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.