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

Preterm Birth Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03977259
• Other study ID #: 2019P000893
• Status: Recruiting
• Phase: N/A
• Start date: January 31, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2023
• Source: Brigham and Women's Hospital
• Contact: Kaitlin Drouin, MA
• Phone: 617-732-8546
• Email: kdrouin[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 21 Days

Eligibility

Inclusion Criteria:

• Inpatient in Brigham and Women's Hospital NICU

• Gestational age 24 0/7 to 30 6/7 weeks

• Chronologic age <21 days

• Mother providing breast milk

Exclusion Criteria:

• Major congenital anomaly

• Severe fetal growth restriction (birth weight <3rd percentile by Olsen reference)

• Necrotizing enterocolitis, intestinal perforation, other major gastrointestinal pathology

• Triplets or higher order multiples

• Plan for redirection of care and/or anticipated death

• Clinically significant renal or hepatic dysfunction

• Inborn error of metabolism

• Fluid restriction <140 mL/kg/day for 3 or more days

• Grade 3 or 4 intraventricular hemorrhage detected prior to enrollment

• Anticipated transfer <36 weeks' postmenstrual age

• Parents do not consent to use of pasteurized donor human milk

• Infant in non-parental custody

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight	Weight z-score	at study endpoint (36 weeks' postmenstrual age or discharge)
Primary	Length	Length z-score	at study endpoint (36 weeks' postmenstrual age or discharge)
Primary	Fat free mass	Fat free mass estimated with air displacement plethysmography (z-score)	at study endpoint (36 weeks' postmenstrual age or discharge)
Primary	Total brain volume	Total brain volume by MRI	at term equivalent age (38 to 41 weeks' postmenstrual age)
Primary	Cerebellar volume	Cerebellar volume by MRI	at term equivalent age (38 to 41 weeks' postmenstrual age)
Primary	Bayley-III cognitive score	Scaled composite score (continuous), higher score indicates better performance, range of possible scores 55-145	at 2 years' corrected age
Primary	Bayley-III motor score	Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154	at 2 years' corrected age
Secondary	Fat mass	Fat mass estimated with air displacement plethysmography (z-score)	at study endpoint (36 weeks' postmenstrual age or discharge)
Secondary	Weight	Weight z-score	at 2 years' corrected age
Secondary	Height	Height z-score	at 2 years' corrected age
Secondary	Low Bayley-III cognitive score	Scaled composite score <85 (>1 standard deviation below the normative mean)	At 2 years' corrected age
Secondary	Low Bayley-III motor score	Scaled composite score <85 (>1 standard deviation below the normative mean)	At 2 years' corrected age
Secondary	Bayley-III language score	Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154	At 2 years' corrected age
Secondary	Bayley-III language score	Scaled composite score <85 (>1 standard deviation below the normative mean)	At 2 years' corrected age
Secondary	Spacial working memory	Spin the Pots task (number of trials, search time)	at 2 years' corrected age
Secondary	Behavioral inhibition	Mommies and Babies task (number of trials, errors)	at 2 years' corrected age
Secondary	Executive function	Behavioral Rating Inventory of Executive Function - Preschool Version, higher scores indicate more problems	at 2 years' corrected age
Secondary	Behavioral difficulties	Infant-Toddler Symptom Checklist - Long Version, higher scores indicate more problems	at 2 years' corrected age