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BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth.OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively.PATIENTS/METHODS: Prospective, multi-center, observational study in preterm infants born RESULTS: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies.CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

The health benefit of human milk (HM) for preterm infant development is known but the role of human milk oligosaccharides (HMOs) contained in HM remains underexplored. We explored the relationship between exposure to HMOs contained in mother's milk and growth and neurodevelopment at 2-years corrected age in preterm infants.Exclusively breastfed preterm infants born between 27 and 34 weeks of gestation were enrolled in a monocentric prospective observational study, LACTACOL. Samples of breast milk were collected once a week for 7 weeks after birth. HMOs and sialic acid were measured by liquid chromatography. Age and Stages questionnaire (ASQ) version 2 was used to assess 2-year neurodevelopmental outcome. We analyzed the relationship between HMO content and (i) infant neurodevelopment at 2-years, and (ii) growth outcome at discharge and at 2 years. A secondary analysis was performed among Secretor(+) Lewis(+) mothers. Only associations with a false discovery rate of 10% or less according to the Benjamini-Hochberg procedure were considered significant.137 preterm infants (mean gestational age of 31.3 ± 1.7 weeks, mean birth weight of 1494 g ± 336 g) born to 117 mothers (mean age of 30.8 ± 5.0 years) were enrolled. Total HMOs and most individual HMOs and sialic acid concentrations decreased with advancing postnatal age, except for lacto-N-fucopentaose-III and 3-fucosyllactose, which increased. Total HMOs were positively correlated with neonatal length growth (adjusted p = 0.012). Neither total HMOs nor any individual HMO correlated with ASQ score in the overall cohort. However, lacto-N-fucopentaose-III (LNFP-III) was significantly associated with total ASQ score (adjusted p ≤ 0.015) among the 104 infants born to Secretor(+) Lewis(+) mothers.In this exploratory study in very preterm infants, total HMOs and most individual HMOs, except LNFP-III, decreased with advancing postnatal age. Neither the concentration of total HMOs nor that of any individual HMO were associated with ASQ score at 2 years, except for LNFP-III in Secretor(+) Lewis(+) mothers.

The purpose of this study was to compare the structural and physical properties between normal bovine milk and A2 bovine milk fermented using commercial fermentation bacteria mixing with/without Lactiplantibacillus plantarum MWLp-12 and Limosilactobacillus fermentum MWLf-4 screening from human milk. Scanning Electron Microscopy (SEM), SDS-PAGE and inverted fluorescence microscope were used for analyzing the structural differences. Titratable acidity and pH, water holding capacity, rheology, texture performances, and chromaticity value were determined for evaluating differences in the physical properties. We found that A2 fermented milk had better viscosity characteristics and stable structure than normal fermented milk. Importantly, the significant differences in structure and physical properties would affirm that differences structures were existing in casein micelle between normal bovine milk and A2 bovine milk. In addition, the addition of MWLp-12 and MWLf-4 strains could enhance the proteolysis and bring in more pilotaxitic texture leading to the fermented milk possessing a greater texture performance. Therefore, this study will be an interest to the dairy industry for developing novel dairy products, and the two strains will be the potential probiotics to be applied on fermented milk preparation.

Establishment of the gut microbiome during early life is a complex process with lasting implications for an individual's health. Several factors influence microbial assembly; however, breast-feeding is recognized as one of the most influential drivers of gut microbiome composition during infancy, with potential implications for function. Differences in gut microbial communities between breast-fed and formula-fed infants have been consistently observed and are hypothesized to partially mediate the relationships between breast-feeding and decreased risk for numerous communicable and noncommunicable diseases in early life. Despite decades of research on the gut microbiome of breast-fed infants, there are large scientific gaps in understanding how human milk has evolved to support microbial and immune development. This review will summarize the evidence on how breast-feeding broadly affects the composition and function of the early-life gut microbiome and discuss mechanisms by which specific human milk components shape intestinal bacterial colonization, succession, and function.

To evaluate the relationship between maternal COVID-19 infection and the odds of in-hospital exclusive breastfeeding for term newborns.Retrospective descriptive quantitative.A large, urban hospital with more than 6,000 births annually.Term newborns born between March 1, 2020, and March 31, 2021 (N = 6,151).We retrospectively extracted data from electronic health records to evaluate the relationship of maternal COVID-19 infection with the odds of in-hospital exclusive breastfeeding using univariate analysis and logistic regression models. The covariates included insurance type, race/ethnicity, glucose gel administration, length of stay, newborn gestational age, newborn birth weight, and maternal COVID-19 infection.Maternal COVID-19 infection was not significantly related to the odds of in-hospital exclusive breastfeeding (p = .138) after adjustment for covariates in the logistic regression model. However, when newborns who received pasteurized donor human milk supplementation were excluded from the logistic regression model, maternal COVID-19 infection significantly decreased the odds of in-hospital exclusive breastfeeding (p = .043).Maternal COVID-19 infection was not significantly related to the odds of in-hospital exclusive breastfeeding when newborns received donor human milk supplementation. Access to donor human milk for supplementation for term newborns may protect the odds of in-hospital exclusive breastfeeding.

Vaccination is the best strategy against COVID-19. We aimed to determine antibodies against SARS-CoV-2 in breastmilk and serum of mothers vaccinated with the mRNA vaccine.This prospective study included 18 lactating women vaccinated with the BNT162b2 vaccine. Serum and breastmilk were collected before the first dose (T0), at the second dose (T1), 3 weeks after the second dose (T2), and 6 months after the first dose (T3). Serum anti-SARS-CoV-2 Spike (S) Immunoglobulin G (IgG) and Immunoglobulin A (IgA) were measured using a semi-quantitative enzyme-linked immunosorbent assay (ELISA) and secretory antibody (s) IgG and IgA in breastmilk using quantitative analysis.We detected serum anti-S IgG and IgA in all women after vaccination. Specific IgG and IgA were higher at T1, T2, and T3 compared with T0 (P 0.0001). Higher antibody levels were observed at T2 and lower values at T3 versus T2 (P = 0.007). After 6 months, all patients had serum IgG, but three of 18 (16%) had serum IgA. In breastmilk, sIgA was present at T1 and T2 and decreased after 6 months at T3 (P = 0.002). Breastmilk sIgG levels increased at T1 and T2 and peaked at T3 (P = 0.008).Secretory antibodies were transmitted through breastmilk until 6 months after anti-COVID-19 mRNA vaccination. Protection of the newborn through breastfeeding needs to be addressed.

Determining calcium requirements for infants and children is vital due to high calcium needs for growth. Balance studies enable comprehensive measurement of calcium metabolism and can support nutrient requirement development. This systematic review summarizes evidence from mass balance and isotopic studies in children aged 0-4 y to address key questions on calcium loss and absorption/retention identified by an expert group developing calcium requirements. Literature searches were implemented in multiple electronic databases to June 2020. Balance studies assessing calcium intake, loss, absorption, or retention in healthy children were eligible. A newly developed risk-of-bias assessment tool was used for balance studies, and a modified Grades of Recommendation, Assessment, Development, and Evaluation approach determined strength of evidence. Altogether, 23 studies (15 mass balance; 8 isotope) with 485 total participants were included. Only 3 studies were of children6 mo. Mass balance studies suggested infant feed components may influence calcium balance. The random-effects model meta-regression on 42 mass balance study arms showed an average net calcium retention of 40.4% among infants aged 0-6 mo (β = 0.404 [95% CI: 0.302, 0.506]). Isotope studies suggested calcium intake of 240 to 400 mg/d may promote optimal calcium absorption with minimal loss, and intake from human milk may lead to greater absorption and retention efficacy than formula or solid foods. Most studies had low risk of bias. Strength of evidence was low due to variability in infant feedings, limited endogenous and dermal calcium loss measures, and few studies isolating calcium effects. To improve certainty of the body of evidence, more balance studies isolating effects of calcium intake in this age group are needed. Future work on calcium needs should incorporate both balance measures and biological endpoints of importance (e.g. bone mineral density or content) to determine adequate calcium intake for growth in infants and children.

Lipids are a major source of energy during the fetal/neonatal period. Most are received from the mother, either transplacentally during the intrauterine period or via maternal milk after birth. However, in addition to the known nutritional role(s), lipids are now known to bind a variety of cellular receptors to regulate specific patterns in metabolism and gene expression. The expression of these receptors is regulated by various genetic and environmental stimuli, and ligation can activate positive-feedback loops both in the expression and the activity of downstream signaling pathways. In this review, we summarize the role of lipid ligands, cognate receptors, epigenetic regulation, and downstream signaling. Further study of lipid metabolism and downstream signaling pathways can enable specific, disease-focused translational studies.

In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant.Our objective here was to characterize the mammary gland transcriptomes from the above study. We hypothesized that proinflammatory gene expression would be attenuated in the increased DHA group compared with the standard DHA group.In the original trial, mothers delivering at 29 wk gestation at the University of Cincinnati Medical Center and intending to express their milk were randomly assigned to supplementation with 200 mg/d DHA (standard group: STD) or 1000 mg/d DHA (experimental group: EXP) within 7 d of delivery. Here, we conducted RNA-seq transcriptome analysis of n = 5 EXP and n = 4 STD extracellular mammary mRNA samples extracted from the fat layer of milk samples obtained 4 wk postenrollment. Transcripts were assessed for differential expression (false discovery rate adjusted P value 0.05) and clustering between EXP compared with STD groups. Ontological analysis of all differentially expressed genes (DEGs) was performed with Toppcluster.There were 409 DEGs. We observed 5 main groups of biological processes that were upregulated, including those associated with improved immune regulation and management of oxidative stress; and 3 main groups of biological processes that were downregulated, including 1 associated with immune dysregulation. For example, we observed upregulation of inflammation-inhibiting genes including NFKB inhibitor alpha (NFKBIA; fold-change (FC), adjusted P value: FC = 1.70, P = 0.007) and interleukin-18 binding protein (IL18BP: FC = 2.2, adjusted P = 0.02); and downregulation of proinflammatory genes including interleukin 7 receptor (IL7R: FC = -1.9, adjusted P = 0.02) and interleukin 1 receptor like 1 (IL1RL1: FC = -13.0, adjusted P = 0.02).Increased DHA supplementation during lactation can modulate the expression of inflammation-related genes within the mammary gland. This might translate to milk composition with a more optimal inflammasome profile. Future research with a larger clinical trial and greater interrogation of clinical outcomes is warranted.

Most pregnant or lactating women in Canada will not meet iodine requirements without iodine supplementation.To assess the iodine status of 132 mother-infant pairs based on secondary analyses of a vitamin D supplementation trial in breastfed infants from Montréal, Canada.Maternal iodine status was assessed using the breastmilk iodine concentration (BMIC). Singleton, term-born infants were studied from 1-36 months of age. Usual (adjusted for within-person variation) iodine intakes were estimated from urinary iodine and creatinine concentrations. Iodine status was assessed using median urinary iodine concentrations (UICs) and by estimating inadequate intakes by the cut-point method using a proposed Estimated Average Requirement for infants 0-6 months of age (72 μg/d).At 1, 3, and 6 months of age, 70%, 63%, and 3% of infants, respectively, were exclusively breastfed. From 1-36 months of age (n = 82-129), the median UICs were ≥100 μg/L (range, 246-403 μg/L), which is the cutoff for adequate intakes set by the WHO for children2 years. Almost all (98%-99%) infants at 1 and 2 months, 2 and 3 months, and 3 and 6 months of age had usual creatinine-adjusted iodine intakes ≥ 72 μg/d. The median BMIC was higher (P 0.001) at 1 month compared to 6 months of lactation [1 month, 198 μg/kg (IQR, 124-274; n = 105) and 6 months, 109 μg/kg (IQR, 67-168; n = 78)]. At 1 and 6 months, 96% and 79% of mothers, respectively, had a BMIC ≥ 60 μg/kg, the lower limit of a normal reference range. The percentages of mothers that used a multivitamin-mineral (MVM) supplement containing iodine were 90% in pregnancy and 79% and 59% at 1 and 6 months of lactation, respectively.The iodine status of infants was adequate throughout infancy. These results support a recommendation that all women who could become pregnant, who are pregnant, or who are breastfeeding take a daily MVM supplement containing iodine.

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS−based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Objective: To evaluate the complementary feeding practices, food intake, and nutritional status of infants on a cow’s milk protein elimination diet. Methods: A cross-sectional and observational study was conducted to compare infants aged 4-18 months who were on a cow’s milk protein elimination diet with a control group of healthy infants without any dietary restrictions. General information on the child’s health, demographic data, and food consumption were collected. Results: The study included 96 infants in the elimination diet group and 99 in the control group. In the elimination diet group, the median age (in months) of introduction of solid foods (5.0 × 4.0; p < 0.001) and water (5.5 × 4.0; p < 0.05) was later, consumption of soft drinks and industrialized cookies was less frequent (p < 0.05), and a lower index of complementary feeding inadequacies (2.75 × 3.50; p < 0.001) was observed. The elimination diet group presented lower individual values of Z scores for weight/age, weight/height, and body mass index/age, although they were fed with higher amounts of energy (117.4 × 81.3 kcal/kg of weight; p < 0.001) and macro-and micronutrients, except for vitamin A. In the elimination diet group, breast milk and its substitutes contributed to more than 67% of energy intake. Although calcium consumption was a deficit in 31.5% of the infants, none received supplementation. Conclusion: Infants on an elimination diet presented more adequate complementary feeding practices and higher nutritional intake, despite lower body weight values.

Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs).The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk.This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study.A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital.Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.

Secretory immunoglobulin A (SIgA) in human milk plays a central role in complex maternal-infant interactions that influence long-term health outcomes. Governed by genetics and maternal microbial exposure, human milk SIgA shapes both the microbiota and immune system of infants. Historically, SIgA-microbe interactions have been challenging to unravel due to their dynamic and personalized nature, particularly during early life. Recent advances have helped to clarify how SIgA acts beyond simple pathogen clearance to help guide and constrain a healthy microbiota, promote tolerance, and influence immune system development. In this review, we highlight these new findings in the context of the critical early-life window and propose outstanding areas of study that will be key to harnessing the benefits of SIgA to support healthy immune development during infancy.

Exposure of newborns to persistent organic pollutants (POPs) is a public health concern. The objective of this study was to assess the prevalence of POPs in human milk collected from lactating mothers in Lebanon and to investigate the sociodemographic, nutritional, and other lifestyle determinants. Fifty-four breast milk samples were collected as per World Health Organization guidelines. A survey was used to assess the anthropometric and demographic characteristics of participants. Dietary habits were evaluated based on a semiquantitative food frequency questionnaire. Organochlorine pesticides and polychlorinated biphenyls were measured in milk samples with liquid-liquid extraction and gas chromatography. Among the screened POPs, dichlorodiphenyldichloroethylene (DDE) was the only POP detected in breast milk samples and was found in only 17.9% of the samples, with a mean (SD) of 11.6 (5.0) μg/L and a range of 5.7 to 21.4 μg/L. Prepregnancy body mass index and age were positively associated with DDE contamination in breast milk. Women who consumed cereals at least two times per week had detectable DDE contamination in their breast milk. Consumption of potatoes and beans at least once per week was also associated with DDE contamination. Our study is the first to assess the presence of POPs in breast milk in Lebanon. The benefits of breastfeeding compensate for the low prevalence of DDE in the breast milk. Our findings highlight the high need to implement monitoring policies, good agricultural practices, and education programs for breastfeeding mothers.

Objective To explore trajectories of breastfeeding exclusivity and perceived insufficient milk (PIM) over the first 8 weeks postpartum among primiparous women and the association of these trajectories with prepregnancy body mass index (BMI). Design Secondary analysis of data from a randomized controlled trial. Setting Recruitment for the primary study was conducted in Pittsburgh, Pennsylvania. Participants One hundred twenty-two primiparous women with intention to exclusively breastfeed. Methods We used group-based trajectory modeling to classify participants into breastfeeding exclusivity and PIM trajectory groups. We used logistic regression to explore the predictive relationship between prepregnancy BMI and breastfeeding exclusivity and PIM trajectory group memberships. Results We identified two trajectories each for breastfeeding exclusivity and PIM over the first 8 weeks postpartum. For breastfeeding exclusivity, one group (n = 60, 49%) had low initial probability of exclusive breastfeeding with linear decline in likelihood of exclusivity over time. The other group (n = 62, 51%) had greater initial probability of exclusive breastfeeding, which remained constant over time. For PIM, one group (n = 41, 34%) had consistently greater probability of endorsing PIM at each time point, whereas the other group (n = 81, 66%) had consistently low probability of endorsing PIM over time. Prepregnancy BMI did not predict group membership in breastfeeding exclusivity, χ2(1) = 2.8, p = .094, or PIM, χ2(1) = 0.72, p = .397. Conclusion Breastfeeding exclusivity and PIM appeared to be relatively stable phenomena in the postpartum period among a sample of predominately White primiparous women who intended to breastfeed. We did not find a clear association with prepregnancy BMI.

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease which mostly occurs in very low birth weight (VLBW) infants. In addition to decreasing gestational age (GA) or birth weight (BW), artificial formula, delayed initiation or rapidly advanced feeding, severe anemia and systemic infections were associated with NEC. Several studies demonstrated that breast milk, standardized feeding advancement regimens and treatment of anemia are associated with less incidence of NEC. It is not known if including all these interventions in one multifaceted program will lead to significant reduction in NEC.The NICU team at The George Washington University Hospital created a multifaceted interdisciplinary quality improvement project to tackle several aspects of NEC prevention that addressed researched risk factors for NEC. The program was made of four quality improvement protocols: 1) Standardized Structured Feeding Program, 2) Feeding Intolerance Management Algorithm, 3) Enteral Osmolality Control Tool, and 4) Packed Red Blood Cell (RBC) Standardized Transfusion Protocol. This time-series, quasi experimental study design examined the differences in the incidence of NEC between infants with BW1500 g who were admitted to the GW Hospital NICU before and after the program implementation.Data from 408 VLBW infants were included in the study. Although not statistically significant, there was a decreasing trend of NEC incidence in the post-implementation group (n = 199) compared to the pre-implementation group (n = 209), (3.5% vs. 5.3%, p = 0.88). The trend in the incidence of NEC declined further after the introduction of RBC transfusion protocol which was introduced ten month after starting the other elements of the program.Integration of the multifaceted quality improvement program may be associated with a decline in the occurrence of NEC. Further analysis with a larger sample size is required to determine if the changes seen are statistically significant.

