Unveiling Gingival Crevicular Fluid Angiogenic Imbalance in Maternal Periodontitis and Spontaneous Preterm Birth

Alejandra Chaparro^1*Daniela Albers¹Marcela Hernandez²Patricia Hernández²Diego Prieto¹María José Bendek¹María Luisa Mizgier¹Carolina Rojas¹Sebastian E Illanes¹

• ¹University of the Andes, Chile, Las Condes, Chile
• ²University of Chile, Santiago, Chile

Background: Emerging evidence suggests that abnormal angiogenesis and imbalanced angiogenic factors may contribute to the development of spontaneous preterm birth (sPTB). Additionally, pregnancy-related angiogenic changes and increased vascular permeability in periodontal tissues could amplify periodontal inflammation under hormonal influence. Objectives: This study aimed to evaluate the association between gingival crevicular fluid (GCF) levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with sPTB risk and to assess their correlation with periodontal disease severity during early pregnancy. Materials and Methods: There was conducted a prospective cohort study involving 348 pregnant women, with obstetric, clinical and periodontal parameters assessments performed at 11-14 weeks of gestation, including probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), periodontal inflamed surface area (PISA), and plaque index score (PI). GCF samples were collected, and PlGF and sFlt-1 levels were measured using Magpix -Luminex® multiplex technology. Results: sPTB occurred in 3.45% (n=12) of participants. Women with sPTB had a significantly higher GCF PlGF/sFlt-1 ratio (p=0.017) and lower sFlt-1 levels (p=0.003) compared to term pregnancies. A multivariate regression model combining the PlGF/sFlt-1 ratio, PI score, and first-trimester arterial blood pressure showed a predictive AUC of 0.78 (OR 3.36, p=0.008) for sPTB risk. Periodontal parameters, including PD sites > 3 mm and PISA, were significantly worse in sPTB pregnancies (p=0.032 and p=0.047, respectively).Both, PlGF and sFlt-1 levels were elevated in moderate to severe periodontitis compared to gingivitis or healthy status in pregnant women (p<0.0001), with significant positive correlations to inflammatory periodontal clinical parameters (p<0.05). Conclusion: An early pregnancy imbalance in GCF of angiogenic and antioangiogenic factors is associated with increased sPTB risk and greater periodontal inflammation. These findings suggest angiogenic factors in GCF may serve as promising non-invasive biomarkers for identifying women at elevated risk for sPTB.