Planned delivery for pre-eclampsia between 34 and 37 weeks of gestation: the PHOENIX RCT
Authors: Chappell Lucy C , Brocklehurst Peter , Green Marcus , Hardy Pollyanna , Hunter Rachael , Beardmore-Gray Alice , Bowler Ursula , Brockbank Anna , Chiocchia Virginia , Cox Alice , Duhig Kate , Fleminger Jessica , Gill Carolyn , Greenland Melanie , Hendy Eleanor , Kennedy Ann , Leeson Paul , Linsell Louise , McCarthy Fergus P , O’Driscoll Jamie , Placzek Anna , Poston Lucilla , Robson Stephen , Rushby Pauline , Sandall Jane , Scholtz Laura , Seed Paul T , Sparkes Jenie , Stanbury Kayleigh , Tohill Sue , Thilaganathan Basky , Townend John , Juszczak Edmund , Marlow Neil , Shennan Andrew 
Published: November 2022

Background

In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia.

Methods

In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to <37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing.

Findings

Between 29 September 2014 and 10 December 2018, 901 women were recruited. Four hundred fifty women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group [289 (65%) women] compared with the expectant management group [338 (75%) women; adjusted relative risk 0.86, 95% CI 0.79 to 0.94; p = 0.0005]. The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group [196 (42%) infants] compared with the expectant management group [159 (34%) infants; 1.26, 1.08 to 1.47; p = 0.0034]. The results from the per-protocol analysis were similar. There were 9 serious adverse events in the planned delivery group and 12 in the expectant management group.

Interpretation

There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery.

Funding

National Institute for Health and Care Research Health Technology Assessment programme.