Proteomic analysis of exosomes derived from human mature milk and colostrum of mothers with term, late preterm, or very preterm delivery.

The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week of gestation with the differentiation of neural progenitor cells and extends at least until late adolescence, possibly for life. One of the defects of this development is that we know very little about the signals that modulate this sequence of events. The first 3 years of life, during breastfeeding, is one of the critical periods in brain development. In these first years of life, it is believed that neurodevelopmental problems may be the molecular causes of mental disorders. Therefore, we herein propose a new hypothesis, according to which the chemical signals that could modulate this entire complex sequence of events appear in this early period, and the molecular level study of human breast milk and colostrum of mothers who give birth to children in different gestation periods could give us information on proteins influencing this process. In this work, we collected milk and colostrum samples (term, late preterm and moderate/very preterm) and exosomes were isolated. The samples of exosomes and complete milk from each fraction were analyzed by LC-ESI-MS/MS. In this work, we describe proteins in the different fractions of mature milk and colostrum of mothers with term, late preterm, or very preterm delivery, which could be involved in the regulation of the nervous system by their functions. We describe how they differ in different types of milk, paving the way for the investigation of possible new neuroregulatory pathways as possible candidates to modulate the nervous system.

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System.

Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.

[Influence of donor profile on pre and post-pasteurization bacteriology of donated human milk]. / Influencia del perfil de las donantes en la bacteriología pre- y pospasteurización de la leche humana donada.

Introduction: Introduction: breastfeeding is the gold standard for infant's nutrition. Human milk bank is an essential tool to guarantee availability and safety in those situations when breastfeeding is not an option. The manipulation during the extraction of the human milk by the donors is a critical point to ensure an adequate microbiological safety. Therefore, knowing the bacterial flora that prevails in donated milk is essential to draw conclusions that can lead to taking measures in the management of the bank. Objectives: to analyze the prevalence of microorganisms in milk samples donated to the milk bank and how the bacterial flora behaves according to the profile of the donors and the donor milk circuits. Methods: the present work is a retrospective descriptive observational study that analyzes characteristics and the positive microbiological results within our milk bank samples from June 1, 2016 to December 31, 2020. All milk bank donors voluntarily signed an informed consent that authorizes the use of data to investigation. Results: during the study period, a total of 1,587 liters of raw milk were donated by 266 women, highlighting that, despite the SARS-CoV-2 virus pandemic, 2020 has been the year in which more volume of milk has been dispensed. The results show that 221 batches had at least one positive microbiological isolation (149 of them were before and 46 after pasteurization). Pre and post-pasteurization rate varies over the years with a decrease in the pre-pasteurization discard rate (3,9%) and increase in the post-pasteurization rate (5,3%). The most frequently isolated germs found in pre-pasteurization cultures were gram positive cocci and Enterobacter and a decrease in the positivity to S. aureus after establishing an eradication protocol. In post-pasteurization cultures, the most commonly found germs are Bacillus. Regarding the donor's profile, it was found a non statistically significant way that those women with the highest donation volume and/or admission of their offspring in Neonatology were associated with higher frequency of positive cultures. Conclusions: bacteriological analysis of milk samples is an essential part of quality control for a milk bank. Our results reflect a good extraction system and transportation, as well as good training from the bank's professionals. Nevertheless, improvement of processes is necessary to reduce the rate of contamination and the amount of discarded milk.

Introducción: Introducción: la leche humana es el patrón oro en la nutrición de los neonatos. Por ello, los bancos de leche se convierten en elementos esenciales para garantizar su disponibilidad y seguridad cuando la leche materna no está disponible. La manipulación que se realiza de la leche es un punto crítico para asegurar la seguridad microbiológica de las muestras. Por ello, analizar la flora de la leche donada es fundamental para tomar medidas de mejora de los bancos de leche. Objetivos: analizar los resultados microbiológicos positivos en un banco de leche humana entre las muestras de leche cruda donadas y tras su pasteurización y evaluar si existe relación entre los aislamientos, el perfil de la donante y los circuitos de leche donada. Métodos: estudio observacional descriptivo que analiza las características de la leche donada y los resultados microbiológicos positivos de muestras de leche donadas en nuestro banco desde junio de 2016 hasta diciembre de 2020. Todas las donantes firmaron un consentimiento informado. Resultados: durante el período de estudio fueron donados 1587 litros de leche cruda por 266 mujeres destacando que, a pesar de la pandemia, 2020 ha sido el año en el que más volumen se ha dispensado (280 L). Se obtuvieron 221 lotes de leche con al menos un aislamiento microbiológico positivo (14,2 % total), de ellos 149 previos y 46 posteriores a la pasteurización. La tasa de descarte pre y pospasteurización es variable a lo largo de los años con descenso en 2020 prepasteurización (3,9%) e incremento pospasteurización (5,3%). Los gérmenes más frecuentemente aislados fueron cocos grampositivos, seguidos por Enterobacterias prepasteurización detectándose un descenso en la positividad a S. aureus tras establecerse un protocolo de erradicación. En las muestras pospasteurización predomina el género Bacillus. Se ha encontrado una relación aunque no estadísticamente significativa (p > 0,05) entre mujeres con mayor volumen de donación y/o ingreso de su hijo/a en Neonatología y una mayor frecuencia cultivos positivos. Conclusiones: el análisis bacteriológico de las muestras es parte fundamental del control de calidad. Nuestros resultados traducen una buena sistemática de extracción y transporte, así como un buen entrenamiento de los profesionales del banco. No obstante, es necesario mejorar los procesos para reducir la tasa de contaminación y la cantidad de leche desechada.

