Early Prediction Model of Gestational Hypertension by Multi-Biomarkers Before 20 Weeks Gestation

Abstract

Background Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model. Methods This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls. Results In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies ( P <0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83–0.98) compared to the models with those proteins alone as independent predictors of GH. Conclusion Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.

Assessment of maternal serum SERPINC1, E‐selectin, P‐selectin, and RBP4 levels in pregnancies with early‐ and late‐onset preeclampsia

“…In a large‐scale study, thrombophilia was reported to be significantly associated with severe PE, 32 but plasma ATIII levels were did not differ significantly between the group of patients with PE and the control group 33 . Zhou et al emphasized that SERPINC1 levels were significantly higher in women who developed gestational hypertension before 20 weeks of gestation than in those women with uncomplicated pregnancies 34 . On the contrary, in our study, the serum levels of SERPINC1 in the group of patients with EO‐PE were significantly lower than the levels measured in the LO‐PE group and the control group.…”

“…33 Zhou et al emphasized that SER-PINC1 levels were significantly higher in women who developed gestational hypertension before 20 weeks of gestation than in those women with uncomplicated pregnancies. 34 On the contrary, in our study, the serum levels of SERPINC1 in the group of patients with EO-PE were significantly lower than the levels measured in the LO-PE group and the control group. SERPINC1 levels of the patients with LO-PE were significantly lower than the levels measured in the control group.…”

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia

“…To gain insights into the identified proteins’ dynamics during hypertensive vs normotensive pregnancies, we performed a systematic review of studies reporting observational associations of the prioritized proteins with HDPs. Forty-three studies met our inclusion criteria (eFigure 3 in Supplement 1), encompassing 9749 pregnant individuals with protein measurements who enrolled from 1998 to 2020 in their respective studies. Of those, 3122 individuals (32.0%) experienced an HDP, including 939 (9.6%) with gestational hypertension, 2167 (22.2%) with preeclampsia, and 16 (0.2%) without information on HDP subtype.…”

Diagnostic Value of IGFBP-2 in Predicting Preeclampsia before 20 Weeks of Pregnancy: A Prospective Nested Case-Control Study

“…Patients with a history of hypertension, kidney disease, or other conditions causing elevated blood pressure prior to the 20 th week of gestation were excluded. In addition, cases of primary lipid metabolism abnormalities, stillbirth, miscarriage, multiple pregnancies, fetal malformation, thyroid disease, gestational diabetes, and liver and kidney diseases were excluded [ 16 ].…”