Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial

Virginia Chiocchia,E Tsoi ,Sambita Basak,Bee K. Tan ,Asma Khalil,Sujatha Thamban,Jason Waugh,Jacqueline Bamfo,Katarzyna Gajewska‐Knapik ,Zoey Robinson,Laura E. Scholz ,Anna Placzek,Lavinia Margarit,Pensée Wu ,Mark Waterstone,Rita Arya,Pauline Rushby,Cornelia Wiesender,Gabrielle Bambridge,Sue Tohill,Michelle Kemp,S Subair ,Adam Gornall,Ellen Knox,Kate Harding,Janet Cresswell,Vidya Thakur,Ursula Bowler,Derek Tuffnell,Antoinette Johnson,Lucy C Chappell,Melanie Greenland,Jonathan N. Townend ,Nigel Simpson,Ramesh Ganapathy,Marcus E. Green ,Umber Agarwal,Rachael Hunter,Neil Marlow,Stephen Robson,Mohamed Shahin,Jim Thornton,Jenie Sparkes,Jenny Myers,Natasha Singh,Sudha Rao ,Philippa J. Marsden ,Louise Linsell,Sophia Stone,Andrew Shennan,Caroline Everden,Richard J. Howard ,Bini Ajay,Eleanor Hendy,Madhuchanda Dey,Pollyanna Hardy,Peter Brocklehurst,David Churchill,Bhavna Sharma,Helen Cameron,Mark James,Fiona Crosfill,Mark Denbow,Jo Ficquet,Irshad Ahmed,Justine Nugent,Rahila Khan,Angela Garrett,Rehan Ullah Khan ,Jane Sandall,Karen McIntyre,Žarko Alfirević ,Joanna Girling,Edmund Juszczak

doi:10.1016/s0140-6736(19)31963-4

Abstract

SummaryBackgroundIn 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.MethodsIn 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 less than 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.FindingsBetween Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 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 0·79–0·94; 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, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group.InterpretationThere 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.FundingNational Institute for Health Research Health Technology Assessment Programme.

Highlights

Pre-eclampsia is a multisystem disorder of pregnancy, characterised by placental and maternal vascular dys function and associated with substantial morbidity and mortality for the mother and infant
In women with late preterm pre-eclampsia, the optimal time for delivery is less clear, because limitation of maternal disease progression needs to be balanced against complications for the infant either related to ongoing expectant management or those related to planned
We found no published randomised controlled trials evaluating planned delivery against expectant management for women with late preterm pre-eclampsia between 34 and 37 weeks’ gestation, some women with mild pre-eclampsia might have been included in the HYPITAT-1 trial, in women with pregnancy hypertension from 36 weeks’ gestation

Summary

Introduction

Pre-eclampsia is a multisystem disorder of pregnancy, characterised by placental and maternal vascular dys function and associated with substantial morbidity and mortality for the mother and infant. Standard management of pre-eclampsia involves mater nal and fetal assessment and subsequent consideration of timely delivery to minimise maternal and perinatal morbidity, taking into consideration gestational age, progression of maternal disease, and fetal wellbeing. After 37 weeks’ gestation, most national guidelines recommend prompt delivery for a woman with pre-eclampsia[3,4] because maternal risks can be significantly reduced without additional perinatal risks from such an intervention.[5] In women with late preterm pre-eclampsia (between 34 and 37 weeks’ gestation), the optimal time for delivery is less clear, because limitation of maternal disease progression needs to be balanced against complications for the infant either related to ongoing expectant management (including needing emergency delivery, worsening growth restriction, and stillbirth) or those related to planned

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Conclusion