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This Special Issue of Nutrients “Leptin and Metabolic Programming” includes one review article regarding the function of leptin throughout the entire life on cardiometabolic fates and four original articles related to the new function of leptin present in milk and liquid amniotic, its possible relation with other components of breast milk, and how environmental conditions may impact on leptin action and metabolic programming [...]

Necrotizing enterocolitis (NEC) is a significant cause of mortality and morbidity in preterm infants. The pathogenesis of NEC is not completely understood; however, intestinal immaturity and excessive immunoreactivity of intestinal mucosa to intraluminal microbes and nutrients appear to have critical roles. Dietary fats are not only the main source of energy for preterm infants, but also exert potent effects on intestinal development, intestinal microbial colonization, immune function, and inflammatory response. Preterm infants have a relatively low capacity to digest and absorb triglyceride fat. Fat may thereby accumulate in the ileum and contribute to the development of NEC by inducing oxidative stress and inflammation. Some fat components, such as long-chain polyunsaturated fatty acids (LC-PUFAs), also exert immunomodulatory roles during the early postnatal period when the immune system is rapidly developing. LC-PUFAs may have the ability to modulate the inflammatory process of NEC, particularly when the balance between n3 and n6 LC-PUFAs derivatives is maintained. Supplementation with n3 LC-PUFAs alone may have limited effect on NEC prevention. In this review, we describe how various fatty acids play different roles in the pathogenesis of NEC in preterm infants.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

It is unclear whether gestational diabetes mellitus (GDM) alters breast milk composition. We prospectively examined associations of GDM status with concentrations of six potentially bioactive elements (glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), leptin, and adiponectin) in human milk. These were measured at both 1 and 3 months postpartum in 189 fully breastfeeding women. Mixed-effects linear regression assessed GDM status-related differences in these milk bioactives, adjusting for demographics, maternal factors, and diet. At 1 and 3 months postpartum, milk CRP was higher (1.46 ± 0.31 ng/mL; p < 0.001 and 1.69 ± 0.31 ng/mL; p < 0.001) in women with GDM than in women without GDM, whereas milk glucose (−5.23 ± 2.22 mg/dL; p = 0.02 and −5.70 ± 2.22; p = 0.01) and milk insulin (−0.38 ± 0.17 μIU/mL; p = 0.03 and −0.53 ± 0.17; p = 0.003) were lower in women with GDM. These significant associations remained similar after additional adjustment for maternal weight status and its changes. No difference was found for milk IL-6, leptin, and adiponectin. There was no evidence of association between these milk bioactive compounds and 1 h non-fasting oral glucose challenge serum glucose in the women without GDM. This prospective study provides evidence that potentially bioactive elements of human milk composition are altered in women with GDM.

The Australian Feeding Infants and Toddler Study 2021 (OzFITS 2021) is a nationwide survey of Australian caregivers’ infant and toddler feeding practices. Here, we describe breastfeeding rates and duration, use of breastmilk substitutes, and introduction of complementary (solid) foods, including common food allergens. Caregivers (n = 1140) were recruited by a digital marketing company and were interviewed using a structured telephone questionnaire to obtain information. Breastfeeding was initiated in 98% of infants, but the duration of exclusive breastfeeding to six months was less than 1%. Nearly 40% of children continued to receive breastmilk beyond one year, with 10% of toddlers receiving breastmilk at two years. One-quarter of infants were introduced to solid foods between 4 to 5 months, and nearly all infants had received solid foods by 7 months. New guidelines encourage the early introduction of potential food allergens to reduce the risk of allergy, and by 12 months, over 90% of children had been given eggs and peanuts. One-third of children received no breastmilk substitutes during their first year. One-third of infants first received breastmilk substitutes following birth and before discharge from the hospital. Of these infants, 30% ceased breastmilk substitute use after discharge. Our findings suggest a high rate of continued breastfeeding with 44% receiving breastmilk beyond 1 year. One approach to increase the duration of exclusive breastfeeding is to reduce breastmilk substitute use while in hospital.

Many infant formulas are fortified with iron at 8&ndash, 14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf&minus, ) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 &micro, g/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.

Sample preparation is the most critical step in proteomics as it directly affects the subset of proteins and peptides that can be reliably identified and quantified. Although a variety of efficient and reproducible sample preparation strategies have been developed, their applicability and efficacy depends much on the biological sample. Here, three approaches were evaluated for the human milk and plasma proteomes. Protein extracts were digested either in an ultrafiltration unit (filter-aided sample preparation, FASP) or in-solution (ISD). ISD samples were desalted by solid-phase extraction prior to nRPC-ESI-MS/MS. Additionally, milk and plasma samples were directly digested by FASP without prior protein precipitation. Each strategy provided inherent advantages and disadvantages for milk and plasma. FASP appeared to be the most time efficient procedure with a low miscleavage rate when used for a biological sample aliquot, but quantitation was less reproducible. A prior protein precipitation step improved the quantitation by FASP due to significantly higher peak areas for plasma and a much better reproducibility for milk. Moreover, the miscleavage rate for milk, the identification rate for plasma, and the carbamidomethylation efficiency were improved. In contrast, ISD of both milk and plasma resulted in higher miscleavage rates and is therefore less suitable for targeted proteomics.

Inconsistent conclusions from infant sleep and feeding studies may influence parents feeding-related decisions. This study aimed to systematically review the existing literature on infant sleep and its relation to the timing of introduction to complementary foods and type of milk feeding to better understand their role(s) in infant sleep. Cohort, longitudinal, cross-sectional studies, and controlled trials were identified using online searches of five databases up to April 2020. Twenty-one articles with a total of 6225 infants under 12 months-of-age were eligible. Exclusively breastfed infants (≤6 months-of-age) had a greater number of night wakings, but most studies (67%) reported no difference in night-time and 24 h sleep duration compared to formula-fed infants. However, after 6 months-of-age, most studies (>65%) reported breastfed infants to sleep less in the night-time and over 24 h compared to formula-fed infants. Furthermore, studies reported no association between the timing of introduction to complementary foods and infant sleep duration (

(1) Background: Human milk oligosaccharides (HMOs) are present in maternal serum during pregnancy and their composition is altered in gestational diabetes (GDM). HMOs are also in fetal cord blood and in contact with the feto-placental endothelium, potentially affecting its functions, such as angiogenesis. We hypothesized that cord blood HMOs are changed in GDM and contribute to increased feto-placental angiogenesis, hallmark of GDM. (2) Methods: Using HPLC, we quantified HMOs in cord blood of women with normal glucose tolerance (NGT, n = 25) or GDM (n = 26). We investigated in vitro angiogenesis using primary feto-placental endothelial cells (fpECs) from term placentas after healthy pregnancy (n = 10), in presence or absence of HMOs (100 µg/mL) isolated from human milk, 3′-sialyllactose (3′SL, 30 µg/mL) and lactose (glycan control) and determined network formation (Matrigel assay), proliferation (MTT assays), actin organization (F-actin staining), tube formation (fibrin tube formation assay) and sprouting (spheroid sprouting assay). (3) Results: 3′SL was higher in GDM cord blood. HMOs increased network formation, HMOs and 3’SL increased proliferation and F-actin staining. In fibrin assays, HMOs and 3’SL increased total tube length by 24% and 25% (p < 0.05), in spheroid assays, by 32% (p < 0.05) and 21% (p = 0.056), respectively. Lactose had no effect. (4) Conclusions: Our study suggests a novel role of HMOs in feto-placental angiogenesis and indicates a contribution of HMO composition to altered feto-placental vascularization in GDM.

Background: Breast milk is irreplaceable for healthy development. In Mexico, by 2019, the prevalence of exclusive breastfeeding (EBF) was low and the use of breastmilk substitutes (BMSs) was high. Objective: The aim of this work was to evaluate the maternal and child characteristics related to breastfeeding (BF) duration and to the introduction of BMSs for residents of Mexico City (CdMX) and an agricultural town in Morelos. Methods: A cross-sectional study was conducted with 160 mother–child binomials (0–15 months of age) from the megacity CdMX and the agricultural town. Outcomes: EBF and total breastfeeding (TBF) duration, age of transition to BMSs, and the introduction of complementary feeding (CF) were assessed. Associations with maternal and infant factors were assessed using Cox models. Results: The prevalence of EBF in the joint samples at 5.9 months was 32.6% and 5.8% at 6 months. EBF was favored under the following conditions: living in CdMX, receiving prenatal care, no newborn hospitalization, and breastmilk provided as first food at birth. TBF was prolonged under the following conditions: older mother, female children, rooming-in care during puerperium, receiving BF upon discharge after birth, cohabiting with extended family, and having no siblings. The introduction of BMSs predominated under the following conditions: living in an agricultural town, BMSs given after birth before discharge, younger mother, worker mother, and lack of prenatal care. The early introduction of CF (before the fourth month) was 2% for CdMX and 14% for the agricultural town. Conclusions: The agricultural population had a higher risk of the premature interruption of EBF/TBF and the early introduction of BMSs and CF. Protective factors were family-friendly environments and being born in a baby-friendly hospital.

Humans require vitamin A (VA). However, pooled VA data in human milk is uncommon internationally and offers little support for dietary reference intake (DRIs) revision of infants under 6 months. As a result, we conducted a literature review and a meta-analysis to study VA concentration in breast milk throughout lactation across seven databases by August 2021. Observational or intervention studies involving nursing mothers between the ages of 18 and 45, with no recognized health concerns and who had full-term infants under 48 months were included. Studies in which retinol concentration was expressed as a mass concentration on a volume basis and determined using high-, ultra-, or ultra-fast performance liquid chromatography (HPLC, UPLC, or UFLC) were chosen. Finally, 76 papers involving 9171 samples published between 1985 and 2021 qualified for quantitative synthesis. Results from the random-effects model showed that the VA concentration of healthy term human milk decreased significantly as lactation progressed. VA (µg/L) with 95% CI at the colostrum, transitional, early mature and late mature stages being 920.7 (744.5, 1095.8), 523.7 (313.7, 733.6), 402.4 (342.5, 462.3) and 254.7 (223.7, 285.7), respectively (X2 = 71.36, p < 0.01). Subgroup analysis revealed no significant differences identified in VA concentration (µg/L) between Chinese and non-Chinese samples at each stage, being 1039.1 vs. 895.8 (p = 0.64), 505.7 vs. 542.2(p = 0.88), 408.4 vs. 401.2 (p = 0.92), 240.0 vs. 259.3 (p = 0.41). The findings have significant implications for the revision of DRIs for infants under six months.

Background: The present strategy of administering human milk fortifier (HMF) in southwest China (swC) is mainly based on European and American populations’ guidelines. Additionally, some southwest Chinese preterm infants have been observed to develop feeding intolerance (FI) after administration of HMF. In order to develop adapted southwest Chinese guidelines for the administration of HMF to preterm infants and improve fortification strategies, a retrospective cohort study was performed to explore the association of the use of HMF and FI. Objective: To explore the association between HMF and FI in preterm infants and provide recommendations for its use in swC. Methods: This cohort study included 298 preterm infants from West China Second University Hospital. Maternal and infant clinical data were collected from electronic patient records. The infant cohort was divided into two groups based on the use/nonuse of HMF. The association between HMF and FI was evaluated using multivariate analysis. Nonlinear relationships and threshold effects were evaluated using generalized additive models and two-piecewise linear regression models. Results: The multivariate analysis confirmed that there is no significant association between HMF use and FI, but significant risk factors for FI include early HMF initiation (p = 0.02), full-strength HMF initiation (p = 0.04), and fast HMF supplementation rates (p = 0.004). Through smooth curve fitting and threshold effect analysis, we found that two inflection points, an initial concentration of HMF > 24 mg/mL and a HMF supplementation rate > 12.5 mg/mL/d, significantly increased FI risk. Conclusions: Routine HMF fortification can be safely used in preterm infants with gestational age < 32 wk or birth weight < 1500 g in swC, and we advise initiating fortification when enteral milk intake reaches 100 mL/kg/day, with an HMF concentration of 1:50 and if tolerated, increase to 1:25 more than 38 h. The recommended HMF supplementation rate differs from current guidelines and provides evidence for developing southwest Chinese guidelines. A prospective trial is needed in order to validate this proposal.

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

Human milk (HM) components may influence infant growth and development. This study aimed to investigate relationships between infant body composition (BC) and HM lactose, insulin, and glucose (concentrations and calculated daily intakes (CDI)) as well as 24-h milk intake and maternal BC at 3 months postpartum. HM samples were collected at 2 months postpartum. Infant and maternal BC was assessed with bioimpedance spectroscopy. Statistical analysis used linear regression accounting for infant birth weight. 24-h milk intake and CDI of lactose were positively associated with infant anthropometry, lean body mass and adiposity. Higher maternal BC measures were associated with lower infant anthropometry, z-scores, lean body mass, and adiposity. Maternal characteristics including BC and age were associated with concentrations and CDI of HM components, and 24-h milk intake. In conclusion, 24-h intake of HM and lactose as well as maternal adiposity are related to development of infant BC.

The nutritional requirements of preterm infants are challenging to meet in neonatal care, yet crucial for their growth, development and health. Aberrant maturation of the gastrointestinal tract and the microbiota could affect the digestion of human milk and its nutritional value considerably. Therefore, the main objective of the proposed research is to investigate how the intestinal microbiota of preterm and full-term infants differ in their ability to extract energy and nutrients from oligosaccharides and glycoproteins in human milk. This pilot study will be an observational, single-center study performed at the Neonatal Intensive Care Unit at Isala Women and Children’s Hospital (Zwolle, The Netherlands). A cohort of thirty mother–infant pairs (preterm ≤30 weeks of gestation, n = 15, full-term 37–42 weeks of gestation, n = 15) will be followed during the first six postnatal weeks with follow-up at three- and six-months postnatal age. We will collect human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants. A combination of 16S rRNA amplicon sequencing, proteomics, peptidomics, carbohydrate analysis and calorimetric measurements will be performed. The role of the microbiota in infant growth and development is often overlooked yet offers opportunities to advance neonatal care. The ‘From Mum to Bum’ study is the first study in which the effect of a preterm gut microbiota composition on its metabolic capacity and subsequent infant growth and development is investigated. By collecting human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants at each timepoint, we can follow digestion of human milk from the breast of the mother throughout the gastrointestinal tract of the infant, or ‘From Mum to Bum’.

Intracerebral hemorrhage (ICH) occurs when brain blood vessels rupture, causing inflammation and cell death. 2-Fucosyllactose (2FL), a human milk oligosaccharide, has potent antiapoptotic and anti-inflammatory effects. The purpose of this study was to examine the protective effect of 2FL in cellular and rodent models of ICH. Hemin was added to a primary rat cortical neuronal and BV2 microglia coculture to simulate ICH in vitro. IBA1 and MAP2 immunoreactivities were used to determine inflammation and neuronal survival. Hemin significantly increased IBA1, while it reduced MAP2 immunoreactivity. 2FL significantly antagonized both responses. The protective effect of 2FL was next examined in a rat ICH model. Intracerebral administration of type VII collagenase reduced open-field locomotor activity. Early post-treatment with 2FL significantly improved locomotor activity. Brain tissues were collected for immunohistochemistry and qRT-PCR analysis. 2FL reduced IBA1 and CD4 immunoreactivity in the lesioned striatum. 2FL downregulated the expression of ER stress markers (PERK and CHOP), while it upregulated M2 macrophage markers (CD206 and TGFβ) in the lesioned brain. Taken together, our data support that 2FL has a neuroprotective effect against ICH through the inhibition of neuroinflammation and ER stress. 2FL may have clinical implications for the treatment of ICH.

Micronutrients are dietary components important for health and physiological function, and inadequate intake of these nutrients can contribute to poor health outcomes. The risk of inadequate micronutrient intake has been shown to be greater among low-income Hispanics and postpartum and lactating women. Therefore, we aimed to determine the risk of nutrient inadequacies based on preliminary evidence among postpartum, Hispanic women. Risk of micronutrient inadequacy for Hispanic women (29–45 years of age) from the Southern California Mother’s Milk Study (n = 188) was assessed using 24 h dietary recalls at 1 and 6 months postpartum and the estimated average requirement (EAR) fixed cut-point approach. Women were considered at risk of inadequate intake for a nutrient if more than 50% of women were consuming below the EAR. The Chronic Disease Risk Reduction (CDRR) value was also used to assess sodium intake. These women were at risk of inadequate intake for folate and vitamins A, D, and E, with 87.0%, 93.4%, 43.8%, and 95% of women consuming less than the EAR for these nutrients, respectively. Lastly, 71.7% of women consumed excess sodium. Results from this preliminary analysis indicate that Hispanic women are at risk of inadequate intake of important micronutrients for maternal and child health.

Funder: Medical Research Council; Grant(s): Unit programmes: MC_UU_12015/2 and MC_UU_00006/2, Funder: Wellcome Trust, Growth and nutrition during early life have been strongly linked to future health and metabolic risks. The Cambridge Baby Growth Study (CBGS), a longitudinal birth cohort of 2229 mother-infant pairs, was set up in 2001 to investigate early life determinant factors of infant growth and body composition in the UK setting. To carry out extensive profiling of breastmilk intakes and composition in relation to infancy growth, the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) was established upon the original CBGS. The strict inclusion criteria were applied, focusing on a normal birth weight vaginally delivered infant cohort born of healthy and non-obese mothers. Crucially, only infants who were exclusively breastfed for the first 6 weeks of life were retained in the analysed study sample. At each visit from birth, 2 weeks, 6 weeks, and then at 3, 6, 12, 24, and 36 months, longitudinal anthropometric measurements and blood spot collections were conducted. Infant body composition was assessed using air displacement plethysmography (ADP) at 6 weeks and 3 months of age. Breast milk was collected for macronutrients and human milk oligosaccharides (HMO) measurements. Breast milk intake volume was also estimated, as well as sterile breastmilk and infant stool collection for microbiome study.

The aim of this systematic review was to summarize concentrations of human milk oligosaccharides (HMOs) in the Chinese population. We searched articles originally published in both Chinese and English. When compiling data, lactation was categorized into five stages. We found that 6′-sialyllactose, lacto-N-tetraose, and lacto-N-neotetraose decreased over lactation. Conversely, 3′-fucosyllactose increased over lactation. Our study represents the first systematic review to summarize HMO concentrations in Chinese population. Our findings not only provide data on HMO profiles in Chinese population but suggest future directions in the study of the metabolism of HMOs.

In this study, we propose a simple, cost-effective, and sensitive high-performance liquid chromatography with fluorescence detection (HPLC-FLD) for the simultaneous determination of seven bisphenols (bisphenol F (BPF), bisphenol E (BPE), bisphenol B (BPB), BADGE (bisphenol A diglycidyl ether), BADGE∙2H2O, BADGE∙H2O, BADGE∙2HCl) in human breast milk samples. The dispersive solid phase extraction (d-SPE) coupled with solid phase extraction (SPE) procedure performed well for the majority of the analytes with recoveries in the range 57–88% and relative standard deviations (RSD%) of less than 9.4%. During the d-SPE stage, no significant matrix effect was observed thanks to the application of different pairs of salts such as zirconium-dioxide-based sorbents (Z-Sep or Z-Sep +) and primary secondary amine (PSA) or QuEChERS Enhanced Matrix Removal-Lipid (EMR-Lipid) and PSA. The method limits of quantification (mLOQs) for all investigated analytes were set at satisfactory low values in the range 171.89–235.11 ng mL−1. Analyte concentrations were determined as the average value from human breast milk matrix samples. The results show that the d-SPE/SPE procedure, especially with the application of EMR-Lipid and PSA, could be used for further bisphenol analyses in human breast milk samples.

The polyamine content of human breast milk, which is the first exogenous source of polyamines for the newborn, can be affected by several factors associated with the mother, the infant, or breastfeeding itself. The aim of this study was to evaluate the influence of different breastfeeding factors on the polyamines found in human milk. For this study, a cohort of 83 mothers was considered for up to 4 months, and a subgroup of 33 mothers were followed during the first six months of breastfeeding. Two breast milk samples were collected at each sampling point (foremilk and hindmilk) and the polyamine content was determined by UHPLC-FL. Polyamine levels varied considerably between the mothers and tended to decrease over time. Putrescine was the minor polyamine, whereas spermidine and spermine contents were very similar. The concentrations of the three polyamines were significantly higher in hindmilk than foremilk (p &lt, 0.001). Spermidine and spermine levels decreased significantly through the lactation progress (p &lt, 0.05). Finally, slightly higher levels of polyamines were observed in the milk of mothers providing partial, rather than full, breastfeeding, although the differences were not significant. The polyamine content in human milk was found to change during a single feed (foremilk versus hindmilk) and as lactation progressed, mainly in response to the specific circumstances of the newborn.

(1) Background: The aim of the conducted research was to analyze the squalene content in infants’ food. (2) Methods: The experimental material included human milk collected from 100 women from Poland and three different infant formulas. The breast milk fat was extracted according to the Rose–Gottlieb method (AOAC), while the squalene content was determined using the high-performance liquid chromatography (HPLC) method. (3) Results: The highest amount of squalene was identified in the milk of women aged 18–25 (p < 0.05), and its content in milk decreased with the age of lactating women. Moreover, the greatest amount of squalene was identified in milk from the first lactation period (colostrum), while in mature milk, its content was more than two times lower. There was a correlation between breastfeeding BMI and the squalene content in milk (r = 0.78). (4) Conclusions: The conducted research shows that the level of squalene in human milk depends on physiological factors such as the lactation period and individual factors (age, BMI). The results of the conducted research indicate that breast milk is richer in squalene than modified milk. This study shows the importance of breastfeeding and indicates the superiority of breast milk over infant formulas.

Phenylketonuria (PKU) management aims to control phenylalanine (Phe) intakes. In newborns and infants this implies possible titration of Human milk (HM) with supplementation of Phe-free formula. HM benefits, better if prolonged, are well known in healthy populations, suggesting it may be used in PKU patients. Despite that, the current literature does not define recommendations on how best perform it in such a population. The main purpose of this study was to evaluate nutrition approaches in newborns and infants affected by PKU and to define if differences can influence the duration of breastfeeding. Data from 42 PKU infants were reviewed. Of these, 67% were breastfed with the use of three different approaches. The type of approach used impacted the duration of breastfeeding, which was longer when using a pre-measured amount of Phe-free formula administered prior to HM. This is the first study to suggest a specific method for breastfeeding in PKU. Considering widely known breastfeeding benefits, both for patients and their mothers, our data should encourage adequate awareness on how to choose correct breastfeeding modalities.

Although the World Health Organization (WHO) and UNICEF recommend that infants should be exclusively breastfed for the first 6 months of life, evidence is scarce on how the mother’s undernourishment status at delivery and maternal dietary factors influence human milk (HM) composition during the first 6 months of life in regions with high food insecurity. The maternal undernourishment status at delivery, maternal diet, and HM nutrients were assessed among 46 women and their 48 vaginally born infants in Bangui at 1, 4, 11, 18, and 25 weeks after birth through 24-h recalls and food consumption questionnaires from December 2017 to June 2019 in the context of the "Mother-to-Infant TransmIssion of microbiota in Central-Africa" (MITICA) study. High food insecurity indexes during the follow-up were significantly associated with them having lower levels of many of the human milk oligosaccharides (HMOs) that were measured and with lower levels of retinol (aß-coef = −0.2, p value = 0.04), fatty acids (aß-coef = −7.2, p value = 0.03), and amino acids (aß-coef = −2121.0, p value < 0.001). On the contrary, women from food-insecure households displayed significantly higher levels of lactose in their HM (aß-coef = 3.3, p value = 0.02). In parallel, the consumption of meat, poultry, and fish was associated with higher HM levels of many of the HMOs that were measured, total amino acids (aß-coef = 5484.4, p value < 0.001), and with lower HM levels of lactose (aß-coef = −15.6, p value = 0.01). Food insecurity and maternal diet had a meaningful effect on HM composition with a possible impact being an infant undernourishment risk. Our results plead for consistent actions on food security as an effective manner to influence the nutritional content of HM and thereby, potentially improve infant survival and healthy growth.

Animal studies have shown that human milk oligosaccharides (HMOs) are important in early brain development, yet their roles have not been assessed in humans. The purpose of this study was to determine the associations of HMOs with MRI indices of tissue microstructure and regional cerebral blood flow (rCBF) in infants. Mother–infant pairs (N = 20) were recruited at 1 month postpartum. Milk was assayed for the concentrations of the HMOs 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), and 6′-sialyllactose (6′SL). Diffusion and arterial spin labeling measures were acquired using a 3.0-Tesla MRI scanner. Multiple linear regression was used to assess the voxel-wise associations of HMOs with fractional anisotropy (FA), mean diffusivity (MD), and rCBF values across the brain. After adjusting for pre-pregnancy BMI, sex, birthweight, and postmenstrual age at time of scan, a higher 2′FL concentration was associated with reduced FA, increased MD, and reduced rCBF in similar locations within the cortical mantle. Higher 3FL and 3′SL concentrations were associated with increased FA, reduced MD, and increased rCBF in similar regions within the developing white matter. The concentration of 6′SL was not associated with MRI indices. Our data reveal that fucosylated and sialylated HMOs differentially associate with indices of tissue microstructure and rCBF, suggesting specific roles for 2′FL, 3FL, and 3′SL in early brain maturation.

Background The infant gut microbiota is critical for promoting and maintaining early life health. Bacteria coated by secretory immunoglobulin A (sIgA) may help commensal bacteria colonize the gastrointestinal tract. The study aimed to analyze the composition of sIgA-coated and sIgA-uncoated bacterial communities at genus level, and lactobacilli and bifidobacterial communities at species level in human breast milk (HBM), infant, and maternal feces. Results Eleven pregnant women were recruited successfully. HBM, infant feces during colostrum, transition, and mature stages, and maternal feces within the mature stage were collected. sIgA-coated and sIgA-uncoated bacteria were separated with magnetic-activated cell sorting. Then 16S rRNA sequencing, bifidobacterial groEL gene sequencing, and lactobacilli groEL gene sequencing were performed to analyze the bacterial community. The richness of sIgA-coated bacteria was significantly higher than that of sIgA-uncoated bacteria in HBM. PCoA revealed that the compositions of sIgA-coated and sIgA-uncoated bacteria were different among HBM, infant and maternal feces. The dominant sIgA-coated bacteria in those samples were Escherichia/shigella and the dominant sIgA-uncoated bacteria was Pseudomonas. Higher relative abundance of sIgA-uncoated Bifidobacterium was found in the three lactation stages in infant feces compared to the corresponding HBM, and a higher relative abundance of sIgA-uncoated Faecalibacterium was found in maternal feces compared to HBM and infant feces. For the bifidobacterial community, PCoA analysis revealed a significantly different Bifidobacterium composition only in the sIgA-uncoated segments of infant feces and maternal feces. sIgA-coated and sIgA-uncoated B. longum subsp. infantis and B. pseudocatenulatum was dominant in infant feces and maternal feces, respectively. Additionally, the relative abundance of sIgA-uncoated B. longum subsp. infantis was significantly higher in infant feces compared to that in maternal feces. For the Lactobacillus community, the composition was significantly different in infant and maternal feces, while at species level, L. paragasseri and L. mucosae were dominant in infant and maternal feces, respectively. Conclusion HBM, infant, and maternal feces showed distinct diversity and composition of both sIgA-coated and sIgA-uncoated bacteria at genus level. Infant and maternal feces showed similar diversity and similar composition of Bifidobacterium at species level. The same Bifidobacterium species could be detected both in sIgA-coated and sIgA-uncoated form.

Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant gut microbial colonization and composition is the mode of infant feeding. While infant formula milk has been designed to resemble human milk as much as possible, the gut microbiome of infants who receive formula milk differs from that of infants who are fed human milk. A diverse microbial population in human milk and the microbes seed the infant gut microbiome. Human milk contains nutritional components that promote infant growth and bioactive components, such as human milk oligosaccharides, lactoferrin, and immunoglobulins, which contribute to immunological development. In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants’ gut and health.

Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, either after natural infection or vaccination, but whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers remains inconclusive. Herein, we evaluated the levels of IgG, IgA, and secretory IgA (SIgA) antibodies against the spike protein of SARS-CoV-2 in 43 lactating mothers who received at least two doses of either an mRNA-based vaccine (Pfizer/BioNTech, Moderna; n = 34) or an adenovirus-based vaccine (AstraZeneca; n = 9). We also accessed the potential persistence of SARS-CoV-2 IgA, IgG, and secretory IgA (SIgA) antibodies from vaccinated women in the GI tract of the infants by means of a static in vitro digestion protocol. Our data depict that, although slightly reduced, the IgA antibodies produced after vaccination resist both the gastric and intestinal phases of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. Additionally, SIgA antibodies were found to greatly resist the gastric phase of digestion albeit showing some reduction during the intestinal phase. The evaluation of the vaccine induced Ig profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract provide important information about the potential protective role of this form of passive immunity that could help decision making during the COVID-19 pandemic and beyond.

We aimed to investigate dietary vitamin A (DVA) intake, serum vitamin A (SVA) concentrations, and breast milk vitamin A (BMVA) concentrations of urban lactating Chinese women and explore the associated factors. We recruited 326 lactating women from ten cities in China and collected their dietary information, blood samples, and breast milk samples. SVA and BMVA were assessed with high-performance liquid chromatography. Mann–Whitney U tests, Kruskal–Wallis H tests, Chi-square tests, Spearman correlation tests, and multiple regression analyses were conducted. The median (25th, 75th) of DVA, SVA and BMVA were 372.36 (209.12, 619.78) μg RAE/day, 1.99 (1.71, 2.35) μmol/L, and 1.67 (1.13, 2.15) μmol/L, respectively. Only 3.1% of lactating women met the recommended nutrient intake of Vitamin A (VA), and 20.6% had a BMVA level below 1.05 μmol/L. Compared to underweight or normal weight women, overweight or obese lactating women had lower DVA and BMVA but higher SVA (p = 0.022; p = 0.030; p = 0.003). Multiparous women had a higher risk of inadequate BMVA (p = 0.023) than primiparous women. SVA and BMVA were positively associated with DVA, especially for lactating women not using VA supplements (β = 0.174, 95%CI = 0.025, 0.324, p = 0.022; β = 0.501, 95%CI = 0.208, 0.795, p = 0.001). There was no association between SVA and BMVA (β = 0.165, 95%CI = −0.037, 0.366, p = 0.109). In conclusion, VA nutritional status among Chinese urban lactating women needs more attention, especially for those who are obese, overweight, or higher parity. Increased DVA may contribute to increased BMVA.

International audience; Most viruses use several entry sites and modes of transmission to infect their host (parenteral, sexual, respiratory, oro-fecal, transplacental, transcutaneous, etc.). Some of them are known to be essentially transmitted via arthropod bites (mosquitoes, ticks, phlebotomes, sandflies, etc.), and are thus named arthropod-borne viruses, or arboviruses. During the last decades, several arboviruses have emerged or re-emerged in different countries in the form of notable outbreaks, resulting in a growing interest from scientific and medical communities as well as an increase in epidemiological studies. These studies have highlighted the existence of other modes of transmission. Among them, mother-to-child transmission (MTCT) during breastfeeding was highlighted for the vaccine strain of yellow fever virus (YFV) and Zika virus (ZIKV), and suggested for other arboviruses such as Chikungunya virus (CHIKV), dengue virus (DENV), and West Nile virus (WNV). In this review, we summarize all epidemiological and clinical clues that suggest the existence of breastfeeding as a neglected route for MTCT of arboviruses and we decipher some of the mechanisms that chronologically occur during MTCT via breastfeeding by focusing on ZIKV transmission process.

Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth, and nutrition plays a crucial role in lung growth and repair. A practical nutritional approach for infants at risk of BPD or with established BPD is provided based on a comprehensive literature review. Ideally, infants with BPD should receive a fluid intake of not more than 135-150 mL/kg/day and an energy intake of 120-150 kcal/kg/day. Providing high energy in low volume remains a challenge and is the main cause of growth restriction in these infants. They need a nutritional strategy that encompasses early aggressive parenteral nutrition and the initiation of concentrated feedings of energy and nutrients. The order of priority is fortified mother's own milk, followed by fortified donor milk and preterm enriched formulas. Functional nutrient supplements with a potential protective role against BPD are revisited, despite the limited evidence of their efficacy. Specialized nutritional strategies may be necessary to overcome difficulties common in BPD infants, such as gastroesophageal reflux and poorly coordinated feeding. Planning nutrition support after discharge requires a multidisciplinary approach to deal with multiple potential problems. Regular monitoring based on anthropometry and biochemical markers is needed to guide the nutritional intervention. info:eu-repo/semantics/publishedVersion

Cytokines play a huge role in many biological processes. Their production, release and interactions are subject to a very complex mechanism. Cytokines are produced by all types of cells, they function very differently and they are characterized by synergism in action, antagonism, and aggregation activity, opposing action of one cytokine, overlapping activity, induction of another cytokine, inhibition of cytokine synthesis at the mRNA level as well as autoregulation-stimulation or inhibition of own production. The predominance of pro-inflammatory cytokines leads to a systemic inflammatory response, and anti-inflammatory-to an anti-inflammatory response. They regulate the organism’s immune response and protect it against sudden disturbances in homeostasis. The synthesis and activity of cytokines are influenced by the central nervous system through the endocrine system (pituitary gland, adrenal glands).

An ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the sensitive determination and unambiguous confirmation of residues of per and polyfluorinated alkyl substances (PFAS) in breastmilk, retail milk and infant formulas following two sample preparation methods. Sample pre-treatment was carried out by a simplified QuEChERS method without requiring dSPE or any further clean-up. The method was validated in accordance with the requirements of Commission Decision 657/2002/EC with slight modifications. The method displayed good linearity with R2 ranging from 0.9843–0.9998 for all target PFAS. The recovery and within-laboratory reproducibility of the method (n = 63) were in the range 60–121% and 5–28%, respectively. The decision limit, detection capability and limit of quantitation ranged from 30–60 ng kg−1 to 40–100 ng kg−1 and 5–50 ng kg−1, respectively. Acceptable matrix effect values in the range −45–29% were obtained with uncertainty of measurement lower than 25% for all target PFAS. The method displays its suitability for the sensitive and high-throughput confirmatory analysis of C4–C14 PFAS in breastmilk, dairy milk and infant formulas.

In this context of COVID-19 pandemic, great interest has been aroused by the potential maternal transmission of SARS-CoV-2 by transplacental route, during delivery, and, subsequently, through breastfeeding. Some open questions still remain, especially regarding the possibility of finding viable SARS-CoV-2 in breast milk (BM), although this is not considered a worrying route of transmission. However, in BM, it was pointed out the presence of antibodies against SARS-CoV-2 and other bioactive components that could protect the infant from infection. The aim of our narrative review is to report and discuss the available literature on the detection of anti-SARS-CoV-2 antibodies in BM of COVID-19 positive mothers, and we discussed the unique existing study investigating BM of SARS-CoV-2 positive mothers through metabolomics, and the evidence regarding microbiomics BM variation in COVID-19. Moreover, we tried to correlate metabolomics and microbiomics findings in BM of positive mothers with potential effects on breastfed infants metabolism and health. To our knowledge, this is the first review summarizing the current knowledge on SARS-CoV-2 effects on BM, resuming both “conventional data” (antibodies) and “omics technologies” (metabolomics and microbiomics).

The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk of diarrheal disease, respiratory disease, otitis media, and in later life, less risk of chronic disease. These benefits may be mediated by antibodies, glycoproteins, glycolipids, oligosaccharides, and leukocytes. More recently, human milk extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs and proteins, that may transmit information from the mother to promote infant growth and development. Maternal health conditions can influence hMEV composition. This review summarizes hMEV biogenesis and functional contents, reviews the functional evidence of hMEVs in the maternal–infant health relationship, and discusses challenges and opportunities in hMEV research.

As shown in many studies, one of the earliest statistically significant indicators of the development of many autoimmune diseases (ADs) is the appearance in the blood of antibodies with catalytic activities (abzymes) hydrolyzing different autoantigens. Antibodies-abzymes having different enzymatic activities are a specific and essential feature of some ADs. Most abzymes are harmful to humans. Free histones in the blood are damage-associated proteins, and their administration to animals drives systemic inflammatory and toxic effects. Myelin basic protein (MBP) is the most critical component of the axon myelin-proteolipid sheath. Hydrolysis of MBP by abzymes leads to the disruption of nerve impulses. Here, we analyzed the possible pathways for the formation of unusual antibodies and abzymes that exhibit polyspecificity in recognition during complex formation with partially related antigens and possess the ability to catalyze several different reactions for the first time. Using IgGs of HIV-infected and multiple sclerosis patients against five individual histones (H1–H4), MBP, and DNA, it was first shown that abzymes against each of these antigens effectively recognize and hydrolyze all three antigens: histones, MBP, and DNA. The data obtained indicate that the formation of such polyspecific abzymes, whose single active center can recognize different substrates and catalyze several reactions, can occur in two main ways. They can be antibodies against DNA–protein complex hybrid antigenic determinants containing proteins and nucleic sequences. Their formation may also be associated with the previously described phenomenon of IgG extensive LH half-molecule (containing one L-light and one H-heavy chains) exchange leading to H2L2 molecules containing HL halves with variable fragments recognizing different antigens.

