Our results indicate that it is feasible to use BC as a supplement to MM during the first weeks of life to increase enteral protein intake in preterm infants. Plasma tyrosine levels may be a good marker for excessive protein intake. A larger randomized trial is required to test the safety and possible short- and long-term clinical benefits of BC supplementation during the first weeks of life for preterm infants.

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.

We found poor validity for the discharge diagnosis of necrotising enterocolitis. In future, a better way of defining the disease is needed for large-scale epidemiologic research.

Introduction. We suspected that the incidence of NEC in Denmark had increased during the last 20 years but hypothesized that this could be explained by the increased neonatal survival. Methods. We conducted a retrospective, observational cohort study of all registered liveborn infants in Denmark in the period from January 1, 1994 to December 31, 2014. Data were obtained from the Medical Birth Registry, National Patient Register, and Cause of Death register in Denmark. The primary outcome was the registration of NEC (ICD-10: DP77.9) during a hospital admission within 6 months after birth. The statistical analysis used ‘death before NEC’ as a competing risk. Results. The cohort consisted of 1,351,675 infants, of which 8,059 died. There was a strongly significant decreasing risk of death over the period for the all infants (p<0.0001 in all gestational age groups). In total, 994 infants were diagnosed with NEC which lead to an incidence of 7.4 per 10,000 live-born infants. During the observation period, the incidence increased from 6.3 to 7.9 per 10,000 births (p = 0.006). When accounting for ‘death before NEC’ as a competing risk, the increase could be explained by the increased neonatal survival. There was, however, a GA-group/epoch interaction (p = 0.008) in the cause-specific hazard ratios with a trend towards an increasing risk of NEC in the most preterm infants and a decreasing risk of NEC in the term infants. Conclusion. While the overall incidence of NEC increased over the study period, the overall risk of NEC did not increase when considering the increased survival. Nevertheless, there seemed to be an increased risk of NEC in the most premature infants which was masked by a decreased risk in the term infants. This study suggests that research to prevent NEC in the most preterm infants is more important now than ever.

An analysis of the pattern of clinical and radiographic findings in a 2006-2015 population of NEC cases supported Bell's 1978 staging system. However, the separation between NEC and spontaneous intestinal perforation still poses a difficult task.