Feeding Bovine Colostrum to Preterm Infants (PreColos)

Bovine Colostrum as Nutrition for Preterm Infants in the First Days of Life: A Pilot Feasibility Study

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Necrotizing Enterocolitis; Meningitis; Feeding Intolerance; Extrauterine Growth Retardation
• Intervention / Treatment: Dietary supplement: Bovine colostrum

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Foshan Women and Children's Hospital (FWCH)
    • Shenzhen, Guangdong, China, 518133
      • Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH)
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet (RH)
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital (HH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Infants are fed according to the standard feeding practices at each hospital. At FWCH & SBMCH babies are fed infant formula supplemented to mother's own milk (if avaible), and at RH, babies are fed donor milk supplemented to Mother'w own milk (if avaible).
Experimental: Colostrum group; Infants are fed bovine colostrum supplemented to mother's own milk (if avaible) for max. 10 days at RH and 14 days at FWCH & SBMCH.	Dietary supplement: Bovine colostrum; The BC powder to be used in this study is donated from a Danish company, Biofiber Damino. The raw colostrum used for production is collected within 1-2 milking from healthy Danish dairy cows (Danish Holstein). Antibiotic residues are screened upon collection and those tested positive are not used for production. Intact colostrum is pasteurized, low temperature spray-dried, and sterilized by γ-irradiation.; Other Names: Cow's colostrum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is the tolerability of bovine colostrum feeding	The main purpose of this feasibility pilot study is to investigate whether preterm infants can tolerate bovine colostrum as their first nutrition supplemented to mother's own milk (if available). Presence of feeding intolerance is defined as at any time when feeding is withheld by the neonatologists from day 1-7 and from day 8-14.	From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometry data	Body weight, body length, and head circumference are measured as anthropometry data	Weekly measured from birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Days to regain birth weight		From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Days on parenteral nutrition	Days on PN are the total number of days that a participant receiving any i.v. nutrients other than glucose.	From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Time to full enteral feeding	Full enteral feeding is defined as participants receiving 160ml/kg/d at copenhagen site, or more than 120 ml/kg/d at Chinese sites for a consecutive period of 72 hours.	From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Combined incidence of serious infections and NEC	Serious infections/NEC includes sepsis and meningitis, according the diagnostic criteria at each hospital, and Bell stage II or III NEC.	From birth until the recruited subject reaches postmenstrual age at 37 weeks or discharge home, whichever comes first
Plasma citrulline level	Citrulline concentration is measured in plasma as a biomarker for absorptive enterocyte mass and/or function	On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
Lactase activity and intestinal permeability	Lactase activity and intestinal permeability is measured non-invasively by measuring the urinary ratio of lactulose/lactose, and lactulose/mannitol after the three sugars are administered.	On day 7±1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Routine blood tests	Routine blood tests include blood gas analysis, liver enzymes, BUN, creatinine, Na, K, and phosphate.	On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
Plasma amino acid composition	Plasma amino acids will be analyzed at each hospital to investigate whether BC feeding provides a normal range of plasma amino acid pattern.	On day 7±1 at RH & HH and on day 7±1 and 14±1 at FWCH & SBMCH
Plasma bovine IgG level	The concentration of intact bovine IgG will be measured in the plasma samples from the participants who receive BC supplementation, in order to investigate how much intact bovine IgG is absorbed from the intestine and circulating in the blood. This will only be measured in the participants at RH due to practical reasons.	On day 7±1 at RH for phase A and B
Fecal bovine IgG	The concentration of intact bovine IgG will be measured in the fecal samples from participants who receive BC supplementation, in order to investigate whether bovine IgG can survive digestion.	On day 7±1 at RH & HH and day 7±1 and 14±1 days
Fecal short chain fatty acids (SCFAs)	Fecal SCFAs will be measured as an indicator of bacterial fermentation of the unabsorbed nutrients in the colon.	On day 7±1 at RH & HH and day 7±1 and 14±1 days
Fecal microbiota composition	Microbiota composition in fecal samples will be determined using non-culture-based techniques	On day 7±1 at RH & HH and day 7±1 and 14±1 days

Collaborators and Investigators

• Sponsor: Per Torp Sangild
• Investigators: Study Director: Per T. Sangild, PhD, +45 35 33 26 98

Publications and helpful links

Helpful Links

• The current clinical trial is a part of the NEOMUNE project.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: January 21, 2014
• First Submitted That Met QC Criteria: February 2, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Preterm infants; Bovine colostrum; Feeding intolerance; Postnatal growth; Intestinal maturation; Necrotizing enterocolitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing; Meningitis
• Other Study ID Numbers: H-3-2013-136

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No