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Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants

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

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 61539

Special Issue Editor

Prof. Dr. Nadja Haiden

E-Mail Website
Guest Editor
Department of Clinical Pharmacology, Medical University of Vienna, Wien, Austria
Interests: preterm infants; parenteral nutrition; body composition; human milk composition; donor milk; necrotizing enterocolitis; microbiota; micrombiome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue “Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants” is to explore new insights in the field of infant formulae research and the efforts to get closer to breastmilk—the gold standard in infant nutrition.

Breastmilk provides an optimal composition of balanced nutrients for the term infant. In addition, human milk contains substances with bioactive, anti-infective, anti-inflammatory, and metabolic properties, causing a variety of sustainable short- and long-term effects in the growing infant that are not attainable when cow milk-based formula is fed. In the last decade, human milk research has focused on the immunomodulating effects of probiotics and oligosaccharides included in breastmilk and how breastmilk is “individualized“ by the mother via a specific breast milk microbiome.

Infant formula purports to be a simulation of human milk or its suitability as a complete or partial substitute for human milk. A lot of efforts have been made to improve the composition of the formula and the immunomodulating properties to come closer to the gold standard.

We invite investigators to contribute original research articles that will provide new insights into the efforts made to improve infant formula and get it as close as possible to breastmilk.  

Prof. Nadja Haiden
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Breastmilk
  • Infant formula
  • Term infant
  • Properties
  • Functional nutrients
  • Microbiome

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Published Papers (7 papers)

