The clinical impact of maternal weight on offspring health: lights and shadows in breast milk metabolome.

INTRODUCTION: Pre-pregnancy overweight and obesity, depending on maternal nutrition and metabolic state, can influence fetal, neonatal, and long-term offspring health, regarding cardio-metabolic, respiratory, immunological, and cognitive outcomes. Thus, maternal weight can act, through mechanisms not fully understood, on the physiology and metabolism of some fetal organs and tissues, to adapt themselves to the intrauterine environment and nutritional reserves. These effects can occur by modulating gene expression, neonatal microbiome, and through breastfeeding. AREAS COVERED: In this paper, we investigated the potential effects of metabolites found altered in breast milk (BM) of overweight/obese mothers, through an extensive review of metabolomics studies, and the potential short and long-term clinical effects in the offspring, especially overweight, glucose homeostasis, insulin resistance, oxidative stress, infections, immune processes, neurodevelopment. EXPERT OPINION: Metabolomics seems the ideal tool to investigate BM variation depending on maternal or fetal/neonatal factors. In particular, BM metabolome alterations according to maternal conditions were recently pointed out in cases of gestational diabetes, preeclampsia, intrauterine growth restriction and maternal overweight/obesity. In our opinion, even if BM is the food of choice in neonatal nutrition, the deepest comprehension of its composition in overweight/obese mothers could allow targeted supplementation, to improve offspring health and metabolic homeostasis.

Metabolomics and fetal-neonatal nutrition: between "not enough" and "too much".

Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases.

Breast Milk and COVID-19: From Conventional Data to "Omics" Technologies to Investigate Changes Occurring in SARS-CoV-2 Positive Mothers.

In this context of COVID-19 pandemic, great interest has been aroused by the potential maternal transmission of SARS-CoV-2 by transplacental route, during delivery, and, subsequently, through breastfeeding. Some open questions still remain, especially regarding the possibility of finding viable SARS-CoV-2 in breast milk (BM), although this is not considered a worrying route of transmission. However, in BM, it was pointed out the presence of antibodies against SARS-CoV-2 and other bioactive components that could protect the infant from infection. The aim of our narrative review is to report and discuss the available literature on the detection of anti-SARS-CoV-2 antibodies in BM of COVID-19 positive mothers, and we discussed the unique existing study investigating BM of SARS-CoV-2 positive mothers through metabolomics, and the evidence regarding microbiomics BM variation in COVID-19. Moreover, we tried to correlate metabolomics and microbiomics findings in BM of positive mothers with potential effects on breastfed infants metabolism and health. To our knowledge, this is the first review summarizing the current knowledge on SARS-CoV-2 effects on BM, resuming both "conventional data" (antibodies) and "omics technologies" (metabolomics and microbiomics).

The Human Breast Milk Metabolome in Overweight and Obese Mothers.

Pre-pregnancy body mass index (BMI) is a major relevance factor, since maternal overweight and obesity can impair the pregnancy outcome and represent risk factors for several neonatal, childhood, and adult conditions, including excessive weight gain, cardiovascular disease, diabetes mellitus, and even behavioral disorders. Currently, breast milk (BM) composition in such category of mothers was not completely defined. In this field, metabolomics represents the ideal technology, able to detect the whole profile of low molecular weight molecules in BM. Limited information is available on human BM metabolites differences in overweight or obese compared to lean mothers. Analyzing all the metabolomics studies published on Medline in English language, this review evaluated the effects that 8 specific types of metabolites found altered by maternal overweight and obesity (nucleotide derivatives, 5-methylthioadenosine, sugar-alcohols, acylcarnitine and amino acids, polyamines, mono-and oligosaccharides, lipids) can exert on the risk of offspring obesity development and other potentially associated health outcomes and complications. However, metabolites variations in samples collected from overweight and obese mothers and the potentially correlated effects highlighted below still need further investigations and should be confirmed in future metabolomics studies on larger samples. Finally, the positive or negative influence of maternal overweight and obesity on the offspring, potentially exerted by breastfeeding, should be analyzed in close correlation with maternal age, genetic and environmental factors, including diet, and taking into account the interactions occurring between BM metabolites and lactobiome. The evaluation of all the factors affecting BM metabolites in overweight and obese mothers can lead to the comprehensive description of such biofluid and the related effects on breastfed subjects, potentially highlighting personalized needs of BM supplementation or short- and long-term prevention strategies to optimize offspring health.

The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development.

Modified embryonic-fetal development resulting in low birth weight may lead to a reduced nephron endowment, hypertension and renal diseases in adulthood. Regarding the involvement of genetic factors, several environmental conditions may also contribute towards reducing the number of nephrons in the fetus and infant, subsequently constituting a health burden in later life. To date no methods of investigation for the early detection of a reduced nephron reserve are available. However, more structured studies should be implemented to investigate the role of angiotensin-converting enzyme inhibitors in managing proteinurias and glomerulosclerosis in children with renal conditions characterized by reduce nephron number and glomerular hypertrophic changes. In view of the current lack of specific methods of investigation and management, close monitoring of children and young adults at risk of reduced renal reserve should be carried out to enhance the early detection of potential changes in renal function.

Incidence of epilepsy in extremely low-birthweight infants (<1,000 g): a population study of central and southern Sardinia.

PURPOSE: With the development of intensive care, the survival of extremely low-birthweight (ELBW) infants (<1,000 g) has greatly improved. The aim of our study was to report the incidence of epilepsy after a follow-up of >7 years in a population of ELBW children, born in central and southern Sardinia between 1991 and 2000. METHODS: We analyzed data of 104 children. All infants had had serial cranial ultrasound echography (CUE) in the neonatal period and some also had magnetic resonance imaging (MRI). At last follow-up we evaluated the occurrence of epilepsy through a review of clinical charts and a structured telephone interview. RESULTS: In 11 (10.6%) of 104 of children we observed febrile seizures (FS). Epilepsy occurred in 9 (8.6%) of 104 ELBW children, and in these patients a frequent positive family history for epilepsy and/or FS was present. In four epilepsy patients CUE was highly pathologic, showing intraventricular hemorrhage (IVH) of grade IV and in two mildly abnormal (IVH of grade I-II). In three additional children with normal neonatal ultrasound scan, a later magnetic resonance imaging (MRI) study revealed lesions related to neonatal insult. DISCUSSION: In our ELBW population, epilepsy had an incidence clearly superior to that expected in infancy (8.6% vs. 0.6-0.8%). A frequent positive familiar history for epilepsy and/or FS suggests that a genetic predisposition may also play a role. Subjects with highly abnormal CUE are a subgroup with high risk for seizures; however, epilepsy can occur even with normal CUE.

A longitudinal 1H-NMR metabolomics analysis of urine from newborns with hypoxic-ischemic encephalopathy undergoing hypothermia therapy. Clinical and medical legal insights.

Perinatal asphyxia is an event affecting around four million newborns worldwide. The 0.5 to 2 per 1000 of full term asphyxiated newborns suffer from hypoxic-ischemic encephalopathy (HIE), which is a frequent cause of death or severe disability and, as consequence, the most common birth injury claim for obstetrics, gynaecologists, and paediatricians. Perinatal asphyxia results from a compromised gas exchange that leads to hypoxemia, hypercapnia, and metabolic acidosis. In this work, we applied a metabolomics approach to investigate the metabolic profiles of urine samples collected from full term asphyxiated newborns with HIE undergoing therapeutic hypothermia (TH), with the aim of identifying a pattern of metabolites associated with HIE and to follow their modifications over time. Urine samples were collected from 10 HIE newborns at birth, during hypothermia (48 hours), at the end of the therapeutic treatment (72 hours), at 1 month of life, and compared with a matched control population of 16 healthy full term newborns. The metabolic profiles were investigated by 1H NMR spectroscopy coupled with multivariate statistical methods such as principal component analysis and orthogonal partial least square discriminant analysis. Multivariate analysis indicated significant differences between the urine samples of HIE and healthy newborns at birth. The altered metabolic patterns, mainly originated from the depletion of cellular energy and homeostasis, seem to constitute a characteristic of perinatal asphyxia. The HIE urine metabolome changes over time reflected either the effects of TH and the physiological growth of the newborns. Of interest, the urine metabolic profiles of the HIE non-surviving babies, characterized by the increased excretion of lactate, resulted significantly different from the rest of HIE population.

