Outcome measures
The study outcomes were composite. Composite adverse neonatal outcome
included neonatal death, adverse respiratory outcomes (RDS,TTN ),
hypoglycemia, newborn sepsis, confirmed seizures, stroke, IVH,
cardiopulmonary resuscitation, mechanical ventilation,
umbilical-cord-blood arterial pH < 7.0 or base excess
< -12.5, a 5-minute Apgar score ≤ 3, and prolonged
hospitalization (≥ 5 days). As indicated by previous studies, these
outcomes were chosen as they are associated with significant risks of
neonatal mortality or long-standing neonatal morbidities, including
hypoxic ischemic encephalopathy [16, 12]. Secondary outcomes
included neonatal resuscitation (metabolic acidosis and/or resuscitation
at birth), metabolic complications (hypoglycemia and/or difficulties
feeding), and respiratory support (both invasive and non-invasive).
Non reassuring fetal status was defined as catergory III [17] or
persistent category II fetal heart rate pattern with abnormal labor
progress [18], non-reactive NST associated with recurrent
decelerations among non-laboring women [19], absent or reverse
umbilical artery end diastolic flow in the setting of IUGR [20].
Clinical chorioamnionitis included maternal fever in association with
uterine fundal tenderness, maternal tachycardia, fetal tachycardia,
purulent or foul amniotic fluid [21]. Mild metabolic acidosis was
defined as pH= 7.20 – 7.30 and BE = -6 − -12, moderate acidosis
consisted in pH= 7 – 7.19 and BE = -12 − -16, while severe acidosis was
pH < 7 and BE < -16. CPAP and oxygen administration
represented non-invasive respiratory support, as opposed to mechanical
ventilation, the invasive respiratory support. Neonatal sepsis was
defined as a clinical syndrome prompting antibiotic treatment, with or
without positive cultures. Cerebral lesions were suspected clinically,
screened by neonatal brain ultrasound, and confirmed on MRI. (For
details about specific definitions of outcomes please see Table S1) .