Clinical trial NCT03822104: Bovine Colostrum as a Human Milk Fortifier for Preterm Infants
Official title: Bovine Colostrum to Fortify Human Milk for Preterm Infants: A Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Feeding Intolerance
Necrotizing Enterocolitis
Postnatal Growth
Late-Onset Neonatal Sepsis
Keywords: Very Preterm Infants
Human Milk Fortifier
Bovine Colostrum
Enteral Feeding
Nutrition
Human milk
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2019-01-30
Enrollment: 139
Sex: ALL
Minimum age (years): 5
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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)

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of feeding intolerance
timeFrame: 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
Secondary outcomes:
measure: Body weight
timeFrame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
measure: Body length
timeFrame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
measure: Head circumference
timeFrame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
measure: Incidence of necrotizing entercolitis (NEC)
timeFrame: From the start of intervention to hospital discharge, or up to 14 weeks
measure: Incidence of late-onset sepsis (LOS)
timeFrame: From the start of intervention to hospital discharge, or up to 14 weeks
measure: Time to reach full enteral feeding
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Days on parenteral nutrition
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Length of hospital stay
timeFrame: From birth to hospital discharge, or up to 14 weeks
Other outcomes:
measure: Volume of gastric residual
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Color of gastric residual
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Incidence of bloody gastric residual
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Frequency of stool per day
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Amount of the stool
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Color of the stool
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Consistency of the stool
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Total daily volume of enteral nutrition (EN) and parenteral nutrition (PN)
timeFrame: From birth to hospital discharge, or up to 14 weeks
measure: Levels of macronutrients intake from EN and PN
timeFrame: From birth to hospital discharge, or up to 14 weeks
Locations:
city: Shenzhen
country: China
facility: Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH)
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Nanshan People's Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Per T Sangild
role: STUDY_CHAIR
affiliation: Shenzheng Baoan Maternity and Child Healthcare Hospital
name: Ping Zhou
role: PRINCIPAL_INVESTIGATOR
References: