The gut microbiome of extremely preterm infants randomized to the early progression of enteral feeding

Abstract Background Early progression of feeding could influence the development of the gut microbiome. Methods We collected fecal samples from extremely preterm infants randomized to receive either early (feeding day 2) or delayed (feeding day 5) feeding progression. After study completion, we compared samples obtained at three different time points (week 1, week 2, and week 3) to determine longitudinal differences in specific taxa between the study groups using unadjusted and adjusted negative binomial and zero-inflated mixed models. Analyses were adjusted for a mode of delivery, breastmilk intake, and exposure to antibiotics. Results We analyzed 137 fecal samples from 51 infants. In unadjusted and adjusted analyses, we did not observe an early transition to higher microbial diversity within samples (i.e., alpha diversity) or significant differences in microbial diversity between samples (i.e., beta diversity) in the early feeding group. Our longitudinal, single-taxon analysis found consistent differences in the genera Lactococcus, Veillonella, and Bilophila between groups. Conclusions Differences in single-taxon analyses independent of the mode of delivery, exposure to antibiotics, and breastmilk feeding suggest potential benefits of early progression of enteral feeding volumes. However, this dietary intervention does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Trial Registration ClinicalTrials.gov identifier: NCT02915549. Impact Early progression of enteral feeding volumes with human milk reduces the duration of parenteral nutrition and the need for central venous access among extremely preterm infants. Early progression of enteral feeding leads to single-taxon differences in longitudinal analyses of the gut microbiome, but it does not appear to increase the diversity of the gut microbiome in the first 28 days after birth. Randomization in enteral feeding trials creates appealing opportunities to evaluate the effects of human milk diets on the gut microbiome.

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Early Routine vs. Selective Human Milk Fortification in Extremely Preterm Infants

Case Medical Research ◽

10.31525/ct1-nct04284280 ◽

2020 ◽

Author(s):

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Extremely Preterm ◽

Extremely Preterm Infants

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

BMJ Open ◽

10.1136/bmjopen-2021-053400 ◽

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.

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Short versus Extended Duration of Trophic Feeding to Reduce Time to Achieve Full Enteral Feeding in Extremely Preterm Infants: An Observational Study

Neonatology ◽

10.1159/000472247 ◽

2017 ◽

Vol 112 (3) ◽

pp. 211-216 ◽

Cited By ~ 2

Author(s):

Ariel A. Salas ◽

Nazia Kabani ◽

Colm P. Travers ◽

Vivien Phillips ◽

Namasivayam Ambalavanan ◽

...

Keyword(s):

Observational Study ◽

Preterm Infants ◽

Enteral Feeding ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Extended Duration ◽

Full Enteral Feeding ◽

Trophic Feeding

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Exclusive Human Milk VS Preterm Formula: Randomized Trial in Extremely Preterm Infants

Pediatric Research ◽

10.1038/pr.2011.229 ◽

2011 ◽

Vol 70 ◽

pp. 4-4 ◽

Cited By ~ 1

Author(s):

E A Cristofalo ◽

R J Schanler ◽

C L Blanco ◽

S Sullivan ◽

R Trawoeger ◽

...

Keyword(s):

Human Milk ◽

Randomized Trial ◽

Preterm Infants ◽

Preterm Formula ◽

Extremely Preterm ◽

Extremely Preterm Infants

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Early progressive feeding in extremely preterm infants: a randomized trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy012 ◽

2018 ◽

Vol 107 (3) ◽

pp. 365-370 ◽

Cited By ~ 6

Author(s):

Ariel A Salas ◽

Peng Li ◽

Kelli Parks ◽

Charitharth V Lal ◽

Camilia R Martin ◽

...

Keyword(s):

Preterm Infants ◽

Enteral Feeding ◽

Primary Outcome ◽

Central Venous Access ◽

Venous Access ◽

Feeding Group ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Postmenstrual Age ◽

