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Human Milk Composition and Children Nutrition: Latest Advances and Prospects

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Pediatric Nutrition".

Deadline for manuscript submissions: closed (25 July 2024) | Viewed by 13431

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Dr. Chiara Peila

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Guest Editor

SC Neonatology U., Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
Interests: human milk; preterm nutrition; donor human milk; fortification human milk

Special Issue Information

Dear Colleagues,

The mother’s own milk is always considered the first choice for nutrition of all neonates, including preterm infants; in fact, it is tailored to meet infants’ specific nutritional requirements. Furthermore, human milk is a “dynamic” system: its composition changes and is influenced by several conditions, such as term–preterm delivery, maternal diet, metabolic abnormalities and pathologies. It is well-known that breastfeeding improves several outcomes, both in the short and the long term, as a result of specific biological active components and immunomodulatory factors.

This dynamic and bioactive fluid allows mother–infant signalling over lactation, guiding the infant in developmental and physiological processes. It has been proposed that nutrition signals during the early postnatal period may influence metabolic developmental pathways and induce permanent changes to metabolic disease susceptibility. It exerts protection and life-long biological effects, playing a crucial role in promoting healthy growth and optimal cognitive development.

However, the complexity of human milk composition and the synergistic mechanisms responsible for its beneficial health effects have not yet been unravelled.

Filling this knowledge gap will shed light on the biology of the developing infant and will contribute to the optimization of infant feeding, particularly that of the most vulnerable infants.

The current Special Issue aims to welcome original studies and literature reviews further exploring the biological role and function of human milk components, as well as the mechanisms underlying the beneficial effects associated with breastfeeding. Furthermore, research focused on evidence-based interventions to improve both breastfeeding duration and women’s breastfeeding experience is also welcome.

Dr. Chiara Peila
Guest Editor

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Keywords

human milk composition
breastfeeding
human milk benefits
infant feeding
newborn nutrition

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Published Papers (8 papers)

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Research

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15 pages, 1898 KiB

Open AccessArticle

Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk

by Hanin Diab, Taylor Fuquay, Palika Datta, Ulrich Bickel, Jonathan Thompson and Kaytlin Krutsch

Nutrients 2024, 16(17), 2886; https://doi.org/10.3390/nu16172886 - 28 Aug 2024

Viewed by 1905

Abstract

Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5–30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide’s bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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26 pages, 941 KiB

Open AccessArticle

Changes in the Fatty Acid Profile of Lactating Women Living in Poland—A Comparison with the Fatty Acid Profile of Selected Infant Formulas

by Aleksandra Purkiewicz and Renata Pietrzak-Fiećko

Nutrients 2024, 16(15), 2411; https://doi.org/10.3390/nu16152411 - 25 Jul 2024

Viewed by 911

Abstract

The present study examined the fatty acid content of human milk from Polish women living in the Warmia and Mazury region with regard to different lactation periods and compared it with the fatty acid content of selected infant formulas. The analysis included samples of breast milk—colostrum (n = 21), transitional milk (n = 26), and mature milk (n = 22). Fat was extracted using the Rose-Gottlieb method, and the fatty acid profile was determined by gas chromatography with a flame ionization detector (FID). The proportion of SFAs (saturated fatty acids) > MUFAs (monounsaturated fatty acids) > PUFAs (polyunsaturated fatty acids) was determined in each fraction of breast milk and infant formula. Palmitic, oleic, and linoleic acids predominated in breast milk and infant formulas. Colostrum contained lower contents of selected SFAs (caprylic, capric, lauric) and higher contents of selected MUFAs (ercucic) and PUFAs (arachidonic and docosahexaenoic) (p < 0.05) relative to transitional and mature milk. Infant formulas were distinguished from human milk in terms of their SFA (caproic, caprylic, lauric, arachidic), MUFA (oleic), and PUFA (linoleic, α-linoleic) content. It should be noted that infant formulas contained significantly lower trans fatty acid (TFA) content—more than thirty-six and more than nineteen times lower than in human milk. Furthermore, human milk contained branched-chain fatty acids (BCFAs) at 0.23–0.28%, while infant formulas contained only trace amounts of these acids. The average ratio of n-6 to n-3 fatty acids for human milk was 6.59:1 and was close to the worldwide ratio of 6.53 ± 1.72:1. Both principal component analysis (PCA) and cluster analysis (CA) indicated significant differences in the fatty acid profile relative to lactation and a different profile of infant formulas relative to breast milk. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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13 pages, 1832 KiB

