Bovine Colostrum for Preterm Newborns

NCT03085277 | Completed DMC

• 1 other identifier: Precolos-RCT
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 8

Brief Summary

Feeding intolerance is a common problem in very preterm infants due to their immature digestive system. This intolerance extends the time to full enteral feeding and thereby also prolongs the time on parenteral nutrition (PN). Prolonged time to full enteral feeding may predispose these infants to a higher risk of growth retardation, infections and organ dysfunctions (e.g. liver, brain). Mother's own milk (MM) is considered the optimal nutrition for preterm infants and is superior to infant formula (including preterm formula, PF) in stimulating gut maturation, feeding tolerance, resistance against necrotizing enterocolitis (NEC) and late-onset sepsis (LOS), and long-term neurodevelopmental outcomes. However, MM is often absent, or not available in sufficient amounts, during the first days or weeks after preterm delivery. Human donor milk (DM) is probably a better supplement to MM than PF, but DM is not available for all hospitals. To supplement insufficient MM during the early neonatal period in hospital settings with no access to donor milk, we suggest that bovine colostrum (BC) may be used instead of PF for very preterm infants during early life. BC, the first milk from cows after birth, is a rich source of protein and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and various growth factors, such as IGF-I and -II, EGFs, and TGF-β. BC has repeatedly been shown to improve gut maturation and NEC/LOS resistance in a well-established piglet model of preterm infants. We suggest a randomized, controlled trial to investigate the effects of BC vs. PF, supplemented to MM during the first 2 weeks, on the time to full enteral feeding in very preterm infants.

Conditions

Enteral Feeding Intolerance; Necrotizing Enterocolitis; Late-Onset Neonatal Sepsis

Keywords

Bovine colostrum; Preterm formula; Very preterm infants; Enteral feeding

Outcome Measures

Primary Outcomes (1)

• Time to full enteral feeding

  Full feeding volume is defined as the first day a participant receives 120 ml/kg/d for a consecutive period of 72 hours.

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

Secondary Outcomes (8)

• Combined incidence of severe neonatal infections (NEC, LOS, Meningitis) and mortality

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

• The presence of feeding intolerance

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

• Volume and color of gastric residual

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

• Days on PN

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

• Days to regain birth weight

  From the start of intervention until discharge home or reach a postconceptional age of 37 weeks, whichever comes first

Study Arms (2)

Preterm Formula

ACTIVE COMPARATOR

MM is always the first priority, when available. When MM is not available, or the available amounts do not fulfill the needs, infants in this group will receive preterm formula, as the supplementary diets following the standard feeding guidelines in the participating hospitals.

Dietary Supplement: Preterm Formula

Bovine Colostrum

EXPERIMENTAL

MM is always the first priority, when available. When MM is not available, or the available amounts do not fulfill the needs, infants in this group will receive Bovine Colostrum (BC), as the supplementary diets. BC feeding follows the same guideline as the control group in terms of initiation time (within 24-48h of age) and volume (5-10 ml/kg) and advancing rate (5-20 ml/kg/d). BC intervention should not exceed postnatal day 14.

Dietary Supplement: Bovine Colostrum

Interventions

Bovine Colostrum DIETARY_SUPPLEMENT

Bovine colostrum (BC) is the first milk from cows after birth and we suggest that BC may be used to supplement MM, instead of infant formula or DM. BC is a rich source of protein (up to 150 g/L) and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and various growth factors, such as, IGF-I and -II, EGFs, and TGF-β. BC has repeatedly been shown to have beneficial effects in a well-established piglet model of preterm infants, using various feeding regimens, including a gradual regimen that would mimic enteral feeding for preterm infants without access to MM during the first week.

Bovine Colostrum

Preterm Formula DIETARY_SUPPLEMENT

Preterm formula is a type of infant formula designed for preterm infants. It is used when mother's own milk is not available or not in sufficient amount as the enteral feeding for preterm infants in hospitals that do not have donor human milk.

Preterm Formula

Eligibility Criteria

• Age: Up to 2 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants with gestational age between 26+0 and 31+6 weeks
• Delivered at participating hospitals or transferred from other hospitals within 24 h of age
• Signed parental consent

You may not qualify if:

• Major congenital anomalies or birth defects
• Congenital infection defined as suspected TORCHES infections: Toxoplasmosis, Rubella, CMV, Herpes, Hepatitis, Coxcackie, Syphilis, Varicella Zoster, HIV, Parvo B19
• Perinatal asphyxia with blood pH \< 7.0 (umbilical or first neonatal)
• Extremely small for gestational age (birth weight z-score ≤ - 3)
• No realistic hope of immediate survival
• Has received any formula feeding prior to randomization

Sponsors & Collaborators

• Per Torp Sangild: lead
• Sixth Affiliated Hospital, Sun Yat-sen University: collaborator
• Maternal and Child Health Hospital of Foshan: collaborator
• Shenzhen People's Hospital: collaborator
• Shenzhen Luohu Maternal and Child Health Hospital: collaborator
• University of Chinese Academy of Sciences - Shenzhen Hospital: collaborator
• Longgang District People's Hospital of Shenzhen: collaborator
• Shenzhen Nanshan Maternity and Child Healthcare Hospital: collaborator
• Dongguan Women and Children's Hospital: collaborator

Study Sites (8)

Dongguan Women and Children's Hospital

Dongguan, Guangdong, China

Location

Foshan Maternal and Child Health Hospital

Foshan, Guangdong, China

Location

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

Longgang District Central Hospital of Shenzhen

Shenzhen, Guangdong, China

Location

Shenzhen Luohu Maternal and Child Health Hospital

Shenzhen, Guangdong, China

Location

Shenzhen Nanshan Maternal and Child Health Hospital

Shenzhen, Guangdong, China

Location

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Location

University of Chinese Academy of Sciences-Shenzhen Hospital

Shenzhen, Guangdong, China

Location

Related Publications (2)

• Yan X, Pan X, Ding L, Dai Y, Chen J, Yang Y, Li Y, Hao H, Qiu H, Ye Z, Shen RL, Li Y, Ritz C, Peng Y, Zhou P, Gao F, Jiang PP, Lin HC, Zachariassen G, Sangild PT, Wu B. Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial. Clin Nutr. 2023 Aug;42(8):1408-1417. doi: 10.1016/j.clnu.2023.06.024. Epub 2023 Jun 28.

  PMID: 37437359 DERIVED

• Juhl SM, Ye X, Zhou P, Li Y, Iyore EO, Zhang L, Jiang P, van Goudoever JB, Greisen G, Sangild PT. Bovine Colostrum for Preterm Infants in the First Days of Life: A Randomized Controlled Pilot Trial. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):471-478. doi: 10.1097/MPG.0000000000001774.

  PMID: 29019855 DERIVED

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 Sangild, PhD

  University of Copenhagen

  STUDY CHAIR

Study Design

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

Model Details: When a preterm infant is delivered at these hospitals or transferred from other hospitals on the day of birth, responsible neonatologists/PIs/co-PIs will evaluate the infant for its eligibility. If the infant fulfills the recruitment criteria, parent(s) are informed and explained about the study and asked for permission to recruit their babies. After confirmed consent, the infant will be, per hospital, randomized to two groups in a 1:1 ratio. Infants should be recruited and randomized as soon as possible after birth and no later than 48 h. The first supplemental enteral feeding (PF or BC) can be given as soon as the infants are randomized. Randomization will be stratified by birth weight \< 1000 g, birth weight ≥ 1000 g, and randomly permuted blocks of size 4 and 6 will be used. A random sequence list will be generated by computer software for each hospital and a corresponding sequence number can only be checked to see allocation after informed consent is given and the baby is enrolled.

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: March 21, 2017
• Study Start: July 1, 2017
• Primary Completion: October 23, 2020
• Study Completion: November 18, 2020
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)