An investigation of association between human milk mineral patterns and infant growth.

Introduction: Human milk is widely acknowledged as the optimal food for infant aged 0 ~ 6 months. While there has been extensive documentation on the mineral and trace element composition of human milk, results on the relationship between mineral content and infant growth remain mixed. This cross-sectional study aims to explore human milk mineral patterns and to investigate associations between human milk mineral patterns, human milk metabolomic profile and infant growth. Methods: A total of 200 breast milk samples from seven cities in China was included. Human milk mineral and trace elements was detected by inductively coupled plasma mass spectrometer (ICP-MS). K-means cluster analysis was utilized to derived human milk mineral patterns. Untargeted human milk metabolomic profiles was determined using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differences of infant growth rate and metabolomic profiles were then compared across patterns identified. Results: Three human milk mineral patterns were identified. Cluster I was characterized as the highest levels of potassium, magnesium and calcium, while the lowest levels of copper, zinc, manganese and selenium. Cluster II showed the most abundant sodium, iron, zinc, manganese and selenium. Cluster III had the lowest levels of sodium, potassium, magnesium, iron and calcium. Infants of cluster I showed significantly higher length-for-age z score (0.60 ± 2.03, p = 0.03). Compared with other clusters, samples of cluster I showed lower expression of metabolites of arachidonic acid (ARA) and nicotinate and nicotinamide metabolism pathway. Discussion: A human milk mineral pattern was identified which is related to increased infant growth rate and altered metabolic signature. Future work is needed to understand these human milk patterns in terms of biologic mechanisms and generalization to other populations.

From frozen to feeding: storage characteristics of banked donor human milk used in a single level IV academic neonatal intensive care unit.

Background: The storage time of banked donor human milk (DHM) administered in an academic hospital to critically ill preterm neonates was previously unknown. Objective: This study was designed to determine the storage time of banked DHM by measurements obtained at the hospital level (by lot finish date) and individual patient level (by feeding date) over 2-year observation period. Results: Both methods of measuring storage time (hospital-level and patient-level) showed that DHM was stored on average 8 ±1 months before use. Variations in storage time fluctuated across months with a minimum and maximum storage duration of 119 to 317 days. Most infants received a median of 3 [2-5 IQR] unique lots of DHM. Conclusion: The storage time of DHM was successfully measured. Over 95% of DHM received was stored longer than 6 months. Storage times varied widely, uncovering a potential area of future research.

Physiology of Human Lactation and Strategies to Support Milk Supply for Breastfeeding.

Despite advances across the globe in breastfeeding initiation rates, many families continue to report they are not meeting their breastfeeding goals. Concerns about milk supply, infant nutritional intake, and infant weight gain are among the most commonly cited reasons for early breastfeeding cessation. Nurses working with individuals during the perinatal period are uniquely positioned to educate families and offer evidence-based interventions to promote optimal milk supply, infant growth, and maternal mental and physical health. Such interventions include early and frequent skin-to-skin care, emptying of the breast, and professional lactation support. By implementing such evidence-based practices in the first hours after birth and connecting families to lactation support in the first 14 days, nurses can begin to help families achieve their breastfeeding goals.

Unpredictable supplementation of vitamin D to infants in the neonatal intensive care unit: An experimental study.

AIM: Extremely premature infants receive nutrition and medication through nasogastric tubes. Breastmilk given accordingly is subject to fat loss. This study aimed to investigate whether this could also apply to vitamin D. METHODS: A questionnaire investigated vitamin D administration at a level III neonatal intensive care unit in Sweden in 2021. Feeding simulations with breastmilk and various vitamin D mixtures were done accordingly. After administration, vitamin D3 concentration was analysed using chromatography with mass spectrometry, followed by repeated simulations with vitamin D mixtures without breastmilk in 2023. RESULTS: The questionnaire was completed by 10 persons. Vitamin D was administered as drops using an enteral syringe and a nasogastric tube in conjunction with a breastmilk meal. In the feeding simulations, vitamin D3 concentration after administration was significantly higher using a syringe alone compared to standard administration. When vitamins were administered according to standard but without breastmilk, 100% of the vitamin D and 40% of the multivitamins were lost. The vitamins adhered to the material, mainly in the nasogastric tube. CONCLUSION: Our findings indicate that standard vitamin D supplementation in the neonatal intensive care unit may be unpredictable when administered by enteral syringe and nasogastric tube. We suggest using direct oral administration whenever possible.

Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study.

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. Methods: Hospitalized infants and young children (aged 21 d to <18 mo) with respiratory, cardiac, and/or neurological symptoms suggestive of thiamine deficiency were treated with parenteral thiamine (100 mg daily) for ≥3 d alongside other treatments and re-examined systematically. Clinical case reports were reviewed by 3 pediatricians, who determined TRD or non-TRD status. Children in a community comparison group were matched by age, sex, and residence. Venous whole blood ThDP and MTh were determined by high-performance liquid chromatography fluorescence detection and ETKac in washed erythrocytes by ultraviolet spectrophotometry. Associations between biomarkers were assessed using Spearman correlations, and biomarker cutoffs predictive of TRD and ETKac >1.25 were explored using area under the receiver operating characteristic curve framework. Results: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants <6 mo had MTh <90 µg/L. ThDP and ETKac, but not MTh, were significantly different between 152 children with TRD and 122 without TRD, but overlapping distributions undermined prediction of individual responses to thiamine. Conclusions: Although ETKac, ThDP, and MTh are useful biomarkers of population thiamine status, none of the biomarkers reliably identified individual children with TRD. ThDP is more practical for population assessment because preparing washed erythrocytes is not required.This trial was registered at clinicaltrials.gov as NCT03626337.

Gut microbiota in preterm infants receiving breast milk or mixed feeding.

BACKGROUND: Preterm birth is the leading cause of mortality in newborns, with very-low-birth-weight infants usually experiencing several complications. Breast milk is considered the gold standard of nutrition, especially for preterm infants with delayed gut colonization, because it contains beneficial microorganisms, such as Lactobacilli and Bifidobacteria. AIM: To analyze the gut microbiota of breastfed preterm infants with a birth weight of 1500 g or less. METHODS: An observational study was performed on preterm infants with up to 36.6 wk of gestation and a birth weight of 1500 g or less, born at the University Hospital Dr. José Eleuterio González at Monterrey, Mexico. A total of 40 preterm neonates were classified into breast milk feeding (BM) and mixed feeding (MF) groups (21 in the BM group and 19 in the MF group), from October 2017 to June 2019. Fecal samples were collected before they were introduced to any feeding type. After full enteral feeding was achieved, the composition of the gut microbiota was analyzed using 16S rRNA gene sequencing. Numerical variables were compared using Student's t-test or using the Mann-Whitney U test for nonparametric variables. Dominance, evenness, equitability, Margalef's index, Fisher's alpha, Chao-1 index, and Shannon's diversity index were also calculated. RESULTS: No significant differences were observed at the genus level between the groups. Class comparison indicated higher counts of Alphaproteobacteria and Betaproteobacteria in the initial compared to the final sample of the BM group (P < 0.011). In addition, higher counts of Gammaproteobacteria were detected in the final than in the initial sample (P = 0.040). According to the Margalef index, Fisher's alpha, and Chao-1 index, a decrease in species richness from the initial to the final sample, regardless of the feeding type, was observed (P < 0.050). The four predominant phyla were Bacteroidetes, Actinobacteria, Firmicutes, and Proteobacteria, with Proteobacteria being the most abundant. However, no significant differences were observed between the initial and final samples at the phylum level. CONCLUSION: Breastfeeding is associated with a decrease in Alphaproteobacteria and Betaproteobacteria and an increase of Gammaproteobacteria, contributing to the literature of the gut microbiota structure of very low-birth-weight, preterm.

Cost analysis of establishing and operating the first human milk bank at Da Nang Hospital for Women and Children in Vietnam: an activity-based costing ingredients study.