Our knowledge about the complexity of human milk, in particular fatty acid, protein, and oligosaccharide profiles, has increased considerably in recent years. However, little attention has been paid to nucleotides, which account for ∼2% to 5% of the nonprotein nitrogen fraction of breast milk and provide important cellular and metabolism functions for the infant. We examined literature published in the past 25 years to provide an updated review of concentrations of nucleotides in breast milk across lactational stages in mothers around the world. The free mononucleotides found in highest concentrations in breast milk are, from highest to lowest in the order of cytidine 5'-monophosphate, uridine 5'-monophosphate, and adenosine 5'-monophosphate, guanosine 5'-monophosphate, and inosine 5'-monophosphate. Levels of nucleotides varied considerably amongst individual mothers and with stage of lactation. They could be further influenced by time of day and season and the mother's diet. Levels of free nucleotides varied between studies undertaken in different regions; however, in studies that measured total potentially available nucleotides levels, regional differences were not apparent. Some studies report higher amounts in colostrum and transition milk compared with mature milk, whereas other studies report the converse. Recently, clinical studies showed that there are benefits to supplement nucleotides in infant formula. Although comparing data in the literature remains a challenge because of different milk collection methodologies and measurement protocols used by different studies, the information may provide insights for designing of formula products for infant at different stages of development.

Bifidobacteria are widely used as a probiotic for their health-promoting effects. To promote their growth, bifidogenic prebiotics, including human milk oligosaccharides (HMOs), have been added to supplements and infant formula. However, the efficacy of both probiotic and prebiotic interventions is often debated, as clinical responses vary significantly by case. Here, we review clinical studies that aimed to proliferate human-residential Bifidobacterium (HRB) strains in the gut, and we highlight the difference between responders and non-responders to such interventions through an ecological, niche-based perspective and an examination of the prevalence of genes responsible for prebiotic assimilation in HRB genomes. We discuss the criteria necessary to better evaluate the efficacy of probiotic and prebiotic interventions and the recent therapeutic potential shown by synbiotics.

PURPOSE: Despite recommendations from the World Health Organization and the American Academy of Pediatrics to exclusively breastfeed infants for their first 6 months of life, 75% of women do not meet exclusive breastfeeding guidelines and 60% do not meet their own breastfeeding goals. Numerous observational studies have linked maternal psychological distress (e.g., perceived stress, anxiety, depression) with non-optimal breastfeeding outcomes, such as decreased proportion and duration of exclusive breastfeeding. The physiological mechanisms underlying these associations, however, remain unclear. METHODS: For this narrative review, we evaluated the evidence for relationships between maternal psychological distress and lactation and breastfeeding outcomes in pregnancy and postpartum and the possible physiological mechanisms that facilitate these relationships. We searched PubMed using the following terms: “stress”, “anxiety”, “depression”, “breastfeeding”, and “lactation”. A further hand-search was conducted to ensure a thorough review of the literature. FINDINGS: Among the studies examined, methods used to assess maternal psychological distress were not uniform, with some studies examining perceived distress via a variety of validated tools and others measuring biological measures of distress, such as cortisol. Evidence supports a role for psychological distress in multiple breastfeeding outcomes, including delayed secretory activation and decreased duration of exclusive breastfeeding. One physiological mechanism proposed to explain these relationships is that psychological distress may impair the release of oxytocin, a hormone that plays a critical role in milk ejection during lactation. Continued impairment of milk ejection may lead to decreased milk production due to incomplete emptying of the breast during each feed. Maternal distress may also yield elevated levels of serum cortisol and decreased insulin sensitivity, which are associated with decreased milk production. The relationship between psychological distress and breastfeeding is likely to be bidirectional, however, in that breastfeeding appears to reduce maternal distress, again possibly via their effects on the pleasure/reward and calming effects of oxytocin on the mother. This suggests interventions to support lactation and breastfeeding goals in women who score high on measures of psychological distress would be beneficial for both maternal and infant well-being. IMPLICATIONS: Evidence to date suggests that maternal psychological distress may impair lactation and breastfeeding outcomes, but stronger study designs and rigorous assessment methods are needed. A better understanding of the physiological mechanisms leading to impaired lactation may assist in the development of early interventions for mothers experiencing distress. In addition, stress-reducing programs and policies should be investigated for their potential to improve breastfeeding outcomes.

BACKGROUND: The human milk microbiome may contribute to the benefits of breastfeeding by providing bacteria to the infant gastrointestinal tract. Many women pump their milk, but the effect of pumping on the milk microbiome is unknown. OBJECTIVES: Our objective was to determine the effects of pumping supplies on the pumped human milk microbiome. METHODS: This was an in-home, randomized, crossover trial of 2 collection methods. Women (n = 52) pumped twice within 3.5 h, once with their own breast pumps and milk collection supplies (OWN SUPP) and once with a hospital-grade pump and sterile collection supplies (STER SUPP). Pumping order was randomized. The milk microbiome was characterized by aerobic culturing and 16S ribosomal RNA gene sequencing. RESULTS: Milk collected with OWN SUPP yielded more total aerobic and gram-negative bacteria than milk collected with STER SUPP, reflecting a 6.6 (adjusted OR; 95% CI: 1.7, 25; P = 0.006) higher odds of containing >10(4) total aerobic CFU/mL and 19 (adjusted OR; 95% CI: 4.1, 88; P

Background Breast milk feedings are the optimal feeding choice for premature infants. Clinicians depend on accurate nutrient profiles of the breast milk in order to make informed decisions regarding the need for nutrient supplementation. Existing data for nutrient composition of preterm breast milk are dated and not representative of the current population of women delivering prematurely in the United States. Objectives The purpose of this prospective, longitudinal, single-center observational study was to measure the macronutrient and micronutrient composition of breast milk expressed by mothers, including women who self-identify as black, delivering preterm infants at ≤33 completed weeks of gestation. Methods We collected breast milk samples from mothers of preterm infants admitted to the neonatal intensive care unit at Augusta University Medical Center from January 2019 through November 2019. Mother's milk samples were collected on postpartum days 7, 14, 21, and 28 and analyzed for macronutrients (energy, fat, protein, and carbohydrates) and micronutrients (sodium, potassium, chloride, calcium, phosphorus, magnesium, vitamin D, and zinc). Results Thirty-eight mothers, mean age 27 ± 5.1 y and majority black (66%), provided milk for the study. The mean estimated gestational age and birth weight were 28.2 ± 2.8 weeks of gestation and 1098 ± 347 g, respectively, with 42% of mothers in the cohort delivering before week 28 of pregnancy. Differences in protein, sodium, potassium, calcium, phosphorus, and zinc concentrations based on race, day, and milk volume were identified. Dilution effects for protein, sodium, chloride, and vitamin D concentrations over time were identified. Conclusions Our study is among the first to characterize breast milk composition from women who delivered extremely preterm infants and adds to the evidence that race, gestational age, and volume influence the composition of preterm mother's milk. These factors should be considered when designing mother's milk-based feeds for premature infants.

Background Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment. Objectives The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance. Methods This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function). Results Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): −9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [−1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate

Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes., Statement of Significance: The present work summarizes and discusses for the first time the (gaps in) available evidence on the effects of linoleic acid in an infant diet on infant health outcomes in relation to the recently adapted changes in regulations for the addition of linoleic acid to infant formula.

Breast milk is an emerging matrix for vitamin D assessment of breastfed infants and their mothers. It is considered a more reliable indicator of infant intake than the assessment of maternal circulating vitamin D. With the improved sensitivity of mass spectrometry-based technologies, this method principle has been the recent mainstay for the quantitation of various vitamin D metabolites in breast milk for population-based clinical trials. There are still several areas across the total testing process (pre-analytical, analytical and post-analytical) to be defined and harmonised to translate breast milk vitamin D measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from population-based research to routine clinical use and public health applications. Pre-analytically, the determination of the best form of vitamin D to measure in breast milk requires more evidence. Analytically, standardisation of the methods to allow for comparability of results is required. Post analytically, breast milk vitamin D decision limits are needed to turn the individual numerical outputs into clinically meaningful results. This review aims to synthesise the current evidence and utility of measurement of breast milk vitamin D by LC-MS/MS and to lead a future discussion on best practices to allow for its clinical utility beyond its current research-based use.

Objective To explore the practice of antenatal milk expression (AME) and related outcomes for mother–infant dyads during the first 2 weeks after birth. Data Sources We searched the electronic databases MEDLINE, Embase, CINAHL, Emcare, Maternity & Infant Care Database, Scopus, and Web of Science for relevant literature. We also conducted backward reference searches on relevant publications and nondatabase searches after review of the full texts. Study Selection Articles were eligible for inclusion if they reported primary studies focused on AME, included samples of mother–infant dyads, and were published in English. We did not impose time or design limitations given the sparse availability of literature on AME. We identified 766 articles. After the removal of duplicates, we screened 588 articles, and of these, we included 15 articles in our review. Data Extraction We used the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines to guide data extraction and reporting. We evaluated the quality of evidence using the Melnyk and Fineout-Overholt rating system and the Joanna Briggs Institute critical appraisal tools. Data Synthesis We synthesized data from the included articles into four themes: Breastfeeding Self-Efficacy, Milk Supply, Infant Well-Being, and Infant Feeding Methods. Conclusion AME may support breastfeeding by improving breastfeeding self-efficacy and milk supply and by decreasing early formula use. Synthesized literature on AME shows the safety of the practice and that infants of women who practice AME have a greater likelihood of breastfeeding exclusivity during the short term.

BACKGROUND Developing food-based dietary guidelines (FBDGs) for infants and toddlers is a complex task that few countries have attempted. OBJECTIVES Our objectives are to describe the process of food pattern modeling (FPM) conducted to develop FBDGs for the Dietary Guidelines for Americans, 2020-2025 for infants 6 to

BACKGROUND: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive. OBJECTIVES: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production. METHODS: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum. RESULTS: Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components. CONCLUSIONS: Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials.gov as NCT01174875.

In human milk fat, palmitic acid (16:0) is esterified to the middle (sn-2 or β) position on the glycerol backbone and oleic acid (18:1) predominantly to the outer positions, giving the triacylglycerol (TG) a distinctive stereoisomeric structure that is believed to assist nutrient absorption in the infant gut. However, the fat used in most infant formulas is derived from plants, which preferentially esterify 16:0 to the outer positions. We have previously showed that the metabolism of the model oilseed Arabidopsis thaliana can be engineered to incorporate 16:0 into the middle position of TG. However, the fatty acyl composition of Arabidopsis seed TG does not mimic human milk, which is rich in both 16:0 and 18:1 and is defined by the high abundance of the TG molecular species 1,3-olein-2-palmitin (OPO). Here we have constructed an Arabidopsis fatty acid biosynthesis 1-1 fatty acid desaturase 2 fatty acid elongase 1 mutant with around 20% 16:0 and 70% 18:1 in its seeds and we have engineered it to esterify more than 80% of the 16:0 to the middle position of TG, using heterologous expression of the human lysophosphatidic acid acyltransferase isoform AGPAT1, combined with suppression of LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE 2 and PHOSPHATIDYLCHOLINE:DIACYLGLYCEROL CHOLINEPHOSPHOTRANSFERASE. Our data show that oilseeds can be engineered to produce TG that is rich in OPO, which is a structured fat ingredient used in infant formulas.

Background Recent work has challenged the long-held assumption that appetite functions to maintain stable body mass and fat mass (FM), suggesting instead that appetite matches food intake to energy expenditure and its correlate, fat-free mass (FFM). Whether this scenario applies to young infants, in chronic positive energy balance, remains unknown. Objectives To test associations of components of energy expenditure and body composition with milk intake (MI) and energy intake (EI) in 12-week infants, by reanalyzing published cross-sectional data. Methods Data were available for 48 infants. In addition to anthropometric measurements, we assessed MI and EI by test-weighing, sleeping metabolic rate (SMR) by indirect calorimetry, and FFM, FM, and total energy expenditure (TEE) by doubly labeled water. Mean parental height was calculated as a marker of infant growth drive. Correlation and multiple regression analyses were applied. Results MI and EI correlated with FFM (r = 0.47 and 0.57, respectively; P 0.6). MI and EI correlated with SMR (r = 0.42 and 0.53, respectively; P 0.2). In a multiple regression analysis, MI was independently associated with TEE (partial r = 0.39) and FFM (partial r = 0.35). EI showed similar associations. Mean parental height was correlated with weight gain, MI, and EI. Conclusions As in adults, MI and EI in young infants were strongly associated with FFM and with total and sleeping components of energy expenditure, but not with fatness. The infant's growth drive contributed to these associations. This suggests that appetite is regulated by the rate of energy expenditure, the size of energy-using tissues, and tissue deposition rate, and that the high levels of body fat characteristic of infants may not constrain weight gain.

