Preeclampsia is a serious pregnancy complication caused by abnormal placental development and function. It can lead to high blood pressure and damage to organs such as the liver, kidneys, brain, or cardiovascular system. In these cases, the only definitive treatment is delivery. However, deciding when to deliver is challenging: delaying delivery increases risks for both mother and baby, while delivering too early increases complications related to prematurity.
This study aims to evaluate whether a blood test measuring the sFlt-1/PlGF ratio an angiogenic marker that reflects placental function and predicts complications more accurately than traditional clinical criteria can help determine the optimal timing of delivery in women with severe preeclampsia between 30 weeks and 33 weeks plus 6 days of gestation. It is a multicenter, randomized controlled clinical trial conducted in 11 referral hospitals in Spain and will include 386 singleton pregnancies.
Participants will be randomly assigned to one of two groups. In the control group, standard expectant management will be followed, aiming to continue the pregnancy until 34 weeks if maternal and fetal conditions remain stable, and the sFlt-1/PlGF results will be masked. In the study group, delivery timing will be guided by the sFlt-1/PlGF ratio: if the ratio is greater than 655, delivery will be planned from 30 weeks onward; if greater than 110, delivery will be planned from 34 weeks; and if 110 or lower, pregnancy may continue until 37 weeks.
The study has two primary outcomes. The first is a composite of severe maternal complications, including neurological, hepatic, renal, respiratory, or cardiovascular dysfunction, severe hypertension, placental abruption, or fetal death. The second is a composite of neonatal complications, including admission to the neonatal intensive care unit or neonatal death.
The goal is to demonstrate that using angiogenic markers reduces maternal complications without significantly increasing neonatal complications. If successful, this approach could support more individualized management of early-onset severe preeclampsia, improving maternal safety while carefully balancing the risks of prematurity for the newborn.
Women aged 18 or older
Singleton pregnancies
Diagnosed with severe preeclampsia per 2020 ACOG criteria, between 30.0 and 33.6 weeks by first-trimester ultrasound.
Major fetal malformations
Confirmed genetic syndromes.
Parallel
sFlt-1/PlGF ratio-guided management algorithm
Other interventionManagement will be optimized based on angiogenic factor results. The sFlt-1/PlGF ratio will be determined at 30.0 weeks or at diagnosis between 30.0 and 33.6 weeks of gestation, and weekly measurements will be repeated. Based on predefined thresholds, delivery will be planned as follows: if sFlt-1/PlGF \>655, planned delivery will occur after fetal lung maturation if gestational age is \<35 weeks; if sFlt-1/PlGF \<655 and ≥110, planned delivery will occur after 34 weeks (with prior lung maturation if gestational age is \<35 weeks); and if sFlt-1/PlGF \<110, planned delivery will occur at 37 weeks. If immediate delivery criteria are met, delivery will be recommended regardless of the ratio.
Usual Care
Other interventionThe control arm will receive usual care for severe preeclampsia according to each center's clinical protocols. The sFlt-1/PIGF ratio will be determined at 30 weeks or diagnosis between 30 and 33.6 weeks of gestation, and weekly measurements will be repeated, but the ratio will not be available to the clinician or researchers
Composite adverse maternal and fetal outcomes
Dichotomous outcome: occurrence of ≥1 maternal or fetal complication from randomization to delivery. Complications included: (1) central nervous system dysfunction (eclampsia, Glasgow Coma Scale \<13, stroke, reversible ischaemic neurological deficit, or cortical blindness); (2) hepatic dysfunction (INR \>1.2 without disseminated intravascular coagulation, MELD score \>10, or hepatic hematoma/rupture); (3) renal dysfunction (dialysis, serum creatinine \>1.5 mg/dL, urine output \<0.5 mL/kg/h over 12 h per RIFLE criteria, or need for furosemide); (4) respiratory dysfunction (pulmonary edema, mechanical ventilation, oxygen \>50% for \>1 h, or severe respiratory distress with dyspnoea, crackles, and SaO₂ \<90%); (5) cardiovascular dysfunction (inotropes, left ventricular failure, myocardial infarction, or transfusion \>4 units); (6) resistant hypertension (≥3 drugs at maximal doses or controlled with ≥4); (7) placental abruption; and (8) stillbirth (≥22 weeks, WHO).
The neonatal composite outcome
Dichotomous outcome: Occurrence of ≥1 neonatal complication, defined as neonatal death before 28 days of life or admission to a neonatal intensive care unit or high-dependency unit according to British Association of Perinatal Medicine criteria, between birth and 28 days of life.
Maternal risk prediction using the fullPIERS model
The fullPIERS model is a validated prediction scoring for preeclampsia that incorporates gestational age (weeks), chest pain or dyspnea, oxygen saturation (%), platelet count (×10⁹/L), serum creatinine (mg/dL or µmol/L), and aspartate transaminase (AST, U/L) to estimate the risk of severe maternal complications, primarily within 48 hours after assessment.
Maternal length of hospitalization
Duration of maternal hospitalization, defined as the number of days from randomization to hospital discharge. This is a continuous variable.
Intrauterine growth restriction
Occurrence of prenatal fetal growth restriction (FGR), defined as an antenatal estimated fetal weight \<10th percentile for gestational age on ultrasound, assessed as a dichotomous outcome (yes/no)
Postnatal small for gestational age
Occurrence of small for gestational age (SGA), defined as birthweight \<10th percentile for gestational age and sex, analyzed as a binary outcome
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Hospital Clinic of Barcelona
Lead sponsor
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Collaborator
Instituto de investigación Hospital 12 de Octubre
Collaborator
Hospital de Sant Pau
Collaborator
Fundació Sant Joan de Déu
Collaborator
Hospital Universitario La Paz
Collaborator
Hospital Materno-Infantil de Canarias. Las Palmas de Gran Canaria. Spain
Collaborator
Hospital Son Llatzer
Collaborator
Hospital Clinico Universitario San Cecilio
Collaborator
Hospital Universitario Virgen de la Arrixaca
Collaborator
Fundacion Para La Investigacion Hospital La Fe
Collaborator
Hospital Vall d'Hebron
Collaborator
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