Preeclampsia, a hypertensive disorder that occurs during pregnancy, presents a significant threat to maternal and fetal health (2020). Severe preeclampsia, characterized by high blood pressure and proteinuria, can lead to serious complications such as placental abruption, fetal growth restriction, and even maternal organ failure (Overton et al., 2022; Torres-Torres et al., 2024). The onset of this clinical syndrome is marked by improper placental development (Jung et al., 2022), followed by the secretion of antiangiogenic factors, which is predominantly facilitated by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (Ives et al., 2020).

The pathogenesis of preeclampsia remains incompletely understood, but it is generally believed to be related to abnormal placental implantation, immune maladaptation, endothelial dysfunction, and metabolic disorders (Deer et al., 2023; Jena et al., 2020). Among these factors, endothelial dysfunction is considered a core pathophysiological change (Stepan et al., 2023), which affects hemodynamic stability and nutrient supply to the placenta. Consequently, managing the disease often involves antihypertensive treatments to control blood pressure (Cifkova, 2023), but the ideal treatment regimen that can also improve maternal and fetal outcomes remains a topic of active research.

Recent studies have shown that vitamin D plays a crucial role in pregnancy, not only influencing calcium metabolism (Fleet, 2022) but also modulating immune and vascular functions (de la Guia-Galipienso et al., 2021). Vitamin D deficiency has been linked to an increased risk of developing preeclampsia and adverse pregnancy outcomes (Mansur et al., 2022). This relationship suggests that supplementation with vitamin D could potentially improve pregnancy outcomes, particularly for patients at risk of severe preeclampsia. The role of vitamin D in regulating vascular tone and inflammatory pathways (Argano et al., 2023; Sanz et al., 2020) could provide significant benefits in improving blood pressure control and placental function in preeclampsia patients. Additionally, methyldopa and labetalol are two commonly used antihypertensive medications in managing preeclampsia (van de Vusse et al., 2022). Methyldopa is an alpha-2 adrenergic agonist, commonly used for blood pressure control in pregnancy, while labetalol, a combined alpha and beta-blocker, has been favored for its ability to reduce blood pressure without significantly affecting heart rate (Zhou et al., 2021).

Although these drugs have proven effective in treating hypertension during pregnancy, there is currently a lack of high-quality clinical research evidence regarding whether combining these three agents as a combined strategy for intensive intervention on top of the existing standard regimen (magnesium sulfate + nifedipine) can bring additional clinical benefits beyond simple blood pressure reduction—such as further improving uteroplacental blood flow, correcting serum biomarker disturbances, and ultimately improving pregnancy outcomes. Therefore, this study aims to fill this gap by employing a rigorous controlled design to evaluate the efficacy and safety of adding a triple regimen of vitamin D, methyldopa, and labetalol to the standard treatment of magnesium sulfate and nifedipine. Its unique clinical significance lies in exploring the potential value of an aggressive, multi-target combined treatment regimen for patients who remain at high risk after receiving first-line standard therapy.