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Early exclusive birth/lactating parent's own milk (B/LPOM) feeds have been associated with longer duration of B/LPOM use for infant feedings in healthy term and hospitalized preterm infants. This relationship has not been explored in infants undergoing neonatal surgery (surgical infants).To evaluate the relationship between early exclusive B/LPOM feeds and cumulative B/LPOM patterns during surgical infants' neonatal intensive care unit (NICU) hospitalization.A secondary cross-sectional analysis was performed using the electronic health record data of surgical infants admitted to a level IV NICU between January 2014 and March 2015. Multiple linear regression and Fisher's exact test were used to examine the associations between first NICU feed type and total percentage of diet composed of B/LPOM during NICU stay and continuation of any or exclusive B/LPOM feedings at NICU discharge, respectively.The analysis included 59 infants who required surgery for gastrointestinal, cardiac, or multisystem defects or pregnancy-related complications. Receipt of B/LPOM as the first NICU feed was associated with higher percentage of B/LPOM feeds ( P.001) throughout NICU stay, as well as continuation of any or exclusive B/LPOM feedings at NICU discharge ( P = .03).Early exclusive B/LPOM feeds may be an important predictor for continuation of any B/LPOM use throughout the NICU stay and at NICU discharge. Continued efforts to identify and address gaps in prenatal and postpartum lactation support for parents of surgical infants are needed.Powered studies are needed to corroborate these findings and to explore the potential impact of other factors on duration and exclusivity of B/LPOM use.https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx .

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.

biBackground:/i/bThe microbial community in human milk is associated with many maternal and neonatal factors. This study aimed to investigate the effect of antibiotic exposure on the microbial community structure of colostrum.biMethods:/i/bTwenty women with antibiotic treatment immediately after delivery and 10 age-matched control women were enrolled at the Guangdong Women and Children Hospital. Colostrum samples were collected within postpartum 30 hours. The V4 variable region of the bacterial 16S rRNA gene was sequenced to characterize the microbial profile using Illumina MiSeq platform.biResults:/i/bPhylaiProteobacteria/iandiFirmicutes/iwere the predominant bacteria in colostrum samples. The core and abundant genera in colostrum includediStreptococcus/i,iStaphylococcus/i, andiPseudomonas/i. Compared with the control group, principal coordinate analysis based on the Bray-Curtis distance showed a significant difference in milk microbial community in women with antibiotic exposure, accompanied by a significantly lower alpha diversity and a different microbial ecological network. Furthermore, the relative abundances of generaiActinomyces/i,iAnaerobacter/i, andiClostridium_/isensui_stricto/isignificantly decreased after antibiotic treatment.biConclusions:/i/bThis study provided evidence of alterations in the colostrum microbial community with antibiotic exposure, improving our understanding of the effects of antibiotic treatment on the milk microbiome.

Background: The fetus grows in a sterile womb environment. After birth, the newborn immune system has two immediate hurdles to clear. First immediate suppression of the womb compatible immune system and turn on the immune system of the newborn that can counter the antigenic world. The underlying mechanism of immune fluctuation by milk microRNAs (miRNAs) can be crucial for the treatment of critical or premature newborn. Methods: We collected fourteen samples of each colostrum and mature milk from lactating mothers, four samples of each were used for microarray analysis, and the other ten were used for miRNA expression profiling by real-time PCR. Results: From the microarray, 154 differentially expressed miRNAs were identified, whereas 49 miRNAs were revealed as immune-related miRNAs based on a literature study. Among the 49 miRNAs, 33 were already shown as strongly validated immune-related miRNAs (validated by qPCR, Western Blot, and Luciferase assay) and were considered for further analysis. Twenty-two miRNA expressions were analysed by real-time PCR as their Ct values were within considerable limits. Twelve numbers of miRNAs were significantly downregulated in mature milk compared to colostrum, which were again subjected to bioinformatics analysis to predict the biological mechanisms behind the differentially expressed miRNAs. Conclusion: This study shed light on the human milk exosome miRNA expression dynamics during lactation and their possible role in the gradual skewing of the newborns' immune system. The information is crucial for the development and onset of sepsis in premature newborns in the NICU.

Sialylated human milk oligosaccharides (SHMOs) possess unique biological activities. Qualitative and quantitative analyses of SHMOs at different lactation stages are limited by interference from neutral oligosaccharides, glycan structural complexity, and low detection sensitivity. Herein, our previously developed glycoqueuing strategy was improved and applied to enable an isomer-specific quantitative comparison of SHMOs between colostrum milk (CM) and mature milk (MM). A total of 49 putative structures were determined, including 1 α2,6-linked and 13 α2,3-linked isomers separated from seven newly discovered SHMO compositions. The content of most oligosaccharides was more than 50% lower in MM than in CM, and α2,3-sialylation was observed in 43.74% of SHMOs from CM and 22.95% of SHMOs from MM. Finally, the fucosylation level of the SHMOs increased from 16.45 to 22.28% with prolonged lactation. These findings provide the basis for further studies on the structure-activity relationship of SHMOs and a blueprint to improve infant formula.

Ultraviolet (UV) filters are of great concern due to their wide occurrence, bioaccumulation, and toxicity. Little is known about human exposure to UV filters. A total of 3467 individual human milk samples from 24 Chinese provinces were collected during 2017-2019. The concentrations of 12 UV filters in 100 pooled milk samples were determined. The total UV filter concentration was 78-846 (mean 235 ± 120) ng/g lipid weight. The highest and lowest total mean concentrations were for samples from Qinghai and Sichuan provinces, respectively. A significant positive correlation was found between UV radiation levels and UV concentrations in the samples. The dominant UV filters were 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) and ethylhexyl methoxycinnamate (EHMC), which contributed means of 32 and 22%, respectively, to the total concentrations. Plastic products and sunscreens were probably the sources of UV-P and EHMC in the human milk from China, respectively. The mean 2-(3,5-di

The natural source of human milk fat substitute (HMFS) is a field worth exploring. In this study, tilapia oil was extracted and analyzed. In the triacylglycerol fraction, the contents of sn-2 palmitic acid and total sn-1,3 oleic acid and linoleic acid were 48.01% and 66.62%, respectively. The optimal solvent fractionation conditions were determined to be a tilapia oil-to-acetone ratio of 1:8 (w/v), crystallization temperature of -30°C, and crystallization duration of 16 h, giving a solid fraction yield of 64.20%. In fractionated tilapia oil, the total content of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) and 1,3-dioleoyl-2-palmitoylglycerol (OPO) increased by 20.38%, as determined by reversed-phase liquid chromatography. Ultra-high-performance combined-phase chromatography combined with quadrupole time-of-flight mass spectrometry analysis showed that OPL (17.45%) was the most abundant triacylglycerol in fractionated tilapia oil, followed by OPO (13.90%). Fractionated tilapia oil is thus an excellent source of OPL and has great potential for incorporation in HMFS. PRACTICAL APPLICATION: Human milk fat substitutes are an important component of infant formulas. This work provides an excellent natural source of oil rich in OPL, which has great potential in the field of preparing human milk fat substitutes highly similar to human milk fat.

Objectives. To describe prevalence of breast milk feeding among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and examine associations between breast milk feeding, timing of maternal infection before delivery, and rooming-in status during delivery hospitalization. Methods. We performed a retrospective cohort study using data from Massachusetts, Minnesota, Nebraska, Pennsylvania, and Tennessee of whether people with confirmed SARS-CoV-2 infection during pregnancy in 2020 initiated breast milk feeding at birth. Results. Among 11 114 (weighted number) people with SARS-CoV-2 infection in pregnancy, 86.5% (95% confidence interval [CI] = 82.4%, 87.6%) initiated breast milk feeding during birth hospitalization. People with infection within 14 days before delivery had significantly lower prevalence of breast milk feeding (adjusted prevalence ratio [APR] = 0.88; 95% CI = 0.83, 0.94) than did those with infection at least 14 days before delivery. When stratified by rooming-in status, the association between timing of infection and breast milk feeding remained only among infants who did not room in with their mother (APR = 0.77; 95% CI = 0.68, 0.88). Conclusions. Pregnant and postpartum people with SARS-CoV-2 infection should have access to lactation support and be advised about the importance of breast milk feeding and how to safely feed their infants in the same room. (Am J Public Health. 2022;112(S8):S787–S796. https://doi.org/10.2105/AJPH.2022.307023 )

Introduction In 2018, Switzerland changed its guidelines to support women living with HIV wishing to breastfeed. The exposure of antiretroviral drugs (ARVs) in breastmilk and the ingested daily dose by the breastfed infant are understudied, notably for newer ARVs. This study aimed to quantify ARV concentrations in maternal plasma and breastmilk to determine the milk/plasma ratio, to estimate daily infant ARV dose from breastfeeding and to measure ARV concentrations in infants. Methods All women wishing to breastfeed were included, regardless of their ARV treatment. Breastmilk and maternal plasma samples were mostly collected at mid-dosing interval. Results Twenty-one mother/child pairs were enrolled; of those several were on newer ARVs including 10 raltegravir, 1 bictegravir, 2 rilpivirine, 2 darunavir/ritonavir and 3 tenofovir alafenamide. No vertical HIV transmission was detected (one infant still breastfed). The median milk/plasma ratios were 0.96/0.39 for raltegravir once/twice daily, 0.01 for bictegravir, 1.08 for rilpivirine, 0.12 for darunavir/ritonavir and 4.09 for tenofovir alafenamide. The median estimated infant daily dose (mg/kg) from breastfeeding was 0.02/0.25 for raltegravir once/twice daily, 0.01 for bictegravir, 0.02 for rilpivirine, 0.05 for darunavir/ritonavir and 0.007 for tenofovir alafenamide, resulting in relative infant dose Conclusions ARVs were transferred to a variable extent in breastmilk. Nevertheless, the estimated daily ARV dose from breastfeeding remained low. Differential ARV exposure was observed in breastfed infants with some ARVs being below/above their effective concentrations raising the concern of resistance development if HIV infection occurs. More data on this potential risk are warranted to better support breastfeeding.

We present a mass spectral library-based method for analyzing site-specific N-linked protein glycosylation. Its operation and utility are illustrated by applying it to both newly measured and available proteomics data of human milk glycoproteins. It generates two varieties of mass spectral libraries. One contains glycopeptide abundance distribution spectra (GADS). The other contains tandem mass spectra of the underlying glycopeptides. Both originate from identified glycopeptides in proteolytic digests of human milk and purified glycoproteins, which include tenascin, lactoferrin, and several antibodies. Analysis was also applied to digests of a NIST human milk standard reference material (SRM), leading to a GADS library of N-glycopeptides, enabling the direct comparison of glycopeptide distributions for individual proteins. Tandem spectra underlying each glycopeptide GADS peak are combined to create a second type of library that contains spectra of the underlying glycopeptide spectra. These were acquired by higher-energy (stepped) collision dissociation fragmentation followed by ion-trap fragmentation. Spectra are annotated using MS_Piano, recently reported annotation software. This data, with extensions of a widely used spectral library search and display software, provides accessible mass spectral libraries.

Human milk is the optimal infant nutrition. However, while human-derived metabolites such as lipids and oligosaccharides in human milk are regularly reported, the presence of exogenous chemicals (such as drugs, food, and synthetic compounds) are often not addressed. To understand the types of exogenous compounds that might be present, human milk (n=996) was analyzed by untargeted metabolomics. This analysis revealed that lifestyle molecules such as medications and their metabolites, food, industrial sources such as plasticizers, cosmetics, microbial molecules, and other personal care products are found in human milk. We provide further evidence that some of these lifestyle molecules are also detectable in the newborn’s stool. Thus, this study gives important insight into the types of exposures infants receiving human milk might ingest due to the lifestyle choices, exposure, or medical status of the lactating parent.

Human milk oligosaccharides (HMOs), a group of structurally diverse unconjugated glycans in breast milk, act as important prebiotics and have plenty of unique health effects for growing infants. 2'-Fucosyllactose (2'-FL) is the most abundant HMO, accounting for approximately 30%, among approximately 200 identified HMOs with different structures. 2'-FL can be enzymatically produced by α1,2-fucosyltransferase, using GDP-l-fucose as donor and lactose as acceptor. Metabolic engineering strategies have been widely used for enhancement of GDP-l-fucose supply and microbial production of 2'-FL with high productivity. GDP-l-fucose supply can be enhanced by two main pathways, including

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.

Bifidobacteria are among the first colonizers of the infant gut, and human milk oligosaccharides (HMOs) in breastmilk are instrumental for the formation of a bifidobacteria-rich microbiota. However, little is known about the assembly of bifidobacterial communities. Here, by applying assembly theory to a community of four representative infant-gut associated Bifidobacterium species that employ varied strategies for HMO consumption, we show that arrival order and sugar consumption phenotypes significantly affected community formation. Bifidobacterium bifidum and Bifidobacterium longum subsp. infantis, two avid HMO consumers, dominate through inhibitory priority effects. On the other hand, Bifidobacterium breve, a species with limited HMO-utilization ability, can benefit from facilitative priority effects and dominates by utilizing fucose, an HMO degradant not utilized by the other bifidobacterial species. Analysis of publicly available breastfed infant faecal metagenome data showed that the observed trends for B. breve were consistent with our in vitro data, suggesting that priority effects may have contributed to its dominance. Our study highlights the importance and history dependency of initial community assembly and its implications for the maturation trajectory of the infant gut microbiota., 母乳栄養児の腸内におけるビフィズス菌コミュニティー形成には先住効果が大きな影響を及ぼす --ヒトミルクオリゴ糖利用能力の低いビフィズス菌B. breveが優勢となる仕組み--. 京都大学プレスリリース. 2022-07-27.

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.

