Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial

Yan, Xudong; Pan, Xiaoyu; Ding, Lu; Dai, Yiheng; Yang, Yang; Li, Yuefeng; Hu, Hao; Qiu, Huixian; Ye, Zhenzhi; Shen, René Liang; Li, Yanqi; Ritz, Christian; Peng, Yulin; Zhou, Ping; Gao, Fei; Jiang, Pingping; Lin, Hung‐Chih; Zachariassen, Gitte; Sangild, Per Torp; Wu, Benqing

doi:10.1016/j.clnu.2023.06.024

Cited by 7 publications

(4 citation statements)

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“…Numerous studies in preterm pigs, used as models for infants in different clinical conditions and product combinations, demonstrated clear benefits for the gut, immunity, brain, and metabolic outcomes relative to infant formula [ 10 ]. Following our own infant pilot trials [ 15 , 17 , 18 ] and others in India [ 138 ] and Egypt [ 139 ], the results of much larger trials on preterm infants (total n = 700) at hospitals in Denmark and China were recently reported [ 5 , 13 , 29 ]. The results showed no effects or inconsistent effects of colostrum supplementation.…”

Section: Colostrum Bioactivitymentioning

confidence: 99%

“…They exert local microbial protection in the gut (not only IgA, but also IgG), and these bacteriostatic and immunomodulatory effects may work across species [ 10 , 134 , 135 , 155 ]. The local gut-protective effects of bovine IgG have motivated studies on bovine colostrum as a supplement for preterm infants [ 5 , 13 , 29 , 156 ]. Isolated bovine IgG has been tested in a series of human studies, with promising effects being noted in relation to microbial colonization and gut infections [ 157 ].…”

Section: Bioactivity Of Isolated Milk Fractions or Proteinsmentioning

confidence: 99%

“…Emphasis is placed on the bioactivity of proteins and peptides, but the health effects of milk may originate from multiple milk constituents and fractions, including carbohydrates, lipids, and micronutrients. Inspiration is gained from the author’s studies on intact milk, milk fractions, or isolated milk proteins in experimental pediatrics [ 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The paper does not provide a review of results from scientific studies, but rather a critical reflection on the scientific methodology and epistemology related to milk bioactivity research.…”

Section: Introduction and Rationalementioning

confidence: 99%

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Science and Faith to Understand Milk Bioactivity for Infants

Sangild

2024

Nutrients

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Milk bioactivity refers to the specific health effects of milk components beyond nutrition. The science of milk bioactivity involves the systematic study of these components and their health effects, as verified by empirical data, controlled experiments, and logical arguments. Conversely, ’faith in milk bioactivity’ can be defined as personal opinion, meaning, value, trust, and hope for health effects that are beyond investigation by natural, social, or human sciences. Faith can be strictly secular, but also influenced by spirituality or religion. The aim of this paper is to show that scientific knowledge is frequently supplemented with faith convictions to establish personal and public understanding of milk bioactivity. Mammalian milk is an immensely complex fluid containing myriad proteins, carbohydrates, lipids, and micronutrients with multiple functions across species, genetics, ages, environments, and cultures. Human health includes not only physical health, but also social, mental, and spiritual health, requiring widely different fields of science to prove the relevance, safety, and efficacy of milk interventions. These complex relationships between milk feeding and health outcomes prevent firm conclusions based on science and logic alone. Current beliefs in and understanding of the value of breast milk, colostrum, infant formula, or isolated milk proteins (e.g., immunoglobulins, α-lactalbumin, lactoferrin, and growth factors) show that both science and faith contribute to understand, stimulate, or restrict the use of milk bioactivity. The benefits of breastfeeding for infants are beyond doubt, but the strong beliefs in its health effects rely not only on science, and mechanisms are unclear. Likewise, fear of, or trust in, infant formula may rely on both science and faith. Knowledge from science safeguards individuals and society against ‘milk bioactivity superstition’. Conversely, wisdom from faith-based convictions may protect science from unrealistic ‘milk bioactivity scientism’. Honesty and transparency about the potentials and limitations of both scientific knowledge and faith convictions are important when informing individuals and society about the nutritious and bioactive qualities of milk.

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Section: Colostrum Bioactivitymentioning

confidence: 99%

Section: Bioactivity Of Isolated Milk Fractions or Proteinsmentioning

confidence: 99%

Section: Introduction and Rationalementioning

confidence: 99%

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Science and Faith to Understand Milk Bioactivity for Infants

Sangild

2024

Nutrients

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“…A pilot trial (n = 50) showed that BC supplemented to MOM was well tolerated in VPIs [16,17]. In two subsequent, larger randomized controlled trials (RCTs), the feasibility of using BC as a supplement to MOM in the first weeks of life (compared with preterm formula as supplement to MOM, n = 350) [18], or as a fortifier to human milk later (compared with a conventional fortifier, CF, n = 232) [19], was evaluated. Both trials showed that VPIs supplemented with BC had similar growth and clinical outcomes as VPIs fed formula and CF [18,19].…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota development in very preterm infants following fortification of human milk

Yang,

Hui,

Sangild

et al. 2024

Preprint

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Background: Very preterm infants (VPIs) are born with an immature gut, being sensitive to gut microbiota dysbiosis-related disease like necrotizing enterocolitis. While human milk is the best source of nutrition for VPIs, it requires fortification to meet their nutrient requirements for optimal growth. However, the optimal type of fortifier remains uncertain. Bovine colostrum (BC), rich in protein and bioactive components, may be an alternative to conventional fortifiers (CF). We aimed to investigate the distinct impacts of different bovine fortifiers, BC and CF, on the gut microbiota of VPIs. The gut microbiota of 225 VPIs who were fed human milk fortified with either BC or CF, were profiled by 16S rRNA gene amplicon sequencing of fecal samples collected before, one and two weeks of fortification. Results: Fortifier type affected the microbial community structure to a modest extent, but only explaining 1% of the variance, and no specific taxa differed between the BC and CF groups. This fortifier-derived impact was predominantly observed in VPIs born via caesarean section. Birth mode exhibited transient effects on microbial community structure shortly after birth, with caesarean section-born VPIs dominated by Firmicutes, while vaginally-born VPIs were dominated by Proteobacteria. This birth mode-derived difference diminished with age and disappeared around one month after birth. The fecal pH, increased by BC, was positively correlated with Staphylococcus and Corynebacterium, and negatively with Bifidobacterium abundance. The change in relative abundance of Staphylococcus was negatively correlated with weight gain. Conclusion: Collectively, fortification of human milk with BC or CF does influence the gut microbiota of VPIs but only to a modest extent during early life. Conversely, birth mode appears to be a significant temporary factor influencing the gut microbiota during this period. Our findings are consistent with existing literature and support the idea that the choice of fortifier has limited effects on gut microbiota development in the first month of life of VPIs.

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Systemic immune markers and infection risk in preterm infants fed human milk fortified with bovine colostrum or conventional fortifier, a secondary analysis of the FortiColos trial

Bæk,

Muk,

Aunsholt

et al. 2024

Infection

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Background For very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC), rich in anti-inflammatory milk factors, is considered an alternative. We investigated if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants. Methods For a secondary analysis of a multicenter, randomized controlled trial (NCT03537365), very preterm infants (26–31 weeks gestation, 23% small for gestational age, SGA) were randomized to receive BC (ColoDan, Biofiber, Denmark, n = 113) or conventional fortifier (PreNAN, Nestlé, Switzerland, n = 116). Infection was defined as antibiotic treatment for five or more consecutive days and 29 cytokines/chemokines were measured in plasma before and after start of fortification. Results In general, infection risk after start of fortification was associated with low gestational age, SGA status and antibiotics use prior to fortification. Adjusted for confounders, infants fortified with BC showed more infection episodes (20 vs 12%, P < 0.05) and higher cumulative infection risk (hazard ratio, HR 1.9, P = 0.06), particularly for SGA infants (HR 3.6, P < 0.05). Additionally, BC-fortified infants had higher levels of TH2-related cytokines/chemokines (IL-10, MDC, MCP4) and reduced levels of cytokines related to TH1/TH17-responses (IL-15, IL-17, GM-CSF). The differences were most pronounced in SGA infants, displaying higher levels of TH2-related IL-4, IL-6, and IL-13, and lower interferon-γ and IL-1α levels in the BC group. Conclusion Infants fortified with BC displayed a delayed shift from TH2- to TH1-biased systemic immunity, notably in SGA infants, possibly influenced by multiple confounding factors, alongside elevated antibiotic use, suggesting increased susceptibility to infection.

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Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial

Cited by 7 publications

References 42 publications

Science and Faith to Understand Milk Bioactivity for Infants

Science and Faith to Understand Milk Bioactivity for Infants

Gut microbiota development in very preterm infants following fortification of human milk

Systemic immune markers and infection risk in preterm infants fed human milk fortified with bovine colostrum or conventional fortifier, a secondary analysis of the FortiColos trial

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