Noninferiority Trial of Liquid Human Milk Fortifier (HMF) Hydrolyzed Protein Versus Liquid HMF With Supplemental Liquid Protein

Premature Birth of Newborn Clinical Trial

Official title:

Extensively Hydrolyzed Liquid Human Milk Fortifier Versus Liquid Human Milk Fortifier With Supplemental Liquid Protein

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03001479
• Other study ID #: 27563
• Status: Completed
• Phase: N/A
• Start date: March 13, 2017
• Est. completion date: May 1, 2023

Study information

• Verified date: May 2023
• Source: St. Louis University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Breast milk is readily accepted as the ideal source of nutrition for almost all infants, including premature or very low birth weight infants. However, these high-risk infants require the addition of fortifiers to their milk in order to achieve sufficient levels of calories, vitamins, and minerals for adequate growth. We are currently using a liquid human milk fortifier which does not provide sufficient protein intake, requiring addition of a liquid protein supplement. A new product has been released which provides sufficient protein in the liquid HMF, without the acidification seen in previous products.

This is a prospective, randomized noninferiority study comparing the safety and efficacy of the new HMF with additional protein to our current standard of adding additional protein supplementation on top of the HMF.

Description:

All infants admitted to the Neonatal Intensive Care Unit (NICU) at Cardinal Glennon at gestational age <32 weeks and birthweight <1500g, and whose mothers intend to use breast milk (maternal or donor) will be approached for study participation. Infants can be enrolled at any point up until their feedings become fortified, typically around the 8th day of life.

Eligible infants whose parents consent for participation will be randomized to one of the two study regimens. Sealed envelopes containing the subject treatment group will be prepared from randomization schedules that are computer-generated using a pseudorandom permuted blocks algorithm. Multiples will be randomized together to the same treatment group. The randomization will be block stratified by birth weight (500-1000g and 1001-1500g). Infants will have laboratory values to follow for signs of metabolic acidosis and nutritional status. These labs (BMP, Magnesium, Phosphorous, Alkaline Phosphatase, and prealbumin) will be drawn on study days 1, 15, and 30. Total blood volume for these labs is approximately 1.4 mL, and may be obtained by venipuncture or heel stick. These labs are monitored for nutritional sufficiency in very low birth weight infants already, the only change will be the timing that the labs are obtained.

Infants will remain on their designated HMF until one of 3 different time points: 1) Infant does not tolerate HMF and must be taken off, 2) Infant is no longer receiving breastmilk and is transitioned to a premature formula, or 3) Infant is getting ready to go home and HMF is removed from the feedings.

Hospitalization data will be collected on the infants until they are either discharged from the NICU or until they reach 36 weeks corrected gestational age, whichever occurs first. Data collected will include: birthweight, gestational age, gender, antenatal steroids, APGARs, days of parenteral nutrition, day enteral feedings were initiated, daily enteral volume intake, daily caloric and protein intake, day of HMF and/or liquid protein initiation. Lab data will be recorded as noted above. Growth data will be recorded by daily weights and weekly head circumferences and lengths. Intolerance will be assessed by incidence of feeding intolerance, nil per os (NPO) time, change in diet due to intolerance, incidence of metabolic acidosis, incidence of necrotizing enterocolitis, incidence of spontaneous intestinal perforation, cause of death, and length of hospital stay. Data on NICU complications, including late onset sepsis, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, and use of postnatal steroids (which can affect growth) will also be recorded.

Neurodevelopmental data will be collected on the infants from their first Bayley evaluation in the Nursery Follow-up clinic, usually performed at 15-18 months of age. We will record cognitive, language, and motor scores. We will also collect information on therapy services received, and incidence of blindness or deafness.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Weeks

Eligibility

Inclusion Criteria:

• Very low birth weight, premature infants admitted to the NICU at Cardinal Glennon

• <32 weeks gestational age and birthweight <1500 grams

• receiving maternal or donor breast milk

Exclusion Criteria:

• Infants with an estimated gestational age >32 weeks OR birthweight >1500 grams

• Infants who die before fortification of feedings

• Infants receiving formula

• Infants that did not receive feedings with HMF

• Infants transferred to another hospital prior to discharge

Related Conditions & MeSH terms

• Human Milk
• Premature Birth
• Premature Birth of Newborn

Intervention

Dietary Supplement:
• Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid
HMF with additional hydrolyzed protein

Locations

Country	Name	City	State
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
St. Louis University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight gain, short term	(grams) in first 30 days on HMF	30 days
Primary	Length, short term	(cm) in first 30 days on HMF	30 days
Primary	Head circumference, short term	(cm) in first 30 days on HMF	30 days
Secondary	Weight gain, long term	Weight (grams) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first	36 weeks gestational age or time of hospital discharge
Secondary	Length, long term	Length (cm) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first	36 weeks gestational age or time of hospital discharge
Secondary	Head circumference, long term	Head circumference (cm) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first	36 weeks gestational age or time of hospital discharge
Secondary	feeding intolerance	Signs of feeding intolerance, including loose stools, emesis, metabolic acidosis, necrotizing enterocolitis. Presence or absence of symptoms.	30 days
Secondary	neurodevelopmental outcomes	Bayley Scales of Infant Development III at 18 months of corrected gestational age	18 months corrected gestational age