The microscale thermophoresis (MST) technique was utilized to investigate lactoferrin–drug interaction with the iron chelator, deferiprone, using label-free system. MST depends on the intrinsic fluorescence of one interacting partner. The results indicated a significant interaction between lactoferrin and deferiprone. The estimated binding constant for the lactoferrin–deferiprone interaction was 8.9 × 10−6 ± 1.6, SD, which is to be reported for the first time. Such significant binding between lactoferrin and deferiprone may indicate the potentiation of the drug secretion into a lactating mother’s milk. The technique showed a fast and simple approach to study protein–drug interaction while avoiding complicated labeling procedures. Moreover, the binding behavior of deferiprone within the binding sites of lactoferrin was investigated through molecular docking which reflected that deferiprone mediates strong hydrogen bonding with ARG121 and ASP297 in pocket 1 and forms H-bond and ionic interaction with ASN640 and ASP395, respectively, in pocket 2 of lactoferrin. Meanwhile, iron ions provide ionic interaction with deferiprone in both of the pockets. The molecular dynamic simulation further confirmed that the binding of deferiprone with lactoferrin brings conformational changes in lactoferrin that is more energetically stable. It also confirmed that deferiprone causes positive correlation motion in the interacting residues of both pockets, with strong negative correlation motion in the loop regions, and thus changes the dynamics of lactoferrin. The MM-GBSA based binding free energy calculation revealed that deferiprone exhibits ∆G TOTAL of −63,163 kcal/mol in pocket 1 and −63,073 kcal/mol in pocket 2 with complex receptor–ligand difference in pocket 1 and pocket 2 of −117.38 kcal/mol and −111.54 kcal/mol, respectively, which in turn suggests that deferiprone binds more strongly in the pocket 1. The free energy landscape of the lactoferrin–deferiprone complex also showed that this complex remains in a high energy state that confirms the strong binding of deferiprone with the lactoferrin. The current research concluded that iron-chelating drugs (deferiprone) can be transported from the mother to the infant in the milk because of the strong attachment with the lactoferrin active pockets.

Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many “constitutive” elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.

(1) Background: Food-based dietary guidelines promote population health and well-being through dietary patterns that reduce chronic disease risk while providing adequate energy and nutrients. In Australia, recommended dietary patterns based on servings per day from the five food groups—fruits, vegetables, cereals and grains, meats and alternatives, and dairy—have been developed for toddlers 1–2 years of age. However, no study has assessed the intake of the five food groups in this age group nationally. (2) Aim: To compare daily servings and the percentage of energy from the five food groups and discretionary foods in toddlers 1–2 years old to the Australian Dietary Guidelines. (3) Methods: Dietary intake was assessed using a one-day food record for 475 toddlers. (4) Results: Apart from fruit and dairy, servings of the five food groups were below the recommendations. Two-thirds of toddlers did not consume enough vegetables, and only 10% consumed the recommended number of servings for cereals and grains. On average, toddlers consumed only half the recommended servings of meat and alternatives. Nearly all toddlers (89%) consumed discretionary foods, which accounted for ~12% of total energy. Forty-five percent of toddlers received breastmilk. On average, breastfed toddlers consumed fewer servings from the five food groups than non-breastfed toddlers. Dairy contributed 20% of daily energy in all toddlers; however, this food group accounted for 13% in breastfed and 32% in non-breastfed toddlers on the day of the food record. (4) Conclusions: Compared to the recommendations, alignment with the servings of the five food group foods was not achieved by most toddlers, except for fruit and dairy. Discretionary foods may have displaced nutritious family foods. Consistent with Australian Infant Feeding Guidelines, many toddlers in this study continued to receive breastmilk but the recommended dietary patterns do not include breastmilk. Dietary modeling, including breastmilk as the primary milk source, is urgently needed, along with practical advice on incorporating breastmilk in a toddler’s diet while optimizing food consumption.

Infant formulas have been designed to mimic human milk for infants who cannot be breastfed. The overall goal is to establish similar functional outcomes to assure optimal growth, development, maturation of the immune system, and programming of the metabolic system. However, after decades of improving infant formula, growth patterns and body composition development are still different in formula-fed infants compared to breastfed infants, which could contribute to an increased risk of obesity among formula-fed infants. It has been hypothesized that the lower protein concentration of breast milk compared to infant formula influences infants’ growth and body composition. Thus, several trials in formula-fed infants with different protein intake levels have been performed to test this hypothesis. In this review, we discuss the current evidence on low-protein infant formula and obesity risk, including future perspectives and implications.

Despite the well-known benefits of breastfeeding and the World Health Organization’s breastfeeding recommendations for COVID-19 infected mothers, whether these mothers should be encouraged to breastfeed is under debate due to concern about the risk of virus transmission and lack of evidence of breastmilk’s protective effects against the virus. Here, we provide a molecular basis for the breastfeeding recommendation through mass spectrometry (MS)-based proteomics and glycosylation analysis of immune-related proteins in both colostrum and mature breastmilk collected from COVID-19 patients and healthy donors. The total protein amounts in the COVID-19 colostrum group were significantly higher than in the control group. While casein proteins in COVID-19 colostrum exhibited significantly lower abundances, immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, were upregulated. These proteins were detected with unique site-specific glycan structures and improved glycosylation diversity that are beneficial for recognizing epitopes and blocking viral entry. Such adaptive differences in milk from COVID-19 mothers tended to fade in mature milk from the same mothers one month postpartum. These results suggest that feeding infants colostrum from COVID-19 mothers confers both nutritional and immune benefits, and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from −0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.

The metabolomic profiles of Chinese human milk have been poorly documented. The objective of the study was to explore associations between human milk metabotypes, maternal adiposity, infant growth patterns, and risk of allergies. Two hundred mother–infant dyads from seven cities were randomly selected from the Chinese Human Milk Project (CHMP). Untargeted human milk metabolomic profiles were determined using HPLC-MS/MS. Two human milk metabotypes were identified using principal component analysis. Principal component (PC) 1 was characterized by high linoleic acid metabolites with low purine nucleosides and metabolites of glutamate and glutathione metabolism. PC 2 was characterized by high glycerophospholipids and sphingomyelins content. Higher PC1 scores were associated with slower infant growth rate and higher ambient temperature (p < 0.05). Higher PC 2 scores were related to higher maternal BMI and increased risk of infant allergies (p < 0.05). Future work is needed to understand the biologic mechanisms of these human milk metabotypes.

International organizations recommend mothers practice exclusive breastfeeding (EBF) during the first six months of their infant’s life and introduce complementary feeding (CF) thereafter while continuing breastfeeding. However, the earlier introduction of liquids and foods is common worldwide and may have negative effects on breastfeeding practice, nutrition, and health. In this formative cross-sectional study, we interviewed 143 mothers from semi-rural communities in Tabasco, Mexico, whose infants were 4–6 months old. We explored (1) which feeding practices substituted EBF and (2) which factors were associated with each practice. During the first month of life, 42.7% of infants received formula milk (FM); this proportion increased to 74.5% by the sixth month. Adjusted Poisson regression analyses showed that giving FM was positively related to working away from home (PR 1.27; 95% CI 1.06, 1.54) and the perception that FM is an important food to accompany breast milk (PR 1.38; 95% CI 1.19, 1.70). Giving FM was negatively associated with not being sure the infant is full after breastfeeding (PR 0.75; 95% CI 0.61, 0.92). Regarding CF, less than half (47.5%) of infants had not received it by the fifth month. Factors positively associated with timely CF introduction were: the mother was told during prenatal care visits the optimal age to start CF is 6 months (PR 1.17, 95% CI 1.06, 1.29); she is convinced that giving only breast milk is best for her baby (PR 1.15, 95% CI 1.03, 1.29), and a higher infant weight-for-length (PR 1.04, 95% CI 1.00, 1.08) and length for age (PR 1.04, 95% CI 1.00, 1.09) z-scores at the study visit; conversely, it was negatively associated to the idea that if the infant is not full, she/he should receive formula milk or some other food (PR 0.87, 95% CI 0.78, 0.96). In these communities, EBF is lost to the use of FM and early CF. The factors associated with these inadequate feeding practices are related to returning to work, information received during prenatal visits, and the mother’s beliefs and thoughts. This work will guide the design of an intervention on infant feeding practices for these communities and other similar ones.

