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Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present study investigated differences in the process of gut microbiota colonisation in preterm infants fed with breastmilk or formula with or without probiotics before 12 weeks. This cohort study recruited 138 premature infants, 31 in the breastmilk (BM) group, 59 in the probiotics formula (PF) group and 48 in the non-probiotics formula (NPF) group, according to the feeding practice they received at birth. Gut bacterial composition was identified with 16S rRNA gene sequencing in faecal samples collected at 1 week, 6 weeks and 12 weeks after birth. The alpha diversity was higher in the PF group compared to the other groups at week 1 and 6 (both p &lt, 0.01) but showed no difference at week 12. The beta diversity of the three groups showed a trend towards similarity at the first two stages (p &lt, 0.001 and p = 0.009, respectively) and finally showed no difference at week 12. Canonical redundancy analysis showed that feeding type could explain the difference in gut microbiota composition at week one and six (both p &lt, 0.01). At genus level, Bifidobacterium was enriched in the PF group, while the Enterococcus and Streptococcus was enriched in the NPF group. In summary, formula with probiotics feeding after birth can affect gut microbiota colonisation and lead to a bacterial community with less potential pathogens.

This study investigated the variation in oligosaccharide levels in the breast milk of south Chinese mothers in a prolonged breastfeeding period of up to 400 days postpartum. A total of 488 breast milk samples were collected from 335 healthy mothers at five different time points: 0–5 days, 10–15 days, 40–45 days, 200–240 days, and 300–400 days postpartum. A high-performance anion-exchange chromatography-pulsed amperometric detector (HPAEC-PAD) was used to quantify 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). In this study, we found six oligosaccharides that were present in breast milk from 0 to 400 days postpartum. The median value ranges of individual oligosaccharide components in this study were 1013–2891 mg/L 2′-FL, 193–1421 mg/L 3-FL, 314–1478 mg/L LNT, 44–255 mg/L LNnT, 111–241 mg/L 3′-SL, and 23–602 mg/L6′-SL. HMO levels decreased over the lactation periods, except for 3-FL, which increased throughout lactation. The predominant fucosylated and sialylated HMOs were 2′-FL and 6′-SL at 40–45 days postpartum and changed to 3-FL and 3′-SL at 200–240 days postpartum. Results from this study showed that lactating women continue to provide their offspring with a high level of 2′-FL one year after delivery, suggesting that 2′-FL may play an important role for infants in early life. Our findings also provide further evidence in support of breastfeeding after one-year postpartum.

Breast milk exerts pivotal regulatory functions early in development whereby it contributes to the maturation of brain and associated cognitive functions. However, the specific components of maternal milk mediating this process have remained elusive. Sialylated human milk oligosaccharides (HMOs) represent likely candidates since they constitute the principal neonatal dietary source of sialic acid, which is crucial for brain development and neuronal patterning. We hypothesize that the selective neonatal lactational deprivation of a specific sialylated HMOs, sialyl(alpha2,3)lactose (3′SL), may impair cognitive capabilities (attention, cognitive flexibility, and memory) in adulthood in a preclinical model. To operationalize this hypothesis, we cross-fostered wild-type (WT) mouse pups to B6.129-St3gal4tm1.1Jxm/J dams, knock-out (KO) for the gene synthesizing 3′SL, thereby providing milk with approximately 80% 3′SL content reduction. We thus exposed lactating WT pups to a selective reduction of 3′SL and investigated multiple cognitive domains (including memory and attention) in adulthood. Furthermore, to account for the underlying electrophysiological correlates, we investigated hippocampal long-term potentiation (LTP). Neonatal access to 3′SL-poor milk resulted in decreased attention, spatial and working memory, and altered LTP compared to the control group. These results support the hypothesis that early-life dietary sialylated HMOs exert a long-lasting role in the development of cognitive functions.

Longitudinal variations of macro- and trace elements in human milk (HM) are not well characterised, and therefore, the recommendations for intake for Australian infants require more evidence to ensure accuracy. We aimed to investigate the longitudinal variation of HM macro- and trace-element concentrations (1–12 months) and infant intake (1–6 months) and to investigate the relationships between intake and infant growth parameters at 3 and 6 months, and determine if intake was sufficient when compared to national guidelines. HM samples were collected monthly for the first 6 months and then at 9 and 12 months postpartum from mother–infant dyads (n = 83). Test–weighing was used to determine the volume of HM consumed daily. Element concentrations (Na, Ca, K, Mg, P, I, Se, Zn, Cu, Mn, Mo, and Fe) were measured using ICP-MS, and intake was calculated using the measured concentrations and the volume of HM consumed. The average intake of HM was 776.3 ± 24.0 mL for the infants. Changes in concentration from months 1 to 12 postpartum were observed for all the measured micronutrients (all p &lt, 0.05). The calculated intakes of all the macro- and trace elements showed that 0% to 82% of infants met the current adequate recommendations at varying periods of lactation. The calculated macro- and trace-element intakes were below the adequate intake recommendations, suggesting that they are not reflective of healthy infant requirements. These findings suggest the need for larger studies using sensitive analytical techniques and the revision of current recommendations for breastfed infants.

The metaproteome profiling of cecal contents collected from neonatal piglets fed pasteurized human milk (HM) or a dairy-based infant formula (MF) from postnatal day (PND) 2 to 21 were assessed. At PND 21, a subset of piglets from each group (n = 11/group) were euthanized, and cecal contents were collected for further metaproteome analysis. Cecal microbiota composition showed predominantly more Firmicutes phyla and Lachnospiraceae family in the lumen of cecum of HM-fed piglets in comparison to the MF-fed group. Ruminococcus&nbsp, gnavus was the most abundant species from the Firmicutes phyla in the cecal contents of the HM-fed piglets at 21 days of age. A greater number of expressed proteins were identified in the cecal contents of the HM-fed piglets relative to the MF-fed piglets. Greater abundances of proteins potentially expressed by Bacteroides spp. such as glycoside enzymes were noted in the cecal lumen of HM-fed piglets relative to the MF. Additionally, lyases associated with Lachnospiraceae family were abundant in the cecum of the HM group relative to the MF group. Overall, our findings indicate that neonatal diet impacts the gut bacterial taxa and microbial proteins prior to weaning. The metaproteomics data were deposited into PRIDE, PXD025432 and 10.6019/PXD025432.

Suboptimal nutrient quality/quantity during complementary feeding (CF) can impact negatively on infants’ healthy growth, even with adequate energy intake. CF must supplement at best human milk (HM) or formulas, which show nutritional differences. Considering this, a differentiated CF is probably advisable to correctly satisfy the different nutritional needs. To assess whether current needs at 6–24 months of age can still be met by one single CF scheme or different schemes are needed for breastfed vs. formula/cow’s milk (CM) fed infants, protein, iron and calcium intakes were assessed from daily menus using the same type and amount of solid food, leaving same amounts of HM and follow-up formula at 9 and again 18 months of age, when unmodified CM was added. Depending on the child’s age, calcium- and iron-fortified cereals or common retail foods were used. The single feeding scheme keeps protein intake low but higher than recommended, in HM-fed children while in formula/CM-fed ones, it achieves much higher protein intakes. Iron Population Recommended Intake (PRI) and calcium Adequate Intakes (AI) are met at the two ages only when a formula is used, otherwise, calcium-fortified cereals are needed. ESPGHAN statements on the futility of proposing different CF schemes according to the milk type fed do not allow to fully meet the nutritional recommendations issued by major Agencies/Organizations/Societies for all children of these age groups.

Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, β-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.

Breastfeeding is the best source of nutrition during infancy and is associated with a broad range of health benefits. However, there remains a significant and persistent need for innovations in infant formula that will allow infants to access a wider spectrum of benefits available to breastfed infants. The addition of human milk oligosaccharides (HMOs) to infant formulas represents the most significant innovation in infant nutrition in recent years. Although not a direct source of calories in milk, HMOs serve as potent prebiotics, versatile anti-infective agents, and key support for neurocognitive development. Continuing improvements in food science will facilitate production of a wide range of HMO structures in the years to come. In this review, we evaluate the relationship between HMO structure and functional benefits. We propose that infant formula fortification strategies should aim to recapitulate a broad range of benefits to support digestive health, immunity, and cognitive development associated with HMOs in breastmilk. We conclude that acetylated, fucosylated, and sialylated HMOs likely confer important health benefits through multiple complementary mechanisms of action.

Lutein is a dietary carotenoid preferentially accumulated in the eye and the brain in early life and throughout the life span. Lutein accumulation in areas of high metabolism and oxidative stress such as the eye and the brain suggest a unique role of this ingredient during the development and maturation of these organs of common embryological origin. Lutein is naturally provided to the developing baby via the cord blood, breast milk and then infant diet. The presence of this carotenoid depends on fruit and vegetable intakes and its bioavailability is higher in breastmilk. This paper aims to review the anatomical development of the eye and the brain, explore the presence and selective deposition of lutein in these organs during pregnancy and infancy and, based on its functional characteristics, present the latest available research on the beneficial role of lutein in the pediatric population. The potential effects of lutein in ameliorating conditions associated with increase oxidative stress such as in prematurity will be also addressed. Since consumption of lutein rich foods falls short of government guidelines and in most region of the world infant formulas lack this bioactive, dietary recommendations for pregnant and breastfeeding women and their child can help to bridge the gap.

Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

A primary role of Human Milk Banks (HMBs) is to provide human milk (HM) for preterm infants and to support the mothers of these infants as they establish their own milk supply. A better understanding of the variation in the energy and macronutrients contents of donor human milk (DHM) potentiates targeted nutrition for preterm babies. Therefore, the aim of this study was to assess the variability of energy and macronutrients content in DHM and to investigate the impact of maternal factors and feeding practices on the nutritional value of DHM. The study involved 49 donors registered in the HMB in the Holy Family Hospital in Warsaw, Poland. Samples from each donor were pooled within a maximum of two weeks. The composition of DHM, including energy content, protein, fat, and carbohydrate concentrations, was analyzed using the Miris Human Milk Analyzer. The analyses were performed before the pasteurization process. The mean time of milk donation to HMB was 13.2 ± 6.0 weeks. There were no significant differences in energy and macronutrients contents of DHM in the beginning and at the end of milk donation to HMB, however, HM fat concentration was positively correlated with afternoon feedings (r = 0.289, p = 0.044). The method of feeding (breastfeeding vs. feeding only expressed milk) also did not impact the nutritional value of DHM. Future research for the DHM should include a further cross-sectional observational study with the collection of detailed donor information and characteristics of milk expression and feeding practices to further evaluate the pooling processes and the effect on DHM composition.

The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4–8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.

Background: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. Results: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. Conclusions: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.

Human milk oligosaccharides (HMOs) are important functional biomolecules in human breast milk. Understanding the factors influencing differences in HMO composition and changes in their concentration over lactation can help to design feeding strategies that are well-adapted to infant’s needs. This review summarises the total and individual concentration of HMOs from data published from 1999 to 2019. Studies show that the HMO concentrations are highest in colostrum (average 9–22 g/L), followed by slightly lower concentrations in transitional milk (average 8–19 g/L), with a gradual decline in mature milk as lactation progresses, from 6–15 g/L in breast milk collected within one month of birth, to 4–6 g/L after 6 months. Significant differences in HMO composition have been described between countries. Different HMOs were shown to be predominant over the course of lactation, e.g., 3-fucosyllactose increased over lactation, whereas 2′-fucosyllactose decreased. Recent clinical studies on infant formula supplemented with 2′-fucosyllactose in combination with other oligosaccharides showed its limited beneficial effect on infant health.

OBJECTIVES: Breastfeeding is associated with numerous health benefits in infants, but early life nutrition has not been specifically studied in the neurodevelopmental disorder fragile X syndrome (FXS). Herein, we evaluate associations between the consumption of breast milk during infancy and the prevalence of autism, allergies, diabetes, gastrointestinal (GI) problems and seizures in participants with FXS. METHODS: The study design was a retrospective survey of families enrolled in the Fragile X Online Registry and Accessible Research Database (FORWARD). RESULTS: There was a 73% rate of breastfeeding in the enrolled participants with an 81% rate for at least 3 months, 73% for 6 months and 41% for 12 months of age or longer. There was a 1.7-fold reduction in the prevalence of autism in participants with FXS who were fed breast milk for 12 months or longer and a 1.9-fold decrease in autism in participants reporting no use of any infant formula (P

Our knowledge related to human milk proteins is still limited. The present study determined the changes in multiple human milk proteins during the first six months of lactation, investigated the influencing factors of milk proteins, and explored the impact of milk proteins on infant growth. A total of 105 lactating women and their full-term infants from China were prospectively surveyed in this research. Milk samples were collected at 1–5 days, 8–14 days, 1 month, and 6 months postpartum. Concentrations of total protein and α-lactalbumin were measured in all milk samples, and concentrations of lactoferrin, osteopontin, total casein, β-casein, αs−1 casein, and κ-casein were measured in milk from 51 individuals using ultra performance liquid chromatography coupled with mass spectrometry. The concentration of measured proteins in the milk decreased during the first six months of postpartum (p-trend &lt, 0.001). Maternal age, mode of delivery, maternal education, and income impacted the longitudinal changes in milk proteins (p-interaction &lt, 0.05). Concentrations of αs−1 casein in milk were inversely associated with the weight-for-age Z-scores of the infants (1 m: r −0.29, p 0.038, 6 m: r −0.33, p 0.020). In conclusion, the concentration of proteins in milk decreased over the first six months postpartum, potentially influenced by maternal demographic and delivery factors. Milk protein composition may influence infant weights.

Human milk oligosaccharides (HMOs) are complex unconjugated glycans associated with positive infant health outcomes. This study has examined current knowledge of the effect of maternal diet and nutritional status on the composition of HMOs in breast milk. Using the PRISMA-ScR guidelines, a comprehensive, systematic literature search was conducted using Scopus, Web of Science, Global Health (CABI), and MEDLINE. Titles and abstracts were screened independently by two reviewers against predefined inclusion and exclusion criteria. Fourteen studies met the inclusion criteria and reported on maternal dietary intake (n = 3), maternal body composition indices (n = 9), and dietary supplementation interventions (n = 2). In total, data from 1388 lactating mothers (4011 milk samples) were included. Design methodologies varied substantially across studies, particularly for milk sample collection, HMO analysis, dietary and body composition assessment. Overall, this review has identified potential associations between maternal dietary intake and nutritional status and the HMO composition of human milk, though an abundance and sufficiency of evidence is lacking. Standardised procedures for human milk sample collection and HMO analysis, along with robust and validated nutrition assessment techniques, should be employed to further investigate the impact of maternal nutritional factors on HMO composition.

The present study investigates the influence of selected infant and maternal factors on the energy and macronutrient composition of mature human milk (HM). The study enrolled 77 mothers at 4&ndash, 8 weeks postpartum. Each mother provided 1 sample of HM. Each extracted HM sample was formed by mixing four subsamples of HM, each of which were obtained in one predefined 6-h periods of the day. Among maternal factors, the analysis included: anthropometric data before and after pregnancy, weight gain in pregnancy, body composition, assessed using the Maltron BioScan 920-II to analyze bioimpedance, and dietary intake, assessed with three-day dietary records. Among the neonatal factors, birth weight and length, number of daily feedings and type of delivery were included. The composition of HM, including energy content, protein, fat and carbohydrate concentrations, was analyzed using the Miris human milk analyzer. Pearson&rsquo, s and Spearman&rsquo, s correlation coefficients and multivariable logistic regression models were used to analyze the association between the selected maternal and infant factors and HM milk composition. It was found that total protein content of HM was correlated with pre-pregnancy BMI (Spearman rho = 0.238, p = 0.037), current lean body mass (Spearman rho = &minus, 0.293, p = 0.01) and total water content (Spearman rho = &minus, 0.315, p = 0.005). Carbohydrates were the only macronutrients whose composition was significantly affected by the infant factors. It was reported that higher carbohydrate content was associated with male sex (OR = 4.52, p = 0.049). Our results show that maternal and infant factors, especially maternal pre-pregnancy and current nutritional status and infant sex, interact and affect HM composition, suggesting that macronutrient and energy content in HM may be determined in pregnancy and may have unique compositional profile for every mother&ndash, infant dyad.

The aim of this study was to determine the differences in human milk fatty acid composition in relation to maternal allergy within a large birth cohort study using statistical methods accounting for the correlations that exist in compositional data. We observed marginal differences in human milk fatty acid composition of allergic and non-allergic mothers. However, our results do not support the hypothesis that human milk fatty acid composition is influenced by allergy or that it differs between mothers with or without allergy. Observed differences in our results between transformed and untransformed fatty acid data call for re-evaluation of previous, as well as future, studies using statistical methods appropriate for compositionality of fatty acid data., publishedVersion

Maternal bacteria are shared with infants via breastfeeding. Prebiotics modulate the gut microbiota, promoting health benefits. We investigated whether the maternal diet supplementation with a prebiotic (fructooligosaccharides, FOS) could influence the milk microbiota. Twenty-eight lactating women received 4.5 g of fructooligosaccharides + 2 g of maltodextrin (FOS group) and twenty-five received 2 g of maltodextrin (placebo group) for 20 days. Breast-milk samples were taken before and after the intervention. The DNA from samples was used for 16S rRNA sequencing. No statistical differences between the groups were found for the bacterial genera after the intervention. However, the distances of the trajectories covered by paired samples from the beginning to the end of the supplementation were higher for the FOS group (p = 0.0007) indicating greater changes in milk microbiota compared to the control group. Linear regression models suggested that the maternal age influenced the response for FOS supplementation (p = 0.02). Interestingly, the pattern of changes to genus abundance upon supplementation was not shared between mothers. We demonstrated that manipulating the human milk microbiota through prebiotics is possible, and the maternal age can affect this response.

Despite improvements in nutritional management, preterm infants continue to face high rates of postnatal growth restriction. Because variability in breast milk composition may result in protein and energy deficits, targeted fortification has been advocated. We conducted an interventional study to compare body composition and growth outcomes of very low birth weight infants fed targeted protein-fortified human milk (HM) with those fed standard fortified HM. If mother&rsquo, s own milk was not available, donor milk was used. Weekly analysis of HM with mid-infrared spectroscopy was conducted and additional protein was added to the fortified HM to ensure a protein intake of 4 g/kg/day. Weekly anthropometric measurements were done. Prior to discharge or at 37 weeks, corrected age skinfold thickness (SFT) measurements as well as body composition measurement using air displacement plethysmography were done. Among 36 preterm infants enrolled, those in the targeted group (n = 17) received more protein and had a larger flank SFT at study end than those in the standard group (n = 19). A pilot post-hoc analysis of subjects having at least 30 intervention days showed a 3% higher fat-free mass in the targeted group. Use of a targeted fortification strategy resulted in a higher protein intake and fat-free mass among those receiving longer intervention.

This review aims to discuss the role of nutrition and feeding practices in necrotizing enterocolitis (NEC), NEC prevention, and its complications, including surgical treatment. A thorough PubMed search was performed with a focus on meta-analyses and randomized controlled trials when available. There are several variables in nutrition and the feeding of preterm infants with the intention of preventing necrotizing enterocolitis (NEC). Starting feeds later rather than earlier, advancing feeds slowly and continuous feeds have not been shown to prevent NEC and breast milk remains the only effective prevention strategy. The lack of medical treatment options for NEC often leads to disease progression requiring surgical resection. Following resection, intestinal adaptation occurs, during which villi lengthen and crypts deepen to increase the functional capacity of remaining bowel. The effect of macronutrients on intestinal adaptation has been extensively studied in animal models. Clinically, the length and portion of intestine that is resected may lead to patients requiring parenteral nutrition, which is also reviewed here. There remain significant gaps in knowledge surrounding many of the nutritional aspects of NEC and more research is needed to determine optimal feeding approaches to prevent NEC, particularly in infants younger than 28 weeks and

Necrotizing enterocolitis, a potentially fatal intestinal inflammatory disorder affecting primarily premature infants, is a significant cause of morbidity and mortality in neonates. While the etiology of the disease is, as yet, unknown, a number of risk factors for the development of necrotizing enterocolitis have been identified. One such risk factor, formula feeding, has been shown to contribute to both increased incidence and severity of the disease. The protective influences afforded by breastfeeding are likely attributable to the unique composition of human milk, an extremely potent, biologically active fluid. This review brings together knowledge on the pathogenesis of necrotizing enterocolitis and current thinking on the instrumental role of one of the more prominent classes of bioactive components in human breast milk, glycosaminoglycans.

