Using a New Human Milk Fortifier to Optimize Feeding

Using a New Human Milk Fortifier to Optimize Human Milk Feeding in Very Preterm Infants, a Multicenter Clinical Trial

This study aims to compare the safety and efficacy of a new HMF and those of other HMF used before in very preterm infants.

Study Overview

• Status: Completed
• Conditions: Growth; Preterm Infant
• Intervention / Treatment: Dietary supplement: A new human milk fortifier

Detailed Description

Infants with fortified human milk feeding have the same rate of growth, lower incidence of nosocomial infections and feeding intolerance compared to those with formula feeding during hospitalization. However, the currently human milk fortifiers (HMF) have some nutritional components defects to meet the needs of very preterm infants. New HMF provide higher protein and fat, which are safe and well tolerate to use in preterm infants. Study on safety and efficacy of the new HMF is insufficient in Chinese preterm infant population. Our aims are to compare the safety and efficacy of a new HMF and other HMF used before in very preterm infants. Very low preterm infants with birth weights of 1000-1499g and gestational age 28+0 weeks to 31 + 6 weeks are included. Infants feeding with new HMF are in the experimental group. Infants feeding with other HMF are in the control group, a historically control group. Physical growth, nutritional indexes, incidence of feeding intolerance, and time to achieve full enteral feeding are compared between the two groups.

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210004
      • Nanjing Maternal and Child Health Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200062
      • Children's Hospital of Shanghai Jiao Tong University
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200126
      • Shanghai First Maternity and Infant Hosipital
    • Shanghai, Shanghai, China, 200127
      • Shanghai Children's Medical Center
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants with gestational age between 28+0 weeks to 31+6 weeks, and 1000g≤ birth weight<1500g;
• Delivered in the study centers or transfer to the study centers within 24 hours after birth;
• Own mother's milk or human milk bank were available;
• Only one of the twins is selected in this study;
• Informed consent has been obtained.

Exclusion Criteria:

• Severe congenital malformations, severe asphyxia, intracranial hemorrhage and other diseases;
• Small for gestational age infants (birth weight below the 10th percentile of the reference, Fenton premature infant growth chart (2013)）;
• Enteral feeding is not tolerated in 14 days after birth;
• Infants who have participated in other clinical trials within 1 month;
• Other conditions not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: The new HMF group; Very preterm infants tolerating 80mL/kg/day of enteral feeding for >24 hours are started to receive the new human milk fortifier. Study procedure is from the first day of full-strength fortification feeding to the 21th days of that.	Dietary supplement: A new human milk fortifier; Contents of protein, protein/energy ratio, moderate hydrolysis of whey protein, medium-chain fatty acid are increased in the new HMF
NO_INTERVENTION: Other HMF group; This group is a historical control group using the other HMF. Infants with similar gestational age, birth weight, feeding start time and length of hospitalization are enrolled into the control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth velocity of weight	Weight is tested daily using the same electronic weighing scale in the different study units. Growth velocity of weight is described in g/day.	During the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth velocity of head circumference	Head circumference is measured weekly using a nonelastic measuring tape placed over the largest circumference of the skull weekly. Growth velocity is described in cm/week.	During the procedure
Incidence of feeding intolerance	Feeding intolerance is defined as feeds being withheld for 24 hours or more due to concerns related to feeding.	From the start day of feeding to discharge，an average of 50 days
Time to achieve full enteral feeding	Infants tolerating 120mL/ kg/day of enteral feeding for >24 hours are defined as full enteral feeding.	During the hospitalization，an average of 20 days
The changes of blood hemoglobin	Blood hemoglobin is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as g/dL.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum albumin	Serum albumin is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as g/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum proalbumin	Serum proalbumin is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mg/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum potassium	Serum potassium is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum sodium	Serum sodium is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum phosphorus	Serum phosphorus is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The changes of serum calcium	Serum calcium is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of serum alkaline phosphatase	Serum alkaline phosphatase is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as U/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The change of blood urea nitrogen	Blood urea nitrogen is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The changes of cholesterol	Cholesterol is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
The Change of triglyceride.	Triglyceride is tested twice during the procedure. The change is the difference between baseline and after the intervention, described as mmol/L.	The first day of full-strength fortification feeding, the 21th days of full-strength fortification feeding.
Incidence of abnormal body temperature	Axillary temperature is tested by nurses using clinical electronic thermometers once every four hours. Either low body temperature ( <35℃) or high body temperature ( >37.5℃) is abnormal body temperature.	During the period using HMF, an average of 30 days
Incidence of apnea	Apnea is defined as premature infants with respiratory arrest of more than 20 seconds, accompanied by a slow heartbeat, purple or pale skin, and decreased muscle tone.	During the period using HMF, an average of 30 days
Incidence of abnormal heart rate	Either heart rate increase (>180/min) or decrease (<90/min) is defined as abnormal heart rate.	During the period using HMF, an average of 30 days
Incidence of necrotizing enterocolitis (NEC)	NEC is diagnosed according to the Bell's grade scale.	From birth to discharge, an average of 20 days
Incidence of bronchopulmonary dysplasia (BPD)	BPD is defined as oxygen requirement at 36 weeks' postconceptional age.	From birth to discharge, an average of 40 days
Incidence of sepsis	Both culture confirmed sepsis and clinical sepsis are defined as sepsis in this study.	From birth to discharge, an average of 30 days
Incidence of retinopathy of prematurity (ROP)	ROP is diagnosed by ophthalmologists according to fundus examination.	From birth to discharge, an average of 40 days

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Principal Investigator: Yun Cao, Ph.D., M.D., Children's Hospital of Fudan University, Shanghai, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 16, 2020
• Primary Completion (ACTUAL): April 23, 2021
• Study Completion (ACTUAL): April 23, 2021

Study Registration Dates

• First Submitted: February 23, 2020
• First Submitted That Met QC Criteria: February 23, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: NES-SR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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