Targeted vs Standard Fortification of Breast Milk

NCT03775785 | Unknown

• 1 other identifier: 1/2018
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

BACKGROUND: Human milk (HM) is recommended for all very low birth infants (VLBW)). Breast-milk is highly variable in nutrient content, failing to meet the nutritional demands of VLBW. Fortification of HM is recommended to prevent extra-uterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation. The aim of the study is to evaluate if targeted fortification of human milk may optimize growth and development in preterm infants. STUDY DESIGN: Randomized single blind controlled trial. METHODS \& ANALYSIS: We will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialko, Nutricia - protein, Fantomalt, Nutricia - carbohydrates, Calogen, Nutricia - lipids). The intervention will continue until 37 weeks of post-conception age, or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome - weight gain velocity will be measured starting from the day infants regain their birth weight up to 4 weeks, then weekly until discharge. Secondary outcomes such as neurodevelopment at 12 months of corrected age (CA) will be assessed with Bayley Scale of Development III, repeated at 36 months of CA. Additionally a Wescheler Preschool and Primary Scale of Intelligence IV test will be applied at 3,5 years of CA. Secondary outcomes such as length and head growth, body composition will be assesed at discharge and at 4 months. Incidence of necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) will also be followed.

Conditions

BPD - Bronchopulmonary Dysplasia; NEC - Necrotizing Enterocolitis; Weight Gain; VLBW - Very Low Birth Weight Infant; ROP - Retinopathy of Prematurity

Keywords

enteral nutrition; fortification; tailored enteral nutrition

Outcome Measures

Primary Outcomes (2)

• Growth

  weight will be assessed every day.

  from birth at postmentrual age <32 to up to 37 weeks of post-conceptional age

• Velocity of weight gain in grams

  weight will be assessed every day.

  from birth at postmentrual age <32 to up to 37 weeks of post-conceptional age

Secondary Outcomes (5)

• Neurodevelopmental outcome

  at 12 and 36 weeks of corrected age.

• Necrotizing enterocolitis (NEC)

  from birth at postmentrual age <32 to up to 37 weeks of post-gestational age

• Bronchopulmonary dysplasia (BPD)

  from 28 days at postmentrual age <32 to up to 37 weeks of post gestational age

• Late onset sepsis (LOS)

  from 72 hours of life at postmentrual age <32 up to 37 weeks of post gestational age

• Retinopathy of prematurity (ROP)

  from 3 weeks of life at postmentrual age <32 to 37 weeks of post gestational age

Study Arms (2)

tailored enteral nutrition

EXPERIMENTAL

Tailored Human milk fortification procedure Tailored milk fortification will be done twice a day (8 am and 8 pm) for each following 12 hour nursing shift. Standard fortification will be added first. The remainder amount of protein, lipids and carbohydrates required to meet the recommended by ESPGHAN doses will be acheived by adding single ingrediant nutrients.

Dietary Supplement: Tailored enteral nutrition

standard enteral nutrition

NO INTERVENTION

Standard fortification will be added according to the unit protocol.

Interventions

Tailored enteral nutrition DIETARY_SUPPLEMENT

The mean of three measurements per batch (3 x 2-3ml) will be used to calculate the required amount of extra fat, protein, and carbohydrate for the following 3 days of fortification using a predefined Excel spread sheet (Microsoft Inc, Redmond, Washington). The intervention will consist of adding fat, protein, and/or carbohydrate to achieve target levels of macronutrients. The defined macronutrient concentration in breast milk is 4.4 g/100 mL of fat, 3 g/100 mL of protein, and 8.8 g/ 100 mL of carbohydrate to meet the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines (6.6 g/kg/d of fat, 4.5 g/kg/d of protein, and 13.2 g/kg/d of carbohydrate) assuming an intake of 150 mL/kg/d.

tailored enteral nutrition

Eligibility Criteria

• Age: Up to 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients eligible for the trial must comply with all of the following at randomization:
• Gestational age at birth ≤ 32 weeks
• Enteral feeding of at least 80ml/kg/day
• Donor or maternal milk based enteral feeding (at least 50%)
• Parenteral/legal guardian consent

You may not qualify if:

• \>50% formula based enteral feeding
• Small for gestational age (birth weight \< 3rd percentile)
• Congenital abnormalities which increase the risk of NEC
• NEC
• Withdrawal of feeding \> 7 days
• Sepsis
• Death

Sponsors & Collaborators

• Princess Anna Mazowiecka Hospital, Warsaw, Poland: lead
• Medical University of Warsaw: collaborator
• Institute of Mother and Child: collaborator

Study Sites (2)

Department of Neonatology and Neonatal Intensive Care Warsaw Medical University

Warsaw, 00-315, Poland

RECRUITING

Division of Neonatology and Neonatal Intensive Care, 1st Department of Obstetrics and Gynaecology, The Medical University of Warsaw

Warsaw, 02-015, Poland

NOT YET RECRUITING

Related Publications (1)

• Seliga-Siwecka J, Chmielewska A, Jasinska K. Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (</= 32 weeks): study protocol for a randomized controlled trial. Trials. 2020 Nov 23;21(1):946. doi: 10.1186/s13063-020-04841-x.

  PMID: 33225961 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Enterocolitis, Necrotizing; Weight Gain; Retinopathy of Prematurity

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Retinal Diseases; Eye Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The decision to start fortification will be made by the attending physician blinded to the intervention allocated. An employee outside the research team will feed data into the computer in separate datasheets so that the researchers can analyse data without having access to information about the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a multi-centre superiority randomised parallel group, 1:1 allocation study. After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to receive standard fortification-SF (Bebilon HMF, Nutricia) or targeted fortification -TF (proteins, lipids,carbohydrates). Allocation will be performed electronically.

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 14, 2018
• Study Start: July 1, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 14, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available for 24 months after data analysis completion.
• Access Criteria: researchers

Locations

PL (2)