Longitudinal Changes in the Concentration of Major Human Milk Proteins in the First Six Months of Lactation and Their Effects on Infant Growth

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

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Associations between human milk oligosaccharides and growth in infancy and early childhood

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa010 ◽

2020 ◽

Vol 111 (4) ◽

pp. 769-778 ◽

Cited By ~ 10

Author(s):

Hanna Lagström ◽

Samuli Rautava ◽

Helena Ollila ◽

Anne Kaljonen ◽

Olli Turta ◽

...

Keyword(s):

Human Milk ◽

Causal Relation ◽

Mode Of Delivery ◽

Child Growth ◽

Birth Cohort Study ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Milk Samples ◽

Prepregnancy Bmi ◽

The Impact

ABSTRACT Background Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown. Objective Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed. Methods Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations. Results Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2′-fucosyllactose (2′FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition. Conclusions The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2′FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.

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Simultaneous pasteurization and homogenization of human milk by combining heat and ultrasound: effect on milk quality

Journal of Dairy Research ◽

10.1017/s0022029909990483 ◽

2010 ◽

Vol 77 (2) ◽

pp. 183-189 ◽

Cited By ~ 38

Author(s):

Charles Czank ◽

Karen Simmer ◽

Peter E Hartmann

Keyword(s):

Human Milk ◽

Milk Proteins ◽

Food Preservation ◽

Secretory Iga ◽

Bioactive Components ◽

Laser Scattering ◽

Milk Samples ◽

Donor Human Milk ◽

Preservation Technique ◽

Ultrasound Effect

The combination of ultrasound and heat (thermoultrasound) is an emerging food preservation technique that retains higher quantities of bioactive components compared with current thermal pasteurization practice, but has not yet been assessed for pasteurizing human milk. Artificially contaminated human milk samples were treated with ultrasound (20 kHz, 150 watts) with and without heating. The retention of four human milk proteins was quantified by biochemical assay and laser scattering particle sizing was used to determine the extent of homogenization. While ultrasonic treatment was effective at inactivating Escherichia coli (D4 °C=5·94 min), Staphylococcus epidermidis exhibited resistance (D4 °C=16·01 min). Thermoultrasonic treatment was considerably more effective (Esch. coli D45 °C=1·74 min, D50 °C=0·89 min; Staph. epidermidis D45 °C=2·08 min, D50 °C=0·94 minutes) with a predicted retention (2·8 min treatment, 50°C) of secretory IgA lysozyme, lactoferrin and bile salt stimulated lipase of 91, 80, 77, and 45%, respectively. Homogenization of the milk samples occurred after 5 min and 2 min of ultrasonic and thermoultrasonic treatment, respectively. Thermoultrasonic treatment is an effective method for pasteurizing donor human milk and retaining a greater proportion of bioactive components compared with current practices. However, further studies are required to assess the practicality of applying this technique routinely to donor human milk.

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Dietary Protein Source and Plasma Lipid Profiles of Infants

PEDIATRICS ◽

10.1542/peds.85.4.548 ◽

1990 ◽

Vol 85 (4) ◽

pp. 548-552

Author(s):

Emily Tseng ◽

Susan M. Potter ◽

Mary Frances Picciano

Keyword(s):

Amino Acids ◽

Human Milk ◽

Dietary Protein ◽

Plasma Cholesterol ◽

Plasma Lipid ◽

Lipid Profiles ◽

Plasma Triglyceride ◽

Term Infants ◽

Cholesterol Levels ◽

The Impact

Total cholesterol and triglyceride concentrations were measured in plasma samples taken at 4 and 8 weeks of age from 40 full-term infants who had been fed either human milk or one of three formulas containing casein-to-whey ratios of 82:18, 66:34, or 50:50 to investigate whether dietary protein influenced the development of plasma lipid profiles. Infants fed the formula with the casein-to-whey ratio of 82:18 had significantly higher plasma cholesterol levels at both 4 and 8 weeks of age compared with other groups of infants (P < .05). Infants fed the high-casein formula also showed an increase in plasma cholesterol levels with time (P < .001). Plasma triglyceride concentrations decreased as concentration of casein decreased (P < .05) among the formula-fed groups and increased with time. Infants fed human milk had plasma triglyceride concentrations similar to those infants who had been fed the 82:18 formula at 4 weeks of age; however, triglyceride concentrations eventually fell and were similar to those concentrations in infants who had been fed the 50:50 formula at 8 weeks of age. Results indicate that constituent lipids of human milk or formulas were not determining factors for changes observed in plasma cholesterol levels and triglyceride concentrations among groups. Since formulas differed only in proteins and their constituent amino acids, further investigation of the impact of dietary protein (amino acids) on development of blood lipid profiles in infants is warranted.

