Clinical trial NCT03839173: Growth and Nutritional Status of Very Low Birth Weight Infants Fed a High Protein Exclusive Human Milk Diet
Official title: Growth and Nutritional Status of Very Low Birth Weight Infants Fed a High Protein Exclusive Human Milk Diet
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Premature Infant
Breast Milk Expression
Keywords: premature infant
breast milk
breastmilk
human milk
human milk fortifier
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: Neolac Inc dba Medolac Laboratories
First posted: 2019-02-15
Enrollment: 51
Sex: ALL
Minimum age (years): 23
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Return to birth weight day
timeFrame: birth to 30 days
measure: Growth Velocity
timeFrame: Weekly until 36 weeks post menstrual age or discharge
measure: Mean Serum Magnesium
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean Serum CO2
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
Secondary outcomes:
measure: Mean z-scores
timeFrame: Weekly until 36 weeks post menstrual age or discharge
measure: Mean serum Vitamin D, 1 25 (OH) 2D
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum parathyroid Hormone (PTH)
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Sodium
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Blood Urea Nitrogen (BUN)
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Calcium
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Phosphorus
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Alkaline Phosphatase
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Hemoglobin
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Potassium
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
measure: Mean serum Hematocrit
timeFrame: Every 14 days until 36 weeks post menstrual age or discharge
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta University
state: Georgia
Study officials:
affiliation: Augusta University
name: Amy Gates, RD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1542/peds.2005-1368.
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.
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.
citation: Koletsko B PB, Uauy R. Nutritional Care of Preterm Infants. Basel, Switzerland: Karger, 2014.
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.
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.
citation: 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.
citation: Gates A BJ. [Neonatal Outcomes Augusta Univeristy NICU] Unpublished raw data. Augusta 2017.
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, 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.
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.
citation: 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.
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.
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. doi: 10.1056/NEJM198302033080501.
citation: 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.
citation: 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.
citation: 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.
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.