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Objective To evaluate the incremental value of placental miR-7641 and ferroptosis-related molecular phenotypes beyond mean arterial pressure (MAP) for risk stratification of severe preeclampsia (SPE). Methods This retrospective study enrolled 64 women with SPE and 70 normotensive controls who underwent cesarean delivery between January 2023 and October 2024. Placental miR-7641 was quantified by qRT-PCR, and MDA, COX2, and GPX4 were measured by ELISA/TBA assay. Independent predictors were identified through multivariable logistic regression, and nested models were constructed (Model 1: MAP alone; Model 2: MAP plus independently significant molecular markers). Incremental discrimination was assessed using the net reclassification improvement (NRI), integrated discrimination improvement (IDI), and DeLong test. The SPE group was further stratified by gestational age at delivery into early-onset PE (EOPE; 34 weeks, n = 21) and late-onset PE (LOPE; ≥34 weeks, n = 43) for exploratory subgroup analysis. Results Compared with controls, SPE placentas exhibited significantly elevated miR-7641, MDA, and COX2 levels alongside significantly reduced GPX4 (all P 0.001), with more pronounced alterations in the EOPE subgroup (all Cohen’s d 0.8). In multivariable analysis, MAP (OR = 1.12), miR-7641 (OR = 2.24), and MDA (OR = 1.45) were independently associated with SPE. Model 2 improved the AUC from 0.843 to 0.906 compared with Model 1 (P = 0.008), with an NRI of 0.573 (P 0.001) and an IDI of 0.112 (P 0.001). Sensitivity analyses demonstrated that the associations attenuated but persisted after adjustment for gestational age, supporting the robustness of the findings. Conclusions Placental miR-7641 and MDA provide incremental risk stratification information beyond MAP, with ferroptosis-related molecular phenotypes being more prominent in EOPE. These findings constitute proof of concept; clinical translation awaits external validation.
Hu et al. (Wed,) studied this question.