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.