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Randomized Controlled Trial
. 2023 Dec;27(28):1-22.
doi: 10.3310/CWWH0622.

Planned delivery for pre-eclampsia between 34 and 37 weeks of gestation: the PHOENIX RCT

Lucy C Chappell  1 , Peter Brocklehurst  2 , Marcus Green  3 , Pollyanna Hardy  4 , Rachael Hunter  5 , Alice Beardmore-Gray  1 , Ursula Bowler  4 , Anna Brockbank  1 , Virginia Chiocchia  4 , Alice Cox  1 , Kate Duhig  1 , Jessica Fleminger  1 , Carolyn Gill  6 , Melanie Greenland  4 , Eleanor Hendy  1 , Ann Kennedy  4 , Paul Leeson  7 , Louise Linsell  4 , Fergus P McCarthy  8 , Jamie O'Driscoll  9 , Anna Placzek  4 , Lucilla Poston  1 , Stephen Robson  10 , Pauline Rushby  4 , Jane Sandall  1 , Laura Scholtz  1 , Paul T Seed  1 , Jenie Sparkes  1 , Kayleigh Stanbury  4 , Sue Tohill  6 , Basky Thilaganathan  11 , John Townend  12 , Edmund Juszczak  13 , Neil Marlow  14 , Andrew Shennan  1 ; PHOENIX Study Group
Affiliations
Randomized Controlled Trial

Planned delivery for pre-eclampsia between 34 and 37 weeks of gestation: the PHOENIX RCT

Lucy C Chappell et al. Health Technol Assess. 2023 Dec.

Abstract

Background: In women with late preterm pre-eclampsia (i.e. at 34+0 to 36+6 weeks' gestation), the optimal delivery time is unclear because limitation of maternal-fetal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether or not planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of perinatal or infant outcomes, compared with expectant management, in women with late preterm pre-eclampsia.

Methods: We undertook an individually randomised, triple non-masked controlled trial in 46 maternity units across England and Wales, with an embedded health economic evaluation, comparing planned delivery and expectant management (usual care) in women with late preterm pre-eclampsia. The co-primary maternal outcome was a maternal morbidity composite or recorded systolic blood pressure of ≥ 160 mmHg (superiority hypothesis). The co-primary short-term perinatal outcome was a composite of perinatal deaths or neonatal unit admission (non-inferiority hypothesis). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The primary 2-year infant neurodevelopmental outcome was measured using the PARCA-R (Parent Report of Children's Abilities-Revised) composite score. The planned sample size of the trial was 900 women; the trial is now completed. We undertook two linked substudies.

Results: Between 29 September 2014 and 10 December 2018, 901 women were recruited; 450 women [448 women (two withdrew consent) and 471 infants] were allocated to planned delivery and 451 women (451 women and 475 infants) were allocated to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group [289 (65%) women] than in the expectant management group [338 (75%) women] (adjusted relative risk 0.86, 95% confidence interval 0.79 to 0.94; p = 0.0005). The incidence of the co-primary perinatal outcome was significantly higher in the planned delivery group [196 (42%) infants] than in the expectant management group [159 (34%) infants] (adjusted relative risk 1.26, 95% confidence interval 1.08 to 1.47; p = 0.0034), but indicators of neonatal morbidity were similar in both groups. At 2-year follow-up, the mean PARCA-R scores were 89.5 points (standard deviation 18.2 points) for the planned delivery group (290 infants) and 91.9 points (standard deviation 18.4 points) for the expectant management group (256 infants), both within the normal developmental range (adjusted mean difference -2.4 points, 95% confidence interval -5.4 to 0.5 points; non-inferiority p = 0.147). Planned delivery was significantly cost-saving (-£2711, 95% confidence interval -£4840 to -£637) compared with expectant management. There were 9 serious adverse events in the planned delivery group and 12 in the expectant management group.

Conclusion: In women with late preterm pre-eclampsia, planned delivery reduces short-term maternal morbidity compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater short-term neonatal morbidity (such as need for respiratory support). At 2-year follow-up, around 60% of parents reported follow-up scores. Average infant development was within the normal range for both groups; the small between-group mean difference in PARCA-R scores is unlikely to be clinically important. Planned delivery was significantly cost-saving to the health service. These findings should be discussed with women with late preterm pre-eclampsia to allow shared decision-making on timing of delivery.

Limitations: Limitations of the trial include the challenges of finding a perinatal outcome that adequately represented the potential risks of both groups and a maternal outcome that reflects the multiorgan manifestations of pre-eclampsia. The incidences of maternal and perinatal primary outcomes were higher than anticipated on the basis of previous studies, but this did not limit interpretation of the analysis. The trial was limited by a higher loss to follow-up rate than expected, meaning that the extent and direction of bias in outcomes (between responders and non-responders) is uncertain. A longer follow-up period (e.g. up to 5 years) would have enabled us to provide further evidence on long-term infant outcomes, but this runs the risk of greater attrition and increased expense.

Future work: We identified a number of further questions that could be prioritised through a formal scoping process, including uncertainties around disease-modifying interventions, prognostic factors, longer-term follow-up, the perspectives of women and their families, meta-analysis with other studies, effect of a similar intervention in other health-care settings, and clinical effectiveness and cost-effectiveness of other related policies around neonatal unit admission in late preterm birth.

Trial registration: The trial was prospectively registered as ISRCTN01879376.

Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in Health Technology Assessment; Vol. 27, No. 28. See the NIHR Journals Library website for further project information.

Keywords: EXPECTANT MANAGEMENT; PLANNED DELIVERY; PRE-ECLAMPSIA; PREGNANCY.

Plain language summary

We know that pre-eclampsia is a common condition and can cause serious illness in a pregnant woman or baby. It is unclear how we should best advise women about the timing of delivery if they develop the condition between 34 and 37 weeks of pregnancy. We wanted to compare planned early birth and usual clinical practice (that is, planning birth at 37 weeks of pregnancy, or sooner if needed for clinical reasons). Between September 2014 and December 2018, 901 women with pre-eclampsia between 34 and 37 weeks of pregnancy agreed to take part. Half of the women were randomised to planning the birth of their babies within 48 hours and half were randomised to watching and waiting. During the study we collected pregnancy and birth information and health outcomes for the mother and the baby for 2 years after birth. We found that planned early birth is better for these women, with fewer complications such as severely high blood pressure. We found that more babies in the planned birth group were admitted to the neonatal unit, mainly because they were premature, but they did not have more complications such as breathing problems and they did not stay longer in the unit than babies in the usual clinical practice group. At 2 years old, the babies in both groups had similar scores for development, with their average scores in the normal range. Women with pre-eclampsia and their doctors will be able to make better decisions about the timing of delivery. Because the number of complications was reduced, and there was no difference in complications for the baby (though more babies were admitted to the neonatal unit), women and their doctors may use this information to share decision-making around timing of delivery.

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References

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