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The potential predictive value of miR-181 in women with preeclampsia: a systematic review and meta-analysis

BMC Pregnancy and Childbirth volume 25, Article number: 474 (2025) Cite this article

Abstract

Background

Preeclampsia (PE) is a pregnancy-associated disease that result in maternal and fetal morbidity and mortality worldwide. Several studies demonstrated the alterations in miRs (miRNAs) expression in PE. The aim of the present study was to determine the expression level of miR-181 and whether miR-181 have a diagnostic value in detection of women with PE compared to women without PE.

Methods

A systematic review and meta-analysis were performed based on studies reporting the miRNA expression level of miR-181 in placenta or serum between pregnant women with and without PE. Thus, articles published up to December 17, 2024 were extracted through PubMed, Scopus, Web of Science and Embase. The electronic literature search was conducted independently by two authors to obtain eligible studies based on the screening of title, abstract and full-text and quality appraisal. Subgroup analyses, area under the curve (AUC) were calculated. Standardized mean difference (SMD) was applied as a measure of pooled effect size.

Results

Twelve studies were included in the systematic review and meta-analysis based on inclusion criteria. The results show that the expression level of miR-181 is significantly higher in women with PE compared to women without PE (SMD = 1.84, 95%CI 0.47–3.21, p = 0.008). No publication bias was observed using the Begg’s rank correlation (p = 0.20) and Egger’s linear regression (p = 0.57) tests. Subgroup analyses demonstrated significant correlation between miR-181 levels in placenta or serum with maternal age, gestational age at delivery and birth weight. In addition, the pooled AUC was (0.95 ± 0.038; p < 0.0001) that shows the high diagnostic value of miR-181 in women with PE.

Conclusions

miR-181 can be a promising potential biomarker in the early detection of women with PE compared to women without PE. Albeit, further studies are needed for the more confirmation and validation this result.

Peer Review reports

Introduction

Pregnancy process is highly affected by trophoblast cells and normal human placentation. One of the specificities of human placentation is spiral artery remodeling, which depends on the proliferation, migration, invasion, and differentiation of trophoblast cells. As a result, the impaired function of trophoblast cells along with placenta dysfunction lead to pregnancy disorders including preeclampsia [1, 2]. PE is a pregnancy-related disorder. It is characterized by high blood pressure and proteinuria [3, 4]. PE during the pregnancy results in maternal morbidity, preterm birth, intrauterine growth restriction and mortalities [5]. It is reported that PE affects almost 2–8% pregnancies and has considerable effects on different maternal organ systems such as the cardiovascular system, genitourinary system, cerebrovascular system, renal tissue and brain [6, 7]. The symptoms of preeclampsia not only started in the third trimester, but also may occur any point after 20 weeks of gestation [8, 9]. There are two types of PE, early-onset preeclampsia (EOP) that usually initiated before 34 weeks of gestation and late- onset PE (LOP) occurs after 34 weeks of gestation or at the delivery [10]. PE-related complications may decrease through aspirin prophylaxis if initiated before 16 weeks of gestation [11]. There are several studies regarding the association between PE and aberrant expression of miRNAs. Pregnancies associated with PE suggest a dysregulation of certain microRNAs, particularly those found in the placenta [12, 13]. A better understanding of the role of miRNAs in the development of PE suggests identification of some novel diagnostic and therapeutic biomarkers for PE.

miRNAs as short single-stranded noncoding RNA act as post-transcriptional regulators of gene expression. When miRNAs lie in seed site on the 3´ untranslated region (3´ UTR) of the target mRNA result in mRNA instability, mRNA degradation and translation inhibition or gene silencing [14, 15]. miRNAs are involved in different biological processes such as differentiation, cellular development, proliferation, and apoptosis [16]. Many studies have indicated that the development and the occurrence of many of diseases is associated with dysregulation of miRNAs including diabetes, cancer, infection disease and PE [17,18,19]. The expression patterns of miRNAs change in various human disorders proposing their promising potential as biomarkers for diagnostic, prognostic and treatment responses [20]. Studies have demonstrated that the expression levels of miRNAs across various tissues play an important role in physiological pregnancy as modulator of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and placental angiogenesis [21]. For this reason, Koushki et al. reported the increased levels of miRNA-210 expression in placental tissue from pregnant women with PE [13]. In addition, investigating the expression patterns of other miRNAs such as miRNA-128, -183, -29b and − 15b showed that miRNA expression differs in the normal pregnancy and mild to severe PE [22, 23]. Recent published studies have reported the abnormal expression of placenta or circulating miRNAs in relationship with PE [24, 25]. One of these major miRNAs is miR-181 family [5]. miR-181 family are involved in inhibition of tumor cell proliferation, invasion and apoptosis [26]. There are several studies with the alterations in the expression of miR-181 family in women with PE [3, 27, 28]. However, evaluation of the predictive performance of miR-181 for PE was the main objective of the present systematic review and meta-analysis.

Materials and methods

The protocol stages of this systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [29].

Flow of study selection

The published articles underwent a two-phase screening process for inclusion in the systematic review and meta-analysis, with any disagreements addressed through discussion at each stage, involving a third reviewer to reach a consensus. In the following, we incorporated studies that reported the differences in miRNA expression levels between women diagnosed with preeclampsia and those without PE. Therefore, studies were considered eligible for inclusion if the expression levels of miRNA were assessed in both groups. The articles with the following conditions were excluded: (1) investigated other populations, including animal models and cell lines, (2) were abstracts, brief report, opinions, perspectives, book chapters, review articles, and editorials, (3) did not conduct comparisons between the PE and control groups, (4) reported other primary outcomes, (5) evaluated other microRNAs as diagnostic markers, (6) were not sufficient information about topic for extraction. In general, a preliminary check using the title and summary, then a detailed review of the full-text articles was performed for the selection of eligibility studies.

Electronic databases search

Only articles in English language were treated. Two authors, MK and NAD, who specialize in systematic reviews and meta-analyses, conducted the search strategy. A comprehensive review of literature was conducted through systematic searches of PubMed, Scopus, Embase and Web of Science (WoS) databases up to December 17, 2024. Syntaxes are different based on the database. Key words for the PubMed search included (“preeclampsia OR eclampsia OR pregnancy Toxemia* OR Hypertension-Edema-Proteinuria Gestosis OR Preeclampsia“) AND (miRNA-181 OR microRNA-181 OR non-coding RNA-181), in WoS: (TS = preeclampsia OR eclampsia* OR hypertension pregnancy*) AND (Topic searching (TS) = miRNA-181 OR microRNA-181 OR non-coding RNA-181), for Scopus: Title = preeclampsia and (Title: miRNA-181* OR non-coding RNA-181) and for Embase: eclampsia* OR preeclampsia AND (miRNA-181 or microRNA-181 or mir-181, Small Temporal RNA*). Additionally, grey literature or preprint servers, conference abstracts and reference lists were manually searched to identify potentially relevant studies along with pertinent reviews and editorials. Except two above authors, a third independent author evaluated the potential eligibility of articles. In general, studies associated with PE were only used in the pooled analysis when the sufficient data for the extraction were available.

Information retrieval of included studies and quality appraisal

Two reviewers independently collected the following information from the studies that were incorporated. For this purpose, a pre-set standardized Excel sheet was utilized to gather information. The following data were extracted: the first author’s name, publication year, country, sample size of PE, sample size of control, total sample size (PE + control), maternal age (year), BMI, birth weight (g), gestational age at delivery (wk), type of sample, systolic blood pressure (mmHg) and diastolic blood pressure (mmHg). The expression levels of miR-181 family were applied to the pooled effect size.

The quality of the eligible studies was assessed by two reviewers separately. Each reviewer conducted an independent assessment of the quality of the chosen articles by utilizing a modified version of the Newcastle-Ottawa scale (NOS) designed for observational studies. This scale composed of 4 sections including: (1) study population selection, (2) exposure, (3) comparability, and (4) result. The sum of points obtained from this scale is 9. Therefore, the highest score for any study was 9 points. Following the quality assessment, each study received a point ranging from zero to nine. Zero to five as “low quality”, 5 to 7 as “moderate quality” (5–7), and “high quality” (≥ 8). The reviewers resolved any conflicts in their scoring through conversation.

Main outcome

Main outcome was the comparison of the expression level of miR-181 family between women with or without PE for the determination the diagnostic value of miR-181 in PE.

