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

NCT ID: NCT03001479

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-13
• Study Completion Date: 2023-05-01

Brief 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.

Detailed 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.

Conditions

Human Milk; Premature Birth of Newborn

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Standard: Liquid HMF and liquid protein

This is our standard breast milk fortification in our NICU. One packet (5 mL) of Similac Human Milk Fortifier Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. After infants reach full feedings (160 ml/kg/d), 3 ml/kg of Similac Liquid Protein Fortifier is added (0.5 g/kg protein). This is increased to 6 ml/kg (1 g/kg protein) the next day.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention: HMF Hydrolyzed Protein Concentrated Liquid

One packet (5 mL) of Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. Feedings then continue to be advanced to full volume (160 ml/kg/d).

Group Type: EXPERIMENTAL

Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid

Intervention Type: DIETARY_SUPPLEMENT

HMF with additional hydrolyzed protein

Interventions

Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid

HMF with additional hydrolyzed protein

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Maximum Eligible Age: 2 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Louis University

OTHER

Sponsor Role: lead

Responsible Party

Catherine Cibulskis, MD

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Catherine C Cibulskis, MD

Role: PRINCIPAL_INVESTIGATOR

St. Louis University

Locations

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Countries

United States

Other Identifiers

27563

Identifier Type: -

Identifier Source: org_study_id