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

Study Overview
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Brief Summary
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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.

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

Conditions
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Very Low Birth Weight Infant

Intervention / Treatment
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* Other: Standard fortification
* Other: Target fortification
* Other: BUN adjustable fortification


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 21 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard fortification<br> | Other: Standard fortification<br>* 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.<br>|
| Experimental: Target fortification<br> | Other: Target fortification<br>* 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.<br>|
| Experimental: BUN adjustable fortification<br> | Other: BUN adjustable fortification<br>* 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.<br>|

What is the study measuring?
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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 |