Preterm Human Milk Research Articles

Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants.

Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p < 0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Concentrations of protein, carbohydrates, and fat from morning samples were predictive of evening concentrations to different extents (R(2) = 0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability of evening values by morning values was not influenced by the week of lactation at sampling or by individual patients. In repeated-measures analysis of variance performed on 11 patients who completed the whole 7-week period, over time, there was a significant decrease in fat, energy, and protein contents, whereas carbohydrates content remained unchanged. Day-night differences remained significant only for fat content. Circadian variations in fat and energy concentrations of HM are consistent over the first 7 weeks of lactation. There are no consistent circadian variations in HM protein and carbohydrates. Over a given day, there are little variations in protein and carbohydrates content, but fat concentrations are more variable, and evening values are less well predicted by morning sample analysis than values for protein or carbohydrates.

Nutrition of the preterm infant

Nutrition is of great importance for the preterm infant. It is not only essential for survival, but also makes provision for rapid development of many organs outside the uterus which process normally takes place in the third trimester of pregnancy. It is for future life essential that all factors that might influence the development are as optimal as possible, including nutrition. However, there might also be an upper limit to the intake of some ingredients in the neonatal period. The rate of growth of the preterm infant is five times higher compared to term infants and the breast of the mother delivering preterm might yet be ready to produce the optimal composition of milk. Preterm infants receiving mothers milk only are known to show a lower gain in weight and length than the so called reference fetus. It is therefore at least questionable if preterm human milk can be used to define the nutritional needs of the preterm infant. To define the optimal composition and amounts of nutrients for the preterm infant a factorial approach can be used. The estimated requirements are calculated from the calculated requirements for maintenance and growth. Though some studies have shown that the protein content of milk from mothers who delivered preterm can be higher in the first few weeks after birth compared to milk of term delivering mothers, soon after there is a rapid decline in protein content after which period the content is not different from the term delivered mother. Providing exclusively mothers own milk leads to suboptimal growth and insufficient accretion of minerals. The needs of the preterm infant in energy, protein, lipids, carbohydrates, minerals, pro- and prebiotics to provide optimal nutrition in the first days after birth are discussed in the paper. It is concluded that nowadays early, aggressive nutrition directly after premature birth with the immediate introduction of amino acids and rapid introduction of lipids is advised. Enteral feeding should be started very soon after birth, preferably on the first day of life and increased in the days thereafter. The first choise for enteral feeding is mothers own milk, supplemented from the second week with a fortifier. Special preterm formula might serve as a good alternative in case when breast milk is not available.

Endogenous Human Milk Peptide Release Is Greater after Preterm Birth than Term Birth1–3

Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enzymatic activity, thereby resulting in an altered peptide profile. This study examined differences in peptides present between milk from women delivering at term and women delivering prematurely. Nano-LC tandem mass spectrometry was employed to identify naturally occurring peptides and compare their abundances between term and preterm human milk samples at multiple time points over lactation. Term milk samples were collected from 8 mothers and preterm milk was collected from 14 mothers. The 28 preterm and 32 term human milk samples were divided into 4 groups based on day of collection (<14, 14-28, 29-41, and 42-58 d). Preterm milk peptide counts, ion abundance, and concentration were significantly higher in preterm milk than term milk. Bioinformatic analysis of the cleavage sites for peptides identified suggested that plasmin was more active in preterm milk than term milk and that cytosol aminopeptidase and carboxypeptidase B2 likely contribute to extensive milk protein breakdown. Many identified milk peptides in both term and preterm milk overlapped with known functional peptides, including antihypertensive, antimicrobial, and immunomodulatory peptides. The high protein degradation by endogenous proteases in preterm milk might attenuate problems because of the preterm infant's immature digestive system. This trial was registered at clinicaltrials.gov as NCT01817127.

TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an upregulation of intestinal matrix metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC. The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity. Timp-1-treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity. TIMP-1 inhibited MMP-2 activity, which induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosis. One of the putative mechanisms associated with HBM protection against NEC is mediated by TIMP-1, which downregulates MMP-2 activity, inhibits the degradation of occluding, and preserves tight junctions and gut barrier integrity.

Effect of holder pasteurisation on human milk glycosaminoglycans.