Statistical analysis

As aforementioned, the main outcome was expression levels of miR-181 family that presented as means with standard deviation. Maybe the expression levels of miR-181 reported as graph in some studies, in this case, we used from GetData Graph Digitizer version 2.26.0.20 to extract miRNA values from figures. The SMDs and 95% CI was used to combine the data and measure the effect sizes to determine differences between the preeclampsia and control groups. A random-effects model DerSimonian and Laird method were utilized to calculate weighted average of the SMD. Standard deviations (SDs) of the mean difference were calculated using the following formula: SD = square root [(SDpre-treatment)2 + (SDpost treatment)2– (2R × SDpre-treatment × SDpost-treatment)], assuming a correlation coefficient (R) = 0.5. If standard error was used in the primary study, standard deviation was determined using the formula SD = SE*√n. In cases where a range was provided, the standard deviation was approximated by the formula (max-min)/4. If the expression levels of miR-181 was reported in the median and interquartile range (IQR), mean and SD values were estimated using a method previously defined [30]. Heterogeneity was evaluated applying the Chi-square Q and I2 statistic. Higgins I-square highlights the discrepancy between the study results and measures the extent of the observed variation that is genuine, specifically attributable to between-study differences rather than random error. The classification of heterogeneity was derived from the Cochrane Handbook, which indicates that I2 values of less than 30%, between 30% and 60%, and greater than 60% correspond to low, moderate, and high heterogeneity, respectively. Sensitivity analysis was conducted to assess how each study influenced the pooled effect size by using the “leave-one-out” method, The process entails systematically omitting each study from the analysis, beginning with the study that possesses the largest sample size and proceeding to those with progressively smaller sizes [31]. Furthermore, subgroup analysis was performed according to the subgroups of maternal age, gestational age at delivery, birth weight of infant, type of sample and proteinuria (mg/24 h). Subgroup analysis was conducted solely on those groups that included a minimum of two studies. Funnel plot was utilized to evaluate publication bias by charting precision per standardized difference in means. The Begg’s and Egger’s tests were used to confirm the presence of publication bias among studies as statistics [32, 33]. The trim-and-fill analysis was applied as indictive of notable publication bias. In addition, a random-effects meta-regression analysis was performed using an unrestricted maximum likelihood approach, to explore the impact of covariates such as maternal age, gestational age at delivery, BMI, birth weight, the rate of proteinuria and type of sample on the expression levels of miR-181 as a diagnostic biomarker in women with preeclampsia compared to non-preeclampsia group. The overall effect size was represented by a diamond. The parameters of sensitivity, specificity, positive likelihood ratios (PLRs), and negative likelihood ratios (NLRs) were estimated. Furthermore, area under the receiver operator characteristic curve was depict to examine the diagnostic power of miR-181 family. The area under the curve (AUC) value of 1.0 indicates an ideal diagnostic capability, while an AUC value approaching 0.5 reflects a poor diagnostic capability [34]. A P < 0.05 was concerned statistically significant. Comprehensive Meta-Analysis (CMA) V3 software was employed for the analysis of extracted data (Biostat, NJ).

Results

Process of systematic selection of studies

A total of 45 articles were found, of these, 35 articles were excluded due to being duplicates rather than original works, lacking PE as a result, failing to compare PE with control groups, focusing on populations other than women (such as animals or cell lines), not investigating miRNA expression levels, or being limited to abstracts. Ten articles along with 2 articles from citation searching included for inclusion in the systematic review and meta-analysis. A flow diagram depicting this selection process is shown in Fig. 1.

Fig. 1
figure 1

Flow diagram of study selection

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Demographic characteristics of the primary studies

Characteristics of all 12 articles selected in the systematic review and meta-analysis are thoroughly outlined in Table 1. The articles were published from 2007 to 2023 with a total of 1051 sample size, 444 women with and 607 without PE. The minimum participant involved in PE and control groups was seven. The largest sample size consisted of 126 participants in the PE group and 287 participants in the control group. Of the 12 articles, 7 articles were from China, 2 articles from USA, one study from Spain, Denmark and Egypt. Therefore, most of articles were originated from China. Zheng Y et al., study included two sub-studies with the same the target population. The most sample source of miR-181 family was placenta, reported in 8 studies. Three studies used serum plasma in one study. Generally, 60% of the included studies did not differentiate the type of PE. QRT-PCR was a main technique in the detection of the expression levels of mir-181 in almost all studies. The maternal age of women with preeclampsia ranged between 23.8 and 46 years. The gestational age at delivery started from 30 to 40 weeks in 10 studies, while, in 2 studies was not presented. The birth weight of infants was not reported in 4 publications. The presence of proteinuria as major symptom of preeclampsia was reported in most of studies. In addition, we carried out the quality appraisal of included studies using NOS scale. The quality of the studies was ranged from moderate to strong across all investigations. The NOS score of original articles included in the systematic review is presented in Table 2.

