Maternal plasma TIMP-4 levels combined with clinical risk factors for the early prediction of pregnancy-induced hypertension

Objective The objective of this study was to create a model for early predicting pregnancy-induced hypertension (PIH) using plasma markers and clinical risk factors. Methods A nested case-control study was performed at the Laboratory Department of Guangzhou Women and Children's Medical Center. From a prospective cohort of tens of thousands of unselected women with singleton pregnancies at 8-20 weeks gestation, maternal plasma samples were obtained from 73 women who subsequently developed PIH (PIH group) and 146 gestational age- and maternal age-matched women with normotensive pregnancies (control group). Proteins extracted from the plasma samples were screened by microchip and verified by ELISA. Clinical risk factor data were analyzed retrospectively. Results Compared to the control group, high concentrations of tissue inhibitor of metalloproteinase-4 (TIMP-4) were found in women with PIH (P = 0.000). Univariate risk factor analysis identified three variables with significant differences between the groups: family history of PIH (P = 0.031), body mass index (BMI; P < 0.001), and non-glucose-6-phosphate dehydrogenase deficiency-induced anemia (P < 0.027). Multiple regression analyses revealed a significant relationship of PIH with TIMP-4 levels, BMI, and family history (combined area under the receiver operating characteristic curve = 0.820). Conclusion Upregulation of plasma TIMP-4 might contribute to PIH processes. Potential risk factors of this disease may include a family history of PIH and BMI. The combination of TIMP-4 levels and these risk factors may have some predictive values for PIH. Future multicenter studies including greater numbers of samples, analyzed proteins, and risk factors are needed to obtain a higher predictive value of the model for the clinical diagnosis of PIH.