In this study, changes of carotenoids in breast milk were observed longitudinally for up to one year. Our study aimed to analyze the profile of carotenoids in breast milk and maternal/cord plasma and its correlation with dietary intake in Guangzhou. Plasma and breast milk samples of five stages during lactation (i.e., colostrum; transitional milk; and early, medium, and late mature milk) were collected from lactating mothers. The food frequency questionnaire (FFQ) was used for collecting data on dietary intake in the corresponding stages. Levels of lutein, zeaxanthin, β-cryptoxanthin, β-carotene, and lycopene were analyzed by high-performance liquid chromatography. We found that the total carotenoid level decreased gradually with the extension of lactation and eventually stabilized. Among them, the content of lutein increased from colostrum to transitional milk and decreased thereafter until it plateaued in the mature milk. Furthermore, lutein was reported as the dominant nutrient in maternal plasma, cord plasma, transitional milk, and mature milk at up to 400 days postpartum, while beta-carotene was predominant in colostrum. The content of β-carotenoid in middle and late mature breast milk was related to dietary intake (r = 1.690, p < 0.05). Carotenoid level in cord blood was lower than that in the mother’s plasma and was related to the carotenoid intake in the mother’s diet. Correlation of carotenoids between maternal and umbilical cord blood, breast milk, and maternal blood could well reflect the transport of carotenoids. These findings may help to guide mothers’ diets during breastfeeding.

Possible alterations of maternal immune function due to psychological stress may reflect immunoactive factor levels in breast milk. This study aimed to assess the association between maternal distress and breast milk levels of secretory IgA (SIgA), IgM, IgG, and lactoferrin (LF). We hypothesized that this association is moderated by maternal social support achieved from others during lactation. The study group included 103 lactating mothers and their healthy five-month-old infants. Maternal distress was determined based on the State Anxiety Inventory and the level of salivary cortisol. Social support was assessed using the Berlin Social Support Scales. Breast milk samples were collected to test for SIgA, IgM, IgG, and LF using the ELISA method. Milk immunoactive factors were regressed against maternal anxiety, social support, salivary cortisol, and infant gestational age using the general regression model. Maternal anxiety was negatively associated with milk levels of LF (β = −0.23, p = 0.028) and SIgA (β = −0.30, p = 0.004), while social support was positively associated with milk IgG (β = 0.25, p = 0.017). Neither anxiety nor social support were related to milk IgM. No association was found between the level of maternal salivary cortisol and immunoactive factors in milk. Our results suggest that maternal psychological wellbeing and social support may affect milk immune properties.

A cross-sectional single-center study was designed to compare the fatty acids profile, particularly docosahexaenoic acid (DHA) levels, between milk banking samples of donor human milk and mother&rsquo, s own milk (MOM) for feeding preterm infants born before 32 weeks&rsquo, gestation. MOM samples from 118 mothers included colostrum (1&ndash, 7 days after delivery), transitional milk (9&ndash, 14 days), and mature milk (15&ndash, 28 days and &ge, 29 days). In the n-3 polyunsaturated fatty acids (PUFAs) group, the levels of &alpha, linolenic acid (C18:3 n3) and DHA (C22:6 n3) showed opposite trends, whereas &alpha, linolenic acid was higher in donor human milk as compared with MOM, with increasing levels as stages of lactation progressed, DHA levels were significantly lower in donor human milk than in MOM samples, which, in turn, showed decreasing levels along stages of lactation. DHA levels in donor human milk were 53% lower than in colostrum. Therefore, in preterm infants born before 32 weeks&rsquo, gestation, the use of pasteurized donor human milk as exclusive feeding or combined with breastfeeding provides an inadequate supply of DHA. Nursing mothers should increase DHA intake through fish consumption or nutritional supplements with high-dose DHA while breastfeeding. Milk banking fortified with DHA would guarantee adequate DHA levels in donor human milk.

Fat globule size and phospholipid (PL) content in human milk (HM) were investigated. HM was classified into three groups depending on fat content (A &lt, B &lt, C). PL content (mg/100 g HM) was significantly higher in the C group (p &lt, 0.05), indicating its positive relationship with HM fat content. When the PL content was normalized (mg/g fat), that of group A was significantly higher (p &lt, 0.05) and fat droplet size in group C was slightly larger, suggesting that HM fat content is affected by fat droplet numbers to a larger extent than by fat droplet size. A correlation between PC and SM content in HM was observed regardless of fat content, while correlation between PE and either PC or SM increased in the order of C &gt, B &gt, A, hence the composition and content of PL species in HM varied according to its fat content.

(1) Background: Milk fat globule membrane (MFGM), composing fat droplets responsible for lipid transport in breast milk, has been shown to possess immunological and antimicrobial effects. Standard formulas (SF) are devoid of MFGMs during the production process. The study’s aim was to evaluate the safety and benefits of MFGMs supplementation in children. (2) Methods: We searched four databases for randomized controlled trials evaluating the supplementation of MFGMs in children. Growth parameters were chosen as the primary outcome. (3) Results: Twenty-four publications of seventeen studies were included. Meta-analyses assessing the primary outcomes at the age of 4 months included four studies (814 children) comparing the MFGM-supplemented formulas and SF, and two trials (549 children) comparing the MFGM-supplemented formulas and breastfeeding. The primary outcomes were non-inferior in all the experimental MFGM formulas compared to SF, or even represented more similar results to breastfed infants. The promising effects, including a lower incidence of acute otitis media and improved cognitive development, cannot be firmly confirmed due to the small amount of existing evidence. No significant adverse effects were reported in any of the assessed products. (4) Conclusions: The available data signaled beneficial effects and a good safety profile, requiring future research with well-designed trials.

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.