Table 1 Demographic characteristics of included studies in the systematic review and meta-analysis
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Table 2 Risk of bias or study quality assessment of included studies using Newcastle-Ottawa scale (NOS) checklist
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Meta-analysis of main outcome

A meta-analysis based on random-effect model was conducted for the diagnostic value of miR-181 in women with preeclampsia compared with non-preeclampsia. The expression level of miR-181 family was significantly higher in women with PE compared to women without PE (SMD = 1.84, 95%CI 0.47–3.21, p = 0.008) (Fig. 2). A significant heterogeneity was detected among included studies (Q-value: 11.09, df = 13, z-value = 3.67, I2 = 0.00%, p-value = 0.00). As a result of, subgroup analysis was performed based on following variables.

Fig. 2
figure 2

Forest plot of SMD of the expression level of miR-181 in placenta and circulation among women with vs. without PE

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Subgroup analysis indicated increased levels of miR-181 expression in both serum or plasma (SMD = 2.16, 95%CI 0.84–3.49) and placenta (SMD = 2.16, 95%CI 0.84–3.49), but this increase was higher in serum than placenta of women with PE compared to control group. The expression level of miR-181 in PE women with infants with birth weight greater than 2500 g was significantly higher compared to women without PE (SMD = 2.53, 95%CI 0.71–4.3, p = 0.006). The expression level was significantly higher in the maternal age of lower than 30 years in women with PE compared to women without PE for miR-181(SMD = 2.87, 95%CI 0.68–5.05, p = 0.010). In addition, the increased level of miR-181 expression was observed in PE women with gestational age at delivery higher than 36 weeks compared to women without PE. The rate of proteinuria had no significant different between subgroups of women with PE. Subgroup analysis are presented in detail in Table 3.

Table 3 Subgroup analysis for the evaluation the effect of following variables in the development of significant heterogeneity in the meta-analysis
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To assess the predictive value of miR-181, we applied the ROC curve to analyse the cut-off value, sensitivity and specificity. The cut-value was calculated using the Youden index. The cut-off value was introduced as the value at which the sum of sensitivity and specificity reached its highest value. The cut-off value for miR-181 was 9.78 with sensitivity 0.84 (95% CI 0.57–0.97) and specificity 1 (95% CI 0.77–1.00). In addition, we further assessed the predictive value using the AUC value, positive likelihood ratio (PLR) and negative likelihood ratio (NLR). The present results with the AUC 0.95 (0.87–1); p < 0.0001, PLR > 0 and NLR = 0.16 suggest the diagnostic value of miR-181. The results of ROC curve are shown in Fig. 3.

Fig. 3
figure 3

ROC curve of miR-181 of placenta tissue in women with PE

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In the following, random-effects meta-regression was performed. The results showed no significant association between the expression levels of miR-181, maternal age, gestational age at delivery, BMI and sample type. While, a significant positive association with birth weight was found (Fig. 4). Detailed meta-regression are summarized in Table 4.

Table 4 Random meta-regression analysis for covariates involved in the diagnostic value of miR-181 family in preeclampsia
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Fig. 4
figure 4

Random-effects Meta-regression curves of the impact of confounder variables of maternal age, BMI, birth weight, gestational age and proteinuria on estimated pooled effect size in women with PE

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Sensitivity analyses were performed to exclude each study starting from the one with the largest sample size down to the smallest using the “leave-one-out” method (Fig. 5). Interestingly, when the studies by L. Hedley et al. and Chen YS et al. were removed, a higher pooled result was observed. Whereas, removing any of the other studies had no significant different effect size compared to the pooled result. Therefore, the results of sensitivity analysis were the pooled effect sizes from SMD = 1.22 to SMD = 2.43 suggesting strong consistency of the total effect size in this meta-analysis. On the other hand, the result of quality appraisal indicated that all studies are ranged from moderate to high quality.

Fig. 5
figure 5

Leave-one-out sensitivity analysis for remove of the study with larger sample size in diabetic patients. Meta-analysis was performed using a random-effects model

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There was no publication bias among included studies through the Begg’s rank correlation (Kendall s Tau with continuity correction = 0.26; Z = 1.28; 2-tailed p-value = 0.20) and Egger’s linear regression (intercept = 1.93; standard error = 3.3; 95% CI = -5.3–9.2; t- value = 0.58; df = 11; 2-tailed p-value = 0.57). Furthermore, the funnel plot depicting precision against standardized mean difference did show a slight asymmetry. This asymmetry was imputed by two studies using trim-and-fill method. The imputed pooled effect size was 0.81 (95% CI– 0.55–2.18). The “classic fail-safe N” method showed that 462 theoretically missing studies are needed to make a nonsignificant the pool estimated effect size (Fig. 6).

Fig. 6
figure 6

Random-effects Funnel plots detailing publication bias in the studies investigating the expression level of miR-181 in women with PE compared with without PE. Circles represent observed published studies; black circles represent imputed unpublished studies

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Discussion

microRNAs have the pivotal role in many regulatory biological processes. In this regard, several studies have demonstrated the aberrant expression of miRNAs in human placenta that is related to the pregnancy diseases developed by trophoblast dysfunction, including PE [35, 36]. One of these miRNAs is miR-181. In the present systematic review and meta-analysis, we observed that the expression level of miR-181 was significantly higher in placenta or serum women with PE compared to placenta or serum women without PE. Furthermore, we found a significant AUC higher from 0.9 which is supporting the diagnostic value of miR-181 in identification of preeclamptic women compared to non-preeclamptic women. Cell line studies have shown the important role of miR-181 in processes such as cell proliferation, apoptosis and invasion [37, 38]. It should be noted that this meta-analysis reported upregulation of miR-181 family in women with PE, which associates well with the results of several studies [17, 39].

As reported so far, many microRNA are involved in the development of human placenta and pregnancy process [40]. Therefore, alterations in the microRNA’s expression could be the initiation of a disorder during the pregnancy such as PE [41]. However, some of these microRNAs have a key role in the detection, and some may have a therapeutic role [42, 43]. miR-181 family is one of the specifically validated miRNAs linked to PE [44, 45]. Increasing evidence have indicated the upregulation of miR-181 in the placenta tissue of women with PE [4, 44]. Furthermore, increased level of miR-181 was observed in the circulation of preeclamptic women [5, 15]. Obtained results in placenta tissue and circulation suggesting the key role of miR-181 in the pathogenesis of PE. miR-181 has the potential to act as a suppressor of tumor cell proliferation, apoptosis, and invasion [38]. Multiple studies have shown that miR-181 involves in target many genes from autophagy pathway. One of them is Atg5 that its inhibition leads to suppressing the autophagy of tumor cells [46]. Another gene is high-mobility group box 1 protein gene (HMGB1), which miR-181-inhibited HMGB1 decreased the autophagy in pancreatic cancer [47]. Among the different functions of miR-181, implication in the pathogenesis of PE through the dysregulation of human trophoblasts is the most important of biological function. Thus, proliferation suppression and apoptosis frequently occur in trophoblasts associated with preeclampsia [48]. Recent studies have demonstrated that cell lines with overexpressed miR-181 result in suppression of proliferation as well as inhibit cell cycle progression at the G2/M phase and promote apoptosis in trophoblast cells in vitro model [1]. Moreover, it has been suggested that miR-181 may regulate embryo implantation, placentation and decidualization via the regulation of the focal adhesion signaling pathway [49]. Invasion has been seen in trophoblast cells similar to cancerous cell [50]. Considering this factor, preeclampsia arises from a deficiency in the initial invasion of trophoblasts, leading to inadequate remodeling of the uterine spiral arteries [51]. As a result, miR-181 are associated with tumor invasiveness. Towards this end, we endeavored to present several studies in this case. Wu et al. discovered that miR-181a-5p has the ability to inhibit the invasion and migration of HTR-8/SVneo cells through its direct interaction with IGF2BP2 [52]. In addition, in that study reported that miR-181 inhibit the invasion activity of trophoblast cell lines through reduction in the invasion related proteins, MMP-2 and MMP-9 [52]. In contrast with the above studies, the invasiveness of trophoblastic cells was also observed following overexpression of miR-181a in the placenta tissue of patients with hypertensive disorder complicating pregnancy [39]. This conflicting could be arising from that PE highly affected the trophoblast cells relative to initiation stage of disease and as a result the invasion and migration of trophoblast cells occur in a patient with the severe PE. Taken together, the aberrant upregulation of miR-181a expression may play a significant role in trophoblast dysfunction and could be a key element in the development of PE.