The objective of this pilot study was to assess the fecal microbiome and different immunological parameters in infant feces and maternal milk from mother&ndash, infant pairs in which the infants were suffering from different gastrointestinal disorders (colic, non-IgE-mediated cow milk protein allergy (CMPA), and proctocolitis). A cohort of 30 mother&ndash, infant pairs, in which the infants were diagnosed with these gastrointestinal disorders or included as healthy controls, were recruited. Bacterial composition of infant feces and breast milk was determined by metataxonomic sequencing. Immunological compounds were quantified using multiplexed immunoassays. A higher abundance of Eggerthellaceae, Lachnospiraceae and Peptostreptococcaceae, and lower abundance of Bifidobacterium and higher abundance of Rothia were registered in fecal samples from the CMPA group. Eggerthellaceae was also significantly more abundant in milk samples of the CMPA group. There were no differences in the concentration of immunological compounds in infant fecal samples between the four groups. In contrast, differences were found in the concentration and/or frequency of compounds related to acquired immunity and granulocyte colony stimulating factor (GCSF) in breast milk samples. In conclusion, a few microbial signatures in feces may explain part of the difference between CMPA and other infants. In addition, some milk immunological signatures have been uncovered among the different conditions addressed in this pilot study.

Preterm delivery complications are the primary cause of death among children under the age of five. Preventive strategies include the use of pasteurized donor human milk (DHM), its fortification with human milk fortifiers (protein supplements), and supplementation with probiotics. Our aim was to examine the impact of DHM and fortified DHM (FDHM) on the mucus adhesion properties of two widely used probiotics. The study covered two forms of human milk fortifier, liquid and powdered, with or without probiotics and storage at 4 &deg, C for 24 h. To test the adhesion properties of the probiotic strains, DHM+probiotics and FDHM+probiotics were prepared and added to immobilized mucus isolated from the stool of healthy Finnish infants. The probiotic adhesion was then measured by liquid scintillation. Our results suggest that addition of liquid or powdered human milk fortifier in donor human milk had no impact on probiotic adhesion. In addition, given the increased adhesion of probiotics suspended in buffer, other matrices should be further studied. These factors need to be considered when designing future intervention strategies using probiotics in preterm infants.

Vitamin A (all-trans-retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. In this study, we review the role of vitamin A in mammary gland metabolism, where retinoid signaling is required not only for morphogenesis and development of the gland and for adequate milk production, but also during the weaning process, when epithelial cell death is coupled with tissue remodeling.

There is growing evidence that omega-3 (n-3) polyunsaturated fatty-acids (PUFAs) are important for the brain development in childhood and are necessary for an optimal health in adults. However, there have been no studies examining how the n-3 PUFA composition of human milk influences infant behavior or temperament. To fill this knowledge gap, 52 breastfeeding mothers provided milk samples at 3 months postpartum and completed the Infant Behavior Questionnaire (IBQ-R), a widely used parent-report measure of infant temperament. Milk was assessed for n-3 PUFAs and omega-6 (n-6) PUFAs using gas-liquid chromatography. The total fat and the ratio of n-6/n-3 fatty acids in milk were also examined. Linear regression models revealed that infants whose mothers&rsquo, milk was richer in n-3 PUFAs had lower scores on the negative affectivity domain of the IBQ-R, a component of temperament associated with a risk for internalizing disorders later in life. These associations remained statistically significant after considering covariates, including maternal age, marital status, and infant birth weight. The n-6 PUFAs, n-6/n-3 ratio, and total fat of milk were not associated with infant temperament. These results suggest that mothers may have the ability to shape the behavior of their offspring by adjusting the n-3 PUFA composition of their milk.

Human milk oligosaccharides have been recognized as an important, functional biomolecule in mothers’ milk. Moreover, these oligosaccharides have been recognized as the third most abundant component of human milk, ranging from 10−15 g/L in mature milk and up to and over 20 g/L reported in colostrum. Initially, health benefits of human milk oligosaccharides were assigned via observational studies on the differences between breastfed and bottle fed infants. Later, pools of milk oligosaccharides were isolated and used in functional studies and in recent years more specific studies into structure−function relationships have identified some advanced roles for milk oligosaccharides in the healthy development of infants. In other research, the levels, diversity, and complexity of human milk oligosaccharides have been studied, showing a wide variation in results. This review gives a critical overview of challenges in the analysis of human milk oligosaccharides. In view of the myriad functions that can be assigned, often to specific structures or classes of structures, it is very relevant to assess the levels of these structures in the human milk correctly, as well as in other biological sample materials. Ultimately, the review makes a case for a comparative, inter-laboratory study on quantitative human milk oligosaccharide analysis in all relevant biological samples.

