Growth and Nutritional Status of Very Low Birth Weight Infants Fed a High Protein Exclusive Human Milk Diet

Study Overview
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Brief Summary
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The purpose of this two-arm investigation is to determine if growth patterns of very low birth weight infants (VLBW) (birth weight 750-1500 grams) fed human milk (maternal or donor) supplemented with a human milk-based fortifier grow according to established guidelines and maintain adequate micronutrient levels.

Detailed Description
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To achieve this goal, the investigators will prospectively analyze the growth and micronutrient status of VLBW infants who are fed human milk (maternal or donor) supplemented with a human-milk-based fortifier with increased protein (Medolac® Human Milk Fortifier). In addition, the investigators will compare the findings to retrospectively collected data for growth rates and micronutrient status of infants who received human milk fortified with cow's milk -based fortifier (Enfamil® Hydrolyzed Liquid Human Milk Fortifier). The investigators hypothesize that a human milk-based fortifier with increased protein will support growth at recommended levels (weight gain of 12-18 g/kg/day, head circumference 0.75-1.0 cm/week, length 0.8-1.1 cm/week)[1-3] and prevent micronutrient deficiency in the VLBW infant Aim 1: To determine if VLBW infants fed human milk, maternal or donor, supplemented with a human milk-based fortifier with increased protein grow at recommended levels for weight, length, and head circumference. To achieve this aim, Z-scores for weight, length, and head circumference will be tracked. Measurements will be taken at birth and then weekly until 36 weeks post-menstrual age (PMA) or discharge from the neonatal intensive care unit (NICU), whichever comes first. Aim 2: To measure nutritional status in VLBW premature infants fed human milk supplemented with a human milk-based fortifier with increased protein. To achieve this aim, serum magnesium, potassium, chloride, blood urea nitrogen (BUN), creatinine, sodium, calcium, phosphorus, CO2, Vitamin D 1, 25 (OH) 2D, parathyroid hormone (PTH), alkaline phosphatase, hemoglobin, hematocrit will be measured within 24 hours of reaching full enteral feedings and repeated seven days later, and then every fourteen days until 36 weeks PMA or discharge, whichever comes first. Urine magnesium and sodium will be measured on the same schedule. Aim 3: To compare growth rates and nutritional status of VLBW infants fed human milk fortified with a human milk-based fortifier to growth rates and nutritional status of those fed human milk fortified with a cow's milk-based fortifier.

Official Title
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Growth and Nutritional Status of Very Low Birth Weight Infants Fed a High Protein Exclusive Human Milk Diet

Conditions
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Premature Infant, Breast Milk Expression

Intervention / Treatment
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* Other: Human milk based human milk fortifier


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birth weight 750-1800 grams Admitted to AU NICU within 24 hours of life Estimated gestational age (EGA) 23 to 33 weeks as confirmed by the Ballard score Birth weight appropriate for gestational age (AGA) defined as >3rd% on a gender-specific Fenton growth curve (Fenton 2013, Calgary, Canada) Enteral feedings initiated within 7 days of life Breastmilk diet, maternal or donor milk Exclusion Criteria: Renal conditions affecting electrolyte metabolism and/or excretion Gastro-intestinal conditions that preclude feeding or affect nutrient absorption (gastroschisis, omphalocele) EGA >33 weeks or birth weight >1800 grams or EGA <23 weeks or birth weight <750 grams Apgar <3 at 5 minutes Grade 3 or higher intraventricular hemorrhage (IVH) Intrauterine growth restriction (IUGR), as defined as <3rd% on a gender-specific Fenton growth curve Congenital anomalies including congenital heart disease or other major defect requiring surgical intervention Intake of cow's milk formula or fortifier before or after the initiation of the study protocol

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 33 Weeks

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Retrospective Chart Review<br>Retrospective Chart Review for historical controls. Historic controls fed cow's milk fortifier | |
| Experimental: Prospective<br>All neonates with birth weights ranging from 750-1500 grams and gestational ages 23-33 weeks admitted to the NICU at Augusta University within 24 hours of life will be eligible for screening within 72 hours of admission and upon parent's or legal guardian's consent. Infants will be fed a human milk fortifier made with donor human milk. Data will be compared with historic control data. | Other: Human milk based human milk fortifier<br>* A human milk fortifier with added minerals made from donor human milk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return to birth weight day | Day of life infant returns to birth weight | birth to 30 days | 
| Growth Velocity | rate of weight gain measured as g/kg/day | Weekly until 36 weeks post menstrual age or discharge | 
| Mean Serum Magnesium | Serum and urine Magnesium | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean Serum CO2 | Serum CO2 | Every 14 days until 36 weeks post menstrual age or discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean z-scores | z-scores for weight, length, and head circumference | Weekly until 36 weeks post menstrual age or discharge | 
| Mean serum Vitamin D, 1 25 (OH) 2D | serum Vitamin D | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum parathyroid Hormone (PTH) | Serum PTH | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Sodium | Serum and urine Sodium | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Blood Urea Nitrogen (BUN) | serum BUN | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Calcium | serum Calcium | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Phosphorus | serum Phosphorus | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Alkaline Phosphatase | serum Alkaline Phosphatase | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Hemoglobin | serum Hemoglobin | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Potassium | serum and urine Potassium | Every 14 days until 36 weeks post menstrual age or discharge | 
| Mean serum Hematocrit | serum Hematocrit | Every 14 days until 36 weeks post menstrual age or discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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premature infant, breast milk, breastmilk, human milk, human milk fortifier