NCT03977259

Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 130 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 1 Day – 21 Days
• Healthy volunteers: Not accepted

Summary

This study is a randomized trial comparing 2 methods of human milk fortification for preterm infants in the neonatal intensive care unit (NICU). All participating infants will receive a human milk diet comprising maternal and/or donor milk plus multi-component and modular fortifiers. In one group (control), the milk will be fortified according to routine standard of care. In the other group (intervention), the fortification will be individually targeted based on the results of point-of-care human milk analysis. Outcomes include physical growth in the NICU and after discharge, brain structure by magnetic resonance imaging at term equivalent age, and neurodevelopment at 2 years.

Detailed description

Human milk is the recommended diet for preterm infants and it requires fortification to meet their high nutrient requirements. This study addresses a gap in knowledge about the optimal strategy for human milk fortification in the neonatal intensive care unit (NICU). Infants will be recruited from a single site (Brigham and Women's Hospital, Boston MA). Eligible infants are NICU inpatients born \<31 weeks' gestation and enrolled within 21 days of birth, whose mothers are providing breast milk. Exclusion criteria include major congenital anomalies, severe fetal growth restriction (weight \<3rd percentile), clinically significant gastrointestinal pathology, triplets or higher order multiples, and expected death or transfer. Infants who require fluid restriction \<140 mL/kg/day will also be excluded. The study period begins when infants have reached full volume (150-160 mL/kg/day) human milk feedings fortified to 24 kcal per ounce. Participants will be randomized to one of two diet groups; twins will be randomized separately. The study diet will continue until 36 weeks' postmenstrual age or hospital discharge, whichever comes first. Available maternal milk will be pooled with donor milk (if needed) to reach the total daily fluid volume; this "base" milk will be analyzed with a point-of-care human milk analyzer (Miris, AB). All infants will receive at minimum the standard human milk fortification (multicomponent fortifier to 24 kcal/oz plus liquid protein 0.27 g/dL). In one group (control), we will follow the standard of care for milk fortification, only adding more protein and/or energy if weight gain is lagging. In the other group (intervention), we will individually target fortification with additional protein and/or energy so that the "base" milk always contains protein 1 g/dL and energy 67 kcal/dL. Outcome measures will include physical growth during the diet intervention period, including gain in weight, length, and head circumference and body composition with air displacement plethysmography at the end of the diet intervention. At term equivalent age, participants will undergo brain magnetic resonance imaging. At 2 years corrected age, outcomes include standard and novel neurodevelopmental tests including the Bayley-III and tests of emerging executive function; and physical size.

Conditions

• Preterm Birth
• Breast Milk Expression
• Nutrition Disorder, Infant
• Brain Development Abnormality
• Neurodevelopmental Disorders

Interventions

Type	Name	Description
OTHER	Individually targeted fortification	Abbott liquid protein and/or medium chain triglyceride are added routinely to ensure that the "base" milk has protein 1 g/dL and calories 67/dL.

Timeline

• Start date: 2020-01-31
• Primary completion: 2025-05-06
• Completion: 2027-08-31
• First posted: 2019-06-06
• Last updated: 2025-06-17

Locations

1 site across 1 country: United States