Bovine Colostrum as a Human Milk Fortifier for Preterm Infants

NCT03822104 | Completed DMC

• 1 other identifier: FortiColos-CN
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of feeding intolerance

  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.

  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 (8)

• Body weight

  Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks

• Body length

  Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks

• Head circumference

  Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks

• Incidence of necrotizing entercolitis (NEC)

  From the start of intervention to hospital discharge, or up to 14 weeks

• Incidence of late-onset sepsis (LOS)

  From the start of intervention to hospital discharge, or up to 14 weeks

Other Outcomes (9)

• Volume of gastric residual

  From birth to hospital discharge, or up to 14 weeks

• Color of gastric residual

  From birth to hospital discharge, or up to 14 weeks

• Incidence of bloody gastric residual

  From birth to hospital discharge, or up to 14 weeks

Study Arms (2)

Bovine Colostrum / intervention group

EXPERIMENTAL

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.

Dietary Supplement: Bovine Colostrum

FM85 / control group

ACTIVE COMPARATOR

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.

Dietary Supplement: FM85

Interventions

Bovine Colostrum DIETARY_SUPPLEMENT

Infants randomized to the intervention group will receive a maximum of 2.8 g bovine colostrum (BC, Biofiber, Gesten, Denmark), as the HMF added to 100 ml of MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants start with 1 g (0.5 g protein) BC per 100 ml human milk on the first day, increased to 2 g (1.0 g protein) on day 3, and finally 2.8 g (1.4 g protein) on day 5 if the infants only receive DM. The intervention lasts until the infants reach postmenstrual age (PMA) 35+6 weeks or in no-need of fortification due to sufficient growth, whichever comes first.

Bovine Colostrum / intervention group

FM85 DIETARY_SUPPLEMENT

Infants randomized to the control group will receive a maximum of 4 g PreNAN FM85 (Nestlé, Vevey, Switzerland) as HMF, added to 100 ml MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants starts with 1 g (0.35 g protein) FM85 per 100 ml human milk on the first day, which will be increased to 3 g (1.05 g protein) on day 3 and finally 4 g (1.4 g protein) on day 5, if the infants only receive DM. The infants will receive FM85 as the HMF as long as additional protein in the milk is needed until discharge.

FM85 / control group

Eligibility Criteria

• Age: 5 Days - 3 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)
• DM is given at the unit when MM is absent (or insufficient in amount)
• 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
• Signed parental consent

You may not qualify if:

• Major congenital anomalies and birth defects
• Infants who have had gastrointestinal surgery prior to randomization
• Infants who have received IF prior to randomization

Sponsors & Collaborators

• Per Torp Sangild: lead

Study Sites (2)

Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH)

Shenzhen, Guangdong, 518133, China

Location

Shenzhen Nanshan People's Hospital

Shenzhen, China

Location

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Neonatal Sepsis

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Per T Sangild

  Rigshospitalet, Denmark

  STUDY CHAIR

• Ping Zhou

  Shenzheng Baoan Maternity and Child Healthcare Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 30, 2019
• Study Start: May 1, 2019
• Primary Completion: June 13, 2021
• Study Completion: July 8, 2021
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

CN (2)