Hemodynamic Effects of Magnesium Sulfate and Prediction of Adverse Outcomes in Severe Preeclampsia: A Multicenter Prospective Cohort Study with Repeated Measures

Hypertensive disorders of pregnancy, particularly preeclampsia with severe features, remain a leading cause of maternal and perinatal morbidity and mortality worldwide. Magnesium sulfate (MgSO₄) is the gold-standard therapy for seizure prophylaxis and treatment, yet its maternal and fetal hemodynamic effects throughout the therapeutic regimen (loading dose, maintenance, and post-infusion period) are incompletely characterized. Furthermore, no study has evaluated whether hemodynamic changes induced by MgSO₄, as assessed by Doppler velocimetry, can predict adverse maternal and perinatal outcomes. This multicenter prospective analytic cohort study with repeated measures will be conducted at four referral maternity hospitals in Northeast Brazil: Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) and Hospital da Mulher do Recife (HMR) in Recife, Pernambuco; and Instituto de Saúde Elpídio de Almeida (ISEA) in Campina Grande, Paraíba and Universidade Federal Uberlândia (UFU). Eligible participants will be pregnant individuals aged ≥18 years with preeclampsia with severe features, singleton pregnancies, live fetuses, and gestational age between 26+0 and 33+6 weeks. Each participant will serve as her own control, undergoing six standardized Doppler ultrasound assessments at defined time points before, during, and after MgSO₄ administration. The study vessels include the uterine arteries, ophthalmic artery, umbilical artery, fetal middle cerebral artery, and ductus venosus. Clinical and laboratory data, including biomarkers (sFlt-1/PlGF ratio, when available), and maternal, fetal, and neonatal outcomes will be recorded systematically. Mixed-effects models for repeated measures and predictive modelling approaches (ROC curves and multivariable models) will be used to: (i) characterize MgSO₄-associated hemodynamic changes over time, and (ii) evaluate the prognostic value of baseline Doppler indices and their longitudinal variations (Δ) for adverse outcomes.