Urinary 1H-NMR Metabolomics in the First Week of Life Can Anticipate BPD Diagnosis.

Despite the advancements in medical knowledge and technology, the etiopathogenesis of bronchopulmonary dysplasia (BPD) is not yet fully understood although oxidative stress seems to play a role, leading to a very demanding management of these patients by the neonatologist. In this context, metabolomics can be useful in understanding, diagnosing, and treating this illness since it is one of the newest omics science that analyzes the metabolome of an individual through the investigation of biological fluids such as urine and blood. In this study, 18 patients admitted to the Neonatal Intensive Care Unit of the Cagliari University Hospital were enrolled. Among them, 11 patients represented the control group and 7 patients subsequently developed BPD. A sample of urine was collected from each patient at 7 days of life and analyzed through 1H-NMR coupled with multivariate statistical analysis. The discriminant metabolites between the 2 groups noted were alanine, betaine, trimethylamine-N-oxide, lactate, and glycine. Utilizing metabolomics, it was possible to detect the urinary metabolomics fingerprint of neonates in the first week of life who subsequently developed BPD. Future studies are needed to confirm these promising results suggesting a possible role of microbiota and oxidative stress, and to apply this technology in clinical practice.

Impaired central arterial elasticity in young adults born with intrauterine growth restriction.

BACKGROUND: Intrauterine growth retardation and prematurity at birth constitute risk factors for future cardiovascular adverse events. Some previous reports have highlighted that subjects born preterm may develop peripheral arterial dysfunction. However, central (aortic) arterial distensibility has not yet been fully investigated in these subjects. METHODS: Sixty subjects were enrolled: thirty were high grade ex-preterm subjects (10 males [M] and 20 females [F], aged 17-28, mean 20.1±2.5 years). They were compared with 30 healthy, age-matched subjects born at term (C, 10 M and 20 F). Central aortic elasticity was assessed non-invasively by calculating two indexes derived from echocardiographic and blood pressure measures: aortic root distensibility and aortic stiffness index. RESULTS: Aortic distensibility was significantly lower (P<0.0001), and aortic stiffness index was significantly higher (P<0.0001) in former preterm individuals than in controls. The above stated indexes were correlated with birth weight (r=0.78, P<0.0001 and r=-0.41, P=0.02, respectively), as well as with gestational age (r=0.54, P=0.002 and r=-0.37, P=0.04, respectively). When excluding the influence of body mass index, intrauterine growth restriction - expressed as birth weight - remains the only determinant of impaired central arterial elasticity. CONCLUSIONS: Since aortic distensibility usually impairs in time, former preterm subjects appear to have a "vascular age" older than their healthy born at term peers. This finding may have important implications for cardiovascular morbidity in later life.

From ureteric bud to the first glomeruli: genes, mediators, kidney alterations.

The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.

Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS.

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3 days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.

Immunohistochemical markers of stem/progenitor cells in the developing human kidney.

The aim of this study was to better define, by immunohistochemistry, the molecular markers of renal stem/progenitor cells localized in the different niches of ten human preterm kidneys with gestational age ranging from 11 up to 25 weeks. Our data evidence the existence of multiple stem/progenitor pools in different zones of the human developing kidney that are characterized by different phenotypes: capsular stem cells were EMA (MUC1)+, MDM2+, Vimentin+ and Wnt1+; progenitors of the sub-capsular nephrogenic zone were MDM2+ and Wnt1+; cap mesenchymal cells were EMA (MUC1)+, CD15+, vimentin+, Wt1+, CD10+, Bcl2+, Wnt1+ and PAX2+; interstitial progenitor cells were Vimentin+, Wt1+ and α1Anti-tripsin+. Our data evidence the existence of multiple stem/progenitor cell pools in the fetal and neonatal human kidney. Progenitors of these different pools are characterized by a peculiar phenotype, indicating a different differentiation stage of these renal progenitors. A better knowledge of the molecular markers expressed by renal stem/progenitors might represent a relevant datum for researchers involved in renal regenerative medicine.