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Longitudinal Changes (2 Months) in Protein Composition of Preterm and Term Human Milk (HM)

Pediatric Research ◽

10.1203/00006450-199904020-01716 ◽

1999 ◽

Vol 45 (4, Part 2 of 2) ◽

pp. 288A-288A

Author(s):

Staffan Polberger ◽

Majvi Mansson ◽

Irene Jakobsson

Keyword(s):

Human Milk ◽

Protein Composition ◽

Longitudinal Changes

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The association of maternal diet and polyamines in human milk: a study among malay ethnic mothers in kuantan, malaysia

International Journal of Engineering & Technology ◽

10.14419/ijet.v7i2.29.13334 ◽

2018 ◽

Vol 7 (2.29) ◽

pp. 287

Author(s):

Puteri Amirah Adib kamaruzzaman ◽

Radiah Abdul Ghani ◽

Muhammad Ibrahim ◽

Nor Azwani Mohd ◽

Shukri .

Keyword(s):

Human Milk ◽

Maternal Education ◽

Maternal Diet ◽

Food Diary ◽

Milk Samples ◽

Education Levels ◽

Diet Pattern ◽

Nursing Mothers ◽

The Mean ◽

Breastfeeding Practice

Human milk contains a lot of nutrient and it offers advantages to infant age less than six months. Polyamines in milk accelerate the infants’ gut maturation and protect babies from the harsh environment. Maternal diet is a factor which can affect the polyamines variability in milk. To date, no research on local diet and the composition of human milk has been investigated. This study aimed to identify an association between Malaysian maternal diet and composition of polyamines in human milk. Seventy nursing mothers were recruited in Pahang and each mother recorded their 24-hours food consumption within a week. Maternal diets were recorded in Nutritionist Pro-software and the macronutrients were calculated. Milk samples were collected from each mother after24 h of food diary. Polyamines in milk were extracted using 0.4 M Perchloric acid, dansylated and quantified using HPLC. The mean age of the respondent was 30.13 years [SD= 3.145].Nursing mothers consumed high carbohydrate [41.4%] compared to fat [23.1%] and protein [13.7%].Spermidine [49.1%] was the highest polyamines in the breast milk samples. A significant correlation were shown between putrescine and dietary carbohydrate [p=0.027] and putrescine and dietary protein [p=0.031].The maternal education levels has no association with maternal diet pattern and breastfeeding practice in this study [p=0.657]. It is suggested that polyamines composition in human milk may be modulated by carbohydrate and protein intake among maternal mother

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Anti-Sars-Cov-2 IgA And IgG In Human Milk After Vaccination Is Dependent On Vaccine Type And Previous Sars-Cov-2 Exposure: A Longitudinal Study.

10.1101/2021.05.20.21257512 ◽

2021 ◽

Author(s):

Marta Selma-Royo ◽

Christine Bauerl ◽

Desiree Mena-Tudela ◽

Laia Aguilar-Camprubi ◽

Francisco Jose Perez-Cano ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Protective Role ◽

Lactating Women ◽

Time Points ◽

Milk Samples ◽

Vaccine Type ◽

Vaccine Impact ◽

Vectored Vaccine ◽

The Impact

Importance: Limited data are available on COVID-19 vaccine impact in lactating women. Objective: To evaluate the impact of different COVID-19 vaccines on specific anti-SARS-CoV-2 IgA and IgG levels in human milk. Design, Settings and Participants: In this prospective observational study in Spain, 75 lactating women from priority groups receiving vaccination against SARS-CoV-2 were included (January to April 2021). Human milk samples were collected at seven-time points. A group with confirmed SARS-CoV-2 infection (n=19) and a group of women from prepandemic time (n=13) were included. Exposure: mRNA vaccines (BNT162b2 and mRNA-1273) and adenovirus-vectored vaccine (ChAdOx1 nCoV-19). Main Outcome(s) and Measure(s): Presence of IgA and IgG against RBD SARS-CoV-2 in breast milk. Results: Seventy-five vaccinated lactating women [mean age, 34.9±3.7 years] of whom 96% were Caucasic and 92% were health care workers. A total of 417 milk samples were included and vaccine distribution was BioNTech/Pfizer (BNT162b2, n=30), Moderna (mRNA-1273, n=21), and AstraZeneca (ChAdOx1 nCoV-19, n=24). For each vaccine, 7 time points were collected from baseline up to 25 days after the 1st dose and same points were collected for mRNA vaccines 30 days after 2nd dose. A strong reactivity was observed for IgG and IgA after vaccination mainly after the 2nd dose. Presence and the persistence of specific SARS-CoV-2 antibodies in breast milk were dependent on the vaccine-type and, on previous virus exposure. High inter-variability was observed, being relevant for IgA antibodies. IgG levels were significantly higher than those observed in milk from COVID-19 women while IgA levels were lower. Women with previous COVID-19 increased the IgG levels after the 1st dose to a similar level observed in vaccinated women after the 2nd dose. Conclusions and Relevance: Breast milk from vaccinated women contains anti-SARS-CoV-2 IgA and IgG, with highest after the 2nd dose. Levels were dependent on vaccine type and previous exposure to SARS-CoV-2. Previous COVID-19 influenced the vaccine effect after a single dose, which could be especially relevant in the design of vaccination protocols . Further studies are warranted to demonstrate the potential protective role of these antibodies against COVID-19 in infants from vaccinated and infected mothers through breastfeeding.

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Comparison of Two Approaches for the Metataxonomic Analysis of the Human Milk Microbiome

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.622550 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lorena Ruiz ◽

Claudio Alba ◽

Cristina García-Carral ◽

Esther A. Jiménez ◽

Kimberly A. Lackey ◽

...

Keyword(s):

16S Rrna ◽

Human Milk ◽

Variable Region ◽

Large Set ◽

Clinical Trial Registration ◽

Variable Regions ◽

Milk Samples ◽

Healthy Women ◽

The Impact ◽

First Time

Recent work has demonstrated the existence of large inter-individual and inter-population variability in the microbiota of human milk from healthy women living across variable geographical and socio-cultural settings. However, no studies have evaluated the impact that variable sequencing approaches targeting different 16S rRNA variable regions may have on the human milk microbiota profiling results. This hampers our ability to make meaningful comparisons across studies. In this context, the main purpose of the present study was to re-process and re-sequence the microbiome in a large set of human milk samples (n = 412) collected from healthy women living at diverse international sites (Spain, Sweden, Peru, United States, Ethiopia, Gambia, Ghana and Kenya), by targeting a different 16S rRNA variable region and reaching a larger sequencing depth. Despite some differences between the results obtained from both sequencing approaches were notable (especially regarding alpha and beta diversities and Proteobacteria representation), results indicate that both sequencing approaches revealed a relatively consistent microbiota configurations in the studied cohorts. Our data expand upon the milk microbiota results we previously reported from the INSPIRE cohort and provide, for the first time across globally diverse populations, evidence of the impact that different DNA processing and sequencing approaches have on the microbiota profiles obtained for human milk samples. Overall, our results corroborate some similarities regarding the microbial communities previously reported for the INSPIRE cohort, but some differences were also detected. Understanding the impact of different sequencing approaches on human milk microbiota profiles is essential to enable meaningful comparisons across studies.Clinical Trial Registrationwww.clinicaltrials.gov, identifier NCT02670278.

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Targeted LC-ESI-MS2 characterization of human milk oligosaccharide diversity at 6 to 16 weeks post-partum reveals clear staging effects and distinctive milk groups

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-020-02819-x ◽

2020 ◽

Vol 412 (25) ◽

pp. 6887-6907 ◽

Cited By ~ 1

Author(s):

Marko Mank ◽

Hans Hauner ◽

Albert J. R. Heck ◽

Bernd Stahl

Keyword(s):

Human Milk ◽

Post Partum ◽

Principal Component ◽

Structural Diversity ◽

Preliminary Evidence ◽

Healthy Development ◽

Milk Samples ◽

Group I ◽

The Impact ◽

Automatic Grouping

Abstract Many molecular components in human milk (HM), such as human milk oligosaccharides (HMOs), assist in the healthy development of infants. It has been hypothesized that the functional benefits of HM may be highly dependent on the abundance and individual fine structures of contained HMOs and that distinctive HM groups can be defined by their HMO profiles. However, the structural diversity and abundances of individual HMOs may also vary between milk donors and at different stages of lactations. Improvements in efficiency and selectivity of quantitative HMO analysis are essential to further expand our understanding about the impact of HMO variations on healthy early life development. Hence, we applied here a targeted, highly selective, and semi-quantitative LC-ESI-MS2 approach by analyzing 2 × 30 mature human milk samples collected at 6 and 16 weeks post-partum. The analytical approach covered the most abundant HMOs up to hexasaccharides and, for the first time, also assigned blood group A and B tetrasaccharides. Principal component analysis (PCA) was employed and allowed for automatic grouping and assignment of human milk samples to four human milk groups which are related to the maternal Secretor (Se) and Lewis (Le) genotypes. We found that HMO diversity varied significantly between these four HM groups. Variations were driven by HMOs being either dependent or independent of maternal genetic Se and Le status. We found preliminary evidence for an additional HM subgroup within the Se- and Le-positive HM group I. Furthermore, the abundances of 6 distinct HMO structures (including 6′-SL and 3-FL) changed significantly with progression of lactation.

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Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

Nutrients ◽

10.3390/nu12030826 ◽

2020 ◽

Vol 12 (3) ◽

pp. 826 ◽

Cited By ~ 1

Author(s):

Meichen Wang ◽

Zhenwen Zhao ◽

Ai Zhao ◽

Jian Zhang ◽

Wei Wu ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Delivery Mode ◽

Human Breast Milk ◽

Lactation Period ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Term Infants ◽

Milk Samples ◽

Lactation Stage

We aimed to identify if maternal and infant factors were associated with neutral human milk oligosaccharides (HMOs) variability and examined the associations between HMOs concentration and infant growth and disease status in healthy Chinese mothers over a 6-month lactation period. We recruited mothers and their full-term infants as our subjects. At 1–5 days, 8–14 days, 4 weeks, and 6 months postpartum, all participants were interviewed to collect breast milk samples, obtain follow-up data and measure infant length and weight at their local hospital. A total of 23 neutral HMOs were analyzed by high performance liquid chromatography (HPLC)- mass spectrometer (MS). Secretor and Lewis phenotype were determined by the concentration of 2′-fucosyllactose (2′-FL) and Lacto-N-fucopentaose (LNFP)-II. The associations between maternal and infant factors with HMOs concentrations were investigated. A total of 464 human breast milk samples were collected from 116 mothers at four different time points. In total, 76.7% mothers were found to be Secretor and Lewis positive phenotype (Se+Le+), 17.2% were Se-Le+, 4.3% were Se+Le-, and 1.7% were Se-Le-. Several individual HMOs, including 2′-FL, Lactodifucotetraose (LDFT), LNFP-I were determined by Secretor phenotype. Most individual HMOs decreased at the later stage of lactation, except 3′-FL. We suggest that Secretor phenotype and lactation stage could influence most of the neutral HMOs. Concentrations of specific HMOs may be associated with maternal age, allergic history, pre-pregnancy body mass index (BMI), parity, delivery mode, infant gestational age and gender.

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Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

Nutrients ◽

10.3390/nu12113391 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3391

Author(s):

Marit Navis ◽

Lauriane Schwebel ◽

Susanne Soendergaard Kappel ◽

Vanesa Muncan ◽

Per Torp Sangild ◽

...

Keyword(s):

Human Milk ◽

Whey Protein ◽

Transit Time ◽

Protein Composition ◽

In Vitro Digestion ◽

Whey Protein Concentrate ◽

Milk Formula ◽

The Impact ◽

Β Lactoglobulin

Human milk is the optimal diet for infant development, but infant milk formula (IMF) must be available as an alternative. To develop high-quality IMF, bovine milk processing is required to ensure microbial safety and to obtain a protein composition that mimics human milk. However, processing can impact the quality of milk proteins, which can influence gastro-intestinal (GI) tolerance by changing digestion, transit time and/or absorption. The aim of this study was to evaluate the impact of structural changes of proteins due to thermal processing on gastro-intestinal tolerance in the immature GI tract. Preterm and near-term piglets received enteral nutrition based on whey protein concentrate (WPC) either mildly pasteurized (MP-WPC) or extensively heated (EH-WPC). Clinical symptoms, transit time and gastric residuals were evaluated. In addition, protein coagulation and protein composition of coagulates formed during in vitro digestion were analyzed in more detail. Characterization of MP-WPC and EH-WPC revealed that mild pasteurization maintained protein nativity and reduced aggregation of β-lactoglobulin and α-lactalbumin, relative to EH-WPC. Mild pasteurization reduced the formation of coagulates during digestion, resulting in reduced gastric residual volume and increased intestinal tract content. In addition, preterm piglets receiving MP-WPC showed reduced mucosal bacterial adherence in the proximal small intestine. Finally, in vitro digestion studies revealed less protein coagulation and lower levels of β-lactoglobulin and α-lactalbumin in the coagulates of MP-WPC compared with EH-WPC. In conclusion, minimal heat treatment of WPC compared with extensive heating promoted GI tolerance in immature piglets, implying that minimal heated WPC could improve the GI tolerance of milk formulas in infants.

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