Algorithm-Based Timing of Delivery Using the sFlt-1/PlGF Ratio in Early-Onset Severe Preeclampsia. (MAP 2 Study : Management Based on Angiogenic Markers in Preeclampsia 2 Study )

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).

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.

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.

Duration of maternal hospitalization, defined as the number of days from randomization to hospital discharge. This is a continuous variable.

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)

Occurrence of small for gestational age (SGA), defined as birthweight <10th percentile for gestational age and sex, analyzed as a binary outcome

Gestational age at delivery (in weeks):

Cesarean delivery will be defined as any surgical delivery of the fetus. The outcome will be analyzed as a dichotomous variable and reported as the proportion of participants undergoing cesarean delivery .

Neonatal morbidity will be assessed using the Morbidity Assessment Index for Newborns (MAIN), a validated composite score based on 47 weighted clinical and laboratory indicators. Scores range from 0 (no morbidity) upward, with higher scores indicating greater neonatal morbidity and worse neonatal health status. Scores of 0-150 represented minimal/no morbidity, 151-500 mild morbidity, 501-800 moderate morbidity, and >800 severe morbidity .

Neonatal complications will include metabolic acidosis (umbilical artery pH <7.00 and base excess <-16), Apgar score <7 at 5 minutes, bronchopulmonary dysplasia, necrotizing enterocolitis stage 2 or 3 according to Bell's classification, Grade III intraventricular haemorrhage (IVH) and periventricular haemorrhagic infarction (PHI), according to the contemporary classification proposed by Parodi (28), periventricular leukomalacia, retinopathy stage 3-5, hypoxic-ischemic encephalopathy (defined by Apgar score <5 at 10 minutes, umbilical artery pH <7.00, or base excess >-16 at 60 minutes, associated with neurological signs), neonatal renal insufficiency (creatinine >1.5 mg/dL), and the need for inotropic agents.

Number of days admitted in the high-dependency care unit

Lenght of neonatal stay from admission to discharge from NICU

Mean uterine artery pulsatility index measured by Doppler ultrasound.

Middle cerebral artery pulsatility index measured by fetal Doppler ultrasound.

Umbilical artery pulsatility index measured by Doppler ultrasound.

Placental dysfunction assessed by histopathological examination according to the Amsterdam consensus classification, including features of maternal vascular malperfusion and fetal vascular malperfusion