Interpretation
PLAP, a membrane-bound glycosylated enzyme, is highly expressed in the syncytiotrophoblastic membranes during gestation104,107. PLAP concentrations in maternal plasma are significantly increased in pregnant women with hypertensive disorders than in those with a normotensive pregnancy101,126,127. Increased PLAP concentrations associated with PE may be a result of placental dysfunction, and they may also represent an informative biomarker of the syncytiotrophoblast function66,126. During pregnancy, syncytiotrophoblastic debris is normally shed into the maternal circulation; however, shedding is significantly increased in pregnancies complicated by PE75,105. Furthermore, replenishment of the syncytiotrophoblast is intense, complicated by necrosis and aponecrosis with increased liberation into the circulation of syncytiotrophoblast-derived particles in PE66. In light with our result, syncytiotrophoblast-derived particles, such as PLAP, can reach the gingival sulcus during early pregnancy, and can be detected in the GCF. Its concentrations are informative of the risk of developing PE and may be potentially used in future multiparametric algorithm for the prediction of the disease.
In recent years, systematic reviews and meta-analyses of randomized clinical trials have suggested that low-dose aspirin administration, particularly in the early stage of pregnancy (<16 weeks of gestation), to women at high risk for PE is associated with a significant risk reduction in the incidence of this disease79,168–173. Furthermore, the ASPRE randomized clinical trial80, inclusive of more than 1,600 participants, reported that administration of aspirin (150 mg /day) between 11 and 14 weeks of gestation in patients screened for PE risk significantly reduced the risk of preterm PE by 62% compared with placebo [OR: 0.38 (95% CI: 0.20–0.74)]. This finding has been recently confirmed by a systematic review and meta-analysis81 of six randomized clinical trials80,174–177. This evidence highlights the importance of implementing effective predictive models to identify patients at risk of developing PE for whom aspirin administration would be of clinical benefit. The predictive model reported herein is based on the measurement of a single biomarker in GCF and systolic blood pressure; therefore, it is non-invasive and inexpensive. Moreover, it displays a potential clinical utility in identifying women during early pregnancy who are at increased risk for developing PE, especially preterm PE, and, as such, warrants further clinical evaluation.