Abstract：
BACKGROUND: For very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC), rich in anti-inflammatory milk factors, is considered an alternative. We investigated if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants.
METHODS: For 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 conventional fortifier (PreNAN, Nestlé, Switzerland, n = 116). Infection was defined as antibiotic treatment for five or more consecutive days and 29 cytokines/chemokines were measured in plasma before and after start of fortification.
RESULTS: In general, infection risk after start of fortification was associated with low gestational age, SGA status and antibiotics use prior to fortification. Adjusted for confounders, infants fortified with BC showed more infection episodes (20 vs 12%, P < 0.05) and 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/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-γ and IL-1α levels in the BC group.
CONCLUSIONS: Infants fortified with BC displayed a delayed shift from TH2- to TH1-biased systemic immunity, notably in SGA infants, possibly influenced by multiple confounding factors, alongside elevated antibiotic use, suggesting increased susceptibility to infection.
METHODS: For 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 conventional fortifier (PreNAN, Nestlé, Switzerland, n = 116). Infection was defined as antibiotic treatment for five or more consecutive days and 29 cytokines/chemokines were measured in plasma before and after start of fortification.
RESULTS: In general, infection risk after start of fortification was associated with low gestational age, SGA status and antibiotics use prior to fortification. Adjusted for confounders, infants fortified with BC showed more infection episodes (20 vs 12%, P < 0.05) and 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/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-γ and IL-1α levels in the BC group.
CONCLUSIONS: Infants fortified with BC displayed a delayed shift from TH2- to TH1-biased systemic immunity, notably in SGA infants, possibly influenced by multiple confounding factors, alongside elevated antibiotic use, suggesting increased susceptibility to infection.
摘要：
背景：对于极早产儿，人乳通常使用基于加工牛乳的配方产品进行强化。完整的牛初乳（BC），牛奶中含有丰富的抗炎因子，被认为是一种替代。我们调查了BC是否会影响早产儿的抗炎/TH2免疫和感染风险。
方法：对于多中心的二次分析，随机对照试验（NCT03537365），极早产儿（妊娠26-31周，23%小于胎龄，SGA)随机接受BC(ColoDan，生物纤维,丹麦,n=113)或常规强化剂(PreNAN，雀巢,瑞士,n=116）。将感染定义为连续五天或更长时间的抗生素治疗，并在开始强化之前和之后在血浆中测量29种细胞因子/趋化因子。
结果：一般来说，开始强化后的感染风险与低胎龄有关，强化前的SGA状态和抗生素使用情况。针对混杂因素进行了调整，强化BC的婴儿表现出更多的感染发作(20%vs12%，P<0.05)和更高的累积感染风险(危险比，HR1.9，P=0.06），特别是对于SGA婴儿（HR3.6，P<0.05）。此外,BC强化的婴儿有更高水平的TH2相关细胞因子/趋化因子（IL-10，MDC，MCP4）和与TH1/TH17应答（IL-15，IL-17，GM-CSF）相关的细胞因子水平降低。差异在SGA婴儿中最为明显，在BC组中显示出更高水平的TH2相关IL-4，IL-6和IL-13，而较低的干扰素-γ和IL-1α水平。
结论：强化BC的婴儿表现出从TH2-到TH1-偏向的全身免疫的延迟转变，特别是在SGA婴儿中，可能受到多种混杂因素的影响，随着抗生素使用的增加，提示对感染的易感性增加。
方法：对于多中心的二次分析，随机对照试验（NCT03537365），极早产儿（妊娠26-31周，23%小于胎龄，SGA)随机接受BC(ColoDan，生物纤维,丹麦,n=113)或常规强化剂(PreNAN，雀巢,瑞士,n=116）。将感染定义为连续五天或更长时间的抗生素治疗，并在开始强化之前和之后在血浆中测量29种细胞因子/趋化因子。
结果：一般来说，开始强化后的感染风险与低胎龄有关，强化前的SGA状态和抗生素使用情况。针对混杂因素进行了调整，强化BC的婴儿表现出更多的感染发作(20%vs12%，P<0.05)和更高的累积感染风险(危险比，HR1.9，P=0.06），特别是对于SGA婴儿（HR3.6，P<0.05）。此外,BC强化的婴儿有更高水平的TH2相关细胞因子/趋化因子（IL-10，MDC，MCP4）和与TH1/TH17应答（IL-15，IL-17，GM-CSF）相关的细胞因子水平降低。差异在SGA婴儿中最为明显，在BC组中显示出更高水平的TH2相关IL-4，IL-6和IL-13，而较低的干扰素-γ和IL-1α水平。
结论：强化BC的婴儿表现出从TH2-到TH1-偏向的全身免疫的延迟转变，特别是在SGA婴儿中，可能受到多种混杂因素的影响，随着抗生素使用的增加，提示对感染的易感性增加。
