Bovine Colostrum to Fortify Human Milk for Preterm Infants A Randomized, Controlled Pilot Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Growth
- Sponsor
- Per Torp Sangild
- Enrollment
- 252
- Locations
- 7
- Primary Endpoint
- Body weight
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Very preterm infants (<32 weeks gestation) with very low birth weight (VLBW, <1500 g) show immaturity of organs and have high nutrient requirements forgrowth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). A fast transition to full EN is important to improve gut maturation and reduce the high risk of late-onset sepsis (LOS), related to their immature immunity in gut and blood. Conversely, too fast increase of EN predisposes to feeding intolerance and necrotizing enterocolitis (NEC). Further, human milk feeding is not sufficient to support nutrient requirements for growth of VLBW infants. Thus, it remains a difficult task to optimize EN transition, achieve adequate nutrient intake and growth, and minimize NEC and LOS in the postnatal period of VLBW infants.
Mother´s own milk (MM) is considered the best source of EN for VLBW infants and pasteurized human donor milk (DM) is the second choice, if MM is absent or not sufficient. The recommended protein intake is 4-4.5 g/kg/d for VLBW infants, when the target is a postnatal growth similar to intrauterine growth rates. This amount of protein cannot be met by feeding only MM or DM. Thus, it is common practice to enrich human milk with human milk fortifiers (HMFs, based on ingredients used in infant formulas) to increase growth, bone mineralization and neurodevelopment, starting from 7-14 d after birth and 80-160 ml/kg feeding volume per day. Bovine colostrum (BC) is the first milk from cows after parturition and is rich in protein (80-150 g/L) and bioactive components. These components may improve gut maturation, NEC protection and nutrient assimilation, even across species. Studies in preterm pigs show that feeding BC alone, or DM fortified with BC, improves growth, gut maturation and NEC resistance during the first 1-2 weeks, relative to DM, or DM fortified with conventional HMFs.On this background, we hypothesize that BC, used as a fortifier for MM or DM, can induce similar growth and better NEC and LOS resistance, than conventional fortifiers. A pilot trial is required 1) to test the feasibility and initial safety of BC as a fortifier (e.g. similar growth rates and clinical variables as conventional fortification), 2) to calculate the sample size for a later, larger RCT with NEC +LOS as the primary outcome, and 3) record paraclinical outcomes associated with type of fortifier.
Detailed Description
The main objectives of this multicentre, non-blinded, pilot, RCT are: 1. To investigate the safety, tolerability and the preliminary effects of BC, used as an HMF for MM and DM in very preterm infants. 2. To facilitate the determination of sample size for a later, larger RCT with NEC- and LOS-free survival as the primary outcome. 3. To assess the feasibility of study procedures, incl. recruitment rates, parental consent, adherence, sample collection, and clinical routines. Participants Parents to eligible very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Children's Hospital in Shenzen, China will be asked for participation. Since this is a pilot trial, a conventional sample size calculation, using only one primary outcome, is not required. The aim is to include 200 infants (100 per group), which is expected to give sufficient strength to demonstrate effects on the chosen feasibility outcomes and secondary blood and stool variables (see protocol). Statistical analyses will be performed blindly on both intention-to-treat and per protocol basis. Continuous outcomes will be summarized as mean and standard deviation (e.g., body weight) or median and interquartile range (e.g. time to reach full enteral feeding). Binary outcomes (e.g. incidence of NEC) will be presented as counts and percentages. To test the preliminary effects of BC, clinical and para-clinical outcomes will be compared between the two groups. The estimates will be presented as relative risk and absolute risk difference, difference between means, or hazard ratio, depending on the type of outcome. The estimates will be presented with a 95% confidence interval. Further statistical analyses are described in the protocol.
Investigators
Per Torp Sangild
Professor
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Body weight
Time Frame: From start of intervention to hospital discharge, or up to 14 weeks
Weight gain in grams from birth to discharge from hospital. Weight at different time points will be calculated into z-scores according to a reference. Delta z-scores will be used to evaluate growth and for comparison between groups.
Incidence of necrotizing entercolitis (NEC)
Time Frame: From start of intervention to hospital discharge, or up to 14 weeks
Number of infants in each group diagnosed with necrotizing enterocolitis (NEC) defined as Bell's stage II or above (Kliegman \& Walsh 1987).
Incidence of late-onset sepsis (LOS)
Time Frame: From start of intervention to hospital discharge, or up to 14 weeks
Number of infants in each group diagnosed with late-onset sepsis defined as clinical signs of infection \>2 days after birth with antibiotic treatment for ≥5 days (or shorter than 5 days if the participant died) with or without one positive bacterial culture in blood or cerebral spinal fluid (CSF).
Secondary Outcomes
- Feeding intolerence(From start of intervention to end of study period at post menstrual age 34+6 weeks, or up to 8 weeks)
- Time to reach full enteral feeding(From birth to full enteral feeding, or up to 8 weeks)
- Days on parenteral nutrition(From birth to end of intervention, or up to 8 weeks)
- Length of hospital stay(From birth until until final discharge, or up to 14 weeks)
- Blood urea nitrogen (BUN)(Weekly from just before to end of intervention at postmenstrual age 34+6 weeks, or up to 8 weeks)
- Blood minerals(Weekly from just before to end of intervention at postmenstrual age 34+6 weeks, or up to 8 weeks)
- Blood haemoglobin(Weekly from just before to end of intervention at postmenstrual age 34+6 weeks, or up to 8 weeks)