The benefits of human milk for preterm infants are mainly the result of its nutritional characteristics and the presence of biologically active compounds. Among these compounds, glycosaminoglycans (GAGs) play an emerging leading role. When mother's milk is unavailable or in short supply, pasteurised donor milk represents an important nutritional alternative. The aim of this study was to evaluate the effect of Holder pasteurisation on the concentration of different GAGs in preterm human milk. Milk samples collected from 9 mothers having delivered preterm were divided into 2 parts. One part of each sample was immediately frozen (-80°C), whereas the other part was pasteurised with the Holder method before being frozen at -80°C. Specific analytical procedures were applied to evaluate the amount, composition, and structure of main human milk GAGs. No significative differences were measured between not-treated and pasteurised samples for total GAGs content, relative percentages of chondroitin sulfate and heparan sulfate, and main parameters related to galactosaminoglycans structure, even if a slight decrease of total GAGs content of ∼18% was observed in treated samples. Our results indicate that the Holder pasteurisation does not significatively affect the concentration of the main human milk GAGs.

Changes in preterm human milk composition with particular reference to introduction of mixed feeding.

To study the changes in composition of preterm milk till 6 months of age. Milk samples from 33, 19, 7 and 12 lactating mothers (delivered <34 weeks) were analyzed on days 7, 28, 90 and 180, respectively. Triglyceride and sodium concentrations increased significantly with time and protein concentration decreased significantly over 180 days. Sodium (P=0.02) and triglyceride concentrations (P=0.06) were higher in milk samples of mothers who had introduced mixed feeding by 6 months post natal age (n=6) compared to exclusively breast-feeding mothers (n=6); but lactose and protein content was not significantly different. Milk of preterm mothers has higher amount of triglycerides and sodium during introduction of mixed feeding.

PO-0121 The Composition Of Preterm Human Milk And Influencing Factors On Protein Content

<h3>Background</h3> Human milk (HM) is unique and the gold standard for feeding preterm infants. However, HM contains insufficient quantity of energy, calcium, phosphorus and protein - the key nutrient - for preterm infants. Low protein intake is associated with poor weight gain, length and neurocognitive outcomes. Therefore, human milk fortifiers have been developed. The aim of Compo-HMA study was to measure the composition and variation in preterm HM, the impact of lactation period and different milk processing types on the nutritional content with MIRIS Human Milk Analyzer (HMA). <h3>Methods</h3> HM was taken from mothers of premature infants born with a birthweight &lt;1500 g and a gestational age &lt;32 weeks. Protein, fat, lactose and energy composition was measured with MIRIS HMA subjected to different milk processing types fresh/fresh pasteurised/thawed/thawed pasteurised. Furthermore, the relation between protein content and lactation days has been evaluated. <h3>Results</h3> Native HM (n = 83) contained in mean 1.1 ± 0.37 g protein, 3.2 ± 0.85 g fat, 6.6 ± 0.34 g lactose and 59.8 ± 10.65 kcal energy/100 ml HM. Maximum variation was observed in protein content with 0.2–2.2 g/100 ml HM. Lactation day correlated significantly with protein content (p &lt; 0.0001; r = -,4243). Processing of HM had no effects on protein-or nutritional level. <h3>Conclusions</h3> Variations in macronutrients from mother to mother are high, particularly in protein. Protein significantly decreased with lactation period. Various conditions of HM processing had no effect on measured nutritional content. MIRIS is an adjuvant tool to provide actual nutrient composition of HM. The results indicate that HM analysis is important for individualised fortification and improves the nutritional management of premature infants.

A metabolomic study of preterm and term human and formula milk by proton MRS analysis: preliminary results

Objective: To investigate changes in global metabolic profile between: 1 – breast milk and formula milk, 2 – breast milk from mothers delivering at different gestational age (GA) collected within one week from delivery, and then week by week until term equivalent age.Methods: Proton magnetic resonance spectroscopy (MRS) was used to analyze the water-soluble and lipid fractions extracted from 50 milk samples, 46 human milk at different GA, from 23 weeks of gestation until term equivalent age and four different formula milks.Results: The formula milk for premature infants was the most similar to breast milk of preterm babies. Breast milk showed higher lactose concentrations than formula milk, that conversely presented higher galactose 1-phosphate and maltose concentrations. Mother’s milk of very preterm babies (23–25 wks of GA) showed a different metabolic profile from preterm infants ≥29 wks of GA with a subsequent trend to similarity around the 30th week of post-natal age. Breast milk from preterm infants of 29–34 wks, collected up to 40 wks of post-natal age showed a temporal change over the first three weeks of lactation, approaching to zero with the achievement of term age.Conclusions: Metabolome is a promising tool to study human and artificial milk global metabolic profile.

