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

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.

Study Overview

• Status: Unknown
• Conditions: Premature Infant; Breast Milk Expression
• Intervention / Treatment: Other: Human milk based human milk fortifier

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Birth weight 750-1800 grams
2. Admitted to AU NICU within 24 hours of life
3. Estimated gestational age (EGA) 23 to 33 weeks as confirmed by the Ballard score
4. Birth weight appropriate for gestational age (AGA) defined as >3rd% on a gender-specific Fenton growth curve (Fenton 2013, Calgary, Canada)
5. Enteral feedings initiated within 7 days of life
6. Breastmilk diet, maternal or donor milk

Exclusion Criteria:

1. Renal conditions affecting electrolyte metabolism and/or excretion
2. Gastro-intestinal conditions that preclude feeding or affect nutrient absorption (gastroschisis, omphalocele)
3. EGA >33 weeks or birth weight >1800 grams or EGA <23 weeks or birth weight <750 grams
4. Apgar <3 at 5 minutes
5. Grade 3 or higher intraventricular hemorrhage (IVH)
6. Intrauterine growth restriction (IUGR), as defined as <3rd% on a gender-specific Fenton growth curve
7. Congenital anomalies including congenital heart disease or other major defect requiring surgical intervention
8. Intake of cow's milk formula or fortifier before or after the initiation of the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Retrospective Chart Review; Retrospective Chart Review for historical controls. Historic controls fed cow's milk fortifier
Experimental: Prospective; 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; A human milk fortifier with added minerals made from donor human milk

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: Neolac Inc dba Medolac Laboratories
• Investigators: Principal Investigator: Amy Gates, RD, Augusta University

Publications and helpful links

General Publications

• Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sanchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23.
• Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, Chan GM, Blanco CL, Abrams S, Cotten CM, Laroia N, Ehrenkranz RA, Dudell G, Cristofalo EA, Meier P, Lee ML, Rechtman DJ, Lucas A. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010 Apr;156(4):562-7.e1. doi: 10.1016/j.jpeds.2009.10.040. Epub 2009 Dec 29.
• Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, Dudell G, Rechtman DJ, Lee ML, Lucas A, Abrams S. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013 Dec;163(6):1592-1595.e1. doi: 10.1016/j.jpeds.2013.07.011. Epub 2013 Aug 20.
• Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub 2012 Feb 27.
• Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. doi: 10.1186/1471-2431-13-59.
• Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellof M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):85-91. doi: 10.1097/MPG.0b013e3181adaee0.
• Kim JH, Chan G, Schanler R, Groh-Wargo S, Bloom B, Dimmit R, Williams L, Baggs G, Barrett-Reis B. Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier. J Pediatr Gastroenterol Nutr. 2015 Dec;61(6):665-71. doi: 10.1097/MPG.0000000000001010. Erratum In: J Pediatr Gastroenterol Nutr. 2016 Jan;62(1):188-9.
• Kumar N, Monga R, Sampath V, Ehrhart B. Prospective Comparison of Enfamil and Similac Liquid Human Milk Fortifier on Clinical Outcomes in Premature Infants. Am J Perinatol. 2017 Dec;34(14):1411-1416. doi: 10.1055/s-0037-1603940. Epub 2017 Jun 21. No abstract available.
• Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics. 2006 Apr;117(4):1253-61. doi: 10.1542/peds.2005-1368.
• Koletsko B PB, Uauy R. Nutritional Care of Preterm Infants. Basel, Switzerland: Karger, 2014.
• Moya F, Sisk PM, Walsh KR, Berseth CL. A new liquid human milk fortifier and linear growth in preterm infants. Pediatrics. 2012 Oct;130(4):e928-35. doi: 10.1542/peds.2011-3120. Epub 2012 Sep 17.
• Gates A BJ. [Neonatal Outcomes Augusta Univeristy NICU] Unpublished raw data. Augusta 2017.
• Thoene M, Hanson C, Lyden E, Dugick L, Ruybal L, Anderson-Berry A. Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants. Nutrients. 2014 Jan 3;6(1):261-75. doi: 10.3390/nu6010261.
• Gross SJ. Growth and biochemical response of preterm infants fed human milk or modified infant formula. N Engl J Med. 1983 Feb 3;308(5):237-41. doi: 10.1056/NEJM198302033080501.
• Ong KK, Kennedy K, Castaneda-Gutierrez E, Forsyth S, Godfrey KM, Koletzko B, Latulippe ME, Ozanne SE, Rueda R, Schoemaker MH, van der Beek EM, van Buuren S, Fewtrell M. Postnatal growth in preterm infants and later health outcomes: a systematic review. Acta Paediatr. 2015 Oct;104(10):974-86. doi: 10.1111/apa.13128.
• Ghandehari H, Lee ML, Rechtman DJ; H2MF Study Group. An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data. BMC Res Notes. 2012 Apr 25;5:188. doi: 10.1186/1756-0500-5-188.
• Food and Drug Administration, HHS. Current good manufacturing practices, quality control procedures, quality factors, notification requirements, and records and reports, for infant formula. Final rule. Fed Regist. 2014 Jun 10;79(111):33057-72.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 25, 2019
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): March 31, 2020

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: premature infant; breast milk; human milk; breastmilk; human milk fortifier
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 1147989-3

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