The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed.Determine whether mother's milk and infant saliva can be used to reliably identify maternal cytomegalovirus (CMV) serostatus and detect infant pCMV acquisition.This was a single-center, prospective cohort study of VLBW infants, and their mothers, born between 2017 and 2020. Maternal milk samples were tested for CMV immunoglobulin G (IgG) using a CMV glycoprotein B binding enzyme-linked immunosorbent assay and the results were compared with maternal serum CMV IgG results. Biweekly paired saliva and urine samples were collected from infants born to mothers with positive or unknown CMV serostatus. Saliva samples were tested for CMV DNA by quantitative real-time polymerase chain reaction (PCR) and compared with urine CMV qualitative PCR results obtained from a clinical laboratory.Among 108 infants without congenital CMV included in the study, 10 (9%) acquired pCMV. Both milk and blood CMV serology results were available for 70 mothers. Maternal milk antibody testing had a sensitivity of 97.2% (95% CI: 85.5-99.9%) and specificity of 91.2% (95% CI: 76.3-98.1%) in establishing CMV serostatus. Paired serially collected saliva and urine samples (n = 203) were available for 66 infants. Saliva PCR had a sensitivity of 30.0% (95% CI: 6.7-65.2%) and specificity of 92.7% (95% CI: 88.1-96.0%) in detecting pCMV acquisition.Maternal breast milk is a reliable alternative sample to determine CMV serostatus. Serial testing of infant saliva was not adequately sensitive for identifying pCMV acquisition in preterm infants.

Breast milk feeding is an important late-onset sepsis reduction strategy in the Neonatal Intensive Care Unit (NICU). However, multiple studies have reported transfer of bacteria-contaminated breast milk to infants. We describe a case of culture-positive breast milk resulting in persistent Enterococcus bacteremia in an infant. Beyond the development of an infant’s innate and specific immunity as well as colonization of the gastrointestinal (GI) tract with commensal organisms, the risk of bacterial translocation from the GI tract into the bloodstream is shaped and modified by maternal health, birth history, and an infant’s NICU course. While freezing and/or pasteurizing breast milk reduces or eliminates its bacterial load, it also diminishes its immunologic and nutritional benefits.

BACKGROUND: This study prospectively investigated the levels of energy metabolism hormones in very preterm neonates to identify their change over time and association with intake of maternal milk as well as weight gain velocity. METHODS: We measured and compared the leptin, adiponectin, ghrelin, and insulin-like growth factor I (IGF-1) levels in the urine of 70 very preterm neonates, before the initiation of any enteral feeding (baseline level) and twice within 14 days on full enteral feeding (FEF). Regression models identified the role of intake of maternal milk on the levels of the tested energy metabolism hormones in the enteral-fed infants. We also analyzed the adequacy of the weight gain velocity defined by the fetal-infant growth reference (FIGR). Additionally, we collected and analyzed the infants’ clinical and feeding characteristics during the birth hospitalization. RESULTS: The preterm infants’ baseline levels of the energy metabolism hormones significantly predicted their increase at the end of two weeks of observation on FEF. The leptin level was associated with increased intake of maternal milk, whereas the feeding volume was associated with increased ghrelin and IGF-1, and decreased leptin and adiponectin. Infants with comparable FIGR had higher leptin levels than those with inadequate weight gain velocity. CONCLUSION: Early postnatal levels of leptin, adiponectin, ghrelin, and IGF-1 predicted the increase of these hormones in the fully enteral fed very preterm neonates. Moreover, greater intake of maternal milk by the study infants contributed to an increased leptin-associated weight gain velocity.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman’s body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Background: Insulin, insulin-like Growth Factor-1 (IGF-1), and obestatin in human milk originate from the circulation. There is also limited knowledge about the influence of body fat on the levels of these hormones in human milk. Research Aim: To determine (1) the influence of body fat on levels of insulin, IGF-1, and obestatin in human milk and serum/plasma during the postpartum period; (2) the changes in the levels of these hormones in human milk and serum/plasma postpartum; and (3) the presence of IGF-1 mRNA in human milk. Methods: In this prospective, longitudinal, observational cohort study, levels of insulin, IGF-1, and obestatin were measured up to 30 days postpartum in milk and serum/plasma of 58 participants with adequate (≤ 32%) or excess (> 32%) total body fat determined by electrical bioimpedance. Student’s t test and repeated-measures analysis of variance were used to evaluate the differences between groups. Pearson’s test was used to analyze the associations. Results: The milk from participants with excess body fat had higher insulin and IGF-1 levels and lower obestatin levels than that of participants with adequate body fat at 3–7, 14–15, and 30 days postpartum (adjusted p < .001). The levels of insulin, IGF-1, and obestatin were significantly higher in human milk than in serum/plasma ( p < .05) and correlated with maternal body fat ( p < .001). Conclusions: Maternal body fat was associated with elevated insulin and IGF-1 levels and decreased obestatin levels in human milk up to 30 days postpartum.

Carbonic anhydrases (CA, EC 4.2.1.1) catalyze the hydration of carbon dioxide and take part in many essential physiological processes. In humans, 15 CAs are characterized, including the only secreted isoenzyme CA VI. CA VI has been linked to specific processes in the mouth, namely bitter taste perception, dental caries, and maintenance of enamel pellicle, and implicated in several immunity-related phenomena. However, little is known of the mechanisms of the above. In this study, we characterized human CA VI purified from saliva and milk with biophysical methods and measured their enzyme activities and acetazolamide inhibition. Size-exclusion chromatography showed peaks of salivary and milk CA VI corresponding to hexameric state or larger at pH 7.5. At pH 5.0 the hexamer peaks dominated. SDS- PAGE of milk CA VI protein treated with a bifunctional crosslinker further confirmed that a majority of CA VI is oligomers of similar sizes in solution. Mass spectrometry experiments confirmed that both of the two putative N-glycosylation sites, Asn67 and Asn256, are heterogeneously glycosylated. The attached glycans in milk CA VI were di- and triantennary complex-type glycans, carrying both a core fucose and 1 to 2 additional fucose units, whereas the glycans in salivary CA VI were smaller, seemingly degraded forms of core fucosylated complex- or hybrid-type glycans. Mass spectrometry also verified the predicted signal peptide cleavage site and the terminal residue, Gln 18, being in pyroglutamate form. Thorough characterization of CA VI paves way to better understanding of the biological function of the protein.

Background: Exclusive breast milk is the recommended nutrition by the World Health Organization (WHO) until six months of age, followed by introducing foods with continual breastfeeding. Bisphenol A (BPA) is a synthetic chemical used as a monomer in polycarbonate plastics and epoxy resins. Human exposure to BPA can cause numerous adverse health effects such as diabetes, obesity and cardiovascular disease, with children and infants as the most susceptible groups. Thus, this study aimed to determine BPA concentration in the colostrum of 64 mothers hospitalized at the University Hospital Professor Polydoro Ernani de São Thiago through the ELISA technique. We also assessed possible associations between breast milk BPA concentration and lactogenesis II. The results showed that all the breast milk samples contained a high concentration of BPA with a median value of 34.18 ng/mL. In addition, exposure to BPA did not alter the nutritional status of the mother; however, BPA concentration in mothers is influenced by the consumption of food packaged in plastic containers. The total daily intake of BPA in breastfed babies was 19.5 µg/kg/day and 28.5 µg/kg/day was recorded in the 95th percentile of the body weight per day, which is higher than the maximum daily intake by the European Food Safety Authority. This is of public health importance as a high concentration of BPA in the breast milk of the lactating mothers in this study could cause severe health problems in these mothers and much more in the infants breastfeeding on these BPA-contaminated breast milk.

To compare breast milk volume between manual method and breast pump expression in mothers of preterm infants at different time point of first week.Randomized controlled trial.Postpartum ward of Obstetrics department and tertiary level neonatal intensive care unit (NICU) in a single institution in Orissa between October, 2020 and May, 2021.Mothers who delivered before 34 completed weeks of gestation.Manual breastmilk expression (ME) group using Marmet technique and breast pump milk expression (PE) group using pigeon manual breast pump, initiated milk expression within one hour of delivery.Expressed breast milk (EBM) volume in mothers of preterm infants at different time point of first week, and cumulative milk volume.Out of 170 mothers (83 PE and 87 ME group), 7-days milk volume data was available for 137 (71 ME and 66 PE) mothers. In per protocol analysis for 126 mothers (63 in each group), the median (IQR) EBM volume on day 2 and day 7 of ME and PE groups were similar [10 (5,20) vs 12 (5,28), P=0.10] and [280 (220-356) vs 280 (220-360), P=0.66]. The median (IQR) cumulative EBM volume over first 7 days in ME group was not significantly different from PE group [733 (593-995) vs 848.5 (571-1009)] P=0.55). A similar number of mothers in the PE and ME group [56 (88.9%) vs 58 (92%); P=0.14] provided exclusive breast milk for their neonates during the first week. Similar results were found on intention to treat analysis.EBM volume expressed was comparable between mothers expressing manually or with breast pump.

