Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia

Abstract

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11-14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11-14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01-1.11; p = 0.004 and OR:1.008, 95% CI 1.000-1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.

Keywords: cohort study; gestation; placental biomarkers; pre-eclampsia; risk prediction model.

Figure 1

Flow chart of the study population.

Figure 2

(A) Placental alkaline phosphatase (PLAP) concentrations (pg/mL) in gingival crevicular fluid (GCF) in pregnancy according to the presence or absence of pre-eclampsia. (B) Plasma and GCF-PLAP concentrations at 11–14 weeks of gestation in women with and without pre-eclampsia. GCF, gingival crevicular fluid; PLAP, placental alkaline phosphatase.

Figure 3

(A) Area under the receiver operating characteristic curve (AUC-ROC) of PLAP-GCF concentration and systolic blood pressure at 11–14 weeks of gestation versus the development of pre-eclampsia. (B) Area under the receiver operating characteristic curve (AUC-ROC) of the concentration of PLAP-GCF and systolic blood pressure versus the development of preterm pre-eclampsia. (C) Area under the receiver operating characteristic curve (AUC-ROC) of the concentration of PLAP-GCF and systolic blood pressure at 11–14 weeks gestation versus pre-eclampsia > 37 weeks of gestation. GCF, gingival crevicular fluid; PLAP, placental alkaline phosphatase.