Maternal serum endostatin at gestational weeks 16-20 is elevated in subsequent pre-eclampsia but not in intrauterine growth retardation

Abstract

Objective. Endostatin, an important anti-angiogenic factor produced by endothelial cells, is elevated in established pre-eclampsia. We measured maternal serum endostatin concentrations in early pregnancy associated with later pre-eclampsia and intrauterine growth retardation (IUGR). Design. Retrospective case-control study. Setting. University Central Hospital. Sample. Serum samples were collected at 12-15 and 16-20 gestational weeks from a total of 124 pregnant women of whom 49 developed pre-eclampsia, 16 gave birth to infants with IUGR without pre-eclampsia, and 59 remained normotensive giving birth to healthy, normal-weight infants. Methods. Enzyme-linked immunosorbent assay. Main outcome measures. Endostatin concentrations in serum. Results. At 12-15 gestational weeks, there was no difference in median endostatin concentrations between the groups. At 16-20 gestational weeks, the median endostatin concentration was higher in the women with subsequent pre-eclampsia (p=0.026), especially preceding a later severe form of the disease (p=0.041), than in the controls. The results were further confirmed by receiver operating characteristic (ROC) analysis showing an area under the curve (AUC) of 0.64 (95% confidence interval: 0.50-0.81) for endostatin to identify subsequent pre-eclampsia, and 0.71 (0.53-0.89) in cases of severe pre-eclampsia. Optimal cut-off values were determined and used for calculations of sensitivity and specificity, which were 80 and 52% (cut-off value = 58.0 g/L) in pre-eclampsia, and 80 and 65% (cut-off value = 65.5 g/L) in the severe form of the disease. Conclusions. The concentrations of endostatin in maternal serum at 16-20 weeks' of gestation are associated with an increased risk of pre-eclampsia but not IUGR.