Systemic immune markers and infection risk in preterm infants fed human milk fortified with bovine colostrum or conventional fortifier, a secondary analysis of the FortiColos trial

BackgroundFor very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC) is rich in anti-inflammatory milk factors and considered an alternative. Our objective was to investigate if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants. MethodsIn a secondary analysis of a multicenter, randomized controlled trial (NCT03537365), very preterm infants (26-31 weeks gestation, 23% small for gestational age, SGA) were randomized to receive BC (ColoDan, Biofiber, Denmark, n=113) or a conventional fortifier (PreNAN, Nestle, Switzerland, n=116). Infection was defined as antibiotic treatment for five or more consecutive days. Levels of 29 cytokines and chemokines were measured in plasma before and after start of fortification. ResultsInfants fortified with BC showed more infection episodes (20 vs. 12%, P<0.05) and tendency to higher cumulative infection risk (hazard ratio, HR 1.9, P=0.06), particularly for SGA infants (HR 3.6, P<0.05). Additionally, BC-fortified infants had higher levels of TH2 related cytokines and chemokines (IL-10, MDC, MCP4) and reduced levels of cytokines related to TH1/TH17 responses (IL-15, IL-17, GM-CSF). The differences were most pronounced in SGA infants, displaying higher levels of TH2-related IL-4, IL-6, and IL-13, and lower interferon-{gamma} and IL-1 levels in the BC group ConclusionInfants fortified with BC show delayed transition from TH2-to TH1-biased systemic immunity, especially for SGA infants. This was associated with more frequent antibiotic use, indicating elevated sensitivity to infection. Thus, an anti-inflammatory milk supplement like BC may delay systemic immune development in preterm infants with effects depending on weight at birth.