TRAIL Is Decreased Before 20 Weeks Gestation in Women with Hypertensive Disorders of Pregnancy

OBJECTIVE: The present study evaluated maternal plasma protein profiles before the onset of hypertensive disorders of pregnancy (HDP) to assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and HDP before 20 weeks gestation and to evaluate the discriminatory performance of plasma TRAIL levels for HDP. METHODS: A 2-phase discovery/validation study was designed. In the discovery phase, a nested case-controlled study was performed using plasma sampled at 8 to 20 weeks gestation from 20 women who later developed HDP and from 20 age- and gestational week-matched controls. Plasma was analyzed using a human protein microarray technology designed to simultaneously detect 507 proteins. The functional annotation and clustering of the differentially expressed proteins were performed using DAVID and the GO database. TRAIL levels were further validated in an independent study using plasma obtained at 8 to 20 weeks gestation from 53 women who later developed HDP and from 106 matched controls, and 62 clinical risk factors were investigated. RESULTS: In the protein microarray analysis, 23 proteins were differentially expressed between the two groups. The ELISA showed that women who later developed HDP had significantly lower TRAIL levels compared to women with uncomplicated pregnancies. The multivariable Cox regression analysis identified the following three factors that were entered into the final Cox regression model: gravidity (OR = 2.02, 95% CI 1.00–4.09), pre-pregnancy BMI (OR = 1.46, 95% CI 1.21–1.76) and TRAIL levels (OR = 0.97, 95% CI 0.94–0.99). The model had a significantly better discriminatory power (AUC = 0.83, 95% CI 0.75–0.88) compared to TRAIL alone as an independent predictor of HDP (AUC = 0.59, 95% CI 0.51–0.67). CONCLUSION: Twenty-three differentially expressed proteins before 20 weeks gestation might be associated with the pathogenesis of HDP. Plasma TRAIL levels were associated with the development of HDP, and the combination of plasma TRAIL levels with pre-pregnancy BMI and gravidity had a good discriminatory performance for HDP before 20 weeks gestation.