Definitions
PE was defined by the presence of hypertension (systolic blood pressure (BP) of 140 mmHg or higher and/or diastolic BP of 90 mmHg or higher on at least two occasions 4 hours apart) accompanied by proteinuria (> 300 mg/24h or a urine protein/creatinine ratio > 0.3 mg/mmol) after 20 weeks of gestation in previously normotensive women (22). Severe PE was defined according to the American College of Obstetricians and Gynecologists as: systolic BP> 160 mmHg or diastolic BP > 110 mmHg on two occasions at least 4 hours apart, thrombocytopenia (platelet count less than 100x109), impaired liver function (blood concentrations of liver enzymes to twice normal and/or severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses), renal insufficiency (serum creatinine concentration greater than 1.1 mg/dl in absence of other renal diseases), pulmonary edema or new-onset cerebral or visual disturbances (23). Early-onset cases were considered when admission occurred before 34 weeks of gestation and gestational age was calculated according to the crown-rump length at first-trimester ultrasound scan (24).
Fetal growth restriction (FGR) was defined according to the Delphi consensus for early-onset form (25). Severe FGR was defined as persistent (6-hour apart) absent or reversed end-diastolic velocities in the umbilical artery (UA) or ductus venosus (DV) pulsatility index (PI) >95th centile.
Adverse neonatal outcome was defined by the presence of any of the following criteria: (i) stillbirth; (ii) neonatal death (before 28 days of age); (iii) neonatal metabolic acidosis (umbilical artery pH< 7.0 plus base deficit ≥ -16); (iv) 5-min Apgar score< 7; (v) bronchopulmonary dysplasia (oxygen requirement at 36 weeks corrected gestation unrelated to an acute respiratory episode); (vi) necrotizing enterocolitis (including only Bell’s stage 2 or 3); (vii) grade III or IV intraventricular hemorrhage; (viii) cystic periventricular leukomalacia; (ix) stage 3-5 retinopathy of prematurity; (x) hypoxic ischemic encephalopathy (10 minutes Apgar score ≤ 5 and/or pH 7.00 in first 60 minutes of life and/or base deficit ≥ -16 in first 60 minutes associated with abnormal conscious level and seizures and/or weak suck and/or hypotonia and/or abnormal reflexes); (xi) acute renal failure (serum creatinine greater than 1.5 mg/dL); and/or (xii) cardiac failure (requiring inotropic agents).