Open AccessArticle

Longitudinal Correlations between Molecular Compositions of Stratum Corneum and Breast Milk Factors during Infancy: A Prospective Birth Cohort Study

by Risa Fukuda, Kyongsun Pak, Megumi Kiuchi, Naoko Hirata, Naoko Mochimaru, Ryo Tanaka, Mari Mitsui, Yukihiro Ohya and Kazue Yoshida

Nutrients 2024, 16(12), 1897; https://doi.org/10.3390/nu16121897 - 16 Jun 2024

Viewed by 1061

Abstract

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-β1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers’ breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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Figure 1
Flowchart outlining the methodological procedures for following up the mother–infant pairs. The stratum corneum (SC) components of the infants were measured using a confocal Raman spectrometer (CRS), Tewameter, and Corneometer at 0, 1, 2, 6, and 12 months. The mothers completed questionnaires and provided breast milk samples when their infants were 0, 1, 2, and 6 months. Full article ">Figure 2
Changes in the molecular composition of the stratum corneum (SC) over time based on confocal Raman spectroscopy (CRS) measurements. The depth profile (mean ± standard deviation) of water content (a), natural moisturizing factor (NMF) (b), ceramide (c), cholesterol (d), and lactic acid (e) for each month of age are shown. The data are marked at 0 months (red), 1 month (orange), 2 months (purple), 6 months (green), and 12 months (light blue). Error bars indicate 95% confidence intervals. The mean of five measurements was considered as each participant’s representative value. Full article ">Figure 3
Changes over time in transforming growth factors (TGFs)-β1 and 2, immunoglobin A (IgA), and lactoferrin levels in breast milk. The median TGF-β1 (a), TGF-β2 (b), IgA (c), and lactoferrin (d) levels in the breast milk of mothers. The black dots indicate the value of the breast milk factors for each month of age (39 for 0 months, 35 for 1 month, 32 for 2 months, 32 for 6 months, and 33 for 12 months).The box plots represent medians with 25th and 75th percentile values, min–max range, and outliers. Full article ">Figure 4
Correlation analysis of molecular components in the stratum corneum (SC) measured by confocal Raman spectroscopy and breast milk factors for each month of age. Correlation coefficients and 95% confidence intervals between the median area under the receiver operating curve by depth (0–4, 4–8, 8–20, and 0–20 μm) for water content (a), natural moisturizing factor (NMF) (b), ceramide (c), cholesterol (d), and lactic acid (e) measured at 0, 1, 2, 6, and 12 months and levels of breast milk factors including transforming growth factor (TGF)-β1 and 2, immunoglobin A (IgA), and lactoferrin measured at 0, 1, 2, and 6 months are shown (<a href="#app1-nutrients-16-01897" class="html-app">Figure S4</a>). Water content and ceramide and cholesterol levels tended to be negatively correlated with all breast milk factors during the entire period, while NMF and lactoferrin levels were positively correlated with all breast milk factors. Full article ">Figure 5
Correlation analysis of the stratum corneum (SC) hydration and transepidermal water loss (TEWL) in the SC and breast milk factors for each month of age. Correlation coefficients and 95% confidence intervals between the median of SC hydration and TEWL measured at 0, 1, 2, 6, and 12 months and the levels of breast milk factors including transforming growth factors (TGFs)-β1 and 2, immunoglobin A (IgA), and lactoferrin measured at 0, 1, 2, and 6 months are shown (<a href="#app1-nutrients-16-01897" class="html-app">Figure S5</a>). TGF-β1 and 2 levels correlated positively with SC hydration for almost the entire period, while IgA and lactoferrin levels correlated negatively. TEWL was partially positively correlated with all breast milk factors. Full article ">

14 pages, 1134 KiB

Open AccessArticle

Sampling Procedures for Estimating the Infant Intake of Human Milk Leptin, Adiponectin, Insulin, Glucose, and Total Lipid

by Majed A. Suwaydi, Ching Tat Lai, Zoya Gridneva, Sharon L. Perrella, Mary E. Wlodek and Donna T. Geddes

Nutrients 2024, 16(3), 331; https://doi.org/10.3390/nu16030331 - 23 Jan 2024

Cited by 1 | Viewed by 1454

Abstract

Limited attention is given to the efficacy of protocols for the estimation of infant intake of milk components when investigating their impact on infant outcomes. We compared the actual measured intake of human milk components with estimations derived from 15 protocols to determine the most reliable approach for estimating intake of HM leptin, adiponectin, insulin, glucose, and total lipid. Twenty mothers who were 3–5 months postpartum completed a 24 h milk profile study with pre-/post-feed milk samples collection. The true infant intake (control group) based on 24 h milk intake (MI) was compared to estimated infant intakes using concentrations from five sampling protocols that were multiplied by one of true infant MI, considered mean MI (800 mL), or global mean MI (766 mL). The mean measured concentrations of six samples (three sets of pre- and post-feed samples, from morning (06:00–09:00), afternoon (13:00–16:00), and evening (19:00–22:00)) multiplied by the true infant MI, mean considered MI, and global mean MI produced the most accurate estimates of infant intake of these components. Therefore, in the absence of 24 h measurements and sampling, a sampling protocol comprising three sets of pre-/post-feed samples provides the most reliable infant intake estimates of HM leptin, adiponectin, insulin, glucose, and total lipid. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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9 pages, 544 KiB

Open AccessArticle

Preeclampsia and Its Impact on Human Milk Activin A Concentration

by Alessandra Coscia, Lorenzo Riboldi, Elena Spada, Enrico Bertino, Stefano Sottemano, Ignazio Barbagallo, Giovanni Livolti, Fabio Galvano, Diego Gazzolo and Chiara Peila

Nutrients 2023, 15(19), 4296; https://doi.org/10.3390/nu15194296 - 9 Oct 2023

Cited by 1 | Viewed by 1353

Abstract

Background: It is known that preeclampsia affects lactogenesis. However, data on the effects of this pathology on human milk neurobiomarker composition are not available. The aim of this study is to investigate the effects of this gestational pathology on activin A levels, a neurobiomarker known to play an important role in the development and protection of the central nervous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an Enzyme-linked immunosorbent assay (ELISA) test. To investigate the effect of preeclampsia on the activin A concentration in the three lactation phases, a mixed linear model with a unistructural covariance structure, with the mother as the random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between preeclamptic and normotensive women. The only significant effect is related to the lactation phase: the difference between colostrum and mature milk (p < 0.01) was significant. In conclusion, these results allow us to affirm that breast milk’s beneficial properties are maintained even if preeclampsia occurs. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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12 pages, 3780 KiB

Open AccessFeature PaperArticle

Circadian Variation in Human Milk Hormones and Macronutrients

by Majed A. Suwaydi, Ching Tat Lai, Alethea Rea, Zoya Gridneva, Sharon L. Perrella, Mary E. Wlodek and Donna T. Geddes

Nutrients 2023, 15(17), 3729; https://doi.org/10.3390/nu15173729 - 25 Aug 2023

Cited by 5 | Viewed by 3139

Abstract

There is an inadequate understanding of the daily variations in hormones and macronutrients in human milk (HM), and sample collection protocols vary considerably from study to study. To investigate changes in these milk components across 24 h, 22 lactating women collected small milk samples before and after each breastfeed or expression from each breast. Test weighing was used to determine the volume of HM consumed in each feed. The concentrations of leptin, adiponectin, insulin, fat, and glucose were measured, and the intakes were calculated. A linear mixed model was fitted to assess within-feed and circadian variation in HM feed volume and concentration, and intakes of several components. The average infant intake of HM was 879 g/24 h. Significantly higher pre-feed concentrations were found for adiponectin and glucose and lower post-feed concentrations were found for insulin and fat. Significant circadian rhythms were displayed for leptin, adiponectin, insulin, glucose (both concentration and intake), fat concentration, and milk volume. These findings demonstrate the necessity for setting up standardised and rigorous sampling procedures that consider both within-feed and circadian variations in HM components to gain a more precise understanding of the impacts of these components on infant health, growth and development. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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Figure 1
Changes in human milk feed volume (g) over a 24 h period. Coloured dots represent individual mother’s data with the corresponding coloured best-fit line; solid black line indicates the population average. Full article ">Figure 2
Changes in concentrations of human milk leptin, adiponectin, and insulin over a 24 h period. Average pre-feed sample concentration circadian rhythm is indicated by black dashed line. Average post-feed sample concentration circadian rhythm is indicated by black solid line. Individual mother’s concentrations and rhythms indicated by coloured dots and lines, respectively. Full article ">Figure 3
Changes in concentrations of human milk fat and glucose over a 24 h period. Average pre-feed sample concentration circadian rhythm is indicated by black dashed line. Average post-feed sample concentration circadian rhythm is indicated by black solid line. Individual mother’s concentrations and rhythms indicated by coloured dots and lines, respectively. Full article ">Figure 4
Changes in intakes of human milk leptin, adiponectin, and insulin over a 24 h period. Average circadian rhythm is indicated by black lines. Individual component intakes and rhythms indicated by coloured dots and lines, respectively. Full article ">Figure 5
Changes in intakes of human milk fat and glucose over a 24 h period. Average circadian rhythm is indicated by black lines. Individual component intakes and rhythms indicated by coloured dots and lines, respectively. Full article ">

Review

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16 pages, 639 KiB

Open AccessReview

Modifiable and Non-Modifiable Factors That Affect Human Milk Oligosaccharides Composition

by Małgorzata Konieczna, Anna Koryszewska-Bagińska, Agnieszka Bzikowska-Jura, Magdalena Chmielewska-Jeznach, Sylwia Jarzynka and Gabriela Olędzka

Nutrients 2024, 16(17), 2887; https://doi.org/10.3390/nu16172887 - 28 Aug 2024

Viewed by 595

Abstract

Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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9 pages, 885 KiB

Open AccessPerspective

Fresh Parent’s Own Milk for Preterm Infants: Barriers and Future Opportunities

by Carrie-Ellen Briere and Jessica Gomez

Nutrients 2024, 16(3), 362; https://doi.org/10.3390/nu16030362 - 26 Jan 2024

Viewed by 2112

Abstract

While direct at-the-breast feeding is biologically optimal, Neonatal Intensive Care Unit (NICU) admission due to infant immaturity or illness often necessitates the expression and storage of parent’s milk. The provision of freshly expressed (never stored) parent’s own milk to preterm infants is not widely prioritized, and this article provides an exploration of NICU practices and their implications for feeding premature or ill infants with parent’s own milk. In this article, we discuss the potential biological benefits of fresh parent’s own milk, highlighting its dynamic components and the changes incurred during storage. Research suggests that fresh milk may offer health advantages over stored milk. The authors advocate for further research, emphasizing the need for standardized definitions. Research is needed on the biological impact of fresh milk, both short- and long-term, as well as defining and understanding healthcare economics when using fresh milk. Full article

(This article belongs to the Special Issue Human Milk Composition and Children Nutrition: Latest Advances and Prospects)

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