Assay of adiponectin, leptin, true insulin and ghrelin levels in preterm human milk, and its relationship with infants growth

To understand adiponectin, leptin, insulin and ghrelin levels in preterm colostrum and mature milk and their influence on the growth and development of the premature infant. The study subjects were divided into two groups: preterm group and control group. Specimens of colostrum and mature milk on 42nd day after delivery were collected, the general situation of maternal and infants growth parameters at birth and at postnatal 42 days were recorded. Leptin, adiponectin, insulin and ghrelin levels in colustrum and mature milk were determined and compared. A total of 128 mother-infant pairs were involved. There were 128 specimens of colostrums (80 from preterm group, 48 from control group) and 94 specimens of mature milk(50 from premature group, 44 from control group). The levels of colostrum, mature milk adiponectin, leptin, and insulin were not significantly different between the 2 groups; ghrelin levels in colostrum and mature milk of premature group were significantly lower than those in control group (P = 0.038), adiponectin and leptin levels in colostrum were higher than those of the mature milk (P < 0.05), colostrum ghrelin levels were lower than those of mature milk (P < 0.05). Adiponectin, leptin, and ghrelin showed no significant difference between different gestational age groups ( ≤ 34 weeks group vs. > 34 weeks group). True insulin level of mature milk in 34 weeks group was higher than that of > 34 weeks group (29.3 vs. 21.6 mU/L, P = 0.045); true insulin level in colostrums in ≤ 34 weeks group was lower than that in mature milk (21.7 vs. 29.3 mU/L, P = 0.000). Adiponectin levels in colostrum and 42 days weight gain were negatively correlated (r = -0.362, P = 0.025) . Insulin level in mature milk had a negative correlation with birth weight (r = -0.319, P = 0.029) . Ghrelin levels in colostrum and birth weight, length, head circumference, head circumference on 42(nd) day were positively correlated (r = 0.271,0.261,0.360, P < 0.05); weight, length at 42(nd) day and ghrelin levels showed borderline positive correlation (P = 0.050, 0.058). Many bioactive hormones in milk might participate in the regulation of suitable growth after birth. Premature birth affects hormone levels in breast milk. Breast feeding is very important in preterm infants.

Liquid human milk fortifier significantly improves docosahexaenoic and arachidonic acid status in preterm infants

We report the fatty acid composition of mother׳s own human milk from one of the largest US cohorts of lactating mothers of preterm infants. Milk fatty acid data were used as a proxy for intake at enrollment in infants (n=150) who received human milk with a powder human milk fortifier (HMF; Control) or liquid HMF [LHMF; provided additional 12mg docosahexaenoic acid (DHA), 20mg arachidonic acid (ARA)/100mL human milk]. Mothers provided milk samples (n=129) and reported maternal DHA consumption (n=128). Infant blood samples were drawn at study completion (Study Day 28). Human milk and infant PPL fatty acids were analyzed using capillary column gas chromatography.DHA and ARA were within ranges previously published for US term and preterm human milk. Compared to Control HMF (providing no DHA or ARA), human milk fortified with LHMF significantly increased infant PPL DHA and ARA and improved preterm infant DHA and ARA status.

Storage at −80°C Preserves the Antioxidant Capacity of Preterm Human Milk

It is essential to establish optimum parameters for maintaining the quality of stored milk until the moment of consumption with minimal deterioration of its properties. The aim of the study was to evaluate total antioxidant capacity (TAC) and total oxidation status (TOS) of fresh and freeze-stored samples (at -80°C) of preterm human milk (HM). Samples of colostrum were collected from 98 healthy women within the first 4 days after delivery. The total milk volume collected (6 ml) was divided in two aliquot parts: 3 ml for the fresh analysis which was done immediately after the extraction and 3 ml for storage under freezing conditions at -80°C for three months. The antioxidant status and oxidative stress of the fresh and stored breast milk were assessed via determination of TAC and TOS levels. The mean gestational age and the birth weight of the infants were 31.26 ± 2.93 weeks and 1620 ± 581.91 g; respectively. There were no significant correlations between maternal age, route of delivery and milk oxidative stress. There was no significant difference between the levels of TAC, TOS and the oxidative stress index in fresh and freeze-stored samples of colostrum in preterm HM (p > 0.05). Freeze storage of preterm HM at -80°C for three months preserves the antioxidant capacity without changing oxidative status of HM, which could be noteworthy for the preterm infant nutrition.