Full Enteral Feeding

ABSTRACT Background Due to insufficient evidence, extremely preterm infants (≤28 wk of gestation) rarely receive early progressive feeding (small increments of feeding volumes between 1 and 4 d after birth). We hypothesized that early progressive feeding increases the number of full enteral feeding days in the first month after birth. Objective The aim of this study was to determine the feasibility and efficacy of early progressive feeding in extremely preterm infants. Design In this single-center randomized trial, extremely preterm infants born between September 2016 and June 2017 were randomly assigned to receive either early progressive feeding without trophic feeding (early feeding group) or delayed progressive feeding after a 4-d course of trophic feeding (delayed feeding group). Treatment allocation occurred before or on feeding day 1. The primary outcome was the number of full enteral feeding days in the first month after birth. Secondary outcomes were death, necrotizing enterocolitis (NEC), culture-proven sepsis, growth percentiles at 36 wk postmenstrual age, use of parenteral nutrition, and need for central venous access. Results Sixty infants were included (median gestational age: 26 wk; mean ± SD birth weight: 832 ± 253 g). The primary outcome differed between groups (median difference favoring the early feeding group: +2 d; 95% CI: 0, 3 d; P = 0.02). Early progressive feeding reduced the use of parenteral nutrition (4 compared with 8 d; P ≤ 0.01) and the need for central venous access (9 compared with 13 d; P ≤ 0.01). The outcome of culture-proven sepsis (10% compared with 27%; P = 0.18), restricted growth (weight, length, and head circumference <10th percentile) at 36 wk postmenstrual age (25% compared with 50%; P = 0.07), and the composite outcome of NEC or death (27% compared with 20%; P = 0.74) did not differ between groups. Conclusion Early progressive feeding increases the number of full enteral feeding days in extremely preterm infants. This trial was registered at www.clinicaltrials.gov as NCT02915549.

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PIH18 ANALYSIS OF NECROTIZING ENTEROCOLITIS COSTS AMONG EXTREMELY PRETERM INFANTS FED EXCLUSIVELY HUMAN-MILK BASED DIET VS. HUMAN-MILK FORTIFIED WITH BOVINE-MILK BASED SUPPLEMENTS

Value in Health ◽

10.1016/s1098-3015(10)72895-3 ◽

2010 ◽

Vol 13 (3) ◽

pp. A183-A184

Author(s):

V Ganapathy ◽

JW Hay ◽

J Kim

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Bovine Milk ◽

Extremely Preterm ◽

Extremely Preterm Infants

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342 Maternal Predictors of Human Milk Intake in Extremely Preterm Infants

Archives of Disease in Childhood ◽

10.1136/archdischild-2012-302724.0342 ◽

2012 ◽

Vol 97 (Suppl 2) ◽

pp. A100-A101

Author(s):

S. Omarsdottir ◽

A. Adling ◽

L. Legnevall ◽

A. E. Bonamy ◽

M. Vanpee

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Milk Intake ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Maternal Predictors

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Intake and Macronutrient Content of Human Milk Given to Extremely Preterm Infants

Journal of Human Lactation ◽

10.1177/0890334414546354 ◽

2014 ◽

Vol 30 (4) ◽

pp. 442-449 ◽

Cited By ~ 18

Author(s):

Elisabeth Stoltz Sjöström ◽

Inger Öhlund ◽

Andreas Tornevi ◽

Magnus Domellöf

Keyword(s):

Human Milk ◽

Preterm Infants ◽

Macronutrient Content ◽

Extremely Preterm ◽

Extremely Preterm Infants

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Concentrated Preterm Formula as a Liquid Human Milk Fortifier at Initiation Stage in Extremely Low Birth Weight Preterm Infants: Short Term and 2-year Follow-up Outcomes

Nutrients ◽

10.3390/nu12082229 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2229 ◽

Cited By ~ 1

Author(s):

Yung-Chieh Lin ◽

Yen-Ju Chen ◽

Chao-Ching Huang ◽

Chi-Chang Shieh

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Human Milk ◽

Preterm Infants ◽

Volume Ratio ◽

Extremely Low Birth Weight ◽

Improvement Project ◽

Preterm Formula ◽

Extremely Preterm ◽

Extremely Preterm Infants

Human milk (HM) must be accurately fortified for extremely low birth weight (ELBW) preterm infants with human milk fortifiers (HMFs). Powdered HMF has some limitations in terms of sterilization and accuracy. A concentrated preterm formula (CPF) may serve as a safe liquid HMF to facilitate growth. Hence, we launched a quality improvement project for fortification accuracy of minute volume HM. A CPF, Similac Special Care 30 (SSC30), was newly introduced as an HMF when daily feeding reached 100 cm3/kg. CPF + HM (1:2 volume ratio), CPF + HM (1:1 volume ratio), and powdered HMF + HM (1 packet in 25 cm3) represented three fortification stages. Fortification shifted to powdered HMF while tolerable feeding reached 25 cm3/meal. The outcome was compared before (Period-I, January 2015 to June 2016, n = 37) and after the new implement (Period-II, July 2016 to December 2017, n = 36). Compared with the Period-I group, the Period-II group had significantly higher daily enteral milk intake in the first 4 weeks of life, and higher percentages of fortification in the HM-fed infants in the first 8 weeks after birth. The Period-II group also significantly increased in body weight growth in terms of z-score at term equivalent age (p = 0.04) and had better language and motor performance at 24 months old (p = 0.048 and p = 0.032, respectively). Using the liquid CPF as a strategical alternative fortification of HM might be beneficial for extremely preterm infants in terms of growth as well as neurodevelopment.

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