Human milk is the most complete and ideal form of nutrition for the developing infant. The composition of human milk consistently changes throughout lactation to meet the changing functional needs of the infant. The human milk proteome is an essential milk component consisting of proteins, including enzymes/proteases, glycoproteins, and endogenous peptides. These compounds may contribute to the healthy development in a synergistic way by affecting growth, maturation of the immune system, from innate to adaptive immunity, and the gut. A comprehensive overview of the human milk proteome, covering all of its components, is lacking, even though numerous analyses of human milk proteins have been reported. Such data could substantially aid in our understanding of the functionality of each constituent of the proteome. This review will highlight each of the aforementioned components of human milk and emphasize the functionality of the proteome throughout lactation, including nutrient delivery and enhanced bioavailability of nutrients for growth, cognitive development, immune defense, and gut maturation.

Cow&rsquo, s milk allergy (CMA) belongs to one of the most common food allergies in early childhood affecting 2&ndash, 3% of children under 3 years of age. However, approximately 1% of adults remain allergic to cow&rsquo, s milk, often showing severe reactions even to traces of milk. In our study, we recruited patients with different clinical manifestations of CMA, including patients with anaphylaxis and less severe symptoms. We assessed the sensitization patterns and allergic responses of these subgroups through different immunological and cell-based methods. Sera of patients were investigated for IgE against whole cow&rsquo, s milk and its single allergens by CAP- FEIA. In a newly developed in-house multiplex dot assay and a basophil activation test (BAT), cow&rsquo, s milk allergens, in addition to human breast milk and single allergens from cow&rsquo, s and human milk were analyzed for IgE recognition and severity of CMA in the included patients. Both the CAP-FEIA routine diagnostic and the multiplex dot test could differentiate CMA with severe from milder allergic reactions by means of the patients&rsquo, casein sensitization. The BAT, which mirrors the clinical response in vitro, confirmed that basophils from patients with severe reactions were more reactive to caseins in contrast to the basophils from more moderate CMA patients. By means of this improved component-resolved diagnosis of CMA, individual sensitization patterns could be assessed, also taking sensitization against human milk into consideration.

Maternal antibody transfer to the newborn provides essential support for the infant&rsquo, s na&iuml, ve immune system. Preterm infants normally receive maternal antibodies through mother&rsquo, s own breast milk (MBM) or, when mothers are unable to provide all the milk required, donor breast milk (DBM). DBM is pasteurized and exposed to several freeze&ndash, thaw cycles, which could reduce intact antibody concentration and the antibody&rsquo, s resistance to digestion within the infant. Whether concentrations of antibodies in MBM and DBM differ and whether their survival across digestion in preterm infants differs remains unknown. Feed (MBM or DBM), gastric contents (MBM or DBM at 1-h post-ingestion) and stool samples (collected after a mix of MBM and DBM feeding) were collected from 20 preterm (26&ndash, 36 weeks gestational age) mother&ndash, infant pairs at 8&ndash, 9 and 21&ndash, 22 days of postnatal age. Samples were analyzed via ELISA for the concentration of secretory IgA (SIgA), total IgA (SIgA/IgA), total IgM (SIgM/IgM) and IgG. Total IgA, SIgA, total IgM and IgG concentrations were 55.0%, 71.6%, 98.4% and 41.1% higher in MBM than in DBM, and were 49.8%, 32.7%, 73.9% and 39.7% higher in gastric contents when infants were fed with MBM than when infants were fed DBM, respectively. All maternal antibody isotypes present in breast milk were detected in the infant stools, of which IgA (not sIgA) was the most abundant.

The influence of types of human milk (HM)&mdash, raw own mother&rsquo, s milk (OMM), pasteurized OMM, and donor milk (DM)&mdash, was evaluated for growth in premature infants fed exclusively HM with controlled nutritional intakes using daily individualized HM fortification (IHMF). Growth and nutritional intakes were prospectively collected in preterm infants (&lt, 32 weeks) fed IHMF and compared in infants fed predominantly (&ge, 75%) OMM and DM. The influence of HM types (raw OMM, pasteurized OMM, and DM) on growth were also evaluated in the whole population. One-hundred and one preterm infants (birth weight 970 &plusmn, 255 g, gestational age 27.8 &plusmn, 1.9 weeks) were included. Energy (143 &plusmn, 8 vs. 141 &plusmn, 6 kcal/kg/day, p = 0.15) and protein intakes (4.17 &plusmn, 0.15 vs. 4.15 &plusmn, 0.14 g/kg/day, p = 0.51) were similar in both groups. Infants receiving predominantly OMM (n = 37), gained significantly more weight (19.8 &plusmn, 2.0 vs. 18.2 &plusmn, 2.2 g/kg/day, p = 0.002) and length (1.17 &plusmn, 0.26 vs. 0.99 &plusmn, 0.36 cm/week, p = 0.020) than those fed predominantly DM (n = 33). Stepwise multivariate analysis (n = 101) suggests that raw OMM was the major determinant of growth, contributing 22.7% of weight gain. Length gain was also related to OMM (raw + pasteurized) intakes, explaining 4.0% of length gain. In conclusion, at daily controlled similar protein and energy intakes, OMM had significant beneficial effects on weight and length versus DM in VLBW infants. This difference could be partially explained by the use of raw OMM.

