Trial Outcomes & Findings for Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk (NCT NCT04325308)

NCT ID: NCT04325308

Last Updated: 2025-09-23

Results Overview

Estimated by air displacement plethysmography. FFM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: NA
• Target enrollment: 150 participants
• Primary outcome timeframe: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
• Results posted on: 2025-09-23

Participant Flow

Participant milestones

Measure	Protein-enriched Human Milk Diet Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Overall Study STARTED	75	75
Overall Study COMPLETED	52	53
Overall Study NOT COMPLETED	23	22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk

Baseline characteristics by cohort

Measure	Protein-enriched Human Milk Diet n=75 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.	Total n=150 Participants Total of all reporting groups
Age, Continuous	26 weeks of gestation n=93 Participants	26 weeks of gestation n=4 Participants	26 weeks of gestation n=27 Participants
Sex: Female, Male Female	43 Participants n=93 Participants	29 Participants n=4 Participants	72 Participants n=27 Participants
Sex: Female, Male Male	32 Participants n=93 Participants	46 Participants n=4 Participants	78 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=93 Participants	7 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=93 Participants	68 Participants n=4 Participants	138 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	45 Participants n=93 Participants	38 Participants n=4 Participants	83 Participants n=27 Participants
Race (NIH/OMB) White	29 Participants n=93 Participants	36 Participants n=4 Participants	65 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	75 Participants n=93 Participants	75 Participants n=4 Participants	150 Participants n=27 Participants

PRIMARY outcome

Timeframe: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

Estimated by air displacement plethysmography. FFM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.

Outcome measures

Measure	Protein-enriched Human Milk Diet n=52 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=53 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Fat-free Mass(FFM)-For-age Z-score	-1.7 Z-score Standard Deviation 1.4	-1.6 Z-score Standard Deviation 1.5

SECONDARY outcome

Timeframe: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

Estimated by air displacement plethysmography. FM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.

Outcome measures

Measure	Protein-enriched Human Milk Diet n=52 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=53 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Fat Mass(FM)-For-age Z-score	1.0 Z-score Standard Deviation 1.1	1.3 Z-score Standard Deviation 1.2

SECONDARY outcome

Timeframe: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer

Body fat estimated by air displacement plethysmography. BF measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.

Outcome measures

Measure	Protein-enriched Human Milk Diet n=52 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=53 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Body Fat(BF)-For-age Z-score	1.8 Z-score Standard Deviation 1	1.9 Z-score Standard Deviation 1.2

SECONDARY outcome

Timeframe: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)

Weight, length, and head circumference measurements. Measurements were converted into Z-scores based on Fenton growth curves (2013). They were calculated at birth and at 36 weeks. This outcome represents the change in weight, length, and head circumference Z-score during the course of the study (i.e., the Z-score at birth was subtracted from the Z-score at 36 weeks).

A value of 0 represents that the infant's Z-score is the same at the beginning and the end of the study. Positive values indicate the increase in the infant's Z-score during the study; negative values indicate the decrease in the infant's Z-score during the study.

Outcome measures

Measure	Protein-enriched Human Milk Diet n=65 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=63 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Anthropometric Measurements Weight	-1.0 Z-score Standard Deviation 0.7	-1.2 Z-score Standard Deviation 0.8
Anthropometric Measurements Length	-1.5 Z-score Standard Deviation 1.0	-1.9 Z-score Standard Deviation 1.3
Anthropometric Measurements Head circumference	-0.9 Z-score Standard Deviation 0.8	-1.3 Z-score Standard Deviation 1.1

SECONDARY outcome

Timeframe: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)

Weight gain in g/kg/day

Outcome measures

Measure	Protein-enriched Human Milk Diet n=65 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=63 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Growth Rate	14.7 g/kg/day Standard Deviation 2.5	13.9 g/kg/day Standard Deviation 2.5

SECONDARY outcome

Timeframe: 36 weeks or hospital discharge (whichever occurred first)

Diagnosis of growth failure (weight < 10th percentile using the 2013 Fenton growth curves)

Outcome measures

Measure	Protein-enriched Human Milk Diet n=65 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=63 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Number of Participants With Postnatal Growth Failure	31 Participants	30 Participants

SECONDARY outcome

Timeframe: From birth up to 120 days following birth

Diagnosis of necrotizing enterocolitis stage 2 or 3

Outcome measures

Measure	Protein-enriched Human Milk Diet n=75 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Number of Participants With Diagnosis of Necrotizing Enterocolitis	1 Participants	3 Participants

SECONDARY outcome

Timeframe: From birth up to 120 days following birth

Diagnosis of intestinal perforation

Outcome measures

Measure	Protein-enriched Human Milk Diet n=75 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Number of Participants With Diagnosis of Intestinal Perforation	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Birth to 120 days

Death prior to 121 days of life

Outcome measures

Measure	Protein-enriched Human Milk Diet n=65 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=63 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Death	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Birth to 120 days

Diagnosis of sepsis with positive blood cultures

Outcome measures

Measure	Protein-enriched Human Milk Diet n=75 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Culture-proven Sepsis	22 Participants	16 Participants

SECONDARY outcome

Timeframe: Birth to 28 days

Time to full enteral feeding days

Outcome measures

Measure	Protein-enriched Human Milk Diet n=68 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=71 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Number of Days Alive and Receiving Full Enteral Feeding	18 days Interval 11.0 to 21.0	14 days Interval 5.0 to 18.0

SECONDARY outcome

Timeframe: Birth to 28 days

Population: Not collected

Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Birth to 120 days or discharge, whichever occurs first

From day of admission to day of hospital discharge to home

Outcome measures

Measure	Protein-enriched Human Milk Diet n=69 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=70 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Duration of Hospital Stay in Days	107 days Interval 87.0 to 120.0	107 days Interval 79.0 to 120.0

SECONDARY outcome

Timeframe: Birth to 28 days

Highest serum BUN value in the first 28 days after birth

Outcome measures

Measure	Protein-enriched Human Milk Diet n=69 Participants Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=69 Participants Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Serum BUN	33 mg/dL Standard Deviation 24	37 mg/dL Standard Deviation 31

OTHER_PRE_SPECIFIED outcome

Timeframe: Birth to 36 weeks postmenstrual age

Determined by molecular analyses of fecal samples

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years of corrected age

Determined by Bayley assessment

Outcome measures

Outcome data not reported

Adverse Events

Protein-enriched Human Milk Diet

Serious events: 6 serious events

Other events: 31 other events

Deaths: 6 deaths

Usual Human Milk Diet

Serious events: 4 serious events

Other events: 30 other events

Deaths: 5 deaths

Serious adverse events

Measure	Protein-enriched Human Milk Diet n=75 participants at risk Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 participants at risk Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
Gastrointestinal disorders Necrotizing enterocolitis	1.3% 1/75 • From birth up to 120 days following birth	4.0% 3/75 • From birth up to 120 days following birth
Gastrointestinal disorders Spontaneous intestinal perforation	6.7% 5/75 • From birth up to 120 days following birth	5.3% 4/75 • From birth up to 120 days following birth

Other adverse events

Measure	Protein-enriched Human Milk Diet n=75 participants at risk Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Protein-enriched human milk diet: 1.2 g of human-based protein will be added to each 100 ml of human milk administered	Usual Human Milk Diet n=75 participants at risk Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Usual human milk diet: Human-based protein will not be added to the human milk administered.
General disorders Growth failure	41.3% 31/75 • From birth up to 120 days following birth	40.0% 30/75 • From birth up to 120 days following birth

Additional Information

Ariel Salas

University of Alabama at Birmingham

Phone: 2059344680

Email: asalas@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place