Alessandra Reali

A metabolomic study of preterm human and formula milk by high resolution NMR and GC/MS analysis: preliminary results

Objective: The aim of the present study was to investigate the metabolic profile of preterm human breast milk (HBM) by using a metabolomic approach. Methods: NMR spectroscopy and GC/MS were used to analyze the water-soluble and lipid fractions extracted from milk samples obtained from mothers giving birth at 26–36 weeks of gestation. For the sake of comparison, preterm formula milk was also studied. Results: The multivariate statistical analysis of the data evidenced biochemical variability both between preterm HBM and commercial milk and within the group of HBM samples. Conclusions: The preliminary results of this study suggest that metabolomics may provide a promising tool to study aspects related to the nutrition and health of preterm infant.

Clinical impact of human breast milk metabolomics.

Metabolomics is a research field concerned with the analysis of metabolome, the complete set of metabolites in a given cell, tissue, or biological sample. Being able to provide a molecular snapshot of biological systems, metabolomics has emerged as a functional methodology in a wide range of research areas such as toxicology, pharmacology, food technology, nutrition, microbial biotechnology, systems biology, and plant biotechnology. In this review, we emphasize the applications of metabolomics in investigating the human breast milk (HBM) metabolome. HBM is the recommended source of nutrition for infants since it contains the optimal balance of nutrients for developing babies, and it provides a range of benefits for growth, immunity, and development. The molecular mechanisms beyond the inter- and intra-variability of HBM that make its composition unique are yet to be well-characterized. Although still in its infancy, the study of HBM metabolome has already proven itself to be of great value in providing insights into this biochemical variability in relation to mother phenotype, diet, disease, and lifestyle. The results of these investigations lay the foundation for further developments useful to identify normal and aberrant biochemical changes as well as to develop strategies to promote healthy infant feeding practices.

Perinatal nutrient restriction reduces nephron endowment increasing renal morbidity in adulthood: A review

Perinatal malnutrition has been included among the causes of renal disease in adulthood. Here, we consider the relationships between early supply of specific nutrients (such as protein, fat, vitamins and electrolytes) and renal endowment. Prenatal and postnatal nutrition mismatch is also discussed. In addition, this article presents the role of nutrition of both mothers and pre-term infants on nephron endowment, with final practical considerations.

Individualized fortification of breast milk in 41 Extremely Low Birth Weight (ELBW) preterm infants.

BACKGROUND The use of breast milk presents numerous early and long-term advantages for ELBW preterms. However, breast milk without fortification does not cover the high nutritional needs of such patients. The aim of our study was to assess the effect of individualized fortification of breast milk on the growth of ELBWs hospitalized in a neonatal intensive care unit (NICU). METHODS Retrospective single-center observational study. RESULTS We assessed the growth of 41 consecutive ELBWs (21 females, 20 males) with gestational ages between 23 and 30 weeks (mean GA 26.31±1.8) fed with breast milk in an individualized way. The rate of growth as the mean weight increase with breast milk fortification was 16.04±3.13 g/kg/day, more than the growth of the fetus in the uterus (~15 g/kg/day). This result was confirmed also among the ELBWs of lower GA. However, only 24.4% of all the ELBWs at the time of discharge from the NICU presented an appropriate weight for their gestational age. No cases of Necrotizing Enterocolitis (NEC) were observed. CONCLUSIONS Despite high growth velocity, the ELBWs failed to remain in the same percentiles of birth and, at discharge, only 27.7% had a weight of >10 centiles. Further studies are needed to improve growth during early critical phases of development.

Role of rHuEpo on blood transfusions in preterm infants after the fifteenth day of life.

The specific aim of the study was to assess the safety and efficacy of recombinant human erythropoietin (rHuEpo) in reducing the need for blood transfusions in preterm infants after the 15th day of life. Between 1 October 1994 and 1 October 1995, 107 preterm infants, gestational age < or = 34 weeks, were admitted to the Neonatal Intensive Care Unit and received rHuEpo subcutaneously, 900 U/kg week-1, 3 times weekly, supplemented with iron and vitamin E. Treatment was started at 8 days of life and lasted from a minimum of 6 weeks to a maximum of 3 months. A total of 116 preterm infants of the same gestational age, admitted to the Neonatal Intensive Care Unit from 1 January 1992 to 31 December 1992, served as controls. Entry criteria were gestational age < or = 34 weeks and no major congenital malformation. There were no differences in routine care between the two groups. Hematological measurements and transfusion requirements were followed during therapy. The infants were divided into two groups according to birth weight (< 1500 g and > or = 1500 g), and for each group the number of patients who received blood transfusions and when blood transfusions occurred, before or after the 15th day of life, was recorded. There was a statistically significant difference only for transfusions carried out after the 15th day of life (p < 0.002). No adverse effects attributable to rHuEpo during the treatment were noted. The results indicate that early rHuEpo treatment, in combination with iron supplements, is effective in reducing the need for blood transfusions in preterm infants after the 15th day of life.