Three COVID-19 vaccines are licensed for emergency use in the USA: the Pfizer/BioNTech and Moderna/NIH mRNA-based vaccines, and the Johnson & Johnson (J&J)/Janssen human adenovirus (Ad26) vaccine. These vaccines have immunized [~]160 million people nationwide, comprising [~]53% Pfizer, 39% Moderna, and 8% J&J recipients [1]. Although at varying stages of clinical investigation for use in children, no COVID-19 vaccines are yet available for this population, posing a significant public health concern. One method to protect infants and young children may be passive immunization via antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work [2] and other recent reports [3-5] examining the milk Ab response to mRNA-based COVID-19 vaccination have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG-dominant. In this report, we present a comparative assessment of the milk Ab response elicited by not only the Pfizer and Moderna vaccines, but importantly, the J&J vaccine as well. This analysis revealed that compared to mRNA vaccine recipients, 49% - 63% fewer J&J vaccine recipient milk samples were positive for Spike-specific IgG, with positive samples exhibiting significantly lower mean IgG titers. J&J recipient milk samples contained significantly less specific IgA than Moderna recipient milk samples, which exhibited significantly greater relative IgA increases compared to both Pfizer and J&J recipients. Absolute and relative vaccine-induced secretory Ab titers were similarly low for all groups, though [~]25% more Moderna recipients exhibited a relative increase compared to Pfizer and J&J recipients. These data indicate that J&J vaccine poorly elicits Spike-specific Ab in milk compared to mRNA-based vaccines and that this vaccine should be considered a last choice for immunizing those intending to elicit a strong Ab response in their milk. These data also suggest that Moderna vaccine elicits a superior, albeit moderate, milk (s)IgA response, and highlight the need to design vaccines with optimal protection of the breastfeeding infant in mind.

The field of postdischarge nutrition for preterm infants arose when concerns that using diets suitable for term infants—breastfeeding without fortification or standard formulas—might not meet the postdischarge nutritional needs of infants born preterm, who often exhibited growth restriction and evidence of undernutrition. A decade ago, there were already 27 randomized controlled trials (RCTs) of nutritional supplementation from which an eligible subsample of trials have provided evidence on whether nutritional fortification of human milk or nutrient-enriched formula favorably affects postdischarge growth in these infants. These RCTs also allowed exploration of the quality of growth, bone mineralization, and the ad libitum–fed infant’s own regulation of milk volume and nutrient intake. Importantly, such RCTs, augmented by observational data on the links between growth and neurodevelopment, have allowed exploration of the potential impact of postdischarge nutrition on neurocognitive function. However, the interpretation of published data and the implication for practice has proven difficult and contentious. In this review, we examine, and to an extent reanalyze, existing evidence to elucidate its strengths and limitations, with the goal of adding more clarity to the ways in which this sizeable body of clinical scientific research may have a positive impact on the postdischarge nutritional approach to infants born preterm.

The benefits of feeding human milk to human infants are well-established. Preterm infants, particularly those born with very low birthweight (VLBW

Aim The intestinal microbiota contributes to infant's intestine homeostasis. This study aimed to analyse how probiotics derived from breast milk promote infant intestinal development in rat pups. Methods and results The effect of potential probiotics derived from breast milk on development of intrauterine growth retardation (IUGR) newborn rats' intestine was investigated. Limosilactobacillus oris ML-329 and Lacticaseibacillus paracasei ML-446 exhibited good hydrophobicity percentages (p < 0.05). ML-446 showed a significant effect on intestinal length and weight (p < 0.05). Meanwhile, the villus height of the IUGR newborn rats fed with ML-329 was significantly higher compared with those fed with Lacticaseibacillus rhamnosus GG (p < 0.05). Moreover, ML-329 and ML-446 both significantly stimulated the proliferation and differentiation of intestinal epithelial cells by increasing the number of ki67-positive cells, goblet cells, and lysozyme-positive Paneth cells (p < 0.05) through Wnt and Notch pathway. Conclusions The proliferation and differentiation stimulating effects of ML-329 and ML-446 on IECs in the jejunum, ileum, and colon were mediated by activating the Wnt pathway with increased expression of wnt, lrp5, and β-catenin genes and accumulation of β-catenin, and by downregulating the Notch signalling pathway with decreased expression of the activated notch protein. Significance and Impact of the Study Lactobacillus could facilitate IUGR rat pups' intestinal development and enhance the proliferation of Paneth cells and goblet cells. These findings provide further insights into promotion of the intestinal development by breast milk-derived beneficial microbes in early life of the IUGR newborn rats.

