Planned delivery to improve postpartum cardiac function in women with preterm pre-eclampsia: the PHOEBE mechanisms of action study within the PHOENIX RCT
McCarthy FP., O’Driscoll J., Seed P., Brockbank A., Cox A., Gill C., Green M., Marber M., Poston L., Placzek A., Shennan A., Sparkes J., Leeson P., Thilaganathan B., Chappell LC.
BackgroundWomen whose pregnancies are affected by hypertensive disorders of pregnancy, in particular preterm pre-eclampsia, are at increased risk of long-term cardiovascular morbidity and mortality.ObjectivesTo investigate the hypothesis that prolongation of a pregnancy affected by preterm pre-eclampsia managed by expectant management compared with planned early delivery would result in worse cardiovascular function 6 months postpartum.DesignA randomised controlled trial.Setting28 maternity hospitals in England and Wales.ParticipantsWomen who were eligible for the Pre-eclampsia in HOspital: Early iNductIon or eXpectant management (PHOENIX) study were approached and recruited for the PHOEBE study. The PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) study was a parallel-group, non-masked, multicentre, randomised controlled trial that was carried out in 46 maternity units across England and Wales. This study compared planned early delivery with expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia who were 34 weeks’ gestation to less than 37 weeks’ gestation and having a singleton or dichorionic diamniotic twin pregnancy.InterventionsPostpartum follow-up included medical history, blood pressure assessment and echocardiography. All women had blood sampling performed on at least two time points from recruitment to the 6-month follow-up for assessment of cardiac necrosis markers.Main outcome measuresPrimary outcome was a composite of systolic and/or diastolic dysfunction (originally by 2009 guidelines then updated by 2016 guidelines, with an amended definition of diastolic dysfunction). Analyses were by intention to treat, together with a per-protocol analysis for the primary and secondary outcomes.ResultsBetween 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited across 28 maternity units in England and Wales. A total of 133 women were allocated to planned delivery, 137 women were allocated to expectant management and a further 150 received non-randomised expectant management within usual care. The mean time from enrolment to delivery was 2.5 (standard deviation 1.9) days in the planned delivery group compared with 6.8 (standard deviation 5.3) days in the expectant management group. There were no differences in the primary outcome between women in the planned delivery group and those in the expectant management group using either the 2009 (risk ratio 1.06, 95% confidence interval 0.80 to 1.40) or the 2016 definition (risk ratio 0.78, 95% confidence interval 0.33 to 1.86). Overall, 10% (31/321) of women had a left ventricular ejection fraction ConclusionsPreterm pre-eclampsia results in persistence of hypertension in the majority of women with late preterm pre-eclampsia at 6 months postpartum and systolic dysfunction in 10%. Pre-eclampsia should not be considered a self-limiting disease of pregnancy alone.Future workInterventions aimed at reducing cardiovascular dysfunction.Trial registrationCurrent Controlled Trials ISRCTN01879376.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 12. See the NIHR Journals Library website for further project information.