BACKGROUND: Breastfeeding is the biological norm for feeding infants and young children. When mothers' breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam. METHODS: An activity-based costing ingredients (ABC-I) approach was employed, with the cost perspective from service provision agencies (specifically, the project conducted at Da Nang Hospital for Women and Children and Development Partners). Estimated financial costs, based on actual expenditures, were measured in 2023 local currency and then converted to 2023 US dollars (USD). We examined three scenarios: 1) direct start-up costs + indirect start-up costs + implementation costs, 2) direct start-up costs + implementation costs, and 3) capital costs + implementation costs over the 6.5 years of operation. RESULTS: The total start-up cost was USD 616,263, with total expenditure on direct activities at USD 228,131 and indirect activities at USD 388,132. Investment in equipment accounted for the largest proportion (USD 84,213). The monthly costs of Da Nang HMB were USD 25,217, 14,565, and 9,326, corresponding to scenarios 1, 2, and 3, respectively. Over HMB's 6.5 years of operation, on average, the unit costs were USD 166, USD 96, and USD 62 for DHM received and USD 201, USD 116, and USD 74 for pasteurized DHM meeting specified criteria in the corresponding scenarios. Unit costs were highest in the initial six months, decreased, and reached their lowest levels after a year. Then, the unit costs experienced an increase in late 2020 and early 2021. CONCLUSION: Although the unit cost of DHM in Da Nang HMB is comparable to that in certain neighboring countries, intentional measures to reduce disposal rates, improve HMB efficiency, motivate more community-based donors, and establish an HMB service network should be implemented to lower costs.

Human milk composition and infant anthropometrics: overview of a systematic review with clinical and research implications.

BACKGROUND: Despite global public health organizations endorsing breastfeeding or human milk (HM) as the optimal source of nutrition for infants, detailed knowledge of how HM composition influences infant growth is lacking. In this commentary we summarize and interpret the key findings of a large systematic review on HM components and child growth (N = 141 articles included). We highlight the most consistent associations, discuss study quality issues, explore socio-economic and time trends in this body of research, and identify gaps and future research directions. KEY FINDINGS OF SYSTEMATIC REVIEW: We grouped HM components into three categories: micronutrients (28 articles), macronutrients (57 articles), and bioactives (75 articles). Overall, we struggled to find consistent associations between HM components and infant growth. The majority of studies (85%) were of moderate or low-quality, with inconsistent HM collection and analysis strategies being identified as the most substantial quality concerns. Additional quality issues included failing to account for potential confounding by factors such as breastfeeding exclusivity and maternal body mass index. CONSIDERATIONS FOR FUTURE HUMAN MILK RESEARCH: Many opportunities exist for the future of HM research. Using untargeted metabolomics will expand our understanding of HM components beyond previously defined and well-understood components. Machine learning will allow researchers to investigate HM as an integrated system, rather than a collection of individual components. Future research on HM composition should incorporate evidence-based HM sampling strategies to encompass circadian variation as well as infant consumption. Additionally, researchers need to focus on developing high quality growth data using consistent growth metrics and definitions. Building multidisciplinary research teams will help to ensure that outcomes are meaningful and clinically relevant. CONCLUSION: Despite a large body of literature, there is limited quality evidence on the relationship between HM composition and infant growth. Future research should engage in more accurate collection of breastfeeding data, use standardized HM collection strategies and employ assays that are validated for HM. By systematically evaluating the existing literature and identifying gaps in existing research methods and practice, we hope to inspire standardized methods and reporting guidelines to support robust strategies for examining relationships between HM composition and child growth.

Total Nitrite and Nitrate Concentration in Human Milk and Saliva during the First 60 Days Postpartum-A Pilot Study.

Nitric oxide (NO) in human milk may have important functions in lactation and infant health. This longitudinal pilot cohort study investigated the total nitrite and nitrate (NOx) concentration in human milk and maternal saliva during the first 60 days postpartum. Additionally, we explored the association between selected breastfeeding variables and milk and saliva NOx concentration. Human milk and maternal saliva samples were collected on days 2, 5, 14, 30, and 60 postpartum and analyzed for NOx concentration. Breastfeeding data were collected through self-assessed questions. Data analyses were performed using mixed models. The concentration of NOx in milk was significantly higher during the first 30 days compared to day 60, and there was a positive association between milk and saliva NOx concentrations throughout the entire study period. In absolute numbers, partially breastfeeding mothers had a lower concentration of NOx in milk on day 2 compared to exclusively breastfeeding mothers (8 vs. 15.1 µM, respectively). Partially breastfeeding mothers reported a later start of secretory activation and fewer mothers in this group started breastfeeding within the first hour after birth. Due to the small numbers, these differences could not be statistically evaluated. Further research is warranted to elucidate the role of NO in lactation success and breastfeeding outcomes.

Impact of Holder Pasteurization and Preanalytical Handling Techniques on Fat Concentration in Donor Human Milk: A Scoping Review.

BACKGROUND: Donor human milk (DHM) is an essential source of nutrition among high-risk infants (e.g., premature and low-birth weight). Holder pasteurization, a common step in DHM processing, is known to partially alter the composition of DHM; however, the impact on fat composition is historically inconsistent. OBJECTIVES: This scoping review aimed to broadly review the literature on the impact of Holder pasteurization on the fat content in DHM, with a focus on preanalytical sample mixing. METHODS: A systematic search of original, peer-reviewed research articles was conducted on 11 July, 2022. Articles were included if they compared matched raw (control) and Holder-pasteurized human milk samples and measured total lipids, cholesterol, and individual classes of fatty acids. Article review and selection was conducted by 2 independent reviewers. RESULTS: The search yielded 26 original, peer-reviewed research articles published between 1978 and 2022. Overall methodology varied considerably between studies. When study methods described any mixing for collecting raw milk, 1 (17%) of the 6 of studies reported a small change in total fat concentration following pasteurization (<5%). Alternatively, among studies that did not describe methods for mixing raw milk to ensure a representative sample, 10 (56%) of the 18 reported a significant change (≥± 5%) in total fat concentration, with changes ranging from -28.6% to +19.4%. CONCLUSIONS: This review suggests that inconsistent findings regarding the impact of Holder pasteurization on fat may be related to study methodologies, particularly preanalytical sample mixing. More research considering the role of preanalytical handling procedures and methodologies is necessary to help clarify the impact of Holder pasteurization on human milk composition.

Identification and Prioritization of Organic Pollutants in Human Milk from the Yangtze River Delta, China.

Pollutants in human milk are critical for evaluating maternal internal exposure and infant external exposure. However, most studies have focused on a limited range of pollutants. Here, 15 pooled samples (prepared from 467 individual samples) of human milk from three areas of the Yangtze River Delta (YRD) in China were analyzed by gas chromatography quadrupole time-of-flight mass spectrometry. In total, 171 compounds of nine types were preliminarily identified. Among these, 16 compounds, including 2,5-di-tert-butylhydroquinone and 2-tert-butyl-1,4-benzoquinone, were detected in human milk for the first time. Partial least-squares discriminant analysis identified ten area-specific pollutants, including 2-naphthylamine, 9-fluorenone, 2-isopropylthianthrone, and benzo[a]pyrene, among pooled human milk samples from Shanghai (n = 3), Jiangsu Province (n = 6), and Zhejiang Province (n = 6). Risk index (RI) values were calculated and indicated that legacy polycyclic aromatic hydrocarbons (PAHs) contributed only 20% of the total RIs for the identified PAHs and derivatives, indicating that more attention should be paid to PAHs with various functional groups. Nine priority pollutants in human milk from the YRD were identified. The most important were 4-tert-amylphenol, caffeine, and 2,6-di-tert-butyl-p-benzoquinone, which are associated with apoptosis, oxidative stress, and other health hazards. The results improve our ability to assess the health risks posed by pollutants in human milk.

2'-Fucosyllactose Inhibits Human Norovirus Replication in Human Intestinal Enteroids.

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2'-fucosyllactose (2'FL) in the same pocket as HBGAs for some HuNoV strains. We evaluated the effect of 2'FL on the replication of a globally dominant GII.4 Sydney [P16] HuNoV strain using human intestinal enteroids (HIEs) from adults and children. A significant reduction in GII.4 Sydney [P16] replication was seen in duodenal and jejunal HIEs from multiple adult donors, all segments of the small intestine from an adult organ donor and in two pediatric duodenal HIEs. However, 2'FL did not inhibit HuNoV replication in two infant jejunal HIEs that had significantly lower expression of α1-2-fucosylated glycans. 2'FL can be synthesized in large scale, and safety and tolerance have been assessed previously. Our data suggest that 2'FL has the potential to be developed as a therapeutic for HuNoV gastroenteritis.

Equations to estimate human milk intake in infants aged 7 to 10 months: prediction models from a cross-sectional study.

BACKGROUND: Obtaining valid estimates of nutrient intake in infants is currently limited by the difficulties of accurately measuring human milk intake. Current methods are either unsuitable for large-scale studies (i.e., the gold standard dose-to-mother stable isotope technique) or use set amounts, regardless of known variability in individual intake. OBJECTIVES: This cross-sectional study aimed to develop equations to predict human milk intake using simple measures and to carry out external validation of existing methods against the gold standard technique. METHODS: Data on human milk intake were obtained using the dose-to-mother stable isotope technique in 157 infants aged 7-10 mo and their mothers. Predictive equations were developed using questionnaire and anthropometric data (Model 1) and additional dietary data (Model 2) using lasso regression. Bland-Altman plots and intraclass correlation coefficients (ICC) also assessed the validity of existing methods (FITS and ALSPAC studies). RESULTS: The strongest univariate predictors of human milk intake in infants of 8.3 mo on average (46% female) were infant age, infant body mass index (BMI), number of breastfeeds a day, infant formula consumption, and energy from complementary food intake. Mean [95% confidence interval (CI)] differences in predicted versus measured human milk intake [mean (SD): 762 (257) mL/day] were 0.0 mL/day (-26, 26) for Model 1 (ICC 0.74) and 0.5 mL/day (-21, 22) for Model 2 (ICC 0.83). Corresponding differences were -197 mL/day (-233, -161; ICC 0.32) and -175 mL/day (-216, -134; ICC 0.41) for the methods used by FITS and ALSPAC, respectively. CONCLUSIONS: The Human Milk Intake Level Calculation provides substantial improvements on existing methods to estimate human milk intake in infants aged 7-10 mo, while utilizing data commonly collected in nutrition surveys. Although further validation in an external sample is recommended, these equations can be used to estimate human milk intake at this age with some confidence. This clinical trial was registered at http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379436) as ACTRN12620000459921.

The human milk endocannabinoidome and neonatal growth in gestational diabetes.

Objective: Endocannabinoids and their N-acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed in utero to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth. Methods: Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated. Results: Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (ß=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring. Conclusion: The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months. Clinical trial registration: ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).

Having Enough Milk to Sustain a Lactation Journey: A Call to Action.

The rates of human milk feeding are suboptimal worldwide. Recommendations for healthy, term mother-infant dyads include early breastfeeding initiation, frequent skin-to-skin contact, and frequent breastfeeding. The normal physiology of lactation can be affected by prenatal factors such as diabetes, obesity, and excessive gestational weight gain. Furthermore, birth-related factors such as early-term gestation, stressful labor, unscheduled cesarean birth, and postpartum hemorrhage can additionally disrupt recommended practices such as early initiation of breastfeeding and skin-to-skin contact. Given that the first 2 to 3 days postpartum are critical to achieving timely secretory activation and establishing an adequate volume of milk, a proactive approach to care can include building awareness of risk factors and development of protocols for the effective early initiation of lactation.

Comparison of protein digestibility of human milk and infant formula using the INFOGEST method under infant digestion conditions.

Many improvements have been made to bring infant formula (IF) closer to human milk (HM) regarding its nutritional and biological properties. Nevertheless, the protein components of HM and IF are still different, which may affect their digestibility. This study aimed to evaluate and compare the protein digestibility of HM and IF using the infant INFOGEST digestion method. Pooled HM and a commercial IF were subjected to the infant INFOGEST method, which simulates the physiological digestion conditions of infants, with multiple directions, i.e., the curd state, SDS-PAGE, molecular weight distribution, free amino acid concentration, and in vitro protein digestion rate. HM underwent proteolysis before digestion, and tended to have a higher protein digestion rate with finer curds during gastric digestion, than the IF. However, multifaceted analyses showed that the protein digestibility of HM and IF was not significantly different after gastrointestinal digestion. In conclusion, the infant INFOGEST method showed that the digestibility of HM and IF proteins differed to some extent before digestion and after gastric digestion, but not at the end of gastrointestinal digestion. The findings of this study will contribute to the refinement of IFs with better protein digestibility in infant stomach.