Metabolomics technology and their application to the study of the viral infection.

OBJECTIVE: In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. METHODS: The (1)H-NMR, UHPLC/MS/MS(2), UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. RESULTS: The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. CONCLUSIONS: The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.

High prevalence of interatrial septal aneurysm in young adults who were born preterm.

BACKGROUND: The cardiovascular vulnerability of young adults who were born preterm was first acknowledged over a decade ago. AIMS: (1) To examine the echocardiographic characteristics of a group of young adults born preterm with an extremely low birthweight (<1000 g; ex-ELBW) in comparison with healthy controls born at term (C); (2) to identify a correlation between the potential echocardiographic abnormalities detected in ex-ELBW and their anthropometric parameters, age, presence of respiratory distress, patency of ductus arteriosus, length of stay in Neonatal Intensive Care Unit. METHODS: Thirty-seven ex-ELBW (11 males, 26 females; mean age: 22.2 ± 1.8 years) were compared with 37 C (11 males, 26 females). Both groups underwent standard mono- and bi-dimensional transthoracic echocardiogram with color Doppler. RESULTS: No statistically significant differences were detected between the two groups regarding mono-dimensional echocardiography or Doppler measurements (p = ns). Conversely, a statistically significant difference was observed between the prevalence of interatrial septal aneurysm (ASA) in ex-ELBW compared to C (p = 0.0016). A significant association was likewise observed between ASA and the presence of both respiratory distress at birth (p < 0.05) and patency of the ductus arteriosus (p < 0.05). CONCLUSIONS: A significant prevalence of ASA was detected in ex-ELBW subjects compared to C, underlining a probable correlation with respiratory distress and patent ductus arteriosus. In view of the association between ASA and stroke in young adults devoid of other cerebrovascular risk factors, this unexpected observation suggests that all ex-preterm subjects should undergo transthoracic or transesophageal echocardiographic examination with the aim of detecting this potentially emboligenic cardiac abnormality.

Metabolomics in neonatal life.

Metabolomics (or metabonomics) is based on the systematic study of the complete set of metabolites in a biological sample and is considered the most innovative of the 'omics' sciences. The metabolome is currently regarded as the 'new clinical biochemistry' it is the most predictive phenotype, through consideration of epigenetic differences. Among more than 5000 papers listed in PubMed on this topic in the last three years, less than 60 refer to neonatal life. Aim of this review is to present the clinical applications of metabolomics in neonatology, including results of recent studies performed in experimental models and newborns.

Urinary NGAL and hematic ADMA levels: an early sign of cardio-renal syndrome in young adults born preterm?

BACKGROUND: Prematurity at birth is a known risk factor for the development of an early chronic renal disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well established biomarker of kidney injury, while high blood levels of asymmetric dimethylarginine (ADMA) are associated with the future development of adverse cardiovascular events and cardiac death. AIMS: (1) to verify the presence of statistically significant differences between urinary NGAL and hematic ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) (2) to seek correlations between NGAL and ADMA levels, which would indicate the presence of an early cardio-renal involvement in ex-ELBW. METHODS: Twelve ex-ELBW subjects (six males and six female, mean age: 23.9 ± 3.2 years) were compared with 12 C (six males and six female). Urinary NGAL and hematic ADMA levels were assessed. RESULTS: Urinary NGAL levels were higher in ex- ELBW subjects compared to C (p < 0.05), as well as hematic ADMA concentrations (p < 0.05). A statistically significant correlation was found between urinary NGAL and ADMA (r = -0.60, p < 0.04). CONCLUSIONS: Our preliminary findings support the hypothesis that in ex-ELBW subjects the development of an early chronic kidney disease contributes towards inducing an increase in the atherosclerotic process and in the risk of future adverse cardiovascular events.

Soluble CD14 subtype (sCD14-ST) presepsin in critically ill preterm newborns: preliminary reference ranges.

Soluble CD14 subtype (sCD14-ST), also named presepsin, is a 13 kDa truncated form of soluble CD14 (sCD14), consisting of 64 amino acid residues. Systemic inflammation and sepsis are characterized by an early, significant increase in sCD14-ST presepsin blood concentration and thus, this small polypeptide has been proposed as a novel, reliable biomarker for the management of sepsis. We enrolled twenty-six consecutive non-septic preterm newborns with gestational age (GA) between 26 and 36 weeks) admitted to NICU after the first day of life for various severe diseases. sCD14-ST presepsin was measure on whole blood samples by a rapid commercial available chemiluminescent enzyme immunoassay (CLEIA) based on a non-competitive CLEIA. The mean sCD14-ST presepsin blood level in 26 preterm newborns was 643.1 ng/L, with a standard deviation (SD) of 303.8 ng/L; the median value was 578 ng/L. Our results clearly suggest no correlation between GA and sCD14-ST presepsin blood level between 26 and 36 weeks and thus it is reasonable to adopt a unique reference range for preterm newborns.

Significant QT interval prolongation and long QT in young adult ex-preterm newborns with extremely low birth weight.

BACKGROUND: The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing upward trend, despite the possibility of neuro-cerebral consequences in later life. To date, scarce information is available on the effect of extreme prematurity on cardiovascular system. AIM: To verify the presence of standard echocardiographic and ECG alterations in ex-ELBW young healthy adults. METHOD: A color Doppler echocardiogram and an ECG were performed on 24 ex-ELBW (4 males and 20 females; mean: 23.2 ± 3.3 years), compared with 24 healthy subjects born at term (C). ECG parameters examined: PR, QT, QT(c), and QT dispersion (QT(d)). Gestational age, birth weight, and duration of stay in neonatal intensive care unit were obtained from clinical records. RESULTS: Transthoracic echocardiography did not reveal differences between ex-ELBW and C, while a significant difference was displayed by ex-ELBW with regard to PR (141.5 ± 13.4 ms vs. 164.2 ± 24.0 ms, p < 0.0003), QT(c) (417.0 ± 23.6 ms vs. 369.9 ± 19.5 ms, p =0.00001), and QT(d) (30.4 ± 14.1 ms vs. 24.6 ± 8.2 ms, p < 0.00001). In two patients (8.3%), QT(c) exceeded the upper limit of normal range. A statistically significant inverse correlation was observed between QT(c) and gestational age (r = -0.67, p < 0.0003). CONCLUSIONS: QT(c) and QT(d) in ex-ELBW were found to be at the upper limit of normal range and correlated with gestational age and birth weight; in two cases, QT(c) exceeded the upper limit. This study, irrespective of the pathophysiological mechanism involved, underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval. SUMMARY: QT(c) and QT(d) in young adults previously born preterm with an ELBW (401-1000 g) were generally found to be at the upper limit of normal range and correlated with gestational age and birth weight. This finding underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval.

Clinical metabolomics and urinary NGAL for the early prediction of chronic kidney disease in healthy adults born ELBW.

BACKGROUND: Clinical metabolomics is a recent "omic" technology which is defined as a global holistic overview of the personal metabolic status (fingerprinting). This technique allows to prove metabolic differences in different groups of people with the opportunity to explore interactions such as genotype-phenotype and genotype-environment type, whether normal or pathological. AIM: To study chronic kidney injury 1) using urine metabolomic profiles of young adults born extremely low-birth weight (ELBW) and 2) correlating a biomarker of kidney injury, urinary neutrophil gelatinase-associated lipocalin (NGAL), in order to confirm the metabolomic injury profile. METHOD: Urine samples were collected from a group of 18 people (mean: 24-year-old, std: 4.27) who were born with ELBW and a group of 13 who were born at term appropriate for gestational age (AGA) as control (mean 25-year-old, std: 5.15). Urine samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Urine NGAL (uNGAL) was measured using ARCHITECT (ABBOTT diagnostic NGAL kit). RESULTS: With a multivariate approach and using a supervised analysis method, PLS-DA, (partial least squares discriminant analysis) we could correlate ELBW metabolic profiles with uNGAL concentration. Conversely, uNGAL could not be correlated to AGA. CONCLUSIONS: This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status of exELBW. This was confirmed by the use of uNGAL as a biomarker which may predict a subclinical pathological process in the kidney such as chronic kidney disease.