To better understand the variability of the type and level of serum proteins in human milk, the milk serum proteome of Chinese mothers during lactation was investigated using proteomic techniques and compared to the milk serum proteome of Dutch mothers. This showed that total milk serum protein concentrations in Chinese human milk decreased over a 20-week lactation period, although with variation between mothers in the rate of decrease. Variation was also found in the composition of serum proteins in both colostrum and mature milk, although immune-active proteins, enzymes, and transport proteins were the most abundant for all mothers. These three protein groups account for many of the 15 most abundant proteins, with these 15 proteins covering more than 95% of the total protein concentrations, in both the Chinese and Dutch milk serum proteome. The Dutch and Chinese milk serum proteome were also compared based on 166 common milk serum proteins, which showed that 22% of the 166 serum proteins differed in level. These differences were observed mainly in colostrum and concern several highly abundant proteins. This study also showed that protease inhibitors, which are highly correlated to immune-active proteins, are present in variable amounts in human milk and could be relevant during digestion.

We thank Bernard and colleagues for their careful reading and interest in our article Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants [...]

Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into adulthood, and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk have been suggested as mediators of the beneficial long-term effect of breastfeeding on BP and BLP. We aimed to investigate associations between n-3 LC-PUFA content in breast milk at 4 months postpartum and offspring BP and BLP in early life. BP and BLP were measured at 4, 18, and 36 months. Statistical analyses were sex-stratified and adjusted for gestational age, maternal pre-pregnancy body mass index (BMI), and maternal educational level. Based on 336 mother-child dyads, high n-3 LC-PUFA in breast milk was inversely associated with systolic and diastolic BP in boys at 4 months (&beta, = &minus, 20.0 (95% CI = &minus, 33.4, &minus, 6.7), p = 0.004 and &beta, 10.2 (95% CI = &minus, 19.8, &minus, 0.5), p = 0.039, respectively), inversely associated with HDL cholesterol, and directly associated with triglyceride in girls at 4 months (&beta, 0.7 (95% CI = &minus, 1.1, &minus, 0.3), p = 0.001 and &beta, = 3.1 (95% CI = 1.0, 5.2), p = 0.005, respectively). Associations observed at the later time points were non-significant. Furthermore, we observed sex-specific changes over time in both size and direction of the associations. Our results indicate that early intake of n-3 LC-PUFA can affect early development in cardiometabolic factors such as BP and BLP in a sex-specific manner. Follow-up and further investigation in later childhood is planned.

This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant HMOs that serve as prebiotics and immunomodulators. Gut immaturity in preterm infants leads to difficulties in tolerating enteral feeding and bacterial colonization and a high sensitivity to NEC, particularly when breast milk is insufficient. Due to the immaturity of the preterm infants, their response to HMOs could be different from that in term infants. The concentration of HMOs in human milk is highly variable and there is no evidence to support a specifically adapted high concentration in preterm milk. Further, the gut microbiota is not only different but also highly variable after preterm birth. Studies in pigs as models for preterm infants indicate that HMO supplementation to formula does not mature the gut or prevent NEC during the first weeks after preterm birth and the effects may depend on a certain stage of gut maturity. Supplemented HMOs may become more important for gut protection in the preterm infants when the gut has reached a more mature phase.

Breastfeeding has many established health benefits, but its impact on asthma development is uncertain. Breastfeeding appears to have a positive and dose-dependent impact on respiratory health, particularly during early childhood and in high-risk populations; however, the strength and causality of these associations are unclear. It is challenging to compare results across studies due to methodological differences and biological variation. Resolving these inconsistencies will require well-designed, prospective studies that accurately capture asthma diagnoses and infant feeding exposures (including breastfeeding duration, exclusivity, and method of feeding), account for key confounders, evaluate dose effects, and consider effect modification and reverse causality. Mechanistic studies examining human milk bioactives and their impact on lung health and asthma development are beginning to emerge, and these will be important in establishing the causality and mechanistic basis of the observed associations between breastfeeding and asthma. In this review, we summarize current evidence on this topic, identify possible reasons for disagreement across studies, discuss potential mechanisms for a causal association, and provide recommendations for future research.

An elevated serum phosphorus (P) has been anecdotally described in premature infants receiving human milk fortified with donor human milk-derived fortifier (HMDF). No studies have prospectively investigated serum P in premature infants receiving this fortification strategy. In this single center prospective observational cohort study, extremely premature infants ≤1250 grams (g) birth weight (BW) were fed an exclusive human milk-based diet receiving HMDF and serum P levels were obtained. We evaluated 93 infants with a mean gestational age of 27.5 ± 2.0 weeks (Mean ± SD) and BW of 904 ± 178 g. Seventeen infants (18.3%) had at least one high serum P level with a mean serum P of 9.2 ± 1.1 mg/dL occurring at 19 ± 11 days of life. For all infants, the highest serum P was inversely correlated to the day of life of the infant (p &lt, 0.001, R2 = 0.175) and positively correlated with energy density of HMDF (p = 0.035). Serum P was not significantly related to gender, BW, gestational age, or days to full feeds. We conclude that the incidence of hyperphosphatemia was mild and transient in this population. The risk decreased with infant age and was unrelated to gender, BW, or ethnicity.

Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas.

From an evolutionary standpoint, allergy has only recently emerged as a significant health problem. Various hypotheses were proposed to explain this, but they all indicated the importance of rapid lifestyle changes, which occurred in industrialized countries in the last few decades. In this review, we discuss evidence from epidemiological and experimental studies that indicate changes in dietary habits may have played an important role in this phenomenon. Based on the example of dietary fiber, we discuss molecular mechanisms behind this and point towards the importance of diet-induced changes in the microbiota. Finally, we reason that future studies unraveling mechanisms governing these changes, along with the development of better tools to manipulate microbiota composition in individuals will be crucial for the design of novel strategies to combat numerous inflammatory disorders, including atopic diseases.

In Mexico, infants (0–2 years old) show the highest prevalence of vitamin A deficiency (VAD), measured by serum retinol concentrations. Thus, we consider that low vitamin A (VA) intake through breast milk (BM) combined with poor weaning practices are the main factors that contribute to VAD in this group. We combined the assessment of VA status in lactating women using BM retinol and a stable isotope ‘dose-to-mother’ technique to measure BM production in women from urban and agricultural areas. Infants’ mean BM intake was 758 ± 185 mL, and no difference was observed between both areas (p = 0.067). Mean BM retinol concentration was 1.09 μmol/L, which was significantly lower for the agricultural area (p = 0.028). Based on BM retinol concentration, 57% of women were VAD; although this prevalence fell to 16% when based on fat content. Regardless of the VA biomarker used here, infants from the urban and agricultural areas cover only 66% and 49% of their dietary adequate intake from BM, respectively (p = 0.054). Our data indicate that VAD is still a public health concern in Mexico. Adopting both methods to assess VA transfer from the mother to the breastfed child offers an innovative approach towards the nutritional assessment of vulnerable groups.

A pasteurization temperature monitoring system has been designed using FoneAstra, a cellphone-based networked sensing system, to monitor simulated flash-heat (FH) pasteurization. This study compared the effect of the FoneAstra FH (F-FH) method with the Sterifeed Holder method currently used by human milk banks on human milk immune components (immunoglobulin A (IgA), lactoferrin activity, lysozyme activity, interleukin (IL)-8 and IL-10). Donor milk samples (N = 50) were obtained from a human milk bank, and pasteurized. Concentrations of IgA, IL-8, IL-10, lysozyme activity and lactoferrin activity were compared to their controls using the Student’s t-test. Both methods demonstrated no destruction of interleukins. While the Holder method retained all lysozyme activity, the F-FH method only retained 78.4% activity (p < 0.0001), and both methods showed a decrease in lactoferrin activity (71.1% Holder vs. 38.6% F-FH; p < 0.0001) and a decrease in the retention of total IgA (78.9% Holder vs. 25.2% F-FH; p < 0.0001). Despite increased destruction of immune components compared to Holder pasteurization, the benefits of F-FH in terms of its low cost, feasibility, safety and retention of immune components make it a valuable resource in low-income countries for pasteurizing human milk, potentially saving infants’ lives.

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = −47.9, 95% confidence interval (CI) = −95.7; −0.18; p = 0.049; β = −89.6, 95% CI = −131.5; −47.7; p < 0.0001; β = −104.1, 95% CI = −151.4; −56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

We previously compared infant outcomes between a powdered human milk fortifier (P-HMF) vs. acidified liquid HMF (AL-HMF). A non-acidified liquid HMF (NAL-HMF) is now commercially available. The purpose of this study is to compare growth and outcomes of premature infants receiving P-HMF, AL-HMF or NAL-HMF. An Institutional Review Board (IRB) approved retrospective chart review compared infant outcomes (born < 2000 g) who received one of three HMF. Growth, enteral nutrition, laboratory and demographic data were compared. 120 infants were included (P-HMF = 46, AL-HMF = 23, NAL-HMF = 51). AL-HMF infants grew slower in g/day (median 23.66 vs. P-HMF 31.27, NAL-HMF 31.74 (p < 0.05)) and in g/kg/day, median 10.59 vs. 15.37, 14.03 (p < 0.0001). AL-HMF vs. NAL-HMF infants were smaller at 36 weeks gestational age (median 2046 vs. 2404 g, p < 0.05). However AL-HMF infants received more daily calories (p = 0.21) and protein (p < 0.0001), mean 129 cal/kg, 4.2 g protein/kg vs. P-HMF 117 cal/kg, 3.7 g protein/kg , NAL-HMF 120 cal/kg, 4.0 g protein/kg. AL-HMF infants exhibited lower carbon dioxide levels after day of life 14 and 30 (p < 0.0001, p = 0.0038). Three AL-HMF infants (13%) developed necrotizing enterocolitis (NEC) vs. no infants in the remaining groups (p = 0.0056). A NAL-HMF is the most optimal choice for premature human milk-fed infants in a high acuity neonatal intensive care unit (NICU).