“Omics” in Human Colostrum and Mature Milk: Looking to Old Data with New Eyes

Human Milk (HM) is the best source for newborn nutrition until at least six months; it exerts anti-inflammatory and anti-infective functions, promotes immune system formation and supports organ development. Breastfeeding could also protect from obesity, diabetes and cardiovascular disease. Furthermore, human colostrum (HC) presents a peculiar role in newborn support as a protective effect against allergic and chronic diseases, in addition to long-term metabolic benefits. In this review, we discuss the recent literature regarding “omics” technologies and growth factors (GF) in HC and the effects of pasteurization on its composition. Our aim was to provide new evidence in terms of transcriptomics, proteomics, metabolomics, and microbiomics, also in relation to maternal metabolic diseases and/or fetal anomalies and to underline the functions of GF. Since HC results are so precious, particularly for the vulnerable pre-terms category, we also discuss the importance of HM pasteurization to ensure donated HC even to neonates whose mothers are unable to provide. To the best of our knowledge, this is the first review analyzing in detail the molecular pattern, microbiota, bioactive factors, and dynamic profile of HC, finding clinical correlations of such mediators with their possible in vivo effects and with the consequent impact on neonatal outcomes.

Multipotent stem cells of mother's milk

In recent years the presence of stem cells (hBSCs: human breastmilk-derived stem cells) and epithelial progenitors has been demonstrated in mother’s milk (MM). Stem cells present in samples of fresh MM exhibit a high degree of vitality and this makes possible the performance of cell cultures and to evaluate the differentiation capacity of the hBSCs. The most important datum that expresses the enormous potential of the use of MM stem cells is the presence of a cell population capable of differentiating into the three mesoderm, endoderm and ectoderm lines. The small number of studies and MM samples analyzed and the different sampling methods applied suggest standardization in the collection, analysis and culture of MM in future studies, in consideration of the well-known extreme variability of MM composition, also from the standpoint of cells. The analysis of literature data confirms the uniqueness of MM and its enormous potential. Proceedings of the 2 nd International Course on Perinatal Pathology (part of the 11 th International Workshop on Neonatology · October 26 th -31 st , 2015) · Cagliari (Italy) · October 31 st , 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

Breast milk stem cells: four questions looking for an answer

The finding of stem/progenitor cells in the maternal milk and the discovery of their multilineage potential, associated with some evidence regarding the ability of maternal cells to cross the gastrointestinal barrier and integrate into the organs of the breastfed neonate, has opened an intriguing debate, regarding the strict relationship between mother and son in the postnatal period. In particular, thanks to the discovery of the presence in high quantities of mammary stem cells, a new vision of maternal milk is emerging, in which breastfeeding appears as an unique occasion for reinforcing the physiological development of the newborn, putting all the formulas at a different level of relevance for the neonate. In this contribution the authors try to give an answer to the following 4 questions: is there heterogeneity and a hierarchy among breast milk stem cells? can stem cells present in breast milk enter into the newborn organism? can breast milk stem cells integrate in the neonatal organs and differentiate toward different tissues, including neurons and neuroglia? could metabolomics be useful for the study of stem cells in the human milk? Proceedings of the 2 nd International Course on Perinatal Pathology (part of the 11 th International Workshop on Neonatology · October 26 th -31 st , 2015) · Cagliari (Italy) · October 31 st , 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

Human breast milk stem cells: a new challenge for perinatologists

The lactating mammary gland contains a stem cells population with multilineage potentialities. Recently it was also shown that breast milk contains a heterogeneous population of stem cells that have the potential to differentiate in vitro , under the control of specific differentiation conditions, into mammary epithelial as well as into adipogenic, chondrogenic and osteogenic cell lineages. While the different types of cells present in the milk is known, what is less understood is the proportion of different milk cell types, their significance for the mother and the infant and factors influencing them. In this manuscript we summarize some of the latest knowledge from in vivo and in vitro investigations on breast milk stem cells, we discuss their potential functions and applications and we present some of our preliminary data obtained in fresh human breast milk cells. Proceedings of the 2 nd International Course on Perinatal Pathology (part of the 11 th International Workshop on Neonatology · October 26 th -31 st , 2015) · Cagliari (Italy) · October 31 st , 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

The small intestinal mucosa and its stem cells

In the first part of this review a brief summary of the embryology and histology of the gastrointestinal tract is provided. In the second part intestinal stem cells (ISCs) are discussed. Several signaling pathways play a crucial role in the crypt base in the regulation of ISC proliferation and self-renewal; Wnt, Notch, BMP, Ephrin, JAK/STAT1, PTEN, AKT, PI3K and many more. Numerous investigators are involved in studying the location, number, and behavior of ISCs within the base of the intestinal crypts. Several markers are espressed by ISCs. Among these, Leucine-rich-repeat-containing G-protein-coupled receptor-5 (Lgr5), Sox9, Prominin-1, DCAMKL-1, EphB2, p-PTEN, p-AKT, Fgfr3, m-TER, and CD44. Stem cell therapy has shown promise for the treatment of some diseases characterized by tissue damage with ischemic and inflammatory lesions like inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Proceedings of the 2 nd International Course on Perinatal Pathology (part of the 11 th International Workshop on Neonatology · October 26 th -31 st , 2015) · Cagliari (Italy) · October 31 st , 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano