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 the end of the feeding intervention. 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 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: Active, not recruiting
• Conditions: Very Low Birth Weight Infant
• Intervention / Treatment: Other: Standard fortification; Other: Target fortification; Other: BUN adjustable fortification

Detailed Description

The end of the feeding intervention is defined as: the infant is 36+0 weeks CA, is discharged home, or receives two oral feeds daily for three consecutive days without top-up. The exception to the 36+0 weeks intervention end-date is in the situation where an infant remains hospitalized but has not completed at least four weeks of the feeding intervention (i.e. 4 weeks following Study Day 1).

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

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System-Brampton Civic Hospital
    • Etobicoke, Ontario, Canada, M9V 1R8
      • William Osler Health System-Etobicoke General Hospital
    • Markham, Ontario, Canada, L3P 7P3
      • Markham Stouffville Hospital
    • Mississauga, Ontario, Canada, L5M 2N1
      • Trillium Health Partners-Credit Valley Hospital
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Partners-Missisauga Hospital
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre
    • North York, Ontario, Canada, M2K 1E1
      • North York General Hospital
    • North York, Ontario, Canada, M3M 0B2
      • Humber River Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health
    • Richmond Hill, Ontario, Canada, L4C 4Z3
      • Mackenzie Health
    • Scarborough Village, Ontario, Canada, M1E 4B9
      • Scarborough Health Network-Centenary Hospital
    • Scarborough Village, Ontario, Canada, M1P 2V5
      • Scarborough Health Network-General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M4C 3E7
      • Michael Garron Hospital
    • Toronto, Ontario, Canada, M5S 1A1
      • University of Toronto
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto-St Michaels Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Sinai Health System-Mount Sinai Hospital
    • Toronto, Ontario, Canada, M6R 1B5
      • 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

Description

Inclusion Criteria:

• ≤1250 g birth weight or Gestational Age <30+0 weeks and <1500 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 anticipated to occur after postnatal day 21.
• Infants with congenital or chromosomal anomalies or brain injury that may affect growth or neurodevelopment.
• 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 before they have completed at least 4 weeks of the feeding intervention.

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
Health Economics	Total cost incurred for in-hospital care	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Weight at follow-up	z score	4 months corrected age
Length at follow-up	z score	4 months corrected age
Head Circumference at follow-up	z score	4 months corrected age
Body composition at follow-up (approximated)	Skinfolds	4 months corrected age
Body composition at follow-up (direct measurement)	Air displacement plethysmography	4 months corrected age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Milk Type Received	Type of milk consumed (i.e. parent, donor)	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Energy and Nutrient Intakes of Infants	Energy in kilocalories and nutrient intakes (i.e. macronutrients and micronutrients)	Study Day 1 to 36 weeks corrected age or hospital discharge, whichever occurs first
Maternal Diet During Lactation	Data on maternal diet during the first month of the intervention using the Canadian Diet History Questionnaire II	Study Day 35±3

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

Publications and helpful links

General Publications

• Beggs MR, Pichardo D, Chrzaniecki A, Kotsopoulos K, Bishara R, Ng E, Tomlinson C, Campbell D, Vaz S, Kiss A, Unger S, O'Connor DL. MaxiMoM InForM: individualised fortification of human milk for very low birthweight infants- protocol of a three-arm randomised clinical trial. BMJ Open. 2025 Oct 5;15(10):e105609. doi: 10.1136/bmjopen-2025-105609.

Helpful Links

• MaxiMoM InForM protocol

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

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): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 1861 (Ministry of Food and Drug Safety (MFDS))

Drug and device information, study documents

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