脐血血清炎症因子干扰素-γ、白介素-12p70、白介素-17A与早产之间的关联

Associations of preterm birth with umbilical cord serum inflammatory cytokines interferon-γ,interleukin-12p70, and interleukin-17A

[背景]早产是新生儿发病和死亡的主要原因,已知感染和炎症是早产的危险因素之一,但各炎症因子水平与早产之间的具体关联需进一步研究。[目的]探讨脐血血清炎症因子水平和早产之间的关联。[方法]数据基于2013年5月—2014年9月在马鞍山市妇幼保健院开展的出生队列研究,本研究共1 433对母婴纳入分析。分娩后立即采集脐带血血样,检测8种血清炎症因子浓度,包括干扰素-γ(IFN-γ)、白介素-1β(IL-1β)、IL-6、IL-8、IL-10、IL-12p70、IL-17A、肿瘤坏死因子-α(TNF-α)。采用Mann-Whitney U检验分析早产组(孕周<37周)和足月组(孕周37~41周)之间脐血血清各炎症因子质量浓度的差异。按三分位数将各炎症因子浓度分为低、中、高水平组,调整混杂因素后,采用二分类logistic回归模型分析脐血血清炎症因子水平与早产之间的关联。[结果]1 433名新生儿中3.3%(47例)为早产儿,脐血血清中IFN-γ、IL-1β、IL-6、IL-8、IL-10、IL-12p70、IL-17A、TNF-α的质量浓度的M(P25~P75)分别为1.40(0.97~2.21)、0.46(0.31~0.64)、1.83(1.08~2.87)、6.98(4.58~10.23)、7.25(5.37~9.30)、0.88(0.61~1.25)、1.56(1.02~2.20)、12.81(8.68~17.73)ng·L^(-1),检出率为94.77%~100.00%。早产组脐血血清中IFN-γ、IL-1β、IL-12p70、IL-17A的中位质量浓度均高于足月组(1.99 vs. 1.40、0.61 vs. 0.46、1.23 vs. 0.86、14.59 vs.12.81 ng·L^(-1))(P<0.01)。调整混杂因素后,与低水平组相比,脐血血清中IFN-γ、IL-12p70、IL-17A高水平组发生早产的OR(95%CI)值为3.09(1.39~6.85)、3.76(1.66~8.53)、2.43(1.16~5.08),而其他炎症因子与早产之间的关联均无统计学意义(P> 0.05)。[结论]脐血血清中IFN-γ、IL-12p70、IL-17A因子水平与早产之间存在正向关联,即高水平炎症因子与早产的发生风险相关。

[Background] Preterm birth is the main cause of neonatal morbidity and death. Infection causing inflammation is known to be one of the risk factors for preterm birth, but the specific associations between the levels of various inflammatory cytokines and preterm birth need further study.[Objective] This study aims to investigate the associations between inflammatory cytokine levels in umbilical cord serum and preterm birth.[Methods] Based on the birth cohort study conducted at Ma’anshan Maternal and Child Health Hospital from May 2013 to September 2014, a total of 1 433 pairs of mothers and infants were included in the analysis. Umbilical cord blood samples were collected immediately after delivery to detect the concentrations of eight serum inflammatory factors, including interferon-γ(IFN-γ),interleukin(IL)-1β, IL-6, IL-8, IL-10, IL-12 p70, IL-17 A, and tumor necrosis factor-α(TNF-α). The Mann-Whitney U test was used to analyze the differences in umbilical cord serum inflammatory cytokine concentrations between the preterm group(gestational age <37 weeks) and the full term group(gestational age 37 to 41 weeks). The participants were divided into low, medium, and high level groups according to tertiles of inflammatory cytokine concentrations. After adjusting for confounding factors, a binary logistic regression model was used to analyze the associations between umbilical cord serum inflammatory cytokine levels and preterm birth.[Results] Among the 1 433 newborns, 3.3%(47 cases) were premature infants. The IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12 p70, IL-17 A, and TNF-α concentrations in umbilical cord serum [M(P25-P75)] were 1.40(0.97-2.21), 0.46(0.31-0.64), 1.83(1.08-2.87), 6.98(4.58-10.23), 7.25(5.37-9.30), 0.88(0.61-1.25), 1.56(1.02-2.20), and 12.81(8.68-17.73) ng·L^(-1), respectively, and the positive rates were from 94.77% to 100.00%. The median concentrations of IFN-γ, IL-1β, IL-12 p70, and IL-17 A in umbilical cord serum of the preterm group were higher than those of the full term group(1.99 vs. 1.40, 0.61 vs. 0.46, 1.23 vs. 0.86, and 14.59 vs. 12.81 ng·L^(-1))(Ps < 0.01). After adjusting for confounding factors, compared with the corresponding low level group, the OR(95% CI) values of preterm birth in the high level groups of IFN-γ, IL-12 p70, and IL-17 A in umbilical cord serum were 3.09(1.39-6.85), 3.76(1.66-8.53), and 2.43(1.16-5.08), respectively, and the associations between other inflammatory cytokines and preterm birth were not statistically significant(Ps > 0.05).[Conclusion] There are positive correlations between IFN-γ, IL-12 p70, and IL-17 A levels in umbilical cord serum and preterm birth, that is, higher levels of inflammatory cytokines are related to a higher risk of preterm birth.