Effect of Extensively Hydrolyzed Liquid Human Milk Fortifier on Growth and Tolerance in Moderately Premature Infants

The purpose of this study is for the researchers to examine the safety and efficacy of liquid human milk fortifier (HMF) in moderately preterm infants compared to powdered human milk fortifier.

Study Overview

• Status: Completed
• Conditions: Complication of Prematurity
• Intervention / Treatment: Dietary supplement: Powder HMF; Dietary supplement: Liquid HMF

Detailed Description

This is a prospective, randomize, double-blinded study in preterm infants born between 28-34 weeks gestation admitted to the NICU at the University of Kansas Hospital. After obtaining informed consent, babies will be randomized to either liquid or powdered HMF using opaque, sealed envelopes with preassigned randomization. The feeding protocol as established in the KU NICU will be followed, beginning with initiation of trophic feeds, and advancement of enteral feeds depending on the gestational age and preceding illnesses. Once infants reach 80ml/kg/day of enteral feeds, human milk will be fortified to 22 kilocalories by adding either liquid or powdered fortifier. The beginning of the study(Study day 1) will be defined as reaching and tolerating 100ml/kg/day of 24 kilocalorie human milk fortified with either liquid or powdered fortifier. Enteral feeds will be advanced per unit protocol until they reach 150-160ml/kg/day and 110-120 kcal/kg/day. the volume of feeds will be adjusted based on the documented weight to provide energy and protein requirements as recommended by the ESPGHAN guidelines. Babies will be followed up until the time of NICU discharge.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inborn preterm infants born between 28 0/7 and 34 0/7 weeks gestation and fed either mother's own milk or donor human milk

Exclusion Criteria:

• Newborn infants <28 weeks and >34 weeks gestation, those with life threatening illness, congenital and chromosomal anomalies, gastrointestinal anomalies or necrotizing enterocolitis and fed premature formula

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Powder HMF; Once patient has reached 80ml/kg/day of enteral feedings, 1 pack of powder HMF will be added to 50 ml of human or donor breast milk, then increased to a maximum of 2 packs for 50 ml following the unit feeding advancement protocol and this will be continued up until 48 hours prior to discharge.	Dietary supplement: Powder HMF; powder human milk fortifier
Active Comparator: Liquid HMF; Once patient has reached 80ml/kg/day of enteral feedings, researchers will add 1 packet (5 ml) of liquid HMF to 50 ml of human or donor breast milk, then increase to 2 packs to 50 ml following the unit feeding protocol and this will be continued up until 48 hours prior to discharge.	Dietary supplement: Liquid HMF; Liquid human milk fortifier

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative weight gain	Weight gain of baby during the course of the study	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier
Change in weight	Weight gain of baby week-to-week, during the course of the study	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier
Linear length	change in length week-to-week during the course of the study	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier
Head growth	Change in head measurements week-to-week during the course of the study	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutrition biomarkers	Measurements of a baby's Ca, P, Mg, Alkaline Phosphatase and Prealbumin will be taken	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier
Tolerance to enteral feeds	number of significant residuals, number of times feeds were held, NEC	Baseline to 36 Weeks post-conceptional age or Study Day 28, whichever is earlier

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Vishal Pandey, MD, University of Kansas Medical Center

Publications and helpful links

General Publications

• Hylander MA, Strobino DM, Dhanireddy R. Human milk feedings and infection among very low birth weight infants. Pediatrics. 1998 Sep;102(3):E38. doi: 10.1542/peds.102.3.e38.
• Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet. 1990 Dec 22-29;336(8730):1519-23. doi: 10.1016/0140-6736(90)93304-8.
• Greer FR, McCormick A. Improved bone mineralization and growth in premature infants fed fortified own mother's milk. J Pediatr. 1988 Jun;112(6):961-9. doi: 10.1016/s0022-3476(88)80227-0. Erratum In: J Pediatr 1988 Dec;113(6):1118.
• Cibulskis CC, Armbrecht ES. Association of metabolic acidosis with bovine milk-based human milk fortifiers. J Perinatol. 2015 Feb;35(2):115-9. doi: 10.1038/jp.2014.143. Epub 2014 Aug 7.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 11, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: nutrition; growth; prematurity; human milk fortifier
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: STUDY00002292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED