Potential Epigenetic Effects of Human Milk on Infants' Neurodevelopment.

The advantages of human milk feeding, especially in preterm babies, are well recognized. Infants' feeding with breast milk lowers the likelihood of developing a diverse range of non-communicable diseases later in life and it is also associated with improved neurodevelopmental outcomes. Although the precise mechanisms through which human milk feeding is linked with infants' neurodevelopment are still unknown, potential epigenetic effects of breast milk through its bioactive components, including non-coding RNAs, stem cells and microbiome, could at least partly explain this association. Micro- and long-non-coding RNAs, enclosed in milk exosomes, as well as breast milk stem cells, survive digestion, reach the circulation and can cross the blood-brain barrier. Certain non-coding RNAs potentially regulate genes implicated in brain development and function, whereas nestin-positive stem cells can possibly differentiate into neural cells or/and act as epigenetic regulators in the brain. Furthermore, breast milk microbiota contributes to the establishment of infant's gut microbiome, which is implicated in brain development via epigenetic modifications and key molecules' regulation. This narrative review provides an updated analysis of the relationship between breast milk feeding and infants' neurodevelopment via epigenetics, pointing out how breast milk's bioactive components could have an impact on the neurodevelopment of both full-term and preterm babies.

Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study.

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENTWhat is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role.What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL's ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary.

The impact of maternal- and neonatal-associated factors on human milk's macronutrients and energy.

OBJECTIVES: To test the impact of specific maternal- and neonatal-associated factors on human milk's macronutrients and energy. METHODS: This study was conducted with the use of a human milk analyzer (HMA, MIRIS, Uppsala, Sweden). Six hundred and thirty samples of raw milk and 95 samples of donor pasteurized milk were delivered from a total of 305 mothers. RESULTS: A significant inverse correlation of fat, protein and energy content with gestational age and birth weight was established. Fat and energy were lower in colostrum, increased in transitional milk and decreased on the 30th day's mature milk compared to transitional. The rate of protein decline from colostrum to mature milk was lower in premature deliveries compared to that of full-terms, resulting in greater contents of protein in preterm mature milk. The upmost amounts of carbohydrates were found in mature milk of preterm deliveries. A positive correlation was found between maternal age and fat contents. In women with higher post-pregnancy BMI levels greater analogies of fat and energy were presented. In women suffering diet-controlled gestational diabetes (GD), lower protein and higher fat and energy levels were found. CONCLUSIONS: Prematurity, maternal age, diet-controlled GD and high post-pregnancy BMI levels were found to impose statistical significant effect on milk's macronutrients and energy.

Maternal diet and breastfeeding duration of infants after NICU hospitalization in Greece: a cohort study.

OBJECTIVES: To investigate the role of maternal diet, personal characteristics and willingness to breastfeed on breastfeeding duration of hospitalized neonates as well as to evaluate the mothers' dietetic intake based on the national recommendations. METHODS: A sample of 161 pregnant women from Athens, Greece was followed up during pregnancy, labor and the first 40 weeks of lactation. The participants attended breastfeeding classes and were interviewed regarding their nutritional habits, personal characteristics and breastfeeding intention. A multivariable logistic regression, adjusted for maternal age, smoking, weeks of gestation, body mass index, mode of delivery was conducted in order to estimate the adjusted odds ratios of breastfeeding for at least 6 months for consuming additional serves of fruit or vegetables from the recommended by the national guidelines. RESULTS: The adjusted odds ratios for breastfeeding at 6 months was 2.15 (p = 0.05) for women consumed ≥3.5 servings of fruits/day. Moreover, the participants reported low conformity with the national dietetic guidelines. CONCLUSIONS: Mothers who consumed the recommended by the NDG fruit servings/day breast-fed their hospitalized newborns for a longer period. Despite the fact that our participants were highly motivated and willing to breast-feed, we argue that this relationship is highly unlikely to be biological.

Mother's breast milk supplemented with donor milk reduces hospital and health service usage costs in low-birthweight infants.

OBJECTIVE: to compare hospital and health service usage costs of feeding low-birthweight (LBW) infants predominantly with their mother's milk, supplemented with donor milk, with donor milk and preterm formula. DESIGN: prospective matching study. SETTING: tertiary public perinatal centre, neonatal intensive care unit (NICU) and donor human milk bank. PARTICIPANTS: 100LBW infants (Group I) fed predominantly with their mother's milk from the first hour of life, supplemented (mainly for the first week of life) with donor milk, were matched on a 1:1 basis with 100LBW infants (Group II) who were fed with donor milk for the first 3 weeks of life followed by preterm formula until hospital discharge. Individualised targeted fortification of human milk was implemented in both study groups. FINDINGS: the costs of hospitalisation, doctor visits and prescription drugs for viral infections until 8 months of age were calculated for each infant. Infants fed predominantly with their mother's milk had significantly shorter hospital stays and lower hospitalisation costs. In Group I infants, the duration of enteral gavage feeding was shorter, resulting in significantly lower costs. Up to 8 months of age, Group I infants experienced fewer episodes of viral infections, and the cost of each doctor visit and drug prescription was lower for these infants. CONCLUSIONS: feeding LBW infants predominantly with their mother's milk reduces hospital and health service usage costs. IMPLICATIONS FOR PRACTICE: feeding LBW infants predominantly with their mother's milk, supplemented with donor milk, followed by exclusive breast feeding seems to result in potential savings in hospital and health service usage costs.

Improved outcomes of feeding low birth weight infants with predominantly raw human milk versus donor banked milk and formula.

OBJECTIVES: To investigate the benefits of treating low birth weight infants predominantly with mother's own raw milk and early initiation of breastfeeding (raw human milk/breast-fed infants), in comparison to feeding only with donor banked milk (until the third week of life) and afterwards a preterm formula until hospital discharge (donor banked/formula-fed infants). METHODS: One hundred and ninety-two predominantly raw human milk-fed infants (70% of raw and 30% of donor milk) were matched to 192 donor/formula-fed ones (on 1:1 ratio). Aggressive nutrition policy and targeted fortification of human milk were implemented in both groups. RESULTS: The two groups show similar demographic and perinatal characteristics. Predominantly raw milk-fed infants regained earlier their birth weight, suffered less episodes of feeding intolerance and presented a higher body length and head circumference at discharge (p < 0.001). Those treated mainly with their mothers' milk were able to initiate breastfeeding almost 2 weeks earlier compared to those fed with donor milk who achieved to be bottle-fed later on post-conceptual age (p < 0.001). Infants being breastfed until the 8th month of life conducted less visits for a viral infection to a pediatrician compared to those in the other group (p < 0.001). CONCLUSIONS: Feeding predominantly with mother's raw milk seems to result in optimal neonatal outcomes.