RESUMEN
Background: Thrombophilia combined with pregnancy poses significant risks for adverse pregnancy outcomes. Unfortunately, there are no indicators at high risk for predicting adverse pregnancy outcomes. This study investigates the predictive efficiency of serum immune-inflammatory markers on adverse pregnancy outcomes. Methods: This retrospective cohort study includes 223 pregnant women diagnosed with thrombophilia who delivered at the Fujian Provincial Hospital South Branch from January 2022 to April 2024. Clinical information and pregnancy outcomes were collected. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship and predictive accuracy between immune-inflammatory markers and adverse pregnancy outcomes were analyzed. Results: In this study, 50 (22.4%) patients had adverse pregnancy outcomes. Significant differences were observed in neutrophils counts, monocytes counts, LDH, SII, and SIRI levels between the adverse pregnancy outcome groups (APOs) and the control groups (P<0.05). The area under the receiver operating characteristic (ROC) curve analysis revealed that SII (AUC=0.762), SIRI (AUC=0.764), and LDH (AUC=0.732) had high predictive values for adverse pregnancy outcomes. Notably, the combined model had the highest AUC of 0.805. Multivariate logistic regression identified SII had the highest odd ratio (OR) (OR=8.512; 95% CI(3.068-23.614)), followed by LDH (OR=4.905; 95% CI (1.167-11.101)), SIRI (OR=3.549; 95% CI(0.847-8.669)), and neutrophils count (OR=1.726; 95% CI (0.563-2.938)) as independent risk factors for adverse outcomes. Conclusion: Elevated levels of immune-inflammatory markers such as SII, SIRI, and LDH level are strong predictors of adverse pregnancy outcomes in thrombophilia-complicated pregnancies. These markers are significantly associated with maternal-neonatal outcomes. Our findings underscore the importance of monitoring immune-inflammatory markers in pregnant women with thrombophilia to improve maternal and neonatal outcomes.
RESUMEN
Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of proangiogenic and antiangiogenic factors. The pigment epitheliumderived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit8, 5ethynyl2'deoxyuridine and Transwell assays. In vitro angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, Fe2+, malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpressioninduced suppression of cell proliferation, invasion and tube formation. PEDF overexpressioninduced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wntßcatenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS.