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).