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中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (05) : 612 -620. doi: 10.3877/cma.j.issn.1673-5250.2021.05.016

论著

血清乳酸脱氢酶检测对子痫前期诊断价值的Meta分析
鞠捷1,1, 李济宇2,2, 顾建娟3,,3(), 刘立卓3,3, 吕芳3,3   
  • 收稿日期:2021-01-25 修回日期:2021-09-06 出版日期:2021-10-01
  • 通信作者: 顾建娟

Diagnostic value of serum lactate dehydrogenase detection in preeclampsia: a Meta-analysis

Jie Ju1,1, Jiyu Li2,2, Jianjuan Gu3,3,(), Lizhuo Liu3,3, Fang Lyu3,3   

  • Received:2021-01-25 Revised:2021-09-06 Published:2021-10-01
  • Corresponding author: Jianjuan Gu
  • Supported by:
    National Natural Science Foundation of China for Youth(81601343)
引用本文:

鞠捷, 李济宇, 顾建娟, 刘立卓, 吕芳. 血清乳酸脱氢酶检测对子痫前期诊断价值的Meta分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2021, 17(05): 612-620.

Jie Ju, Jiyu Li, Jianjuan Gu, Lizhuo Liu, Fang Lyu. Diagnostic value of serum lactate dehydrogenase detection in preeclampsia: a Meta-analysis[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(05): 612-620.

目的

荟萃分析血清乳酸脱氢酶(LDH)检测对子痫前期(PE)的诊断价值。

方法

采用Cochrane系统评价法,应用计算机检索PubMed、Web of Science、Cochrane Library等英文数据库,以及万方数据知识服务平台与中国知网(CNKI)数据库中,关于血清LDH指标诊断PE的研究文献。文献检索时间设定为各数据库建库至2021年4月20日。由2位研究者按照本研究设定的检索策略,独立检索与筛选文献、提取资料,并采用诊断准确性研究的质量评价工具(QUADAS-2)进行文献质量评价后,采用Meta-Disc 1.4、Stata 14.0软件进行Meta分析。血清LDH指标诊断PE的主要结局指标为合并敏感度、特异度、阳性似然比、阴性似然比,诊断比值比(DOR),汇总受试者工作特征(SROC)曲线及其曲线下面积(AUC)。采用血清LDH指标诊断PE的敏感度对数与(1-特异度)对数的Spearman相关系数,评价阈值效应;采用Cochrane-Q检验分析纳入本研究不同文献的研究间异质性,并采用亚组分析进一步探讨该异质性来源。绘制Deeks漏斗图,分析文献发表偏倚。采用Fagan列线图,分析血清LDH检测对PE的临床诊断价值。

结果

对纳入的这8篇文献中血清LDH指标诊断PE价值研究结果如下。①共计纳入2 182例受试者,研究组为PE患者(n=1 182),对照组为正常孕产妇(n=1 000)。②纳入文献基本符合QUADAS-2质量评价标准。③血清LDH指标诊断PE敏感度对数与(1-特异度)对数的Spearman相关系数为0.476(P=0.230),不存在阈值效应。纳入文献存在高度异质性(敏感度:I2=94.52%、P<0.001;特异度:I2=95.80%、P<0.001),故采用随机效应模型进行血清LDH诊断PE的Meta分析,诊断PE的合并敏感度与特异度分别为83%(95%CI:73%~90%)与75%(95%CI:63%~83%),合并阳性似然比与阴性似然比分别为3.28(95%CI:2.27~4.74)与0.22(95%CI:0.14~0.36),合并DOR值为14.59(95%CI:7.83~27.57),SROC-AUC为0.86(95%CI:0.83~0.89);血清LDH诊断PE的文献间异质性来源可能为受试者所在国家[中国:血清LDH指标诊断PE的DOR值为20.43(95%CI:5.71~73.09),I2=90.3%、P<0.001;非中国:血清LDH指标诊断PE的DOR值为9.41(95%CI:5.65~15.67),I2=49.1%、P=0.117]。④Deeks漏斗图显示,各文献基本对称分布于回归线2侧,并且差异无统计学意义(P=0.100)。⑤Fagan列线图显示,血清LDH指标诊断PE的验前概率设定为20%,阳性似然比为3、阴性似然比为0.22时,其验后概率分别为45%与5%。

结论

本研究纳入8篇文献的血清LDH指标诊断PE具有中等诊断价值,诊断敏感度较高,特异度相对较低。受纳入文献样本量和研究质量限制,上述结论尚待更多高质量研究予以验证。

Objective

To explore the diagnostic value of serum lactate dehydrogenase (LDH) in preeclampsia (PE) by Meta-analysis.

