Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1064-1070 ◽  
Author(s):  
Chloe A Autran ◽  
Benjamin P Kellman ◽  
Jae H Kim ◽  
Elizabeth Asztalos ◽  
Arlin B Blood ◽  
...  
Keyword(s):  
At Risk ◽  
Breast Milk ◽  
Human Milk ◽  
Preterm Infants ◽  
Low Birthweight ◽  
Post Partum ◽  
Estimating Equation ◽  
Necrotising Enterocolitis ◽  
Almost All ◽  
And Control

ObjectiveNecrotising enterocolitis (NEC) is one of the most common and often fatal intestinal disorders in preterm infants. Markers to identify at-risk infants as well as therapies to prevent and treat NEC are limited and urgently needed. NEC incidence is significantly lower in breast-fed compared with formula-fed infants. Infant formula lacks human milk oligosaccharides (HMO), such as disialyllacto-N-tetraose (DSLNT), which prevents NEC in neonatal rats. However, it is unknown if DSLNT also protects human preterm infants.DesignWe conducted a multicentre clinical cohort study and recruited 200 mothers and their very low birthweight infants that were predominantly human milk-fed. We analysed HMO composition in breast milk fed to infants over the first 28 days post partum, matched each NEC case with five controls and used logistic regression and generalised estimating equation to test the hypothesis that infants who develop NEC receive milk with less DSLNT than infants who do not develop NEC.ResultsEight infants in the cohort developed NEC (Bell stage 2 or 3). DSLNT concentrations were significantly lower in almost all milk samples in NEC cases compared with controls, and its abundance could identify NEC cases prior to onset. Aggregate assessment of DSLNT over multiple days enhanced the separation of NEC cases and control subjects.ConclusionsDSLNT content in breast milk is a potential non-invasive marker to identify infants at risk of developing NEC, and screen high-risk donor milk. In addition, DSLNT could serve as a natural template to develop novel therapeutics against this devastating disorder.

scholarly journals Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction

2021 ◽  
Author(s):  
Winok Lapidaire ◽  
Alan Lucas ◽  
Jonathan D. Clayden ◽  
Chris Clark ◽  
Mary S. Fewtrell
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Preterm Infants ◽  
Neonatal Infection ◽  
Necrotising Enterocolitis ◽  
Cognitive Outcome ◽  
Standard Diet ◽  
Risk Of Infection ◽  
Verbal Iq

Abstract Background Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants. Methods Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years. Results An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood. Conclusions Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a ‘human milk’ factor, protecting against infection/NEC, and a ‘nutrient content’ factor. Impact This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood. Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients. Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC. A higher nutrient diet is associated with better cognitive outcome in childhood. Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet.

scholarly journals Human Milk Oligosaccharide, Phospholipid, and Ganglioside Concentrations in Breast Milk from United Arab Emirates Mothers: Results from the MISC Cohort

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2400 ◽  
Author(s):  
Paul McJarrow ◽  
Hadia Radwan ◽  
Lin Ma ◽  
Alastair K.H. MacGibbon ◽  
Mona Hashim ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
United Arab Emirates ◽  
High Performance ◽  
Post Partum ◽  
Human Breast Milk ◽  
Mature Milk ◽  
Cross Sectional ◽  
Significant Difference ◽  
The Individual

Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5–15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers’ transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.

scholarly journals Prebiotic consumption in pregnant and lactating women increases IL-27 expression in human milk

2013 ◽  
Vol 111 (4) ◽  
pp. 625-632 ◽  
Author(s):  
Takayuki Kubota ◽  
Naoki Shimojo ◽  
Ken Nonaka ◽  
Masakatsu Yamashita ◽  
Osamu Ohara ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Mrna Expression ◽  
Control Group ◽  
Control Groups ◽  
Lactating Women ◽  
Future Studies ◽  
Milk Samples ◽  
And Control ◽  
Allergic Disorders

The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.

scholarly journals Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial—the N-forte trial

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e053400
Author(s):  
Georg Bach Jensen ◽  
Fredrik Ahlsson ◽  
Magnus Domellöf ◽  
Anders Elfvin ◽  
Lars Naver ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Preterm Infants ◽  
Ethical Review ◽  
Human Breast Milk ◽  
Human Breast ◽  
Preterm Formula ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Randomised Controlled

IntroductionThe mortality rate of extremely low gestational age (ELGA) (born <gestational week 28+0) infants remains high, and severe infections and necrotising enterocolitis (NEC) are common causes of death. Preterm infants receiving human milk have lower incidence of sepsis and NEC than those fed a bovine milk-based preterm formula. Despite this, fully human milk fed ELGA infants most often have a significant intake of cow’s milk protein from bovine-based protein fortifier. The aim of this study is to evaluate whether the supplementation of human milk-based, as compared with bovine-based, nutrient fortifier reduces the prevalence of NEC, sepsis and mortality in ELGA infants exclusively fed with human milk.Methods and analysisA randomised-controlled multicentre trial comparing the effect of a human breast milk-based fortifier with a standard bovine protein-based fortifier in 222–322 ELGA infants fed human breast milk (mother’s own milk and/or donor milk). The infants will be randomised to either fortifier before reaching 100 mL/kg/day in oral feeds. The intervention, stratified by centre, will continue until the target postmenstrual week 34+0. The primary outcome is a composite of NEC, sepsis or death. Infants are characterised with comprehensive clinical and nutritional data collected prospectively from birth until hospital discharge. Stool, urine, blood and breast milk samples are collected for analyses in order to study underlying mechanisms. A follow-up focusing on neurological development and growth will be performed at 2 and 5.5 years of age. Health economic analyses will be made.Ethics and disseminationThe study is conducted according to ICH/GCP guidelines and is approved by the regional ethical review board in Linköping Sweden (Dnr 2018/193-31, Dnr 2018/384-32). Results will be presented at scientific meetings and published in peer-reviewed publications.Trial registration numberThe study was registered with ClinicalTrials.gov NCT03797157, 9 January 2019.

scholarly journals The Revolution of Breast Milk: The Multiple Role of Human Milk Banking between Evidence and Experience—A Narrative Review

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Pasqua Anna Quitadamo ◽  
Giuseppina Palumbo ◽  
Liliana Cianti ◽  
Paola Lurdo ◽  
Maria Assunta Gentile ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Preterm Infants ◽  
Multiple Role ◽  
Life Saving ◽  
The World ◽  
Human Milk Banking ◽  
Milk Banking ◽  
Main Component

The review recalls the importance of breast milk and deepens the theme of human milk banking, a virtuous reality that is expanding all over the world but is still little known. In the last 15 years, modern biological technologies have crystallized the concept of uniqueness and irreproducibility of human milk, by establishing three new principles: first: human milk: a “life-saving” drug; second: human milk: the best food for preterm infants; and third: human milk: the main component of premature infant care. Our experience teaches us that human milk banking plays many roles that need to be known and shared.

scholarly journals Safety of Cow’s Milk-Derived Fortifiers Used with an All-Human Milk Base Diet in Very Low Birthweight Preterm Infants

2020 ◽  
Vol 15 (7) ◽  
pp. 3-13
Author(s):  
Alan Lucas ◽  
Maushumi Assad ◽  
Jan Sherman ◽  
John Boscardin ◽  
Steven Abrams
Keyword(s):  
Human Milk ◽  
Preterm Infants ◽  
Low Birthweight ◽  
Ductus Arteriosus ◽  
Cow’S Milk ◽  
Very Low Birthweight ◽  
Cow's Milk ◽  
Increased Risk ◽  
Preterm Formula ◽  
The Impact

Background: Very low birthweight (VLBW) preterm infants fed mothers own milk (MOM) need nutritional supplementation, traditionally achieved with cow’s milk derived fortifier (CMDF) and preterm formula (PTF) if MOM is insufficient. CM products have been associated with diverse major morbidities. The current recommendation is to preferentially replace PTF with donor milk (DM) to produce a 100% human milk (HM) base diet, usually fortified with CMDF. Objective: To identify whether CMDF, even when fed with a 100% HM base diet, is related to an increased risk of major morbidities. Methods: We identified a randomized trial with an all-HM base diet, comparing CMDF with a fortifier derived from human milk (HMDF), and two additional studies of this design were generated from raw data as subgroup analyses of a randomized controlled trial and a quasi-experimental study. Using these studies, we calculated the impact of CMDF on major morbidities of death, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA). Results: Each study individually provided support for an increase in major morbidities with CMDF. Meta-analyses of pooled data showed that compared to HMDF, the CMDF group had large in- creases in NEC (RR = 3.3; P = .001), ROP (RR = 2.2; P = .007), PDA (RR = 1.6; P = .009), interruption of feeding (RR = 3.4; P = .001) and a positive mortality/morbidity index based on one or more of death, NEC, sepsis, ROP and BPD (RR = 1.4; P = .006). Conclusions: Despite the increased use of HM in modern neonatal care as a base diet, we found a greater risk of critical morbidities with CMDF compared with HMDF. This burden of morbidity provides evidence that the benefits of an HM base diet, might be, in part, counteracted by multiple adverse outcomes relating to the use of CMDF.

scholarly journals Lack of Evidence for Additional Protein-Energy in Enteral Nutrition for Very Low Birth Weight Preterm Infants: A Systematic Review (P11-086-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lisa Moloney ◽  
Mary Rozga ◽  
Tanis Fenton ◽  
Sharon Groh-Wargo
Keyword(s):  
Enteral Nutrition ◽  
Human Milk ◽  
Preterm Infants ◽  
Low Birthweight ◽  
Infant Nutrition ◽  
Small Sample ◽  
Risk Of Bias ◽  
Control Group ◽  
Limited Evidence ◽  
Protein Energy

Abstract Objectives To investigate the evidence for the effect of protein and energy via enteral nutrition on identified outcomes in very low birthweight preterm infants. Methods A literature search was conducted using EMBASE, CINAHL, Cochrane Central and PubMed databases for the period of January 1980-November 2017 for all peer-reviewed articles examining preterm infant nutrition. A multidisciplinary volunteer expert Workgroup and staff screened articles according to defined inclusion criteria (randomized controlled trials, enteral fed preterm infants with birthweight < 1500 gm, economically developed nations). Studies that evaluated the effect of adding protein-energy in enteral feeding, compared to a control group, were included. Data was extracted and risk of bias was evaluated using the Academy's Quality Criteria Checklist and Cochrane's Risk of Bias Tool. Data was summarized and conclusion statements were developed and graded for each identified outcome using the GRADE framework and Academy methodology. Results The search identified in 25,264 articles, and five articles were included. Two included studies had low risk of bias. The remaining studies had bias in the following Cochrane domains: selection (2), performance (2), and attrition (1). Eight conclusion statements were developed, five were graded as limited evidence, and three were graded as having fair evidence. Protein-energy fortification was found to have a significant positive effect on weight gain (SMD (95%CI): 1.24 (0.26,2.22)) in human milk fed VLBW preterm infants, however, no evidence of effect was found in formula or mixed fed infants. Limited evidence suggests a significant effect on fat free mass (MD (95% CI): 179 g (28.5, 386.5)) after 30 days, but no effect on fat mass. No significant effect was found on necrotizing enterocolitis, anemia, length, head circumference, or days to full feeds. Conclusions Evidence was lacking regarding the effect of protein-energy fortification on identified outcomes in VLBW preterm infants. Available evidence was low in quality due to small sample sizes and heterogeneity in study populations (formula fed, human milk fed), interventions (amount of protein) and reporting of methods (protein prescription vs actual intake) and outcomes. Funding Sources Academy of Nutrition and Dietetics.

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