Metabolomics reveals changes in levels of fecal branched chain amino acids and organic acids in very preterm infants fed human milk fortified with bovine colostrum.

Background & Aims: Human milk is the optimal diet for very preterm infants (VPIs), but it requires nutrient fortification to support growth. Bovine colostrum (BC), rich in intact proteins and bioactive components, could serve as a novel fortifier with potential benefits to VPIs gut health. To evaluate a possible effect of feeding BC on intestinal metabolism, the gut microbiota, and their interaction, we studied the fecal metabolome of VPIs in the first month of life, as compared with a conventional fortifier (CF, based on infant formula ingredients).

Feeding cessation and antibiotics improve clinical symptoms and alleviate gut and systemic inflammation in preterm pigs sensitive to necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a microbiota- and feeding-related gut inflammatory disease in preterm infants. The standard of care (SOC) treatment for suspected NEC is antibiotic treatment and reduced enteral feeding, but how SOC treatment mitigates NEC remains unclear. We explored whether SOC treatment alone or combined with an anti-inflammatory protein (inter-alpha inhibitor protein, IAIP) supplementation improves outcomes in a preterm piglet model of formula-induced NEC.

Enteral plasma feeding improves gut function and immunity in piglets after birth asphyxia.

Introduction: Birth asphyxia may negatively affect gut function and immunity in newborns. Conversely, immunomodulatory milk diets may protect the gut and immune system against damage caused by asphyxia. Using caesarean-derived pigs as models, we hypothesised that enteral feeding with plasma improves gut and immune functions in asphyxiated newborns.

Insulin-like growth factor-1 infusion in preterm piglets does not affect growth parameters of skeletal muscle or tendon tissue.

Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult-onset metabolic disease. Insulin-like growth factor 1 (IGF-1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF-1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

Background: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM.

Cord Obstruction and Delayed Cord Clamping Do Not Affect Gut Function in Neonatal Piglets.

Introduction: Birth-related obstruction of umbilical blood flow may induce hypoxic insults that affect postnatal organ adaptation. Using newborn cesarean-delivered pigs, we hypothesized that cord obstruction during delivery negatively affects physiological transition and gut maturation. Further, we investigated if delayed cord clamping (DCC) improves gut outcomes, including sensitivity to formula-induced necrotizing enterocolitis (NEC)-like lesions.

Science and Faith to Understand Milk Bioactivity for Infants.

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.

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.

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/T2 immunity and infection risk in very preterm infants.

Insulin-like growth factor-1 effects on kidney development in preterm piglets.

Background: Preterm birth disrupts fetal kidney development, potentially leading to postnatal acute kidney injury. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a growth factor that stimulates organ development. By utilizing a preterm pig model, this study investigated whether IGF-1 supplementation enhances preterm kidney maturation.

Neonatal Gut and Immune Responses to β-Casein Enriched Formula in Piglets.

Background: β-casein is the main casein constituent in human milk (HM) and a source of bioactive peptides for the developing gastrointestinal tract and immune system. Infant formulas contain less β-casein than HM, but whether different concentrations of β-casein affect tolerability and gut and immune maturation in newborns is unknown.

Objectives: Using near-term piglets as a model for newborn infants, we investigated whether increasing the β-casein fraction in bovine-based formula is clinically safe and may improve gut and immune maturation.

Enteral plasma supports brain repair in newborn pigs after birth asphyxia.

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia.

Skeletal consequences of preterm birth in pigs as a model for preterm infants.

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment.

Mineral supplementation for very preterm infants fed fortified human milk.

Objectives: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry.

Glucose-regulatory hormones and growth in very preterm infants fed fortified human milk.

Background: Bovine colostrum (BC) contains a range of milk bioactive components, and it is unknown how human milk fortification with BC affects glucose-regulatory hormones in very preterm infants (VPIs). This study aimed to investigate the associations between hormone concentrations and fortification type, birth weight (appropriate/small for gestational age, AGA/SGA), milk intake, postnatal age, and body growth.

Methods: 225 VPIs were randomized to fortification with BC or conventional fortifier (CF).

A Gently Processed Skim Milk-Derived Whey Protein Concentrate for Infant Formula: Effects on Gut Development and Immunity in Preterm Pigs.

Scope: Processing of whey protein concentrate (WPC) for infant formulas may induce protein modifications with severe consequences for preterm newborn development. The study investigates how conventional WPC and a gently processed skim milk-derived WPC (SPC) affect gut and immune development after birth.

Methods And Results: Newborn, preterm pigs used as a model of preterm infants were fed formula containing WPC, SPC, extra heat-treated SPC (HT-SPC), or stored HT-SPC (HTS-SPC) for 5 days.

Early parenteral nutrition is associated with improved growth in very low birth weight infants: a retrospective study.

Objective: To assess the association between early initiation of parenteral nutrition (PN) and body growth in preterm infants with very low birth weight (VLBW).

Design: Causal inference analysis with confounders preselected by causal diagram based on the NeoNutriNet cohort containing data of infants born between 2011 and 2014 from 13 hospitals from 5 continents.

Patients: Neonates with birth weight ≤1500 g.

Adverse Metabolic Phenotypes in Parenterally Fed Neonatal Pigs Do Not Persist into Adolescence.

Background: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

Objectives: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

Methods: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d.

Gut development following insulin-like growth factor-1 supplementation to preterm pigs.

Background: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.

Methods: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days.

Ultra-High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates.

Scope: Ready-to-feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra-high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development.

Methods And Results: UHT-treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants.

Insulin-like growth factor 1 associated with altered immune responses in preterm infants and pigs.

Background: Preterm infants show low blood levels of insulin-like growth factor 1 (IGF-1), known to be negatively correlated with Interleukin-6 (IL-6). We hypothesized that circulating IGF-1 is associated with systemic immune-markers following preterm birth and that exogenous IGF-1 supplementation modulates immune development in preterm pigs, used as model for preterm infants.

Methods: Plasma levels of IGF-1 and 29 inflammatory markers were measured in very preterm infants (n = 221).

Trial-related blood sampling and red blood cell transfusions in preterm infants.

Aim: To determine if trial-related blood sampling increases the risk of later red blood cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion.

Methods: For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance with ethical considerations established by the European Commission. Medical records were reviewed to assess the number and accumulated volume (mL/kg) of blood samples (both clinical- and trial-related).

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

Background & Aims: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM.

Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs.

Introduction: Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.

Methods: Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.

Bovine colostrum as a fortifier to human milk in very preterm infants - A randomized controlled trial (FortiColos).

Background: Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified.

Aims: To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants.

Methods: In an open-label, multicenter, randomized controlled pilot trial (infants 26-31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n = 115) or a conventional fortifier (CF, bovine-milk-based, n = 117) until 35 weeks' postmenstrual age.

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs.

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development.