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

BackgroundEmerging 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 periodon...

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Main Authors: Daniela Albers, María José Bendek, Marcela Hernández, Diego Prieto, Carolina Rojas, María Luisa Mizgier, Patricia Hernández, Sebastián E. Illanes, Alejandra Chaparro
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Dental Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fdmed.2025.1625995/full
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author Daniela Albers
María José Bendek
María José Bendek
Marcela Hernández
Diego Prieto
Carolina Rojas
Carolina Rojas
María Luisa Mizgier
María Luisa Mizgier
Patricia Hernández
Sebastián E. Illanes
Sebastián E. Illanes
Alejandra Chaparro
Alejandra Chaparro
author_facet Daniela Albers
María José Bendek
María José Bendek
Marcela Hernández
Diego Prieto
Carolina Rojas
Carolina Rojas
María Luisa Mizgier
María Luisa Mizgier
Patricia Hernández
Sebastián E. Illanes
Sebastián E. Illanes
Alejandra Chaparro
Alejandra Chaparro
author_sort Daniela Albers
collection DOAJ
description BackgroundEmerging 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.ObjectivesThis 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 methodsA 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.ResultssPTB 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).ConclusionAn 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.
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spelling doaj-art-b2e9bc9c0b45478aa4787e09bbccd5b82025-08-20T03:31:52ZengFrontiers Media S.A.Frontiers in Dental Medicine2673-49152025-07-01610.3389/fdmed.2025.16259951625995Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birthDaniela Albers0María José Bendek1María José Bendek2Marcela Hernández3Diego Prieto4Carolina Rojas5Carolina Rojas6María Luisa Mizgier7María Luisa Mizgier8Patricia Hernández9Sebastián E. Illanes10Sebastián E. Illanes11Alejandra Chaparro12Alejandra Chaparro13Department of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileDepartment of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileCenter for Biomedical Research and Innovation (CIIB), Universidad de Los Andes, Santiago, ChileLaboratory of Periodontal Biology and Department of Pathology and Oral Medicine, Faculty of Dentistry, Universidad de Chile, Santiago, ChileDepartment of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileDepartment of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileCenter for Biomedical Research and Innovation (CIIB), Universidad de Los Andes, Santiago, ChileDepartment of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileCenter for Biomedical Research and Innovation (CIIB), Universidad de Los Andes, Santiago, ChileDepartment of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, ChileCenter for Biomedical Research and Innovation (CIIB), Universidad de Los Andes, Santiago, ChileProgram in Biology of Reproduction, Faculty of Medicine, Universidad de Los Andes, Santiago, ChileDepartment of Oral Pathology and Conservative Dentistry, Periodontics, Faculty of Dentistry, Universidad de Los Andes, Santiago, ChileCenter for Biomedical Research and Innovation (CIIB), Universidad de Los Andes, Santiago, ChileBackgroundEmerging 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.ObjectivesThis 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 methodsA 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.ResultssPTB 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).ConclusionAn 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.https://www.frontiersin.org/articles/10.3389/fdmed.2025.1625995/fullangiogenic factorsperiodontitispregnancyspontaneous preterm birthgingival crevicular fluidbiomarkers
spellingShingle Daniela Albers
María José Bendek
María José Bendek
Marcela Hernández
Diego Prieto
Carolina Rojas
Carolina Rojas
María Luisa Mizgier
María Luisa Mizgier
Patricia Hernández
Sebastián E. Illanes
Sebastián E. Illanes
Alejandra Chaparro
Alejandra Chaparro
Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
Frontiers in Dental Medicine
angiogenic factors
periodontitis
pregnancy
spontaneous preterm birth
gingival crevicular fluid
biomarkers
title Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
title_full Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
title_fullStr Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
title_full_unstemmed Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
title_short Unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
title_sort unveiling the association between angiogenic imbalance in the gingival crevicular fluid in maternal periodontitis and spontaneous preterm birth
topic angiogenic factors
periodontitis
pregnancy
spontaneous preterm birth
gingival crevicular fluid
biomarkers
url https://www.frontiersin.org/articles/10.3389/fdmed.2025.1625995/full
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