Clinical trial NCT02054091: Feeding Bovine Colostrum to Preterm Infants
Official title: Bovine Colostrum as Nutrition for Preterm Infants in the First Days of Life: A Pilot Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Feeding Intolerance
Extrauterine Growth Retardation
Necrotizing Enterocolitis
Sepsis
Meningitis
Keywords: Preterm infants
Bovine colostrum
Feeding intolerance
Postnatal growth
Intestinal maturation
Necrotizing enterocolitis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2014-02-04
Enrollment: 52
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single group for first 12 infants RCT for next 40 infants
Primary purpose: SUPPORTIVE_CARE

Brief summary: Feeding preterm infants is of great challenge in the NICUs. Mother's own milk is considered as the best for the digestive system followed by donor milk. Preterm infant formula is related to more feeding problems and other gut complications in these babies, such as necrotizing enterocolitis. Bovine colostrum contains higher amounts of protein, growth factors and immuno-regulatory components (e.g. immunoglobulins), which has been used in many other situations to promote health. The investigators plan to give bovine colostrum to preterm infants with birth weights between 1000 and 1800 g, or born between 27+0 and 32+6 weeks of gestational age, in order to promote feeding and intestinal health in these babies. This current study is a feasibility pilot study and the investigators hypothesized that supplementing BC to MM (if available) is safe and tolerable when used within the first 10-14 days of life in preterm infants.

Detailed description: Preterm birth (\<37 weeks gestation) occurs in 10% of all pregnancies worldwide and the optimal way to feed a newborn preterm infant, when breast-feeding is impossible, is not clear. Excessive enteral feeding predisposes to various complications and necrotizing enterocolitis (NEC) that occur in 7% of preterm infants born with less than 1500 g body weight. Early feeding with small volumes of milk is applied to promote GIT maturation and add some nutrients and energy. It is assumed that early feeding allows more rapid advancement to full enteral feeding (EN, e.g 120-160 ml/kg/d) and weaning from parenteral nutrition (PN). This is important to reduce PN-related complications (e.g. sepsis) and to better stimulate body and organ (e.g. gut, brain) development. However, it remains unclear what is the best milk diet when mother's own milk (MM) is not available. Infant formula (IF) and banked human donor milk (DM) are the most frequently used alternatives to MM. MM is superior to IF in promoting feeding tolerance, intestinal function, and NEC resistance in preterm infants. Feeding with DM is also believed to be beneficial, relative to IF, although this pasteurized milk obtained from mothers later in lactation may be less beneficial, relative to the first milk, colostrum. There are differences in the amount and composition between human colostrum and bovine colostrum (BC), but relative to mature human milk, BC contains higher amounts of protein, growth factors and immuno-regulatory components (e.g. immunoglobulins). Large amount of protein in BC provides higher enteral protein intake and may enable a reduction in the use of PN and central venous catheters, and hereby reduced risk of infection. Also this may lead to reduced weight loss and improved growth of the brain and the body. In addition, maturational and NEC-protective effects of BC have repeatedly been documented in preterm pigs when BC is used as the first diet after birth. The investigators therefore plan to investigate whether using BC as nutrition for preterm infants in the first weeks of life is safe, tolerable, and helps to provide nutrients and gut maturation , when MM is not in sufficient amounts or not available.

Eligibility criteria: Inclusion Criteria:

* FWCH \& SBMCH: Preterm infants with birth weights between 1000 and 1800 g, delivered at FWCH \& SBMCH, or transferred from other hospitals within 24 h of birth and without any enteral feeding.

RH \& HH: Preterm infants less than 24 hours of age, between 27+0 and 32+6 weeks of gestation, delivered at RH \&HH , or transferred from other hospitals within the first 24 h after birth.

* Signed parental consent

Exclusion Criteria:

* Major congenital anomalies or birth defects
* Congenital infection
* Perinatal asphyxia
* Gestational age at birth \< 28 weeks (FWCH \& SBMCH)
* Extremely SGA infant (weight SD score \< -3 SD)
* Need for mechanical ventilation or cardiovascular support before first BC feeding

Primary outcomes:
measure: The primary outcome is the tolerability of bovine colostrum feeding
timeFrame: From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Secondary outcomes:
measure: Anthropometry data
timeFrame: Weekly measured from birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
measure: Days to regain birth weight
timeFrame: From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
measure: Days on parenteral nutrition
timeFrame: From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
measure: Time to full enteral feeding
timeFrame: From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
measure: Combined incidence of serious infections and NEC
timeFrame: From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
measure: Plasma citrulline level
timeFrame: On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
measure: Lactase activity and intestinal permeability
timeFrame: On day 7±1
Other outcomes:
measure: Routine blood tests
timeFrame: On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
measure: Plasma amino acid composition
timeFrame: On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
measure: Plasma bovine IgG level
timeFrame: On day 7±1 at RH for phase A and B
measure: Fecal bovine IgG
timeFrame: On day 7±1 at RH & HH and day 7±1 and 14±1 days
measure: Fecal short chain fatty acids (SCFAs)
timeFrame: On day 7±1 at RH & HH and day 7±1 and 14±1 days
measure: Fecal microbiota composition
timeFrame: On day 7±1 at RH & HH and day 7±1 and 14±1 days
Locations:
city: Foshan
country: China
facility: Foshan Women and Children's Hospital (FWCH)
state: Guangdong
city: Shenzhen
country: China
facility: Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH)
state: Guangdong
city: Copenhagen
country: Denmark
facility: Rigshospitalet (RH)
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital (HH)
Study officials:
affiliation: +45 35 33 26 98
name: Per T. Sangild, PhD
role: STUDY_DIRECTOR
References: