; 27(S2): 1–7 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.954786 ORIGINAL ARTICLE Urinary metabolomics (GC-MS) reveals that low and high birth weight infants share elevated inositol concentrations at birth Luigi Barberini 1 , Antonio Noto 2 , Claudia Fattuoni 3 , Dmitry Grapov 4 , Andrea Casanova 5 , Gianni Fenu 6 , Mauro Gaviano 6 , Roberta Carboni 2 , Giovanni Ottonello 2 , Maurizio Crisafulli 2 , Vassilios Fanos 2 , and Angelica Dessı ` 2 1 Department of Public Health Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy, 2 Department of Surgical Sciences, Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari, Italy, 3 Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy, 4 NIH West Coast Metabolomics Center, University of California Davis, Davis, CA, USA, 5 Department of Medical Sciences ‘‘M. Aresu‘‘, University of Cagliari, Cagliari, Italy, and 6 Department of Mathematics and Informatics, University of Cagliari, Cagliari, Italy Abstract Objective: Metabolomics is a new ‘‘omics’’ platform aimed at high-throughput identification, quantification and characterization of small molecule metabolites. The metabolomics approach has been successfully applied to the classification different physiological states and identification of perturbed biochemical pathways. The purpose of the current investigation is the application of metabolomics to explore biological mechanisms which may lead to the onset of metabolic syndrome in adulthood. Methods: We evaluated differences in metabolites in the urine collected within 12 hours from 23 infants with IUGR (IntraUterine Growth Restriction), or LGA (Large for Gestational Age), compared to control infants (10 patients defined AGA: Appropriate for Gestational Age). Urinary metabolites were quantified by GC-MS and used to highlight similarities between the two metabolic diseases and identify metabolic markers for their predisposition. Quantified metabolites were analyzed using a multivariate statistics coupled with receiver operator characteristic curve (ROC) analysis of identified biomarkers. Results: Urinary myo-inositol was the most important discriminant between LGA + IUGR and control infants, and displayed an area under the ROC curve ¼ 1. Conclusion: We postulate that the increase in plasma and consequently urinary inositol may constitute a marker of altered glucose metabolism during fetal development in both IUGR and LGA newborns. Keywords GC-MS, inositol, IUGR, metabolomics, OSC-PLS-DA History Received 2 Revised 2 Accepted 22 Published online 222 Introduction Progress in new systems biology methodologies which study metabolic alterations of aetiological processes at the origin of many pathologies are becoming more important. In particular, metabolomics, a new analytical technique defined as the study of the complex system of metabolites, is capable of describing the biochemical phenotype of a biological system [1]. At present, attention is being focused mainly on the formu- lation of new hypotheses concerning the biological mechan- isms that lead to the onset of diabetes and metabolic syndrome in adulthood. Metabolomics has been recently applied to identify several biomarkers (including myo- inositol) for mechanisms which may lead to infantile obesity and the subsequent onset of metabolic diseases [2]. Comprehensive analysis of changes in metabolic profiles during fetal and neonatal life may present an important reference for understanding fundamental biochemical mech- anisms, which may lead to consequent metabolic alterations. Previous investigations have demonstrated that fetal malnu- trition, whether excessive (overnutrition) or insufficient (hyponutrition), can permanently alter the fetus’s metabolic state and increase the risk of chronic diseases later in life. This suggests that neonates with intrauterine growth retard- ation (IUGR) and large-for-gestational-age (LGA) neonates, despite opposing metabolic characteristics during fetal life, at birth may exhibit a common condition of reduced glucose tolerance which can persist into adulthood, and consequently leads to an increased risk of developing metabolic syndrome related pathologies such as obesity and type 2 diabetes [3]. The current investigation compared urine metabolic profiles of IUGR and LGA neonates to controls to identify metabolic similarities between IUGR and LGA and to identify markers for biochemical alterations during fetal life which may lead to the onset of metabolic syndrome in adulthood. Address for correspondence: Prof. Vassilios Fanos, Director Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, University of Cagliari, Cagliari 09124, Italy. Tel: +3907051093403 (direct); +3907051093438 (NICU). E-mail: vafanos@tin.it; vafanos@tiscali.it 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Archivio istituzionale della ricerca - Università di Cagliari