Longitudinal Changes in Lactoferrin Concentrations in Human Milk: A Global Systematic Review*,†

Lactoferrin is the second most abundant whey protein in human milk and is known for its functional benefits, particularly antimicrobial activities. We report a comprehensive evaluation of the published literature on quantitative changes in lactoferrin in term and preterm human milk through the course of lactation. We also considered methods used to quantify lactoferrin. We critically evaluated 94 articles on human milk with 52 meeting study inclusion criteria (2724 women). A descriptive analysis of the data was performed. Lactoferrin concentration was highest during early lactation and rapidly declined to remain relatively unchanged from 1 month to 2 years of lactation. The unweighted mean of mean (±SEM) concentrations of lactoferrin in early milk (<28 days lactation) was 4.91 ± 0.31 g/L (range of means 0.34–17.94 g/L; median 4.03). For mature milk, the mean of means was 2.10 ± 0.87 g/L (range of means 0.44–4.4 g/L; median 1.91). The majority of data were derived from Europe with fewer studies from Africa and South America. There was a paucity of data on preterm milk. This comprehensive dataset explains in detail the longitudinal changes of lactoferrin concentrations in human milk throughout the world and briefly describes factors that may influence these concentrations.

Major losses of fat, carbohydrates and energy content of preterm human milk frozen at −80°C

Long-term storage of human milk (HM) requires freezing at low temperatures, the consequences of which upon macronutrients are unclear. To test the null hypothesis that HM freezing and storage for a range of 1 to 10 weeks at -80 °C does not affect HM fat, protein, lactose and energy contents. Samples of HM were obtained from 20 mothers (60 samples) of preterm infants (25 to 35 weeks gestation), who routinely expressed their milk, every 3 h, using an electric pump, from the second to the seventh week after delivery. All samples were frozen at -80 °C for 8 to 83 days (43.8 days average). After thawing and homogenization, energy and macronutrient contents were measured using an HM analyzer. Fat, carbohydrates and energy contents were significantly lower in thawed HM than in fresh HM (fat, fresh vs thawed: 3.72±1.17 vs 3.36±1.19 g/100 ml, P<0.001; carbohydrates, fresh vs thawed: 5.86±0.71 vs 4.09±0.96 g/100 ml, P<0.001; energy, fresh vs thawed: 64.93±12.97 vs 56.63±16.82 kcal/100 ml, P<0.0001), whereas protein content remained unchanged (protein, fresh vs thawed: 1.14±0.36 vs 1.15±0.37 g/100 ml, P=0.7). The decline in carbohydrates content but not in fat and energy correlated significantly with freezing duration. Freezing at -80 °C significantly decreases the energy content of HM, both from fat and carbohydrates. Since quantitatively the decrease in macronutrients was much higher than that published for HM storage at -20 °C, our results do not support freezing HM at -80 °C as the gold standard for long-term storage. We suggest that caloric intake calculations in preterm infants cannot be established based upon fresh HM data.

Amino acid profiles in term and preterm human milk through lactation: a systematic review.

Amino acid profile is a key aspect of human milk (HM) protein quality. We report a systematic review of total amino acid (TAA) and free amino acid (FAA) profiles, in term and preterm HM derived from 13 and 19 countries, respectively. Of the 83 studies that were critically reviewed, 26 studies with 3774 subjects were summarized for TAA profiles, while 22 studies with 4747 subjects were reviewed for FAA. Effects of gestational age, lactation stage, and geographical region were analyzed by Analysis of Variance. Data on total nitrogen (TN) and TAA composition revealed general inter-study consistency, whereas FAA concentrations varied among studies. TN and all TAA declined in the first two months of lactation and then remained relatively unchanged. In contrast, the FAA glutamic acid and glutamine increased, peaked around three to six months, and then declined. Some significant differences were observed for TAA and FAA, based on gestational age and region. Most regional TAA and FAA data were derived from Asia and Europe, while information from Africa was scant. This systematic review represents a useful evaluation of the amino acid composition of human milk, which is valuable for the assessment of protein quality of breast milk substitutes.

Randomized Trial of Exclusive Human Milk versus Preterm Formula Diets in Extremely Premature Infants

To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.

Similar efficacy of human banked milk and bovine colostrum to decrease incidence of necrotizing enterocolitis in preterm piglets