A simple step to improve fat and energy delivery of human milk delivered via bottle-feeding pump, an experimental study.

BACKGROUND: Enteral feeding pump systems deliver decreased amounts of macronutrients in human milk to neonates. This study determined the macronutrient loss associated with a bottle-feeding pump system and the effect of manually mixing the human milk during extended feeds. METHODS: Macronutrient content from samples of donor human milk was analyzed after simulated extended feeds with a bottle-feeding pump system, using a human milk analyzer. Simulations were repeated using manual mixing of the bottle every 30 min during feeding. The percentage of the baseline was calculated, and one-sample t tests and analysis of variance compared the effect of manual mixing and the duration of feeding on macronutrient delivery. RESULTS: The delivery of fat and energy was lower over time, but manual mixing considerably improved retention. The length of feeding impacted fat delivery, with less fat delivered over time (P < 0.001). Manually mixing significantly increased fat delivery (P < 0.001). Similar results were found for energy, with a significant reduction in energy delivery over time (P < 0.001) and significantly more energy delivered with mixing (P < 0.001). Mixing and the duration of feeding had minimal effect on protein or carbohydrate delivery. CONCLUSIONS: Bottle-feeding pump systems are associated with a significant reduction in the delivery of fat and energy of donor human milk. The manual mixing of donor human milk during prolonged feeds is a simple way to improve fat and energy delivery to the neonate.

A Systematic Review over the Effect of Early Infant Diet on Neurodevelopment: Insights from Neuroimaging.

The optimization of infant neuronal development through nutrition is an increasingly studied area. While human milk consumption during infancy is thought to give a slight cognitive advantage throughout early childhood in comparison to commercial formula, the biological underpinnings of this process are less well-known and debated in the literature. This systematic review seeks to quantitatively analyze whether early diet affects infant neurodevelopment as measured by various neuroimaging modalities and techniques. Results presented suggest that human milk does have a slight positive impact on the structural development of the infant brain-and that this impact is larger in preterm infants. Other diets with distinct macronutrient compositions were also considered, although these had more conflicting results.

Human milk proteins differentiate over the sex of newborns and across stages of lactation.

BACKGROUND & AIMS: Human milk (HM) is a complete food that meets the nutritional and energy demands of the newborns. It contains numerous bioactive components, including functional proteins. Variations in HM energy and lipid content have already been reported related to the newborn's sex, but differences between protein profiles are still scarce. This work aimed to identify differences between HM proteins produced by mothers of female and male newborns, in the lactation stages of colostrum and mature milk, and the metabolic pathways involved. METHODS: A total of 98 HM samples were collected from 39 lactating women and classified according to the newborn's sex, stages of lactation, and three mothers' age groups, and evaluated about protein concentration and one-dimensional electrophoretic profile. Next, to assess samples with the greatest differences, the HM proteins regarding the newborn's sex and the stages of lactation were compared using nano-LC-MS/MS, in 24 HM samples randomly rearranged into four groups: female and male infants, and colostrum and mature milk. Functional classification, metabolic pathways, and protein interaction networks were analyzed by Gene Ontology, KEGG, and STRING, respectively. RESULTS: The soluble protein content of HM decreased throughout lactation, with differences regarding isolated factors, such as mothers' age group, child's sex and stages of lactation, and also in terms of their interactions. A total of 146 proteins were identified, 42 of which showed different abundances over the sexes of newborns and 53 between the stages of lactation. In general, proteins related to metabolic processes were up-regulated for mothers of male infants and in the mature stage of lactation, while proteins related to defense were up-regulated in mothers of female infants and in the colostrum phase. CONCLUSION: This study indicated that there are differentiated and specific nutritional and defense needs of newborns, by sex and by lactation phase, which is highly relevant for a more appropriate supply of food to infants receiving HM from donor mothers.