The correlation between maternal serum sST2, IL-33 and NT-proBNP concentrations and occurrence of pre-eclampsia in twin pregnancies: A longitudinal study

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11⁺⁶  weeks; (2) 24-27⁺⁶  weeks; (3) 28-31⁺⁶  weeks. We found that sST2 and NT-proBNP levels increased as pregnancy progressed in normotensive twin pregnancies and further increased in PE group, while no differences were found in IL-33 levels throughout pregnancy. Then the correlation of biomarker levels with the occurrence of PE was assessed. Our results indicated that combining maternal serum sST2 and NT-proBNP levels yielded the highest predictive value on the occurrence of PE significantly higher than the predictive value of any markers alone. Interestingly, the predictive value of second trimester (AUC = 0.876, 95%CI 0.824-0.928, LR-0.338, LR+7.67, p < 0.001)was higher than that of early-third trimester (AUC = 0.832, 95%CI 0.769-0.896, LR-0.29, LR+3.845, p < 0.001). Serum sST2 and NT-proBNP concentrations during second and early-third trimester were associated with the occurrence of PE in twin pregnancies.