Maternal Salivary miR-423-5p Is Linked to Neonatal Outcomes and Periodontal Status in Cardiovascular-High-Risk Pregnancies

Int J Mol Sci. 2024 Aug 22;25(16):9087. doi: 10.3390/ijms25169087.

Abstract

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes. In this study, we sought to investigate the associations between salivary miRNAs of pregnant women with oral diseases and their effects on neonatal outcomes. Eleven (n = 11) salivary miRNAs from a cohort of pregnant women with oral diseases (n = 32; oral health, H; gingivitis, G; and periodontitis, P) were detected using a previous profiling analysis with an FDR < 0.20 and a fold change (FC) < 0.5 or FC > 2 for the most highly expressed miRNAs. Spearman correlations were performed for 11 salivary microRNAs associated with oral-derived inflammation, which could affect neonatal outcomes during pregnancies at risk for cardiometabolic disease (CMD), defined by the presence of a high pregestational BMI. In addition, ROC curves demonstrated the diagnostic accuracy of the markers used. Upregulation of miR-423-5p expression and a decrease in miR-27b-3p expression were detected in the P-group (p < 0.05), and ROC analysis revealed the diagnostic accuracy of miR-423-5p for discriminating oral diseases, such as gingivitis versus periodontitis (P vs. G, AUC = 0.78, p < 0.05), and for discriminating it from the healthy oral cavity (P vs. H, AUC = 0.9, p < 0.01). In addition, miR-27b-3p and miR-622 were also able to discriminate the healthy group from the P-group (AUC = 0.8, p < 0.05; AUC = 0.8, p < 0.05). miR-483-5p was able to discriminate between the G-group (AUC = 0.9, p < 0.01) and the P-group (AUC = 0.8, p < 0.05). These data support the role of salivary miRNAs as early biomarkers for neonatal outcomes in pregnant women with periodontal disease at high risk for CMD and suggest that there is cross-talk between salivary miRNAs and subclinical systemic inflammation.

Keywords: cardiovascular risk; gestational diabetes; gingivitis; miR-423-5p; microRNAs; neonatal outcomes; obesity; oral health; periodontitis; pregnancy.

MeSH terms

  • Adult
  • Biomarkers
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Female
  • Gingivitis / diagnosis
  • Gingivitis / genetics
  • Gingivitis / metabolism
  • Humans
  • Infant, Newborn
  • MicroRNAs* / genetics
  • Periodontal Diseases* / genetics
  • Periodontal Diseases* / metabolism
  • Periodontitis / genetics
  • Periodontitis / metabolism
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / metabolism
  • Pregnancy Outcome*
  • ROC Curve
  • Saliva* / metabolism

Substances

  • MicroRNAs
  • MIRN423 microRNA, human
  • Biomarkers

Grants and funding

This study is funded by the IRCCS MultiMedica Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica. The funder did not have any role in the design or execution of the study; the collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. All authors had full access to all data analysis outputs (reports and tables) and take responsibility for their integrity and accuracy.