Human Milk Fortification With Adjustable Versus Targeted Method (FAT)

Effect of Adjustable Versus Targeted Human Milk Fortification on Weight Gain in Preterm Infants With Birth Weight <1250 g: A Randomized Controlled Trial

Research question: Do preterm infants born <1250 g achieve better weight gain with targeted fortification compared with the adjustable fortification of human milk?

Hypothesis: Targeted fortification of human milk results in better weight gain in infants with birth weight <1250 gr when compared to the adjustable fortification.

Study design: Open-label, pragmatic, parallel randomized controlled trial in appropriate for gestational age infants with birth weight <1250 g.

Study Overview

• Status: Recruiting
• Conditions: Growth Failure
• Intervention / Treatment: Dietary supplement: Adjustable Human Milk Fortification; Dietary supplement: Targeted Human Milk Fortification

Detailed Description

Human milk is the ideal diet for neonates. However, it does not provide enough energy, protein, and sodium to meet the nutritional requirements of very preterm infants. Postnatal growth failure is common despite the current use of human milk fortifiers. The main human milk fortification methods include:

1. standard HM fortification (SF) which assumes an average composition of breast milk and adds fortifiers in a fixed dosage. It does not account for variations of nutrient content in human milk

2. Individualized human milk fortification which encompasses two methods:

   1. Adjustable HM fortification (AF): Protein supplementation is provided in addition to SF according to blood urea nitrogen (BUN) concentration which reflects the infant's metabolic response to protein intake. However, there are clinical scenarios in which the BUN levels are not a reliable marker of protein intake, such as acute kidney injury.
   2. Targeted HM fortification (TF): Based on routine analyses of HM that are used to adjust fortification to meet the recommended requirements for infants. It does not take into consideration that the requirements of infants may vary.

SF has frequently failed to achieve appropriate weight gain, while individualized (AF or TF) fortification seems to have better performance. However, the evidence to support one method over the other is lacking.

The objective of the study is to compare weekly average weight gain between preterm infants on AF versus TF.

Once the written consent is obtained, the infant will be randomized to AF or TF. The sequence code will be kept in sequential numbered sealed envelopes. Infants from multiple births will be included as 1 unit and randomized to the same arm of the study.

For patients allocated to the TF group, breast milk will be analyzed twice weekly for energy, protein, and sodium contents. The daily protein, fat, and sodium intakes will be then calculated and optimized to meet the recommended dietary reference intake (DRI) for preterm infants with birth weight <1250 g.

For patients allocated to the AF group, weekly BUN measurements will be performed. Based on BUN concentrations, the liquid protein will be added to achieve the targeted BUN level. Additional calories will be added using formula if growth is suboptimal or DRI is not met based on the assumed human milk content for protein and energy.

The intervention will last 4-8 weeks. For all patients, the day the first BUN concentration and milk analyses are done will be day 1 of intervention. The following measurements will be performed on days 7-8, 14-16, 21-23, and 28-30 of intervention: Weight (grams), length and head circumference (centimeters), BUN and sodium concentrations.

Data on maternal and neonatal characteristics will be collected from their electronic and physical charts.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Belal N Alshaikh, MD, MSc; Phone Number: 4039561588; Email: balshaik@ucalgary.ca
• Study Contact Backup: Name: Adriana Reyes Loredo, MD; Email: adriana.reyesloredo@albertahealthservices.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N2T9
      • Recruiting
      • Foothills Medical Centre
      • Contact: Belal Alshaikh, MD
      • Principal Investigator: Belal Alshaikh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants with birth weight <1250 g born at Foothills Medical Centre.
• Appropriate for gestational age (AGA) (according to Fenton's Charts).

Exclusion Criteria:

• Abnormal Newborn Metabolic Screen
• Major congenital anomalies intervention.
• Patients who develop NEC prior to enrollment.
• Patients with confirmed congenital Toxoplasmosis, Syphilis, Rubella, Cytomegalovirus, Herpes simplex virus, Varicella and/or Zika (TORCH infections).
• Patients receiving systemic steroids.
• Patients with acute kidney injury (AKI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adjustable Human Milk Fortification; Human milk fortification based on blood urea levels	Dietary supplement: Adjustable Human Milk Fortification; BUN and sodium concentrations will be measured every week in infants on full enteral feeds with fortified human milk. Liquid protein will be added based on serum urea.
Experimental: Targeted Human Milk Fortification; Human milk fortification based on milk analysis	Dietary supplement: Targeted Human Milk Fortification; Human milk will be analyzed twice weekly. Before the day of analysis, each mother will store fresh milk pumped from 10:00 AM until 8:00 AM of the previous day in a refrigerator and bring it to the hospital. Protein, fat, and sodium supplementation will be added to the human milk to meet the recommended daily intakes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average weight gain in infants on Adjustable versus Targeted human milk fortification	Average weight gain measured as g/kg per day	Weekly for 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometrics in infants on Adjustable versus Targeted human milk fortification	Measurement of head circumference and length in centimeters.	Weekly for 8 weeks
BUN concentration in infants on Adjustable versus Targeted human milk fortification	mmol/L	Weekly for 4 weeks
Incidence of extra uterine growth restriction	Defined as weight less than 10th percentile at 36 weeks corrected age (CA)	At 36 weeks CA

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Belal Alshaikh, MD, MSc, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Preterm infants; Human milk; Fortification
• Additional Relevant MeSH Terms: Failure to Thrive
• Other Study ID Numbers: REB20-2139

Drug and device information, study documents

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