Using a New Human Milk Fortifier to Optimize Feeding

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

Detailed Description
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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.

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

Conditions
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Preterm Infant, Growth

Intervention / Treatment
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* Dietary Supplement: A new human milk fortifier


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 1 Day

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The new HMF group<br>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<br>* Contents of protein, protein/energy ratio, moderate hydrolysis of whey protein, medium-chain fatty acid are increased in the new HMF<br>|
| No Intervention: Other HMF group<br>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?
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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 |