Study unravels the Role of miR-181 in Preeclampsia: A Potential Diagnostic Biomarker for Maternal and Fetal Health

Recent investigation into miR-181 expression levels aimed to determine its potential as a diagnostic biomarker for preeclampsia (PE) in women. Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria, affecting approximately 2-8% of pregnancies and resulting in significant maternal and fetal complications. Recent studies have highlighted the dysregulation of microRNAs (miRNAs) in the pathology of PE, suggesting their possible role as diagnostic and therapeutic tools.

Methodology

The methodology employed a systematic review and meta-analysis using the PRISMA guidelines. Various electronic health databases, including PubMed, Scopus, Embase, and Web of Science, were searched up to December 2024 for studies comparing miR-181 expression levels between women with and without PE. Initial screening found 45 articles, of which 12 met the criteria for inclusion after a rigorous two-phase selection process, predominantly focusing on placental and serum samples. The articles included a total of 1,051 participants-444 being women diagnosed with PE and 607 as controls. Quality appraisal of these studies revealed moderate to high quality based on the Newcastle-Ottawa Scale.

Analysis

The analysis focused on comparing the expression levels of miR-181 in both groups to elucidate its diagnostic potential. Using random-effects meta-analysis, it was found that miR-181 levels were significantly higher in the PE group compared to controls, with a standardized mean difference (SMD) of 1.84 (95% CI: 0.47-3.21, p = 0.008). Heterogeneity was statistically significant, suggesting variability among studies; however, subgroup analyses indicated that the expression was consistently elevated in both serum (SMD = 2.16) and placental samples, particularly in women under 30 years old and those delivering infants with birth weights above 2500g.

Diagnostic Capability

To assess the utility of miR-181 as a diagnostic tool, receiver operating characteristic (ROC) analysis was performed, revealing an area under the curve (AUC) of 0.95, indicating strong diagnostic capability with a sensitivity of 84% and specificity of 100% at an optimal cut-off value of 9.78. Further meta-regression analysis found a positive association between miR-181 levels and infant birth weight but no significant correlations with maternal age or other demographic variables.

Biological Implications

The study underscored the potential role of miR-181 in the biological processes associated with trophoblast dysfunction and indicated its predictive value in identifying women with PE. Findings suggested miR-181 might serve as a significant biomarker for early detection of preeclampsia, which is critical for timely clinical interventions.

Limitations

Limitations noted include the relatively small sample sizes of individual studies, potential biases, and a focus solely on miR-181 without a panel of miRNAs, which could broaden diagnostic efficiency. The analysis was primarily based on third-trimester samples, highlighting the need for further research utilizing early pregnancy samples to explore the timing of dysregulation and its implications for PE pathogenesis.

Conclusion

In conclusion, findings substantiate that miR-181 is consistently upregulated in women with preeclampsia, reflecting its association with trophoblast dysfunction and offering a promising direction for future diagnostic strategies. Further large-scale studies are necessary to validate miR-181's role and enhance the understanding of its contribution to preeclampsia.

Key Points

- -Objective and Background-: The study aimed to investigate the expression levels of miR-181 as a potential diagnostic biomarker for preeclampsia (PE), a pregnancy-related condition that manifests as hypertension and proteinuria, impacting 2-8% of pregnancies and leading to significant health issues for both mother and fetus. There is emerging evidence that dysregulated microRNAs may play a role in the pathophysiology of PE.

- -Methodology-: A systematic review and meta-analysis were conducted following PRISMA guidelines, with searches performed across various electronic health databases through December 2024. Out of 45 initial articles screened, 12 studies were included, focusing on comparisons of miR-181 expression in 1,051 participants (444 with PE and 607 controls), with quality assessments generally indicating moderate to high study quality.

- -Key Findings in Expression Levels-: The meta-analysis revealed that miR-181 levels were significantly elevated in women with preeclampsia compared to controls, with a standardized mean difference (SMD) of 1.84 (95% CI: 0.47-3.21, p = 0.008). Both serum and placental samples indicated consistently higher levels, particularly in younger women (under 30 years) and those with infants weighing over 2500g.

- -Diagnostic Performance-: Receiver operating characteristic (ROC) analysis demonstrated the diagnostic capability of miR-181, reporting an area under the curve (AUC) of 0.95, which signifies high accuracy. The analysis indicated a sensitivity of 84% and a specificity of 100% at an optimal cut-off value of 9.78, highlighting its potential as an effective diagnostic tool for preeclampsia.

- -Biological Implications-: The findings suggest that miR-181 may be involved in trophoblast dysfunction and serves as a valuable biomarker for early detection of preeclampsia, which can be crucial for implementing timely clinical interventions and improving maternal and fetal outcomes.

- -Limitations and Future Directions-: Limitations identified include the relatively small sample sizes within individual studies, potential biases, and the singular focus on miR-181 without considering a broader array of miRNAs. Additionally, the reliance on third-trimester samples underscores the necessity for further research exploring early pregnancy samples to better understand the timing of miRNA dysregulation and its relevance to preeclampsia development.

Reference –

Mehdi Koushki et al. (2025). The Potential Predictive Value Of MiR-181 In Women With Preeclampsia: A Systematic Review And Meta-Analysis. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07589-x.