Human milk oligosaccharides (HMOs) are potent bioactive compounds that modulate neonatal health and are of interest for development as potential drug treatments for adult diseases. The potential of these molecules, their limited access from natural sources, and difficulty in large-scale isolation of individual HMOs for studies and applications have motivated the development of chemical syntheses and in vitro enzymatic catalysis strategies. Whole cell biocatalysts are emerging as alternative self-regulating production platforms that have the potential to reduce the cost for enzymatic synthesis of HMOs. Whole cell biocatalysts for the production of short-chained, linear and small monofucosylated HMOs have been reported but those for fucosylated structures with higher complexity have not been explored. In this study, we established a strategy for producing a difucosylated HMO, lactodifucotetraose (LDFT), from lactose and L-fucose in Escherichia coli. We used two bacterial fucosyltransferases with narrow acceptor selectivity to drive the sequential fucosylation of lactose and intermediate 2′-fucosyllactose (2′-FL) to produce LDFT. Deletion of substrate degradation pathways that decoupled cellular growth from LDFT production, enhanced expression of native substrate transporters and modular induction of the genes in the LDFT biosynthetic pathway allowed complete conversion of lactose into LDFT and minor quantities of the side product 3-fucosyllactose (3-FL). Overall, 5.1 g/L of LDFT was produced from 3 g/L lactose and 3 g/L L-fucose in 24 h. Our results demonstrate promising applications of engineered microbial biosystems for the production of multi-fucosylated HMOs for biochemical studies.

Background Donor milk is the standard of care for hospitalized very low birth weight (VLBW) infants when mother's milk is unavailable; however, growth of donor milk-fed infants is frequently suboptimal. Variability in nutrient composition of donated milk complicates the production of a uniform pooled product and, subsequently, the provision of adequate nutrition to promote optimal growth and development of VLBW infants. We reasoned a machine learning approach to construct batches using characteristics of the milk donation might be an effective strategy in reducing the variability in donor milk product composition. Objective The objective of this study was to identify whether machine learning models can accurately predict donor milk macronutrient content. We focused on predicting fat and protein, given their well-established importance in VLBW infant growth outcomes. Methods Samples of donor milk, consisting of 272 individual donations and 61 pool samples, were collected from the Rogers Hixon Ontario Human Milk Bank and analyzed for macronutrient content. Four different machine learning models were constructed using independent variable groups associated with donations, donors, and donor-pumping practices. A baseline model was established using lactation stage and infant gestational status. Predictions were made for individual donations and resultant pools. Results Machine learning models predicted protein of individual donations and pools with a mean absolute error (MAE) of 0.16 g/dL and 0.10 g/dL, respectively. Individual donation and pooled fat predictions had an MAE of 0.91 g/dL and 0.42 g/dL, respectively. At both the individual donation and pool levels, protein predictions were significantly more accurate than baseline, whereas fat predictions were competitive with baseline. Conclusions Machine learning models can provide accurate predictions of macronutrient content in donor milk. The macronutrient content of pooled milk had a lower prediction error, reinforcing the value of pooling practices. Future research should examine how macronutrient content predictions can be used to facilitate milk bank pooling strategies.

Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P

Breast feeding and human milk are the standards for infant feeding and nutrition. Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk. To date, more than 200 structural different HMOs have been identified and some can be synthesized by the food industry. HMOs are one of the major differences between human milk and formula milk, and current evidence demonstrates their various beneficial effects toward infants' health: acting as anti-adhesive antimicrobials, immune modulators, and intestinal cell response modulators, as well as providing prebiotics effect and neurodevelopment and cognition effects. HMOs compositions vary among mothers, influenced by the stage of lactation, duration of pregnancy and maternal genetic factors. However, there are still some unknown factors affecting the compositions of HMOs and requiring further research for clarification. A combination of preclinical and clinical cohort studies may help to identify whether an individual HMO contributes to disease protection. In recent years, 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) have been approved as food ingredients by official authorities. Infant formulae supplemented with these HMOs are well-tolerated. However, more prospective clinical studies are warranted to elucidate HMOs' significance in infant nutrition. Breast milk feeding remains the best option for infants nutrition and development. Whenever breast milk is not adequate or unavailable, infant formula supplemented with HMOs might be considered as an alternative.

Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile are poorly defined. Thus, we aimed to review the existing evidence on the associations between nongenetic maternal and infant factors and HMO composition. A systematic search was performed on PubMed and Web of Science (without a time restriction) to identify any relevant studies published. In total, 1056 results were obtained, of which 29 articles were selected to be included in this review. The range of factors investigated include lactation stage, maternal pre-pregnancy BMI (ppBMI), maternal age, parity, maternal diet, mode of delivery, infant gestational age, and infant sex. The data suggest that, beyond maternal genetics, HMO composition seems to be influenced by all these factors, but the underlining mechanisms remain speculative. The published evidence is discussed in this review, along with potential implications for infant growth and development. For example, 2'-fucosyllactose, which was reportedly increased in mothers with higher ppBMIs, was also associated with increased infant weight and height. In addition, greater levels of sialylated HMOs after preterm birth may support brain development in these infants.

Summary Background Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy and leads to an altered metabolic profile of human breast milk (HBM). The association between HBM metabolites and neonatal growth in GDM pregnancies has not been thoroughly investigated. Aims The primary aim was to quantify differences in the HBM metabolome between normal and GDM pregnancies. The secondary aim was to identify metabolites associated with neonatal growth during the first year postpartum. Methods In the present study, mothers intending to exclusively breastfeed (BF) and their newborns (mother–infant pairs) were recruited at delivery (n = 129 normal pregnancies and n = 98 GDM pregnancies). HBM samples (colostrum, transition milk, and mature milk) from mothers with normal pregnancies (n = 50) and GDM pregnancies (n = 50) were subjected to metabolomic profiling via liquid chromatography tandem mass spectrometry (LC-MS/MS). Receiver operating characteristic (ROC) analysis revealed the metabolomic fingerprints of GDM-associated mature HBM. Correlations between metabolites and neonatal body weight gain (BWG) were evaluated by Spearman correlation analysis. Results In total, 620 metabolites were identified in each HBM sample; 253 compounds had the same variation patterns, whereas 38 compounds had significantly different pattern transitions between the GDM and normal groups. Moreover, 12, 49 and 28 metabolites exhibited significant differences in the 3 milk types between the 2 groups. Twenty-two metabolites were confirmed by ROC analysis as metabolomic fingerprints in the mature BM of GDM patients. Ten compounds were significantly negatively correlated with neonatal growth, and only 2 unsaturated lipids (eicosatrienoic acid (FA 20:3) and lysophosphatidylcholine (LysoPC) (22:6)) were positively correlated with neonatal BWG. Conclusions GDM is associated with alterations in the HBM metabolome. Only a small subset of compounds are associated with neonatal body weight (BW). Trial registration ChiCTR-ROC-17011508. Prospectively registered on 26 May 2017 ( http://www.chictr.org.cn/listbycreater.aspx ).

BACKGROUND: Formulas often contain high amounts of added sugars, though little research has studied their connection to obesity. OBJECTIVES: This study assessed the contribution of added sugars from formulas during complementary feeding on total added sugar intakes, and the association between these sugars and upward weight-for-age percentile (WFA%) crossing (i.e., participants crossing a higher threshold percentile were considered to have an upward crossing). METHODS: Data from three 24-hour dietary recalls for infants (n = 97; 9–12 months) and toddlers (n = 44; 13–15 months) were obtained in this cross-sectional analysis. Foods and beverages with added sugars were divided into 17 categories. Pearson's correlations were used to test relations between added sugar intake and upward WFA% crossing, followed by multivariable regressions when significant. ANOVA compared intakes of all, milk-based, and table foods between primarily formula-fed compared with breastfed participants. Multivariable regressions were used to test effects of added sugars and protein from all foods compared with added sugars and protein from milk-based sources on upward WFA% crossing. RESULTS: Added sugars from formulas comprised 66% and 7% of added sugars consumed daily by infants and toddlers, respectively. A significant association was observed between upward WFA% crossing and added sugars from milk-based sources after controlling for gestational age, sex, age, introduction to solid foods, mean energy intakes, and maternal pre-pregnancy BMI and education (β = 0.003; 95% CI, 0.000–0.007; P = 0.046). Primarily formula-fed participants consumed nearly twice the energy from added sugars (P = 0.003) and gained weight faster (upward WFA% crossing = 1.1 ± 1.2 compared with 0.3 ± 0.6, respectively; P

Feeding difficulties are common in infants hospitalized in the NICU and can be a challenge to manage. The purpose of this article is to explain how and why the flow rate from the bottle nipple affects physiologic stability in infants and to describe the current evidence available on the flow rates of nipples used in the hospital and after discharge. Study results have indicated that flow rate varies widely among different types of nipples. Within the same type of nipple, there can be significant variability in flow from one nipple to another. Other factors, such as type of infant formula and thickening, also affect flow. Altering the flow rate of the bottle nipple is a relatively simple intervention that may support safe oral feeding.

Background Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are complications of extremely low birth weight (ELBW, ≤ 1000 g) infants. ELBW infants at Texas Children's Hospital receive an exclusive human milk-based diet, which has been associated with a reduction of NEC. Objectives 1) Assess incidence of SIP and NEC (Stage II or greater) in ELBW infants receiving 100% human milk-based diet, 2) Describe mortality rates of ELBW infants with SIP and NEC. Methods Prospective single-center observational cohort study of ELBW infants born between 2010 and 2014 with SIP or NEC (exclusion: congenital anomalies and death within 48 h). Results Of 379 ELBW infants, 345 were eligible. Of these, 28 (8.1%) had SIP and 8 (2.3%) had NEC (medical n = 1, surgical n = 7). SIP infant mortality was 32% (n = 9) compared to 63% (n = 5) for NEC patients. Of SIP infants with PD (n = 25), 52% required subsequent exploratory laparotomy (LAP). Of NEC infants with peritoneal drainage (PD) (n = 2), both required subsequent LAP. Conclusion Using an exclusive human milk-based diet, the incidence of SIP exceeds NEC in ELBW infants at our institution. This shows a changing trend in the incidence of these two diagnoses in the era of human milk, as NEC had previously been more prevalent in ELBW infants. More than half of infants who initially received PD later required LAP. There were no differences in survival outcomes in both SIP and NEC groups based on surgical management.

Background Information on long-term dietary intake is often required for research or program planning, but surveys routinely use short-term assessments such as 24-h recalls (24HRs). Methods to reduce the impact of within-person variation in 24HRs, such as the National Cancer Institute (NCI) method, typically require extensive training and skill. Objectives We introduce the Simulating Intake of Micronutrients for Policy Learning and Engagement (SIMPLE) macro, a new tool to increase the accessibility of 24HR analysis. We explain the underlying theory behind the tool and provide examples of potential applications. Methods The SIMPLE macro connects the core NCI statistical code to estimate usual intake distributions and includes additional code to enable advanced analyses such as predictive modeling. The related SIMPLE-Iron macro applies the full probability method to estimate inadequate iron intake, and the SIMPLE-1D macro is used for descriptive or modeling analyses of data with a single 24HR per person. The macros and associated documentations are freely available. We analyzed data from the US National Health and Nutrition Examination Survey (NHANES) and the Cameroon National Micronutrient Survey to compare the SIMPLE macro to 1) the core NCI code using the Estimated Average Requirement cut point method, and 2) the IMAPP software for iron only, and to demonstrate the applications of the SIMPLE macro for estimating usual intake and predictive modeling. Results The SIMPLE macro generates identical results to the core NCI code. The SIMPLE-Iron macro also produces estimates of inadequate iron intake comparable to the IMAPP software. The examples demonstrate application of the SIMPLE macro to 1) descriptive analyses of nutrient intake from food and supplements (NHANES), and 2) analyses accounting for breast-milk nutrient intake and modeling fortification and supplementation programs (Cameroon). Conclusions The SIMPLE macros may facilitate the analysis and modeling of dietary data to inform nutrition research, programs, and policy.

Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.

Background Human milk oligosaccharides (HMOs) are complex glycans that are highly abundant in human milk. While over 150 HMOs have been identified, it is unknown how individual HMOs change in concentration over 24 months of lactation. Objectives To understand how HMO concentrations change over 24 months of lactation. Methods Breast milk samples were collected from participants in a longitudinal cohort study of Hispanic mother-infant pairs at 1, 6, 12, 18, and 24 months postpartum. Concentrations of 19 of the most abundant HMOs were measured using HPLC. Because the parent study is ongoing and not all participants have finished all time points yet, the sample sizes ranged per time point (n = 207 at 1 month; n = 109 at 6 months; n = 83 at 12 months; n = 59 at 18 months; and n = 28 at 24 months). Approximately 88% of participants were classified as HMO secretors-a genetic factor that affects concentrations of HMOs such as 2'fucosyllactose (2'FL) and lacto-N-fucopentaose I-while the remaining 12% were classified as nonsecretors. Mixed models were used to examine changes in HMO concentrations and relative abundances over the course of lactation. Results The majority of HMOs significantly decreased in concentration over the course of lactation. The exceptions were 2'FL, sialyl-lacto-N-tetraose b, and disialyl-lacto-N-tetraose, which did not change with time, and 3-fucosyllactose (3FL) and 3'-sialyllactose (3'SL), which significantly increased. The concentration of 3FL increased 10-fold, from 195 (IQR 138-415) μg/mL at 1 month to 1930 (1100-2630) μg/mL at 24 months, while 3'SL increased 2-fold, from 277 (198-377) μg/mL to 568 (448-708) μg/mL over the same time period. Conclusions These results indicate that HMOs do not decrease in concentration uniformly across lactation. In particular, 3FL and 3'SL increased over the course of lactation in this cohort. Future studies are required to fully understand the functions of these HMOs.

Human milk oligosaccharides (HMO)s are a key component in human milk and represent an important dietary modulator of infant gut microbiota composition and associated gut-brain axis development and homeostasis. The brain reward system, specifically the mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to nucleus accumbens (NAc) is involved in the motivation and preference for food. The objective of the present study was to determine if HMO fortified diets given during the critical period of reward system development (p21) could affect the structure of the reward system. At weaning (p21), Sprague-Dawley rats were randomized to one of four fortified diet groups: Control, 3′sialyllactose (3′FL), 2′-fucosyllactose (2′FL), or a combination of 3′SL and 2′FL (3′SL + 2′FL). Messenger RNA (mRNA) expression was quantified for DA and appetite associated markers in the VTA and NAc and western blots measured the immediate early gene FosB and its isoform ΔFosB. Females fed the 3′SL + 2′FL fortified diet displayed a decrease in DAT expression in the VTA and an increase in leptin expression in the NAc. Females displayed an overall lower expression of NAc D2, VTA ghrelinR, and VTA leptin. In males, VTA DAT and FosB were negatively correlated with body weight and systemic leptin. Sex differences in the expression of DA markers underscore the need to investigate this phenomenon and understand the functional significance in preventing or treating obesity. This study highlights sex differences in response to HMO supplementation and the need for further investigations into the functional significance of nutritional interventions during DA system development.

International audience; In human milk banks (HMBs), donor milk (DM) is commonly sterilized by Holder pasteurization (HoP). High hydrostatic pressure (HHP) processing is an innovative, alternative method for DM sterilization. We evaluated the impact of HHP processing on the concentration of seven metabolic milk hormones. Eight samples of raw DM were aliquoted. One aliquot was sterilized by HoP (62 • C for 30 min), and another was processed by HHP (350 MPa at 38 • C). Compared with raw DM, HoP milk displayed reduced concentrations of insulin, nesfatin-1, cortisol, leptin, apelin and GLP-1, though adiponectin levels were unchanged. HHP processing maintained the levels of insulin, nesfatin-1, cortisol and leptin at their initial levels in raw DM, reduced apelin and adiponectin levels, but increased GLP-1 level. Sterilization of DM by HHP thus preserves the main metabolic hormones in human milk, underlining the interest of this method for use in HMBs.

Mammary epithelial cells synthesize and secrete norepinephrine (NE) into breast milk to regulate β-casein expression through the adrenergic β2 receptor. We investigated the expression, localization, and roles of NE transporter (NET) in the mammary epithelium during lactation. mRNA and protein levels of NET were determined in primary normal human mammary epithelial cells (pHMECs) and non-malignant human mammary epithelial MCF-12A cells. In nursing CD1 mice, NET localized to the apical membranes of the mammary epithelium. The intracellular NE content of pHMECs incubated with NE increased. Although the β-casein concentration in milk was slightly higher at day 10 than at day 2 of lactation, the NE concentration and lactation-related proteins were only slightly changed on days 2-10. Restraint stress increased the NE concentration in milk from nursing mice and NET protein levels were significantly higher than in non-stressed nursing mice. NET is expressed on the apical membrane of mammary epithelial cells and incorporates NE in milk into cells, potentially regulating the NE concentration in milk.

Summary Background There is limited data on macronutrient content and its variability in mothers’ milk of extremely low birth weight (ELBW) infants. The primary objectives were to determine the mean and the range of macronutrient content in milk from mothers of ELBW infants. Methods A near-infrared milk analyzer was used to measure fat, protein and carbohydrate. Data is presented as mean ± SD, median, and minimum/maximum values. Intraclass correlation coefficients (ICC) and linear regression were used to examine differences between repeat analyses. Results The mean GA and BW of infants were 25.6 ± 1.9 weeks and 678.6 ± 78.6 g respectively. The mean caloric content of 212 milk samples (10 infants) was 20.1 ± 5.4 cals/oz. The mean fat, protein and carbohydrate content were 3.2 ± 1.8, 1.6 ± 0.5 g% and 8.0 ± 0.8 g% respectively. Large subject to subject and day to day variations were observed. The range of calories, fat, protein and carbohydrate content were 10.4–42.3 cals/oz, 0.2–14.1, 0.6–3.3 and 6.4–13.7 g% respectively. Nearly half of all samples had 17 or less cals/oz and 10% had 15 or less cals/oz. There were no significant differences between repeat readings on a single sample. Conclusions Standard fortification in presence of significant variation in macronutrient and caloric content of mother's milk can lead to large day to day variation in macronutrient and caloric intake of ELBW infants. Clinical significance of variable intake from one day to another in infants at high risk of NEC and growth failure is unclear and needs further study.