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Research

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12 pages, 1948 KiB  
Article
Choline Content of Term and Preterm Infant Formulae Compared to Expressed Breast Milk—How Do We Justify the Discrepancies?
by Anna Shunova, Katrin A. Böckmann, Michaela Minarski, Axel R. Franz, Cornelia Wiechers, Christian F. Poets and Wolfgang Bernhard
Nutrients 2020, 12(12), 3815; https://doi.org/10.3390/nu12123815 - 13 Dec 2020
Cited by 20 | Viewed by 3764
Abstract
Choline/phosphatidylcholine concentrations are tightly regulated in all organs and secretions. During rapid organ growth in the third trimester, choline requirement is particularly high. Adequate choline intake is 17–18 mg/kg/day in term infants, whereas ~50–60 mg/kg/day is required to achieve fetal plasma concentrations in [...] Read more.
Choline/phosphatidylcholine concentrations are tightly regulated in all organs and secretions. During rapid organ growth in the third trimester, choline requirement is particularly high. Adequate choline intake is 17–18 mg/kg/day in term infants, whereas ~50–60 mg/kg/day is required to achieve fetal plasma concentrations in preterm infants. Whereas free choline is supplied via the placenta, other choline carriers characterize enteral feeding. We therefore quantified the concentrations and types of choline carriers and choline-related components in various infant formulae and fortifiers compared to breast milk, and calculated the supply at full feeds (150 mL/kg/day) using tandem mass spectrometry. Choline concentration in formula ranged from values below to far above that of breastmilk. Humana 0-VLB (2015: 60.7 mg/150 mL; 2020: 27.3 mg/150 mL), Aptamil-Prematil (2020: 34.7 mg/150 mL), Aptamil-Prematil HA (2020: 37.6 mg/150 mL) for preterm infants with weights < 1800 g, and Humana 0 (2020: 41.6 mg/150 mL) for those > 1800 g, comprised the highest values in formulae studied. Formulae mostly were rich in free choline or phosphatidylcholine rather than glycerophosphocholine and phosphocholine (predominating in human milk). Most formulae (150 mL/kg/day) do not supply the amounts and physiologic components of choline required to achieve fetal plasma choline concentrations. A revision of choline content in formulae and breast milk fortifiers and a clear declaration of the choline components in formulae is required to enable informed choices. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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17 pages, 6662 KiB  
Article
Dietary Oligofructose Alone or in Combination with 2′-Fucosyllactose Differentially Improves Recognition Memory and Hippocampal mRNA Expression
by Stephen A. Fleming, Austin T. Mudd, Jonas Hauser, Jian Yan, Sylviane Metairon, Pascal Steiner, Sharon M. Donovan and Ryan N. Dilger
Nutrients 2020, 12(7), 2131; https://doi.org/10.3390/nu12072131 - 17 Jul 2020
Cited by 22 | Viewed by 4413
Abstract
Mounting evidence suggests that dietary oligosaccharides promote brain development. This study assessed the capacity of oligofructose (OF) alone or in combination with 2′-fucosyllactose (2′-FL) to alter recognition memory, structural brain development, and hippocampal gene expression. Beginning on postnatal day (PND) 2, male pigs [...] Read more.
Mounting evidence suggests that dietary oligosaccharides promote brain development. This study assessed the capacity of oligofructose (OF) alone or in combination with 2′-fucosyllactose (2′-FL) to alter recognition memory, structural brain development, and hippocampal gene expression. Beginning on postnatal day (PND) 2, male pigs received one of three milk replacers formulated to contain OF, OF + 2′-FL, or no oligosaccharides (CON). Pigs were tested on the novel object recognition task using delays of 1 or 48 h at PND 22. At PND 32–33, magnetic resonance imaging (MRI) procedures were used to assess structural brain development and hippocampal tissue was collected for analysis of mRNA expression. Pigs that consumed the OF diet demonstrated increased recognition memory after a 1 h delay, whereas those consuming diets containing OF + 2′-FL displayed increased recognition memory after a 48 h delay. Pigs fed OF or OF + 2′-FL exhibited a larger relative volume of the olfactory bulbs compared with CON pigs. Provision of OF or OF + 2′-FL altered gene expression related to dopaminergic, GABAergic, cholinergic, cell adhesion, and chromatin remodeling processes. Collectively, these data indicate that dietary OF and OF + 2′-FL differentially improve cognitive performance and affect olfactory bulb structural development and hippocampal gene expression. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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12 pages, 502 KiB  
Article
Evaluation of 6′-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets
by Marcia H. Monaco, Dae Hee Kim, Rit B. Gurung and Sharon M. Donovan
Nutrients 2020, 12(4), 1030; https://doi.org/10.3390/nu12041030 - 9 Apr 2020
Cited by 16 | Viewed by 3624
Abstract
Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented [...] Read more.
Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented to infant formula, however, not all forms have been available in large scale. The objective of the study was to investigate the dose-dependent effects of an enzymatically-synthesized 6′-sialyllactose (6′-SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters, and organ microscopic assessment in our pre-clinical neonatal pig model. Two-day-old male and female pigs (n = 47) were provided one of four experimental diets for 21 days. Diets were formulated to contain 0 (CON), 300 (LOW), 600 (MOD), or 1200 (HIGH) mg/L of 6′-SL sodium salt. On days 8 and 22, samples were collected for hematological and histological analyses. Supplemental 6′-SL sodium salt at all doses supported growth and development comparable to those observed in control animals. In addition, serum chemistries, hematology, and organ microscopic structure were unaffected by 6′-SL (p > 0.05). Thus, addition of enzymatically-synthesized 6′-SL to a milk replacer formula supported growth and clinical outcomes similar to the control formula in the neonatal piglet. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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14 pages, 456 KiB  
Article
Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology
by Michał Wiciński, Ewelina Sawicka, Jakub Gębalski, Karol Kubiak and Bartosz Malinowski
Nutrients 2020, 12(1), 266; https://doi.org/10.3390/nu12010266 - 20 Jan 2020
Cited by 192 | Viewed by 20922
Abstract
The first months of life are a special time for the health development and protection of infants. Breastfeeding is the natural and best way of feeding an infant, and positively influences their development and health. Breast milk provides the ideal balance of nutrients [...] Read more.
The first months of life are a special time for the health development and protection of infants. Breastfeeding is the natural and best way of feeding an infant, and positively influences their development and health. Breast milk provides the ideal balance of nutrients for the infant and contains countless bioactive ingredients such as immunoglobulins, hormones, oligosaccharides and others. Human milk oligosaccharides (HMOs) are a very important and interesting constituent of human milk, and are the third most abundant solid component after lactose and lipids. They are a structurally and biologically diverse group of complex indigestible sugars. This article will discuss the mechanisms of action of HMOs in infants, such as their anti-adhesive properties, properties modulating the immune system, and impact on bacterial flora development. Many health benefits result from consuming HMOs. They also may decrease the risk of infection by their interactions with viruses, bacteria or protozoa. The commercial use of HMOs in infant formula, future directions, and research on the use of HMOs as a therapy will be discussed. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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Review

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26 pages, 2211 KiB  
Review
Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review
by Elise Mank, Eva F. G. Naninck, Jacqueline Limpens, Letty van Toledo, Johannes B. van Goudoever and Chris H. P. van den Akker
Nutrients 2020, 12(10), 2916; https://doi.org/10.3390/nu12102916 - 24 Sep 2020
Cited by 9 | Viewed by 3852
Abstract
Feeding preterm infants with mother’s own milk is associated with a reduction in postnatal complications and an improved neurocognitive outcome. Therefore, the bioactive factor composition of human milk has been used as a tool for the development of nutritional supplements with a potential [...] Read more.
Feeding preterm infants with mother’s own milk is associated with a reduction in postnatal complications and an improved neurocognitive outcome. Therefore, the bioactive factor composition of human milk has been used as a tool for the development of nutritional supplements with a potential prophylactic or therapeutic effect. The aim of this systematic review was to provide an overview on bioactive factors which have been studied as supplement to enteral nutrition in randomized controlled trials, and to provide an overview of ongoing trials. MEDLINE, EMBASE, CENTRAL, and clinical trial registers were searched. Studies on the antimicrobial protein lactoferrin were excluded as these were summarized very recently in three separate systematic reviews. Studies on vitamins D, K and iron were also excluded as they are already incorporated in most international guidelines. We identified 17 different bioactive factors, which were investigated in 26 studies. Despite the encouraging potential effects of several bioactive factors, more high-quality studies with a sufficient number of preterm infants are required before a certain factor may be implemented into clinical practice. Three large trials (n > 500) that investigate the effects of either enteral insulin or vitamin A are currently ongoing and could provide more definite answers on these specific supplements. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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25 pages, 2701 KiB  
Review
Sources, Production, and Clinical Treatments of Milk Fat Globule Membrane for Infant Nutrition and Well-Being
by Javier Fontecha, Lauren Brink, Steven Wu, Yves Pouliot, Francesco Visioli and Rafael Jiménez-Flores
Nutrients 2020, 12(6), 1607; https://doi.org/10.3390/nu12061607 - 30 May 2020
Cited by 105 | Viewed by 10747
Abstract
Research on milk fat globule membrane (MFGM) is gaining traction. The interest is two-fold; on the one hand, it is a unique trilayer structure with specific secretory function. On the other hand, it is the basis for ingredients with the presence of phospho- [...] Read more.
Research on milk fat globule membrane (MFGM) is gaining traction. The interest is two-fold; on the one hand, it is a unique trilayer structure with specific secretory function. On the other hand, it is the basis for ingredients with the presence of phospho- and sphingolipids and glycoproteins, which are being used as food ingredients with valuable functionality, in particular, for use as a supplement in infant nutrition. This last application is at the center of this Review, which aims to contribute to understanding MFGM’s function in the proper development of immunity, cognition, and intestinal trophism, in addition to other potential effects such as prevention of diseases including cardiovascular disease, impaired bone turnover and inflammation, skin conditions, and infections as well as age-associated cognitive decline and muscle loss. The phospholipid composition of MFGM from bovine milk is quite like human milk and, although there are some differences due to dairy processing, these do not result in a chemical change. The MFGM ingredients, as used to improve the formulation in different clinical studies, have indeed increased the presence of phospholipids, sphingolipids, glycolipids, and glycoproteins with the resulting benefits of different outcomes (especially immune and cognitive outcomes) with no reported adverse effects. Nevertheless, the precise mechanism(s) of action of MFGM remain to be elucidated and further basic investigation is warranted. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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16 pages, 509 KiB  
Review
The Relationship between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life
by Bożena Cukrowska, Joanna B. Bierła, Magdalena Zakrzewska, Mark Klukowski and Elżbieta Maciorkowska
Nutrients 2020, 12(4), 946; https://doi.org/10.3390/nu12040946 - 29 Mar 2020
Cited by 120 | Viewed by 13133
Abstract
The increase in allergy prevalence observed in recent decades may be a consequence of early intestinal dysbiosis. The intestinal microbiota is formed in the first 1000 days of life, when it is particularly sensitive to various factors, such as the composition of the [...] Read more.
The increase in allergy prevalence observed in recent decades may be a consequence of early intestinal dysbiosis. The intestinal microbiota is formed in the first 1000 days of life, when it is particularly sensitive to various factors, such as the composition of the mother’s microbiota, type of delivery, infant’s diet, number of siblings, contact with animals, and antibiotic therapy. Breastfeeding and vaginal birth favorably affect the formation of an infant’s intestinal microbiota and protect against allergy development. The intestinal microbiota of these infants is characterized by an early dominance of Bifidobacterium, which may have a significant impact on the development of immune tolerance. Bifidobacterium breve is a species commonly isolated from the intestines of healthy breastfed infants and from human milk. This review outlines the most important environmental factors affecting microbiota formation and the importance of Bifidobacterium species (with a particular emphasis on Bifidobacterium breve) in microbiota modulation towards anti-allergic processes. In addition, we present the concept, which assumes that infant formulas containing specific probiotic Bifidobacterium breve strains and prebiotic oligosaccharides may be useful in allergy management in non-breastfed infants. Full article
(This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants)
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