Targeted Fortification of Pasteurized Donor Human Milk

Targeted Fortification of Pasteurized Donor Human Milk to Improve Growth in Very Low Birth Weight Infants

This randomized controlled trial aims to evaluate a modified targeted fortification method of pasteurized donor human milk (PDHM) in very low birth weight infants (VLBWs). Pools of PDHM will be analyzed for macronutrient content using the Miris Human Milk Analyzer. The control arm will receive standard of care, which is PDHM without additional protein fortification. The intervention arm will receive PDHM with a fat content of 3.8g/dL or more, with additional protein fortification of 0.67g/dL. Primary outcome will be rate of malnutrition at hospital discharge or 37 weeks, whichever earlier. Secondary outcomes include body composition, feed tolerance, and morbidity outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Growth Failure; Very Low Birth Weight Infant; Donor Breast Milk
• Intervention / Treatment: Dietary supplement: Protein supplementation; Other: Analysis with Miris Human Milk Analyzer

Detailed Description

Our hospital milk bank provides pasteurized donor human milk (PDHM) to very low birth weight (VLBW) infants without sufficient mother's milk, with the overall aim of lowering the risk of necrotizing enterocolitis in this population. However, with the introduction of PDHM in our setting, rates of suboptimal weight gain have increased (60.2% to 65.7%). This is likely due to the fact that PDHM is often lower in energy and protein than preterm mother's own milk. One solution to delivery adequate nutrition in this VLBWs receiving PDHM, is targeted fortification, which involves measurement of the macronutrient content of human milk, and adding extra macronutrients to reach nutrient goals. In this proposed study, we will conduct a pilot randomized controlled trial of a modified targeted fortification versus standard care. This study will include preterm VLBW infants (<1500g), without congenital conditions resulting in growth restriction, and receiving >25% of PDHM use in the first week of life. 40 patients in each arm will be recruited over a period of 2 years. The intervention group will receive a modified targeted fortification, consisting of selection of high fat PDHM (3.8g/dL or more) with the addition of protein fortification of 0.67g/dL from week 2 of life until a gestational age of 37 weeks or hospital discharge, whichever earlier. The control group will receive usual regular PDHM with standard fortification using human milk fortifier as per current practice. The primary outcome is the rate of suboptimal growth (drop in weight z-score from birth ≥0.8) at discharge or 37 weeks. Secondary outcomes include body composition, feed tolerance, and morbidity outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chengsi Ong; Phone Number: 6394 1646; Email: ong.chengsi@kkh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 8 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Birth weight less than or equal to 1500g
• Born at our study hospital or transferred to study hospital within first week of life
• Achieving at least 40ml/kg/day of enteral feeds by day 7 of life
• Receiving at least 25% of pasteurized donor human milk within first 7 days of life

Exclusion Criteria:

• Diagnosed or suspected inborn errors of metabolism
• Acute or chronic renal impairment
• Congenital disease associated with significant growth impairment (including, but not limited to, Trisomy 21, neonatal encephalopathy and seizures, neonatal tumours, achondroplasia, complex congenital heart disease, anorectal malformations, gastrointestinal disorders)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group (standard fortification); Pasteurized Donor Human Milk (PDHM) will be fortified as per unit protocols, at 1 packet of Human Milk Fortifier (Similac) to every 25ml PDHM at a feed volume of 80ml/kg/day
Experimental: Intervention group (modified targeted fortification); Pasteurized Donor Human Milk (PDHM) will be analyzed using the Miris Human Milk Analyzer, and PDHM with a fat content of 3.8g/dL or higher will be selected. Additional protein will be added using liquid protein fortifier (Similac) at 1ml to every 25ml PDHM to give an additional 0.67g/dL protein.	Dietary supplement: Protein supplementation; Liquid protein fortifier (Similac) will be added at 1ml per 25ml of PDHM at 130ml/kg/day of feed volume.; Other: Analysis with Miris Human Milk Analyzer; PDHM macronutrient content will be analyzed using the Miris Human Milk Analyzer and PDHM with fat content of 3.8g/dL or higher will be selected and provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malnutrition rate	Malnutrition is defined as a decline in weight z-score from birth of 0.8 or more	Hospital discharge or 37 weeks gestation, whichever earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Linear growth	Linear growth will be assessed using z-score changes from birth	Hospital discharge or 37 weeks post menstrual age, whichever earlier
Body composition	Percent fat mass and fat-free mass measured using air displacement plethysmography	Hospital discharge or 37 weeks gestation, whichever earlier
Head circumference growth	Head circumference will be assessed using z-score changes from birth	Hospital discharge or 37 weeks gestation, whichever earlier
High calorie formula use	Proportion of high calorie formula use (e.g. 27kcal/oz or 30kcal/oz formula)	Hospital discharge or 35 weeks gestation, whichever earlier
Bronchopulmonary dysplasia	Proportion of patients with bronchopulmonary dysplasia	Hospital discharge or 37 weeks gestation, whichever earlier
Retinopathy of prematurity	Proportion of patients with retinopathy of prematurity	Hospital discharge or 37 weeks gestation, whichever earlier

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental scores	Bayley Scales of Infant and Toddler Development scale scores	18 to 24 months post menstrual age
Infant motor performance	Test of Infant Motor Performance scores measured by trained physiotherapists	Hospital discharge or 37 weeks gestation, whichever earlier
Duration of hospital stay	Days of hospital stay	Hospital discharge, assessed up to 180 days post menstrual age

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Investigators: Principal Investigator: Chengsi Ong, KK Women's and Children's Hospital, Singapore

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): January 2, 2023
• Study Completion (Anticipated): January 2, 2024

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight; Failure to Thrive
• Other Study ID Numbers: 2020/2493

Drug and device information, study documents

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