Besides, we investigated the predictive ability of miR-181 in the detection of women with PE from women without PE. We found that the high predictive value of miR-181 in the identification women with mild to severe PE compared with women without PE. Therefore, the diagnostic efficiency of miR-181 could be considered in the clinicians’ decisions and in clinical lab.

However, the present study has some limitations: first, the number of samples in the selected studies was relatively small along with limited statistical power. Second, the predictive ability was reported only with a microRNA, while we can expand the predictive ability in future studies with several panels of microRNA. Third, in the present study, all of selected primary studies had samples from third trimester of women with PE, while, studies with miR-181 in first trimester may provide further insights into the relationship between miR-181 and PE. It should be noted that in the current study, the location of the primary studies was different as well as had baseline information. So, future studies with adequate information are necessary.

Conclusions

The present systematic review and meta-analysis revealed that the expression of miR-181 was upregulated in the overall SMD obtained from tissue and serum samples of preeclamptic women. while, subgroup analysis indicated this significant increase was higher in serum of women with PE than tissue. Therefore, the elevated expression of miR-181 is associated with the trophoblast dysfunction and the pathogenesis of PE. As a result, these findings underscore a potential predictive ability for miR-181 in the detection of PE. However, further studies with large-scale population are required to validate the promising diagnostic potential of miR-181.

Data availability

Data is provided within the manuscript or supplementary information files.

Abbreviations

PE:

Preeclampsia

AUC:

Area under the curve

SMD:

Standardized mean difference

PRISMA:

Preferred reporting items for systematic reviews and meta-analysis

miR:

MicroRNA

WoS:

Web of Science

NOS:

Newcastle-Ottawa scale

SD:

Standard deviation

PLR:

Positive likelihood ratios

NLR:

Negative likelihood ratios

IQR:

Interquartile range

CMA:

Comprehensive meta-analysis

EOP:

Early-onset preeclampsia

LOP:

Late-onset preeclampsia

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Acknowledgements

We thank Yasuj University of Medical Sciences, for the support this study.

Funding

The present study was financially supported by grant from Deputy of Research, Yasuj University of Medical Sciences (Grant No: 4020156).

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Mehdi Koushki

  2. Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

    Mehdi Koushki

  3. Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran

    Nasrin Amiri-Dashatan

  4. School of Stomatology, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China

    Maryam Khodadadi

  5. Department of Gynecology and Obstetrics, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

    Elahe Masnavi

  6. Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

    Amir Hossein Doustimotlagh

Authors
  1. Mehdi Koushki
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  2. Nasrin Amiri-Dashatan
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  3. Maryam Khodadadi
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  4. Elahe Masnavi
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  5. Amir Hossein Doustimotlagh
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Contributions

All the authors were involved in the writing the drafted of manuscript. M. K, NA. D, M. Kh and AH. D contributed to the improvement of the selection criteria, the risk of bias assessment strategy, and data extraction criteria. The systematic search in electronic databases and primary screening for the study selection based on eligibility and quality was performed by E. M, NA. D and M. K. All the authors promoted the search strategy. MK, NA. D and AH. M provided statistical expertise. All authors read, provided feedback and approved the final manuscript.

Corresponding author

Correspondence to Amir Hossein Doustimotlagh.

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Ethics approval and consent to participate

The project followed the principles outlined in the Declaration of Helsinki. This study was approved by the Research Ethics Committee of Yasuj University of Medical Sciences (IR.YUMS.REC.1402.147). This is a meta-analysis research as a secondary study and do not need to consent for participants.

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All the authors have consented to the publication of this paper.

Competing interests

The authors declare no competing interests.

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Koushki, M., Amiri-Dashatan, N., Khodadadi, M. et al. The potential predictive value of miR-181 in women with preeclampsia: a systematic review and meta-analysis. BMC Pregnancy Childbirth 25, 474 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12884-025-07589-x

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Keywords

BMC Pregnancy and Childbirth

ISSN: 1471-2393

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