An interventional study of Protein-enriched human milk diet and Usual human milk diet in Prematurity; Extreme, Feeding Disorder Neonatal and Breast Milk Expression, sponsored by University of Alabama at Birmingham. Active, not recruiting at 1 site in United States. Open to participants aged 1 Day to 4 Days. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by University of Alabama at Birmingham · Not applicable, Interventional, and Prevention
The central hypothesis of this clinical trial is that, in extremely preterm infants, protein-enriched human milk diets compared to usual human milk diets during the first 2 weeks after birth increase fat-free mass (FFM)-for-age Z scores and promote maturation of the gut microbiome at term corrected age.
Masked randomized clinical trial in which extremely preterm infants fed human milk will be randomly assigned to receive either a protein-enriched diet (intervention group) or a usual diet (control group) within the first 96 hours after birth.
2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.
This study's enrollment of 150 is above the median of 84 across 1,666 interventional studies indexed under Premature Birth.
Browse Premature Birth studies →University of Alabama at Birmingham is the lead sponsor of 1,421 studies on the registry; 277 are open to participants now.
Of its 164 completed or terminated interventional studies of FDA-regulated products, 130 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth.
Procedure: Protein-enriched human milk diet
Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth.
Procedure: Usual human milk diet
1.2 g of human-based protein will be added to each 100 ml of human milk administered
Human-based protein will not be added to the human milk administered.
Fat-free Mass(FFM)-For-age Z-score
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.
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Fat Mass(FM)-For-age Z-score
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.
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Body Fat(BF)-For-age Z-score
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.
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Anthropometric Measurements
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.
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Growth Rate
Weight gain in g/kg/day
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Number of Participants With Postnatal Growth Failure
Diagnosis of growth failure (weight \< 10th percentile using the 2013 Fenton growth curves)
Time frame: 36 weeks or hospital discharge (whichever occurred first)
Number of Participants With Diagnosis of Necrotizing Enterocolitis
Diagnosis of necrotizing enterocolitis stage 2 or 3
Time frame: From birth up to 120 days following birth
Number of Participants With Diagnosis of Intestinal Perforation
Diagnosis of intestinal perforation
Time frame: From birth up to 120 days following birth
Death
Death prior to 121 days of life
Time frame: Birth to 120 days
Culture-proven Sepsis
Diagnosis of sepsis with positive blood cultures
Time frame: Birth to 120 days
Number of Days Alive and Receiving Full Enteral Feeding
Time to full enteral feeding days
Time frame: Birth to 28 days
Number of Episodes of Feeding Intolerance
Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination
Time frame: Birth to 28 days
Duration of Hospital Stay in Days
From day of admission to day of hospital discharge to home
Time frame: Birth to 120 days or discharge, whichever occurs first
Serum BUN
Highest serum BUN value in the first 28 days after birth
Time frame: Birth to 28 days
Changes in Intestinal Microbiome
Determined by molecular analyses of fecal samples
Time frame: Birth to 36 weeks postmenstrual age
Cognitive Outcomes
Determined by Bayley assessment
Time frame: 2 years of corrected age
| Milestone | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Started | 75 | 75 |
| Completed | 52 | 53 |
| Not completed | 23 | 22 |
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.
| Z-score | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Fat-free Mass(FFM)-For-age Z-score | -1.7 ± 1.4 | -1.6 ± 1.5 |
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.
| Z-score | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Fat Mass(FM)-For-age Z-score | 1.0 ± 1.1 | 1.3 ± 1.2 |
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.
| Z-score | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Body Fat(BF)-For-age Z-score | 1.8 ± 1 | 1.9 ± 1.2 |
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.
| Z-score | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Weight | -1.0 ± 0.7 | -1.2 ± 0.8 |
| Length | -1.5 ± 1.0 | -1.9 ± 1.3 |
| Head circumference | -0.9 ± 0.8 | -1.3 ± 1.1 |
Weight gain in g/kg/day
| g/kg/day | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Growth Rate | 14.7 ± 2.5 | 13.9 ± 2.5 |
Diagnosis of growth failure (weight \< 10th percentile using the 2013 Fenton growth curves)
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Number of Participants With Postnatal Growth Failure | 31 | 30 |
Diagnosis of necrotizing enterocolitis stage 2 or 3
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Number of Participants With Diagnosis of Necrotizing Enterocolitis | 1 | 3 |
Diagnosis of intestinal perforation
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Number of Participants With Diagnosis of Intestinal Perforation | 5 | 4 |
Death prior to 121 days of life
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Death | 6 | 5 |
Diagnosis of sepsis with positive blood cultures
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Culture-proven Sepsis | 22 | 16 |
Time to full enteral feeding days
| days | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Number of Days Alive and Receiving Full Enteral Feeding | 18 (11 to 21) | 14 (5 to 18) |
Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination
| Participants | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Number of Episodes of Feeding Intolerance | 0 | 0 |
From day of admission to day of hospital discharge to home
| days | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Duration of Hospital Stay in Days | 107 (87 to 120) | 107 (79 to 120) |
Highest serum BUN value in the first 28 days after birth
| mg/dL | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Serum BUN | 33 ± 24 | 37 ± 31 |
Determined by molecular analyses of fecal samples
Results for this outcome have not been posted.
Determined by Bayley assessment
Results for this outcome have not been posted.
Collected over From birth up to 120 days following birth. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Protein-enriched Human Milk Diet | 6/75 (8%) | 6/75 (8%) | 31/75 (41.3%) |
| Usual Human Milk Diet | 5/75 (6.7%) | 4/75 (5.3%) | 30/75 (40%) |
| Event | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Spontaneous intestinal perforationGastrointestinal disorders | 5/75 | 4/75 |
| Necrotizing enterocolitisGastrointestinal disorders | 1/75 | 3/75 |
| Event | Protein-enriched Human Milk Diet | Usual Human Milk Diet |
|---|---|---|
| Growth failureGeneral disorders | 31/75 | 30/75 |
| Age, Continuous(weeks of gestation) | Protein-enriched Human Milk Diet | Usual Human Milk Diet | Total |
|---|---|---|---|
| Median | 26 (24 to 27) | 26 (24 to 27) | 26 (24 to 27) |
| Sex: Female, Male(Participants) | Protein-enriched Human Milk Diet | Usual Human Milk Diet | Total |
|---|---|---|---|
| Female | 43 | 29 | 72 |
| Male | 32 | 46 | 78 |
| Ethnicity (NIH/OMB)(Participants) | Protein-enriched Human Milk Diet | Usual Human Milk Diet | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 7 | 12 |
| Not Hispanic or Latino | 70 | 68 | 138 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Protein-enriched Human Milk Diet | Usual Human Milk Diet | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 1 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 45 | 38 | 83 |
| White | 29 | 36 | 65 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Protein-enriched Human Milk Diet | Usual Human Milk Diet | Total |
|---|---|---|---|
| United States | 75 | 75 | 150 |
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