Study population
Women with a singleton viable pregnancy (antenatal stillbirth were
excluded) were classified according to the circumstances at delivery as
spontaneous PTL, pPROM or indicated delivery. The diagnosis of preterm
labor was based on clinical criteria of regular uterine contractions
accompanied by progressive changes in cervical dilation and effacement
[13]. As preterm labor occurred ≥ 34 weeks, tocolytic therapy was
not administered. Women presenting with pPROM between
34+0 and 36+6 weeks’ gestation, who
were not in labor within 24 hours after rupture of membranes and had no
indication for immediate delivery, were expectantly managed as detailed
in the PPROMEXIL trial [14]. Women in whom pPROM was diagnosed after
24+0 weeks, but who had not delivered by
34+0 weeks’ gestation, could also be managed
expectantly. The diagnosis of membrane rupture was confirmed by
visualization of amniotic fluid passing from the cervical canal and
pooling in the vagina, a basic pH test of vaginal fluid, or arborization
(ferning) of dried vaginal fluid, which is identified under microscopic
evaluation. When needed, commercially available test for amniotic
proteins (Amnioquick ® Biosynex) were utilized to confirm pPROM
according to local protocols. A course of therapy with a combination of
a beta lactam and a macrolide antibiotic was left at the discretion of
each study site even when pPROM occurred after 34 weeks, as a
preliminary inquiry had found such practice to be common. Rupture of
membranes was considered as the delivery indication only when
spontaneous labor occurred during expectant management, or if the
patient and/or her obstetrician opted for an elective delivery. Instead,
if onset of labor occurred within 24 hours of rupture of membranes,
spontaneous PTL was the delivery indication. We defined indicated births
as those occurring after labor induction or cesarean delivery without
labor due to maternal, fetal or obstetric complications.
No specific recommendations were given concerning administration of
antenatal corticosteroids, as the study was conducted prior to the
publication of the ALPS trial [15].
The timing of delivery was determined in completed weeks of gestation
such that 34 weeks (for example) included deliveries at
34+0 – 34+6 weeks. Gestational age
was based either on first trimester ultrasound scan or, in women with a
regular cycle, on the first day of the last menstrual period if the
expected date of delivery differed less than 7 days from that estimated
by ultrasound.