Individualized Fortification of Human Milk for Infants Born ≤ 1250 g (MaxiMoM-InForM)

MaxiMoM: Individualized Fortification of Human Milk for Infants Born ≤ 1250 g; a Three Arm Randomized Clinical Trial

Very low birth weight infants have increased nutritional needs. Extra nutrients are added to their human milk feeds to help improve their nutritional status, growth and neurodevelopment. Standard fortification of human milk is routine in most neonatal units in North America, but despite the added nutrients, infants are often discharged from hospitals with poor growth, and their neurodevelopment remains suboptimal. Two individualized fortification methods, target and BUN adjustable, have been proposed to improve the nutrient supply to infants. However, there is currently insufficient evidence to support the implementation of individualized fortification or one method over the other. Therefore, this study will randomly assign very low birth weight infants to receive feeds fortified according to standard, target or BUN adjustable fortification methods until 36 weeks gestational age or hospital discharge whichever occurs first. Feedings will be prepared in milk preparation rooms to ensure caregivers and outcomes assessor remain blinded to feeding allocation. Growth, morbidities, and nutrient intakes will be determined throughout hospitalization and skinfolds assessed at 36 weeks. At 4 months CA, growth and body composition will be determined by air displacement plethysmography and processing speed by electroencephalography on a subset of infants. Neurodevelopment will be assessed using the Bayley Scales of Infant and Toddler Development, at 18-24 months CA.

Study Overview

• Status: Recruiting
• Conditions: Very Low Birth Weight Infant
• Intervention / Treatment: Other: Standard fortification; Other: Target fortification; Other: BUN adjustable fortification

• Study Type: Interventional
• Enrollment (Anticipated): 615
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Deborah O'Connor, PhD RD; Phone Number: 416-813-7844; Email: deborah_l.oconnor@sickkids.ca
• Study Contact Backup: Name: Sharon Unger, MD; Phone Number: 416-586-8593; Email: sharon.unger@sinaihealth.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • Active, not recruiting
      • University of Alberta
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Active, not recruiting
      • William Osler Health System-Brampton Civic Hospital
    • Etobicoke, Ontario, Canada, M9V 1R8
      • Active, not recruiting
      • William Osler Health System-Etobicoke General Hospital
    • Markham, Ontario, Canada, L3P 7P3
      • Active, not recruiting
      • Markham Stouffville Hospital
    • Mississauga, Ontario, Canada, L5B 1B8
      • Active, not recruiting
      • Trillium Health Partners-Missisauga Hospital
    • Mississauga, Ontario, Canada, L5M 2N1
      • Active, not recruiting
      • Trillium Health Partners-Credit Valley Hospital
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Active, not recruiting
      • Southlake Regional Health Centre
    • North York, Ontario, Canada, M2K 1E1
      • Active, not recruiting
      • North York General Hospital
    • North York, Ontario, Canada, M3M 0B2
      • Active, not recruiting
      • Humber River Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Active, not recruiting
      • Lakeridge Health
    • Richmond Hill, Ontario, Canada, L4C 4Z3
      • Not yet recruiting
      • Mackenzie Health
    • Scarborough, Ontario, Canada, M1E 4B9
      • Active, not recruiting
      • Scarborough Health Network-Centenary Hospital
    • Scarborough, Ontario, Canada, M1P 2V5
      • Active, not recruiting
      • Scarborough Health Network-General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Not yet recruiting
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1X8
      • Active, not recruiting
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M4C 3E7
      • Active, not recruiting
      • Michael Garron Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • Active, not recruiting
      • Unity Health Toronto-St Michaels Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Recruiting
      • Sinai Health System-Mount Sinai Hospital
    • Toronto, Ontario, Canada, M5S 1A1
      • Active, not recruiting
      • University of Toronto
    • Toronto, Ontario, Canada, M6R 1B5
      • Active, not recruiting
      • Unity Health Toronto-St Josephs Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≤1250 g birth weight.
• Parental/guardian consent to participate.
• Consent for the use of pasteurized donor milk if mother's milk is not available.

Exclusion Criteria:

• Infant received fortifier or formula before Study Day 1.
• Study Day 1 to occur after day 21 of life.
• Infants with congenital or chromosomal anomalies that may affect growth outcome.
• Enrollment in any other clinical study affecting nutritional management during the feeding intervention.
• Reasonable potential that the infant will be transferred to a NICU where the study protocol will not be continued.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard fortification	Other: Standard fortification; Standard fortification assumes that the nutrient content of human milk is constant and involves use of a standard fixed dose of multi-nutrient fortifier and as appropriate nutrient modulars.
Experimental: Target fortification	Other: Target fortification; Target fortification involves use of a multi-nutrient fortifier as well as weekly analysis of energy and macronutrients of human milk and subsequent addition of fat and protein modulars if needed.
Experimental: BUN adjustable fortification	Other: BUN adjustable fortification; BUN (blood urea nitrogen) adjustable fortification involves use of a multi-nutrient fortifier as well as weekly BUN tests and subsequent addition of a protein modular according to a prescribed algorithm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Composite Score	Bayley Scales of Infant and Toddler Development	18-24 months corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Language Composite Score	Bayley Scales of Infant and Toddler Development	18-24 months CA
Motor Composite Score	Bayley Scales of Infant and Toddler Development	18-24 months CA
Weight Gain during the intervention	Change in z-score	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Length gain during the intervention	Change in z-score	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Head circumference gain during the intervention	Change in z-score	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Body composition at the end of the intervention	Skinfolds	36 weeks corrected age
Serious Morbidity	Composite of death, NEC, late onset sepsis, chronic lung disease or severe retinopathy of prematurity (ROP)	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain--event related potentials	Electroencephalography	At 4 months corrected age
Brain--power	Electroencephalography	At 4 months corrected age
Brain--connectivity	Electroencephalography	At 4 months corrected age
Weight at follow-up		4 months corrected age
Length at follow-up		4 months corrected age
Head Circumference at follow-up		4 months corrected age
Body composition at follow-up	Skinfolds	4 months corrected age
Body composition at follow-up	Air displacement plethysmography	4 months corrected age

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Deborah O'Connor, PhD RD, The Hospital for Sick Children; Principal Investigator: Sharon Unger, MD, Sinai Health System

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Anticipated): July 1, 2026
• Study Completion (Anticipated): July 1, 2026

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 1861

Drug and device information, study documents

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