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

doi:10.3877/cma.j.issn.1673-5250.2021.05.016

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.

Key words: Lactate dehydrogenase, Pre-eclampsia, Diagnosis test, routine, Meta-analysis, Gravida and puerperant

表1 本研究纳入文献的基本特征

文献(第1作者，发表年)	国家	孕产妇例数(例)			进行血清LDH检测时研究组孕产妇		血清LDH指标对2组孕产妇的PE诊断结果(例)
文献(第1作者，发表年)	国家	研究组	对照组	合计	平均年龄(岁)	平均孕龄(周)	假阴性	假阳性	真阳性	真阴性
Peralta^[16]，2004	墨西哥	216	192	408	34	31	63	50	153	142
Khalil^[17]，2014	沙特阿拉伯	30	224	254	29.23	36	0	101	30	123
索海燕^[19]，2017	中国	36	84	120	38.85	24.45	4	8	32	76
蒋利红^[18]，2018	中国	117	50	167	27.68	39.04	15	13	102	37
Kasraeian^[15]，2018	伊朗	270	180	450	30.63	34.69	28	73	242	107
路雪^[21]，2019	中国	300	127	427	30.8	36.3	124	30	176	97
Kulkarni^[7]，2019	印度	50	50	100	25.6	34	8	21	42	29
Dua^[1]，2020	中国	163	93	256	30.14	33.12	43	7	120	86

表1 本研究纳入文献的基本特征

文献(第1作者，发表年)	国家	孕产妇例数(例)			进行血清LDH检测时研究组孕产妇		血清LDH指标对2组孕产妇的PE诊断结果(例)
文献(第1作者，发表年)	国家	研究组	对照组	合计	平均年龄(岁)	平均孕龄(周)	假阴性	假阳性	真阳性	真阴性
Peralta^[16]，2004	墨西哥	216	192	408	34	31	63	50	153	142
Khalil^[17]，2014	沙特阿拉伯	30	224	254	29.23	36	0	101	30	123
索海燕^[19]，2017	中国	36	84	120	38.85	24.45	4	8	32	76
蒋利红^[18]，2018	中国	117	50	167	27.68	39.04	15	13	102	37
Kasraeian^[15]，2018	伊朗	270	180	450	30.63	34.69	28	73	242	107
路雪^[21]，2019	中国	300	127	427	30.8	36.3	124	30	176	97
Kulkarni^[7]，2019	印度	50	50	100	25.6	34	8	21	42	29
Dua^[1]，2020	中国	163	93	256	30.14	33.12	43	7	120	86

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

组别		文献篇数(篇)	DOR值(95%CI)	异质性检验
组别		文献篇数(篇)	DOR值(95%CI)	I²值	P值
样本量(例)
	≤400	5^{[1,7,17,18,19]}	25.18(11.03~57.49)	63.6%	0.027
	>400	3^[15,16,21]	7.34(4.20~12.83)	76.9%	0.013
受试者所在国家
	中国	4^[1,18,19,21]	20.43(5.71~73.09)	90.3%	<0.001
	非中国	4^[7,15,16,17]	9.41(5.65~15.67)	49.1%	0.117
研究组患者平均年龄(岁)
	≤30	3^[7,17,18]	14.70(5.40~40.01)	51.4%	0.128
	>30	5^{[1,15,16,19,21]}	13.76(6.44~29.39)	87.4%	<0.001
研究组患者平均孕龄(周)
	≤34	4^[1,7,16,19]	17.50(5.94~51.58)	85.8%	0.001
	>34	4^{[15,17,18,21]}	11.55(4.97~26.80)	80.3%	0.002

表2 纳入8篇文献的亚组分析结果

组别		文献篇数(篇)	DOR值(95%CI)	异质性检验
组别		文献篇数(篇)	DOR值(95%CI)	I²值	P值
样本量(例)
	≤400	5^{[1,7,17,18,19]}	25.18(11.03~57.49)	63.6%	0.027
	>400	3^[15,16,21]	7.34(4.20~12.83)	76.9%	0.013
受试者所在国家
	中国	4^[1,18,19,21]	20.43(5.71~73.09)	90.3%	<0.001
	非中国	4^[7,15,16,17]	9.41(5.65~15.67)	49.1%	0.117
研究组患者平均年龄(岁)
	≤30	3^[7,17,18]	14.70(5.40~40.01)	51.4%	0.128
	>30	5^{[1,15,16,19,21]}	13.76(6.44~29.39)	87.4%	<0.001
研究组患者平均孕龄(周)
	≤34	4^[1,7,16,19]	17.50(5.94~51.58)	85.8%	0.001
	>34	4^{[15,17,18,21]}	11.55(4.97~26.80)	80.3%	0.002

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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