Serum biomarkers for prediction and diagnosis of preeclampsia; a meta-analysis, data set.

Published: 12 August 2021| Version 1 | DOI: 10.17632/kycndg3djg.1
Ruqaiya Shahid


This meta-analysis was conducted to determine the diagnostic utility of serum biomarkers in preeclampsia (PE). A systematic search was performed on the PubMed literature database and chain references were retrieved. Results: The number of articles retrieved from PubMed was 398. After reading the abstracts, 272 were excluded; of these, six lacked full text in English, 11 were animal studies, 54 were review articles, 19 were abstracts from posters, and 182 were not relevant to the topic. The full texts of 126 articles were read and a further 37 articles were excluded. Thus, 89 studies were identified after reading their full texts. An additional 47 studies were identified based on chain referencing and their full texts were read. The data of a total of 136 studies were entered in the excel datasheets and evaluated. Finally, 25 studies reporting on 13 biomarkers were selected for the meta-analysis. 1. PlGF: In seven studies, the combined effect depicted PlGF was 2.31 times lower in the preeclampsia compared to the controls; p=0.017 2. sFlt: In nine studies, the combined effect showed sFlt was 3.41 times higher in the preeclampsia, compared to the controls; p<0.001 3. sFlt/ PlGF: In four studies, the combined effect model revealed 7.33 times higher value in the preeclampsia compared to the controls; p<0.001 4. sEng: Seven studies evaluated, the combined effect showed sEng to be 2.69 times higher in the preeclampsia; p=0.004 5. HDL: Eight studies evaluated, the pooled effect of HDL displayed a negative effect on the preeclampsia; p=0.011 6. LDL: Five studies analyzed; the pooled effect, 0.317, was not significant; p=0.178 7. Total cholesterol: Four studies assessed, no significant difference between PE and controls, p=0.397 8. Triglycerides: The combined random effect model of seven studies revealed that biomarker was 0.28 times higher in the preeclampsia; p=0.065 9. Adiponectin: Five studies evaluated, 1.89 times lower value in PE; p=0.011. 10. Leptin: Five studies selected, random effect model showed a 1.74 times higher effect of leptin in the preeclampsia, p<0.001 11. APO-A: Four studies were analyzed, no significant difference between the preeclamptic patients and the controls, p=0.175 12. APO-B: In three studies, a significant difference was identified between the preeclamptic patients and the controls, p=0.011 13. TNF: Three studies, no significant difference between the preeclamptic patients and the controls, p=0.84 Conclusion In this study, the values of the serum biomarkers sFlt, PlGF, sFlt/PlGF, HDL, adiponectin, leptin, triglycerides, and APO-B differed significantly between the preeclampsia patients and the pregnant controls. These findings demand advanced evaluation of biomarkers to enhance the diagnostic screening for preeclampsia.


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1. PubMed was searched. The terms used were ‘Preeclampsia, not eclampsia’ ‘biomarkers or marker’ ‘blood or serum or plasma’. The dates of the search spanned from 1980/01/01 to 2017/12/31. 2. Selection of studies: Studies that were selected met the following criteria: 1. They reported on biomarkers in the blood of pregnant pre-eclamptic women. 2. They gave a complete description of their cases and controls. 3. They defined preeclampsia according to the ISSHP, ACOG, or comparable guidelines. Original research papers composed of case controls, cohorts, randomised control trials, cross-sectional studies were included. The relevant papers cited in the articles are also included. Any papers whose full text was not in the English language and those which were reviews, abstracts of posters, and animal studies were excluded. Any studies reporting biomarkers in urine and in the cord or fetal blood were also excluded. 3. Data extraction: The data were compiled in Microsoft Excel datasheets. The recorded variables were the study design, the type, location, and year of each study; the values of the biomarkers in the blood; the serum or plasma of the patients and the controls, p-values, units of measurement and techniques used; the sample size of each study; the results; and the gestational age at the time of sample collection. The recorded statistical measures were the mean ±SD. The standard errors of the mean were converted to standard deviations. When the units of measurement used in studies differed, they were converted to similar units. All studies reporting medians, interquartile ranges, and the multiples of the median were excluded. If multiple values were reported for a single marker, the highest mean value was taken. Trough values were taken, for few markers which are known to be present in low levels in patients with preeclampsia. The biomarkers that were reported in at least two studies were selected for the meta-analysis. 4. Statistical analysis was performed using Stata v-12.0 using the ‘metan’ command. I2 was used to determine the degree of heterogeneity between the markers. If the I2 value was under 50%, the fixed-effects model was used; otherwise, the random-effects model was used. A p-value of under 0.05 was considered significant. The results were interpreted based on the Standardized mean difference (SMD) values.


Biomarkers, Preeclampsia, Systematic Review with Meta-Analysis