The aim of the present study was to assess the efficacy of feeding a higher-density formula (HDF) in infant with congenital heart disease (CHD).In a parallel randomized trial, infants (6 to 12 months) who underwent CHD corrective surgery received either a standard-density formula (SDF, 67 kcal /100 ml) or an HDF (90 kcal/100 ml) after discharge from the intensive care unit for 8 weeks. In addition to the formula, infants could receive breast milk or complementary food. Anthropometry, biochemistry, and formula intake were collected.Sixty-four infants completed the study (n = 32 in each group). All infants gained weight. The mean ± standard deviation (SD) of weight z score at baseline and week-8 were -2.38 ± 10.04 to -1.38 + 0.97 in the SDF group and -2.69 ± 1.19 to -0.89 ± 0.90 in the HDF group (between-group p = 0.0001). Both groups gained length, but showed a decline in length z-score which was significant in the SDF group but not significant in the HDF group. Mid-upper arm circumference and its z score improved in both groups, with more improvement in the HDF group. Serum albumin level was higher in the HDF than the SDF group at week-8, but no significant between-group differences were observed in hemoglobin, serum ferritin, or iron. Symptoms of gastrointestinal intolerance were not reported, but parents of 4 infants in the HDF group complained of their infants' constipation.Feeding infants using a concentrated formula could increase infants' weight gain and growth, and improve the nutritional status after CHD surgery.

Examine the effect of a donor human milk (DHM) program on mothers' own milk feedings at discharge for very low birth weight (VLBW) infants.A single center retrospective analysis of feeding outcomes in preterm infants. Data were assigned as: (1) pre DHM era (2) Bridge DHM era (3) Full DHM era. Each era was divided into infants1500 g (n = 724) or ≥1500 g (n = 784).Both the percentage of mothers' own milk feeds and percent of infants exclusively receiving mothers' own milk at discharge were increased in the1500 g (p = 0.003, p = 0.002) and the ≥1500 g group (p = 0.007, p = 0.004) respectively, following the introduction of DHM for VLBW infants.Practice changes that accompany a donor milk program likely play a prominent role in the provision of mothers' own milk and exclusivity of breast milk feedings at discharge for very low birth weight infants.

A 3-month-old, full term female infant, adequate for gestational age, and exclusively breastfed, was admitted with a 10 day history of generalised scaling erythematous dermatitis, affecting the face (perinasal, nasolabial folds and periauricular), acral and intertriginous areas, with irritability and failure to thrive. Her mother had been treated with isoniazid since the third trimester because of family contact with tuberculosis. Based on a diagnosis of suspected impetiginised eczema, the infant was treated with flucloxacillin and prednisolone, and maternal isoniazid was suspended, with no improvement. Investigations found low serum zinc levels in the infant (33 μg/dL; normal range (NR) >60 μg/dL), normal plasma zinc levels in the mother (111.3 μg/dL; NR 68–120 μg/dL) and lower than the normal range of zinc levels in breast milk (270μg/L; NR 1000–2500 μg/L), suggesting acrodermatitis caused by zinc deficiency. Oral zinc supplementation (3 mg/kg/day) was started with a marked improvement in skin lesions, as well as good weight gain. At the age of 6 months, after food diversification, supplementation was suspended, without any recurrence of symptoms.

Breastfeeding plays a protective role against infections, partially through the prebiotic effect of human milk oligosaccharides (HMOs). Aiming to mimic these beneficial capacities, there is an ongoing search to make infant formula closer to human milk, including by adding oligosaccharides. Over the past two decades, multiple studies have been published on different types of prebiotics and their role in reducing infection rates in infants. This review aims to answer the question of whether there is evidence that the addition of oligosaccharides to infant formula decreases the prevalence of infection, and whether the effect is influenced by the kind of oligosaccharide added. The review of the literature reveals an important heterogeneity, including different types and dosages of prebiotics, different intervention periods and inclusion criteria, etc., making it impossible to formulate a consensus about the efficacy of adding prebiotics to infant formula. We would cautiously suggest that supplementation with galactooligosaccharides (GOSs)/fructooligosaccharides (FOSs) seems to have a beneficial effect on infection rates. For HMOs, more studies about the different types of HMOs are necessary to make any deductions. GOSs alone, inulin, and MOSs (bovine-milk-derived oligosaccharides) do not reduce the incidence of infections. The combination of GOSs and PDX (polydextrose) was found to play a protective role in one study. The evidence of the effect of prebiotics in reducing the use of antibiotics is low. The many lacunas in the direction of study uniformity offer many opportunities for further research.

To analyze and examine the concept of exclusive breast pumping (EP).Breastmilk is the ideal nutrition for infants, yet when breastfeeding is unsuccessful, parents resort to informal breastmilk sharing, artificial formula feeding, or EP. A growing proportion of families exclusively pump yet they often receive guidance from social media rather than healthcare providers because healthcare providers are uninformed about this feeding method.Cumulative Index of Nursing and Allied Health Literature, PubMed, and Google Scholar databases were searched using the following keywords: human milk express*, breast express*, breast milk express, breastmilk express*, exclusive pump, exclusive breast pumping, and exclusive expression.Concept analysis design using Walker and Avant's method.Three defining attributes of (1) absence of direct breastfeeding, (2) breastmilk expression, (3) and an enduring infant feeding pattern of feeding expressed breastmilk only via a bottle were identified. All three attributes are required to confirm the presence of the concept of exclusive pumping. Definitions, antecedents, consequences, and empirical referents are described. Model and contrary cases are discussed.This exclusive pumping concept analysis allows for consistency in terminology in practice and research. EP is a feeding method which can increase the proportion of infants who are fed breastmilk and may reduce the risks that arise from artificial formula feeding.

Infant microbiome assembly is intensely studied in infants from industrialized nations, but little is known about this process in populations living non-industrialized lifestyles. In this study we deeply sequenced infant stool samples from the Hadza hunter-gatherers of Tanzania and analyzed them in a global meta-analysis. Infant microbiomes develop along lifestyle-associated trajectories, with over twenty percent of genomes detected in the Hadza infant gut representing phylogenetically diverse novel species. Industrialized infants, even those who are breastfed, have microbiomes characterized by a paucity of Bifidobacterium infantis and gene cassettes involved in human milk utilization. Strains within lifestyle-associated taxonomic groups are shared between mother-infant dyads, consistent with early-life inheritance of lifestyle-shaped microbiomes. The population-specific differences in infant microbiome composition and function underscore the importance of studying microbiomes from people outside of wealthy, industrialized nations.Recognition of work on indigenous communitiesResearch involving indigenous communities is needed for a variety of reasons including to ensure that scientific discoveries and understanding appropriately represent all populations and do not only benefit those living in industrialized nations. Special considerations must be made to ensure that this research is conducted ethically and in a non-exploitative manner. In this study we performed deep metagenomic sequencing on fecal samples that were collected from Hadza hunter-gatherers in 2013/2014 and were analyzed in previous publications using different methods (1, 2). A material transfer agreement with the National Institute for Medical Research in Tanzania ensures that stool samples collected are used solely for academic purposes, permission for the study was obtained from the National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542) and the Tanzania Commission for Science and Technology, and verbal consent was obtained from the Hadza after the study’s intent and scope was described with the help of a translator. The publications that first described these samples included several scientists and Tanzanian field-guides as co-authors for the critical roles they played in sample collection, but as no new samples were collected in this study, only scientists who contributed to the analyses described here were included as co-authors in this publication. It is currently not possible for us to travel to Tanzania and present our results to the Hadza people, however we intend to do so once the conditions of the COVID-19 pandemic allow it.

Determining the amount of drug transferred into human milk is critical for benefit-risk analysis of taking medication while breastfeeding. In this study, we developed an in vitro and in vivo extrapolation (IVIVE) model to predict human milk/plasma (

We aimed to capture milk feeding type in real time in a racially and socioeconomically diverse population. An electronic tool to assess milk feeding type at every medical visit for children aged 0 to 2 years was designed and incorporated into nursing workflows. The Milk Box tool was successfully added to the electronic clinical workspace of a large health system. There were eight clinics, with diverse characteristics, which incorporated the use of the Milk Box tool over 12 months. Time to 50% uptake of Milk Box varied from 3 to 5 months. Time to >80% uptake varied from 6 to 8 months. Our results show that Milk Box can be quickly incorporated into a clinical workflow when the team is given appropriate training and support. The tool also allows a primary care practice to study local breast milk consumption trends and to provide both individualized and system-level lactation support.

The composition of the microbiome in the early stages of life can directly affect the health of developing infants, and prior evidence suggests that human milk oligosaccharides (HMO) are critical regulators in the maintenance of a healthy gut microbiota in infants. Herein, we conducted an analysis of the gut microbiota of 1-mo-old breastfed infants from Jining and Harbin, China, and a corresponding analysis of the HMO profiles in samples of maternal breast milk. Quantification of HMO was conducted via liquid chromatography-mass spectrometry, and bacterial DNA sequencing was employed for characterization of the fecal microbiota. The abundances of total neutral oligosaccharides, lactodifucotetraose, lacto-N-fucopentaose I, and disialyl-lacto-N-tetraose were significantly increased in samples from the Jining group relative to the Harbin group. Bifidobacterium were the predominant microbial species in infants from both Harbin and Jining, with these levels being significantly higher in the former set. Correlation analyses evaluating microbes and 19 different HMO indicated that HMO were beneficial to the development of the gut microbiota in young infants. The predominance of Bifidobacterium in these microbial communities suggests that their ability to efficiently utilize HMO can contribute to the homeostasis of the gut microflora, with breast milk-derived HMO being critical to the shaping of the gut microbiota in breastfed infants.

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.