Influencia del perfil de las donantes en la bacteriología pre- y pospasteurización de la leche humana donada / Influence of donor profile on pre and post-pasteurization bacteriology of donated human milk

Introducción: la leche humana es el patrón oro en la nutrición de los neonatos. Por ello, los bancos de leche se convierten en elementos esenciales para garantizar su disponibilidad y seguridad cuando la leche materna no está disponible. La manipulación que se realiza de la leche es un punto crítico para asegurar la seguridad microbiológica de las muestras. Por ello, analizar la flora de la leche donada es fundamental para tomar medidas de mejora de los bancos de leche. Objetivos: analizar los resultados microbiológicos positivos en un banco de leche humana entre las muestras de leche cruda donadas y tras su pasteurización y evaluar si existe relación entre los aislamientos, el perfil de la donante y los circuitos de leche donada. Métodos: estudio observacional descriptivo que analiza las características de la leche donada y los resultados microbiológicos positivos de muestras de leche donadas en nuestro banco desde junio de 2016 hasta diciembre de 2020. Todas las donantes firmaron un consentimiento informado. (AU)

Introduction: breastfeeding is the gold standard for infant’s nutrition. Human milk bank is an essential tool to guarantee availability and safety in those situations when breastfeeding is not an option. The manipulation during the extraction of the human milk by the donors is a critical point to ensure an adequate microbiological safety. Therefore, knowing the bacterial flora that prevails in donated milk is essential to draw conclusions that can lead to taking measures in the management of the bank. Objectives: to analyze the prevalence of microorganisms in milk samples donated to the milk bank and how the bacterial flora behaves according to the profile of the donors and the donor milk circuits. Methods: the present work is a retrospective descriptive observational study that analyzes characteristics and the positive microbiological results within our milk bank samples from June 1, 2016 to December 31, 2020. All milk bank donors voluntarily signed an informed consent that authorizes the use of data to investigation. (AU)

The Practicality of Feeding Defatted Human Milk in the Treatment of Congenital Chylothorax.

Introduction: Congenital chylothorax (CC) is a rare and life-threating condition. Since its treatment is founded on the elimination of long-chain fatty acids from the diet, breastfeeding has been traditionally contraindicated. However, breast milk could be very beneficial due to its immunological and nutritional benefits. Only limited research has been published about the usage of modified-fat breast milk (MBM) in chylothorax treatment. Methods and Results: Systematic review methods were used by two independent reviewers. Only a few case report studies (quality assessment on the domains of the GRADE approach), two small controlled studies, a retrospective study, and some test-tube-based laboratory research met the inclusion criteria. Despite this, we have observed a widespread clinical adoption of this novel treatment in health institutions. Data suggest that modified-fat breast milk does facilitate the resolution of chylothoraces. Refrigerated centrifuge (2°C, 3,000 rpm for 15 minutes) and syringe fat removal methods were the most efficient options in terms of fat reduction. Conclusions: Feeding of human milk is advisable in CC and feasible by means of a simple milk defatting procedure. Open questions remain, related to length and degree of fat restriction and need for individualized fortification of defatted breast milk.

Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal / Prenatal treatment with magnesium sulphate: initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels

INTRODUCCIÓN: La administración prenatal de MgSO4ha mostrado su eficacia en reducir la parálisis cerebral y la disfunción motora severa a los 2 años de edad. El objetivo de este trabajo es estudiar la evolución clínica inicial de los neonatos menores de 29 semanas, que han recibido prenatalmente MgS04 con indicación neuroprotectora y dilucidar la asociación entre la dosis de magnesio administrada a la madre y las concentraciones de magnesio en suero neonatal. MATERIAL Y MÉTODOS: Estudio prospectivo de cohortes en el que se incluyó a los neonatos menores de 29 semanas ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Universitario de Vigo desde diciembre del 2012 hasta julio del 2015. Análisis comparativo de resultados perinatales, de morbimortalidad neonatal y magnesemia entre el grupo expuesto prenatalmente al sulfato de magnesio y un grupo control. RESULTADOS: Se incluyó a un total de 42 recién nacidos, en 28 de los cuales sus madres habían recibido MgSO4. Se encontró significación estadística en la variable mortalidad. No hubo diferencias significativas en el resto de las variables estudiadas. Se obtuvo una correlación significativa entre la dosis total de MgSO4 recibida por la madre y los niveles de magnesio del recién nacido en las primeras 24 h de vida (r2 0,436; p < 0,001). CONCLUSIONES: Se ha obtenido una menor mortalidad en el grupo expuesto a MgS04. No se han encontrado efectos secundarios significativos derivados de la administración de MgS04. La dosis de MgSO4 recibida por las madres tiene una relación lineal con los niveles de magnesio obtenidos en los recién nacidos

INTRODUCTION: Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIAL AND METHODS: A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. RESULTS: A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). CONCLUSIONS: A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates

[Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels]. / Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal.

INTRODUCTION: Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIAL AND METHODS: A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. RESULTS: A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). CONCLUSIONS: A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates.