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子痫前期和血压正常女性孕早期及孕中期的免疫生物标志物

First and second trimester immune biomarkers in preeclamptic and normotensive women.

作者信息

Taylor Brandie D, Ness Roberta B, Klebanoff Mark A, Zoh Roger, Bass Debra, Hougaard David M, Skogstrand Kristin, Haggerty Catherine L

机构信息

Department of Epidemiology and Biostatistics, Texas A&M University, School of Public Health, College Station, TX, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.

University of Texas School of Public Health, Houston, TX, United States.

出版信息

Pregnancy Hypertens. 2016 Oct;6(4):388-393. doi: 10.1016/j.preghy.2016.09.002. Epub 2016 Sep 17.

Abstract

INTRODUCTION

Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls.

METHODS

Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions. Preterm preeclampsia was defined as preeclampsia with delivery less than 37weeks of gestation. Associations between immune markers RANTES, interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and beta, transforming growth factor (TGF)-beta and preeclampsia were explored using a modified version of cox regression developed to address data with non-detectable levels. Models were adjusted for body mass index, gestational age of blood sampling, fetal sex, smoking, socioeconomic status and maternal age.

RESULTS

In first trimester samples, IL-12 was associated with preeclampsia (p=0.0255). IFN-gamma (p=0.0063), IL1-beta (p=0.0006), IL5 (p=0.0422) and TNFr (p=0.0460) were associated with preterm preeclampsia only. In second trimester samples, IL1-beta was associated with preeclampsia (p=0.0180) and term preeclampsia (p=0.0454). After correction for multiple comparisons, only IL1-beta remained associated with preterm preeclampsia in the first trimester (p=0.0288).

DISCUSSION

Elevated first trimester IL1-beta appears to be associated with preterm preeclampsia. However, few associations were observed in the second trimester. Systemic immune markers alone may not be useful for preeclampsia prediction.

摘要

引言

循环免疫标志物可能与子痫前期有关,但有必要在妊娠早期及子痫前期各亚型中开展进一步研究。我们检测了208例子痫前期女性和411例血压正常对照者的免疫标志物。

方法

我们的研究嵌套于围产期协作项目中。共有242名女性有孕早期血清样本,392名有孕中期血清样本。子痫前期定义为妊娠20周后出现高血压并伴有蛋白尿或肺水肿、少尿或抽搐。早发型子痫前期定义为妊娠37周前分娩的子痫前期。采用为处理不可检测水平数据而开发的改良版Cox回归,探讨免疫标志物RANTES、白细胞介素(IL)-6、IL4、IL5、IL12、IL10、IL8、IL1-β、干扰素(IFN)-γ、肿瘤坏死因子(TNF)-α和β、转化生长因子(TGF)-β与子痫前期之间的关联。模型对体重指数、采血时的孕周、胎儿性别、吸烟、社会经济状况和产妇年龄进行了校正。

结果

在孕早期样本中,IL-12与子痫前期相关(p = 0.0255)。IFN-γ(p = 0.0063)、IL1-β(p = 0.0006)、IL5(p = 0.0422)和TNFr(p = 0.0460)仅与早发型子痫前期相关。在孕中期样本中,IL1-β与子痫前期相关(p = 0.0180)和足月子痫前期相关(p = 0.0454)。在进行多重比较校正后,仅IL1-β在孕早期仍与早发型子痫前期相关(p = 0.0288)。

讨论

孕早期IL1-β升高似乎与早发型子痫前期有关。然而,在孕中期观察到的关联较少。仅全身免疫标志物可能无助于子痫前期的预测。

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