Preterm birth and formula feeding predispose to necrotizing enterocolitis (NEC) in infants. As mother's milk is often absent following preterm delivery, infant formula (IF) and human donor milk (HM) are frequently used as alternatives. We have previously shown that porcine and bovine colostrum (BC) provide similar NEC protection in preterm piglets relative to IF. We hypothesized that HM exerts similar effects and that this effect is partly species-independent. Preterm piglets (n = 40) received 2 days of total parenteral nutrition, followed by a rapid transition to full enteral feeding (15 ml·kg(-1)·2 h(-1)) for 2 days using BC (n = 13), HM (n = 13), or IF (n = 14). Intestinal passage time and hexose absorption were tested in vivo. Body and organ weights were recorded on day 5, and macroscopic NEC lesions in the gastrointestinal tract were assessed. Intestinal samples were collected for determination of histomorphology, histopathology, tissue IL-6 and IL-8, organic acids, bacterial adherence by fluorescence in situ hybridization score, and digestive enzyme activities. Relative to IF, pigs from BC and HM showed longer intestinal passage time; higher weight gain, hexose absorptive capacity, mucosal proportion, and enzyme activities; lower NEC incidence, organic acid concentration, and IL-8 concentration; and reduced histopathology lesions. Tissue IL-6 concentration and bacterial adherence score were lower for HM, relative to both BC and IF groups. We conclude that BC and HM are both superior to IF in stimulating gut structure, function, and NEC resistance in preterm piglets. BC may be a relevant alternative to HM when mother's milk is unavailable during the first week after preterm birth.

Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase

Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.

Human Milk and the Nutritional Needs of Preterm Infants

Key principles underpinning feeding guidelines for preterm infants include support for developmental care, breastfeeding, milk expression, and creating feeding plans. Early trophic feeding with colostrum and transitional milk improves immune protection and promotes gut maturation. Studies of preterm infants demonstrate that feeding mother's milk (MM) decreases the incidence of infection and necrotizing enterocolitis and improves neurodevelopmental outcome but may decrease ponderal and linear growth. Standard practice in neonatal units is to promote mother's own milk as the feed of choice for all infants. However, it is not feasible or prudent to do so for all preterm infants. Mothers of preterm infants have lower rates of successful breastfeeding compared with those of term infants. MM can contain harmful bacterial or viral pathogens. Although preterm human milk (HM) contains higher concentrations of protein, sodium, zinc, and calcium than mature HM, it falls short of supplying adequate quantities of nutrients required by preterm infants. Therefore, HM supplemented with nutrients is recommended for all infants born before 32 weeks gestation and for certain infants born at 32-36 weeks of gestation. HM is the preferred feed, but preterm formula is an appropriate option when there is an inadequate supply of MM.

Pasteurization of Mother’s Own Milk for Preterm Infants Does Not Reduce the Incidence of Late-Onset Sepsis

Background: Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother’s own milk differ widely among neonatal intensive care units worldwide. Objectives: To investigate whether pasteurization of mother’s own milk for very-low-birth-weight (VLBW) infants influences the incidence and severity of infection-related outcomes. Methods: In this randomized controlled trial, preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) received either raw or pasteurized mother’s own milk during the first 8 weeks of life. The primary outcome was the incidence of proven LOS. A dose-response relation was verified, i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother’s own milk. Results: This study included 303 VLBW infants (mean birth weight: 1,276 g; mean gestational age: 29 weeks) whose baseline and nutritional characteristics were similar. The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk: 22/151 (0.15, CI: 0.08–0.20) and 31/152 (0.20, CI: 0.14–0.27), respectively (RR: 0.71; 95% CI: 0.43–1.17). A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS, regardless of the type of feeding. Conclusion: For preterm infants, pasteurization of mother’s own milk shows a trend towards an increase in infectious morbidity, although no statistical significance was reached. Practices should focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk.

Longitudinal analysis of protein glycosylation and β-casein phosphorylation in term and preterm human milk during the first 2 months of lactation

Human milk proteins provide term and preterm infants with both nutrition and protection. The objective of the present study was to examine longitudinal changes in the protein composition of term and preterm milk during the first 2 months of lactation, focusing on protein phosphorylation and glycosylation. Using gel electrophoresis, the relative concentration and glycosylation status of lactoferrin, secretory Ig A, β-casein, α-lactalbumin, serum albumin, bile salt-stimulated lipase, xanthine oxidoreductase, tenascin and macrophage mannose receptor 1 were measured in milk collected on days 7, 10, 14, 18, 21, 28 and 60 postpartum from preterm mothers (28-32 weeks gestation, n 17). The phosphorylation status of β-casein was also investigated. To determine if these variables differ in term and preterm milk, samples from term mothers (38-41 weeks gestation, n 8) collected on days 7, 14 and 30 of lactation were also analysed. The concentration of the abundant milk proteins decreased during lactation in term and preterm milk (P <0·05). No difference in protein glycosylation was observed, except for the glycoproteins serum albumin and tenascin. The phosphorylation of β-casein varied significantly between term and preterm milk. Further investigation is required to determine whether these modifications affect protein function and are clinically important to preterm infants.