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

Premature Infant Clinical Trial

— MedolacHMF  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03839173
• Other study ID #: 1147989-3
• Status: Enrolling by invitation
• Phase: N/A
• Start date: July 25, 2019
• Est. completion date: March 31, 2020

Study information

• Verified date: July 2019
• Source: Augusta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 51
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 33 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Breast Milk Expression
• Premature Infant

Intervention

Other:
• Human milk based human milk fortifier
A human milk fortifier with added minerals made from donor human milk

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Augusta University	Neolac Inc dba Medolac Laboratories

Country where clinical trial is conducted

United States, 

References & Publications (17)

Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellöf 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Gates A BJ. [Neonatal Outcomes Augusta Univeristy NICU] Unpublished raw data. Augusta 2017.

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. — View Citation

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. — View Citation

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. — View Citation

Koletsko B PB, Uauy R. Nutritional Care of Preterm Infants. Basel, Switzerland: Karger, 2014.

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. — View Citation

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. — View Citation

Ong KK, Kennedy K, Castañeda-Gutiérrez 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. Review. — View Citation

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. Review. — View Citation

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, Sánchez 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. — View Citation

Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawöger 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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Return to birth weight day	Day of life infant returns to birth weight	birth to 30 days
Primary	Growth Velocity	rate of weight gain measured as g/kg/day	Weekly until 36 weeks post menstrual age or discharge
Primary	Mean Serum Magnesium	Serum and urine Magnesium	Every 14 days until 36 weeks post menstrual age or discharge
Primary	Mean Serum CO2	Serum CO2	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean z-scores	z-scores for weight, length, and head circumference	Weekly until 36 weeks post menstrual age or discharge
Secondary	Mean serum Vitamin D, 1 25 (OH) 2D	serum Vitamin D	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum parathyroid Hormone (PTH)	Serum PTH	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Sodium	Serum and urine Sodium	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Blood Urea Nitrogen (BUN)	serum BUN	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Calcium	serum Calcium	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Phosphorus	serum Phosphorus	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Alkaline Phosphatase	serum Alkaline Phosphatase	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Hemoglobin	serum Hemoglobin	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Potassium	serum and urine Potassium	Every 14 days until 36 weeks post menstrual age or discharge
Secondary	Mean serum Hematocrit	serum Hematocrit	Every 14 days until 36 weeks post menstrual age or discharge