Methods

Literature on research of serum LDH in diagnosis of PE in English databases such as PubMed, Web of Science and Cochrane Library, as well as Wanfang Database and China National Knowledge Infrastructure (CNKI) were searched by computer and Cochrane system evaluation method. Literature retrieval time was set from database inception to April 20, 2021. According to retrieval strategy set in this study, two researchers independently searched and screened the literature and extracted data, and evaluated quality of literature by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), and then used Meta-Disc 1.4 and Stata 14.0 software for Meta-analysis. The main outcome indicators of serum LDH in diagnosis of PE were combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR), summary receiver operating characteristics (SROC) curve and area under curve (AUC). Threshold effect was evaluated by Spearman correlation coefficient of sensitivity logarithm and (1-specificity) logarithm of serum LDH in diagnosis of PE. Heterogeneity between studies was analyzed by Cochrane-Q test, and the source of heterogeneity was further explored by subgroup analysis. Publication bias was analyzed by Deeks funnel plot and Fagan nomogram was performed for analysis of clinical diagnosis value of serum LDH for PE.

Results

Results of study on value of serum LDH in diagnosis of PE in the 8 included articles were as follows.①A total of 2 182 subjects with 1 182 cases of PE patients in study group and 1 000 cases of normal pregnant women in control group were included. ②The 8 included literature basically met the criteria of diagnostic accuracy quality evaluation of QUADAS-2. ③Spearman correlation coefficient between logarithm of sensitivity and (1-specificity) logarithm of serum LDH in diagnosis of PE was 0.476 (P=0.230), and there was no threshold effect. There was a high degree of heterogeneity among included literature (sensitivity: I2=94.52%, P<0.001; specificity: I2=95.80%, P<0.001), so random effect model was used for Meta-analysis. Results of Meta-analysis showed that combined sensitivity and specificity of serum LDH in diagnosis of PE were 83% (95%CI: 73%-90%) and 75% (95%CI: 63%-83%), respectively, combined positive likelihood ratio and negative likelihood ratio were 3.28 (95%CI: 2.27-4.74) and 0.22 (95%CI: 0.14-0.36), respectively, combined DOR was 14.59 (95%CI: 7.83-27.57), and SROC-AUC was 0.86 (95%CI: 0.83-0.89). Results of subgroup analysis showed that heterogeneity among included research literature may be caused by different countries of research subjects[China: DOR of serum LDH in diagnosis of PE was 20.43 (95%CI: 5.71-73.09), I2=90.3%, P<0.001; non-China: DOR of serum LDH in diagnosis of PE was 9.41 (95%CI: 5.65-15.67), I2=49.1%, P=0.117]. ④Deeks funnel plot showed that all research literature was basically symmetrically distributed on both sides of the regression line, and the difference was not statistically significant (P=0.100). ⑤Fagan nomogram showed that assuming the pre-test probability of serum LDH in diagnosis of PE was 20%, when positive likelihood ratio was 3 and negative likelihood ratio was 0.22, the post-test probabilities of serum LDH in diagnosis of PE were 45% and 5%, respectively.

Conclusions

Serum LDH has medium diagnostic value for PE in 8 included literature, with high sensitivity and relatively low specificity. Limited by the sample-size and quality of included literature, the above conclusions need to be verified by more high-quality studies.

表1 本研究纳入文献的基本特征
图1 纳入研究的8篇文献的QUADAS-2质量评价结果注:QUADAS-2为诊断准确性研究的质量评价工具
图2 对纳入8篇文献中血清LDH指标诊断PE的敏感度及特异度的Meta分析注:LDH为乳酸脱氢酶,PE为子痫前期
图3 对纳入8篇文献中血清LDH指标诊断PE的阳性似然比和阴性似然比的Meta分析注:LDH为乳酸脱氢酶,PE为子痫前期
图4 对纳入8篇文献中血清LDH指标诊断PE的DOR的Meta分析注:LDH为乳酸脱氢酶,PE为子痫前期,DOR为诊断比值比
图5 纳入8篇文献的血清LDH指标诊断PE的SROC曲线注:LDH为乳酸脱氢酶,PE为子痫前期。SROC曲线为汇总受试者工作特征曲线,SROC-AUC为汇总受试者工作特征曲线下面积
表2 纳入8篇文献的亚组分析结果
图6 纳入8篇文献中血清LDH指标诊断PE的发表偏倚Deeks漏斗图注:LDH为乳酸脱氢酶,PE为子痫前期,DOR为诊断比值比。n为文献纳入样本量
图7 纳入8篇文献血清LDH指标诊断PE的Fagan列线图注:LDH为乳酸脱氢酶,PE为子痫前期
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