Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth

Abstract

Background: Emerging evidence suggests that abnormal angiogenesis and imbalanced angiogenic factors may contribute to the development of spontaneous preterm birth (sPTB). In addition, 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) and sPTB risk and to assess their correlation with periodontal disease severity during early pregnancy.

Materials and methods: A prospective cohort study was conducted involving 348 pregnant women, with obstetric, clinical, and periodontal parameter 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 the participants. The women who had a sPTB had a significantly higher GCF PlGF/sFlt-1 ratio (p = 0.017) and lower sFlt-1 levels (p = 0.003) compared to those who had term pregnancies. A multivariate regression model combining the PlGF/sFlt-1 ratio, PI score, and first-trimester arterial blood pressure showed a predictive area under the curve of 0.78 (odds ratio 3.36, p = 0.008) for sPTB risk. Periodontal parameters, including PD sites >3 mm and PISA, were significantly worse in those with sPTB pregnancies (p = 0.032 and p = 0.047, respectively). Both PlGF and sFlt-1 levels were elevated in pregnant women with moderate to severe periodontitis compared to those with gingivitis or a healthy status (p < 0.0001), with significant positive correlations with inflammatory periodontal clinical parameters (p < 0.05).

Conclusion: An early pregnancy imbalance of angiogenic and antiangiogenic factors in the GCF is associated with increased sPTB risk and greater periodontal inflammation. These findings suggest that angiogenic factors in the GCF may serve as promising non-invasive biomarkers for identifying women at elevated risk for sPTB.

Keywords: angiogenic factors; biomarkers; gingival crevicular fluid; periodontitis; pregnancy; spontaneous preterm birth.

Figure 1

Gingival crevicular fluid concentrations of sFLt-1 and PlGF and their respective ratio in pregnant women at 11–14 weeks gestation in the studied population according to preterm birth development (PTB). (A) sFlt-1 concentration, (B) PlGF concentration, and (C) PlGF/sFlt-1 ratio.

Figure 2

Gingival crevicular fluid concentrations of sFlt-1 and PlGF in pregnant women at 11–14 weeks of pregnancy in the studied population and their respective ratios by periodontal diagnosis status. (A) sFlt-1 concentration and (B) PlGF concentration.

Figure 3

Correlation heatplot between gingival crevicular fluid concentrations of sFlt-1 and plGF and their respective ratios at 11–14 weeks of pregnancy and the periodontal clinical inflammatory parameters of the pregnant women in the studied population. PD, probing depth; CAL, clinical attachment loss; BOP, bleeding on probing; PISA, periodontal inflamed surface area.

Figure 4

(A) Area under the receiver operating characteristic curve (AUC-ROC) of the simple logistic regression analysis including the sFlt-1 concentration in the GCF. (B) AUC-ROC curve of the model including the sFlt-1 concentration in the GCF, plaque index score, and first-trimester arterial blood pressure. (C) AUC-ROC curve of the model including the PlGF/sFlt-1 ratio. (D) AUC-ROC curve of the model including the PlGF/sFlt-1 ratio, plaque index score, and first-trimester arterial blood pressure for the prediction of sPTB risk.