Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants (ENACT+)

Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants: a Randomized Clinical Trial

In this proposed clinical trial, the investigators will randomize 80 very preterm (VPT) infants to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification and determine if providing early protein supplementation through early fortification results in higher FFM-for-age z scores and more diversity in the gut microbiome.

Study Overview

• Status: Active, not recruiting
• Conditions: Prematurity; Enteral Feeding Intolerance; Light-For-Dates
• Intervention / Treatment: Dietary supplement: Early HMF; Dietary supplement: Delayed HMF

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ariel A. Salas, MD, MSPH; Phone Number: 205-934-4680; Email: asalas@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 days (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational age 29 to 33 weeks of gestation
• Birth weight < 1800 g
• Postnatal age < 96 hours

Exclusion Criteria:

• Small for gestational age (<5th percentile)
• Major congenital/chromosomal anomalies
• Terminal illness needing withhold or limit support

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early human milk fortification (HMF) group; A human milk fortifier will be added to the feeds between days 4 to 7, after a total feeding volume greater than 120 ml/kg/day is achieved.	Dietary supplement: Early HMF; Mom's milk or donor milk will be fortified between postnatal day 4 and 7
Active Comparator: Delayed human milk fortification (HMF) group; A human milk fortifier will be added to the feeds between days 10 to 14, after a total feeding volume greater than 120 ml/kg/day is achieved.	Dietary supplement: Delayed HMF; Mom's milk or donor milk will be fortified between postnatal day 10 and 14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat-free mass(FFM)-for-age Z-score	Estimated by air displacement plethysmography	Postnatal day 14 to 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth rate	Weight gain in g/kg/day	Birth to 36 weeks postmenstrual age or hospital discharge
Fecal microbiome composition	Determined by 16S RNA sequencing of bacteria in stool samples	Birth to 36 weeks postmenstrual age
Growth - Weight	Measured weekly in grams and z scores as part of routine care	Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Length	Measured weekly in cm and z scores as part of routine care	Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Head circumference	Measured weekly in cm and z scores as part of routine care	Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with postnatal growth faltering	Diagnosis of growth faltering (decline in weight-for-age z score from birth to 36 weeks postmenstrual age greater than 1.2	Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with diagnosis of necrotizing enterocolitis	Diagnosis of necrotizing enterocolitis stage 2 or 3	Birth to 60 days or discharge
Number of participants with diagnosis of intestinal perforation	Diagnosis of intestinal perforation	Birth to 10 days
Death	Death prior to postnatal day 60	Birth to 60 days
Duration of hospital stay in days	From day of admission to day of hospital discharge to home	Birth to 60 days or discharge, whichever occurs first

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Mead Johnson Nutrition
• Investigators: Principal Investigator: Ariel A. Salas, MD, MSPH, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Actual): November 1, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 31, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: 300009921

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No