Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial

Background Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. Methods The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation ≥24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. Findings Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29 (3%) of 912 neonates of mothers assigned to expectant management (relative risk [RR] 0·8, 95% CI 0·5–1·3; p=0·37). The composite secondary outcome of neonatal morbidity and mortality occurred in 73 (8%) of 923 neonates of mothers assigned to immediate delivery and 61 (7%) of 911 neonates of mothers assigned to expectant management (RR 1·2, 95% CI 0·9–1·6; p=0·32). However, neonates born to mothers in the immediate delivery group had increased rates of respiratory distress (76 [8%] of 919 vs 47 [5%] of 910, RR 1·6, 95% CI 1·1–2·30; p=0·008) and any mechanical ventilation (114 [12%] of 923 vs 83 [9%] of 912, RR 1·4, 95% CI 1·0–1·8; p=0·02) and spent more time in intensive care (median 4·0 days [IQR 0·0–10·0] vs 2·0 days [0·0–7·0]; p<0·0001) compared with neonates born to mothers in the expectant management group. Compared with women assigned to the immediate delivery group, those assigned to the expectant management group had higher risks of antepartum or intrapartum haemorrhage (RR 0·6, 95% CI 0·4–0·9), intrapartum fever (0·4, 0·2–0·9), and use of postpartum antibiotics (0·8, 0·7–1·0), and longer hospital stay (p