Bovine Colostrum as a Human Milk Fortifier for Preterm Infants

Not Applicable

Completed

• Conditions: Postnatal Growth; Necrotizing Enterocolitis; Feeding Intolerance; Late-Onset Neonatal Sepsis
• Interventions: Dietary Supplement: Bovine Colostrum; Dietary Supplement: FM85

• Registration Number: NCT03822104
• Lead Sponsor: Per Torp Sangild

Brief Summary

Very preterm infants (\<32 weeks gestation) show the immaturity of organs and have high nutrient requirements for growth 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 very preterm 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 very preterm infants. Mother´s own milk (MM) is considered the best source of EN for very preterm 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 very low birth 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, the investigators hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers.

Detailed Description

Objectives

1. To test if fortification of human milk with BC reduces feeding intolerance compared with currently used HMF.

2. To verify the safety and tolerability of BC fortification and to monitor the rates of growth, NEC and sepsis, as investigated in a parallel trial in Denmark

Trial design This study is a dual-center, non-blinded, two-armed, randomized, controlled trial.

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 Shenzhen, China will be asked for participation.

Sample size 68 infants per group, 136 in total

Data type Clinical data

A parallel trial on BC used as human milk fortifier is conducting in Denmark (NCT03537365)

Study Timeline

• Study First Submitted: 2019-01-17
• Study First Submitted QC: 2019-01-28
• Study First Posted: 2019-01-30
• Study Start: 2019-05-01
• Primary Completion: 2021-06-13
• Study Completion: 2021-07-08
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-13
• Last Update Posted: 2022-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 139

Inclusion Criteria

1. Very preterm infants born between gestational age 26 + 0 and 30 + 6 weeks (from the first day of the mother's last menstrual period and/or based on fetal ultrasound)
2. DM is given at the unit when MM is absent (or insufficient in amount)
3. Infants judged by the attending physician to be in need of nutrient fortification, as added in the form of HMF to MM and/or DM
4. Signed parental consent

Exclusion Criteria

1. Major congenital anomalies and birth defects
2. Infants who have had gastrointestinal surgery prior to randomization
3. Infants who have received IF prior to randomization

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bovine Colostrum / intervention group	Bovine Colostrum	Preterm infants are supplemented with bovine colostrum (BC) as a fortifier to human milk. BC is the first milk from cows after parturition and is a rich source of protein (80-150 g/L) and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and growth factors. The product is supplied in a sterile, powdered form and consists of unmodified, intact BC.
FM85 / control group	FM85	Preterm infants are supplemented with PreNAN FM85 as fortifier to human milk. PreNAN FM85 contains partially hydrolyzed protein and maltodextrin including vitamins and minerals. The product is supplied in a powdered form.

Primary Outcome Measures

Name	Time	Method
Incidence of feeding intolerance	From start of intervention until the infants reach PMA 35+6 weeks or are not in need of fortification due to sufficient growth, whichever comes first	Number of infants in each group diagnosed with feeding intolerance for at least once. Feeding intolerance is defined as any pause of fortification or withhold of enteral feeding.

Secondary Outcome Measures

Name	Time	Method
Time to reach full enteral feeding	From birth to hospital discharge, or up to 14 weeks	Number of days to full enteral feeding is reached - defined as the time when \>150 ml/kg/d is reached and parenteral nutrition has been discontinued
Days on parenteral nutrition	From birth to hospital discharge, or up to 14 weeks	Number of days that the infant receives intravenous intakes of protein and/or lipid and/or glucose
Length of hospital stay	From birth to hospital discharge, or up to 14 weeks	Number of days in hospital, defined as days from birth until final discharge
Body weight	Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks	Weight gain in grams per kg body weight from birth to discharge. 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.
Body length	Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks	Recorded as a measure of growth in cm by standardized measuring procedures
Head circumference	Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks	Recorded as a measure of head growth in cm by standardized measuring procedures
Incidence of necrotizing entercolitis (NEC)	From the 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)	From the 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)

Trial Locations

Locations (2)

Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH); 🇨🇳 Shenzhen, Guangdong, China

Shenzhen Nanshan People's Hospital; 🇨🇳 Shenzhen, China