A Stepwise, Pilot Study of Bovine Colostrum to Supplement the First Enteral Feeding in Preterm Infants (Precolos): Study Protocol and Initial Results

Abstract

Study protocolThe optimal feeding for preterm infants during the first weeks is still debated, especially when mother’s own milk is lacking or limited. Intact bovine colostrum (BC) contains high amounts of protein, growth factors, and immuno-regulatory components that may benefit protein intake and gut maturation. We designed a pilot study to investigate the feasibility and tolerability of BC as the first nutrition for preterm infants. The study was designed into three phases (A, B, and C) and recruited infants with birth weights of 1,000–1,800 g (China) or gestational ages (GAs) of 27 + 0 to 32 + 6 weeks (Denmark). In phase A, three infants were recruited consecutively to receive BC as a supplement to standard feeding. In phase B, seven infants were recruited in parallel. In phase C (not yet complete), 40 infants will be randomized to BC or standard feeding. Feeding intolerance, growth, time to full enteral feeding, serious infections/NEC, plasma amino acid profile, blood biochemistry, and intestinal functions are assessed. This paper presents the study protocol and results from phases A and B.ResultsSeven Danish and five Chinese infants received 22 ± 11 and 22 ± 6 ml·kg−1·day−1 BC for a mean of 7 ± 3 and 7 ± 1 days which provided 1.81 ± 0.89 and 1.83 ± 0.52 g·kg−1·day−1 protein, respectively. Growth rates until 37 weeks or discharge were in the normal range (11.8 ± 0.9 and 12.9 ± 2.7 g·kg−1·day−1 in Denmark and China, respectively). No clinical adverse effects were observed. Five infants showed a transient hypertyrosinemia on day 7 of life.Discussion and conclusionThe three-phased study design was used to proceed with caution as this is the first trial to investigate intact BC as the first feed for preterm infants. BC supplementation appeared well tolerated and resulted in high enteral protein intake. Based on the safety evaluation of phases A and B, the randomized phase C has been initiated. When complete, the Precolos trial will document whether it is feasible to use BC as a novel, bioactive milk diet for preterm infants. Our trial paves the way for a larger randomized controlled trial on using BC as the first feed for preterm infants with insufficient access to mother’s own milk.

Bovine Colostrum Before or After Formula Feeding Improves Systemic Immune Protection and Gut Function in Newborn Preterm Pigs

“…In the gut, piglets fed with colostrum as minimal enteral nutrition (12), full enteral nutrition (16), or supplementation to donor milk (17,19) showed improved digestive functions, integrity, antiinflammatory responses, and NEC resistance. Several clinical trials are being performed in very preterm infants to document this for its clinical application (14,27,28). A pilot study has demonstrated the feasibility and tolerability of initial colostrum feeding (27,28), which has led to an ongoing randomized clinical trial powered for TFF as the primary outcome in very preterm infants (ClinicalTrials.gov Identifier: NCT03085277).…”

“…Several clinical trials are being performed in very preterm infants to document this for its clinical application (14,27,28). A pilot study has demonstrated the feasibility and tolerability of initial colostrum feeding (27,28), which has led to an ongoing randomized clinical trial powered for TFF as the primary outcome in very preterm infants (ClinicalTrials.gov Identifier: NCT03085277). How colostrum feeding before or after suboptimal formula feeding protects or restores formula-induced intestinal impairment still remains unclear.…”

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review

“…Besides, nearly all studies described here investigated the effects of a single bioactive factor, while a synergistic action between several bioactive factors may be required to sort out its effects. One interesting strategy recently described is the use of bovine colostrum as a fortifier for mother’s milk or as a (partial) replacement for formula as it contains many active and potentially protective bioactive factors [ 67 , 68 , 69 ]. Four studies investigating the effects of bovine colostrum are currently ongoing ( Table S2 in Supplemental Materials).…”

Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection

“…The use of bovine colostrum is under investigation in preterm infants. In the safety phase of a pilot study bovine colostrum was well-tolerated in the pre-term infants, and further studies are ongoing ( 149 ).…”