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NIHR Signal Planned earlier delivery for late pre-eclampsia may be better for mothers

Published on 19 November 2019

doi: 10.3310/signal-000838

If pregnant women develop late pre-eclampsia, after 34 but before 37 weeks of gestation, then planning to deliver their babies within 48 hours of the diagnosis reduces the risk of problems to the mother. This is compared with waiting until 37 weeks or delivering earlier if other problems arise (“expectant management”). However, this benefit needs to be offset against an increased likelihood of the baby being admitted to the neonatal unit.

This trial found that in women with late preterm pre-eclampsia, planned delivery reduces the chance of complications such as hypertension for the mother (65% versus 75% in the expectant management group). While their babies are more likely (42% versus 34%) to be admitted to the neonatal unit, there was not a significantly greater risk of morbidity.

The results of this study of 900 women will aid the decision-making process for women with late pre-eclampsia and the healthcare professionals involved in their care.

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Why was this study needed?

Mild pre-eclampsia affects up to 6% of pregnancies, with severe cases developing in about 1 to 2% of pregnancies. Early signs include high blood pressure and having protein in the urine. Symptoms such as ankle swelling and headaches can occur if the condition progresses. In rare cases, there can be serious complications such as convulsions and stroke as well as stillbirth.

The cause is not yet fully understood, but it is thought to be linked to problems with the placenta. Delivering the baby is the only cure. Less urgent cases are usually monitored with the intent of progressing the pregnancy as far as possible to avoid complications associated with prematurity in the baby. The aim of this study was to determine whether inducing delivery earlier reduces the chance of harm to the mother without harming the baby despite the baby being born before they are considered fully developed.

What did this study do?

The PHOENIX randomised controlled trial allocated 448 women to planned delivery and 451 women to expectant management (usual care). All had late pre-eclampsia.

The trial took place in 46 consultant-led maternity units across England and Wales. Those in the intervention group were scheduled for initiation of delivery within 48 hours of randomisation to enable preparations such as neonatal lung acceleration to take place. Delivery was by induction of labour unless a caesarean section was necessary. Expectant management involved delivery at 37 weeks or sooner as per NICE recommendations.

Longer-term results from this trial are still being collected. For example, it will be useful to know if those infants in the intervention group have a higher incidence of developmental delay.

What did it find?

  • Babies in the planned delivery arm were born on average five days earlier than controls, according to their gestational age.
  • The primary outcome for the baby was a combination of either death or neonatal unit admission. This was higher in the planned delivery group affecting 196 (42%) infants compared with 159 (34%) infants in the expectant management group (adjusted relative risk [aRR] 1.26, 95% confidence interval [CI] 1.08 to 1.47). However, admission was mainly attributed to prematurity, without excessive respiratory or other morbidity, intensity of care, or length of stay, and there were no deaths.
  • The primary maternal outcome was either a recorded high systolic blood pressure of at least 160 mmHg after randomisation or any of the fullPIERS model outcomes (Pre-eclampsia Integrated Estimate of RiSk). This includes specific outcomes such as death, stroke and acute renal failure. The incidence of any of these outcomes was lower in the planned delivery group, affecting 289 (65%) women compared with 338 (75%) women in the expectant management group (aRR 0.86, 95% CI 0.79 to 0.94).
  • Progression to severe pre-eclampsia was the main adverse outcome for both maternal groups, affecting 287 (64%) women in the planned delivery group compared with 334 (74%) women in the expectant management group (aRR 0.86, 95% CI 0.79 to 0.94). There were no strokes, low incidence of other complications and one death that was thought to be unrelated to the trial.
  • Total maternal and infant costs were lower in the planned delivery group compared with the expectant management group, with an adjusted cost saving of £1,478 (95% CI £2,354 to £605).

What does current guidance say on this issue?

Recent NICE guidance on the diagnosis and management of hypertension in pregnancy recommends that women diagnosed before 34 weeks should be monitored until they reach 37 weeks unless the condition worsens. Intravenous magnesium sulphate and a course of antenatal corticosteroids should be offered in line with the NICE guideline on preterm labour and birth.

The advice for women between 34 and 37 weeks is the same, but in addition, it states that if considering a planned birth, it is important to take into account the woman's and baby's condition. A course of antenatal corticosteroids should be considered, in line with the NICE guideline on preterm labour and birth. At 37 weeks and above birth should be initiated within 24 to 48 hours.

What are the implications?

The results of this trial suggest that early planned delivery for late pre-term pre-eclampsia is better for the mother and does no harm to the baby, though at the cost of more admissions to the neonatal unit. If, as the authors of the trial suggest, alternative care strategies such as transitional care to enable mother and child to stay together, then this disadvantage could be minimised. Further long-term results are awaited.

Citation and Funding

Chappell LC, Brocklehurst P, Green ME et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet. 2019;394:1181-90.

This project was funded by the NIHR Health Technology Assessment Programme (project number 12/25/03).

Bibliography

NHS website. Pre-eclampsia. London: Department of Health and Social Care; updated 2018.

NICE. Hypertension in pregnancy: diagnosis and management. NG133. London: National Institute for Health and Care Excellence; 2019.

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Care Excellence; updated 2019.

Why was this study needed?

Mild pre-eclampsia affects up to 6% of pregnancies, with severe cases developing in about 1 to 2% of pregnancies. Early signs include high blood pressure and having protein in the urine. Symptoms such as ankle swelling and headaches can occur if the condition progresses. In rare cases, there can be serious complications such as convulsions and stroke as well as stillbirth.

The cause is not yet fully understood, but it is thought to be linked to problems with the placenta. Delivering the baby is the only cure. Less urgent cases are usually monitored with the intent of progressing the pregnancy as far as possible to avoid complications associated with prematurity in the baby. The aim of this study was to determine whether inducing delivery earlier reduces the chance of harm to the mother without harming the baby despite the baby being born before they are considered fully developed.

What did this study do?

The PHOENIX randomised controlled trial allocated 448 women to planned delivery and 451 women to expectant management (usual care). All had late pre-eclampsia.

The trial took place in 46 consultant-led maternity units across England and Wales. Those in the intervention group were scheduled for initiation of delivery within 48 hours of randomisation to enable preparations such as neonatal lung acceleration to take place. Delivery was by induction of labour unless a caesarean section was necessary. Expectant management involved delivery at 37 weeks or sooner as per NICE recommendations.

Longer-term results from this trial are still being collected. For example, it will be useful to know if those infants in the intervention group have a higher incidence of developmental delay.

What did it find?

  • Babies in the planned delivery arm were born on average five days earlier than controls, according to their gestational age.
  • The primary outcome for the baby was a combination of either death or neonatal unit admission. This was higher in the planned delivery group affecting 196 (42%) infants compared with 159 (34%) infants in the expectant management group (adjusted relative risk [aRR] 1.26, 95% confidence interval [CI] 1.08 to 1.47). However, admission was mainly attributed to prematurity, without excessive respiratory or other morbidity, intensity of care, or length of stay, and there were no deaths.
  • The primary maternal outcome was either a recorded high systolic blood pressure of at least 160 mmHg after randomisation or any of the fullPIERS model outcomes (Pre-eclampsia Integrated Estimate of RiSk). This includes specific outcomes such as death, stroke and acute renal failure. The incidence of any of these outcomes was lower in the planned delivery group, affecting 289 (65%) women compared with 338 (75%) women in the expectant management group (aRR 0.86, 95% CI 0.79 to 0.94).
  • Progression to severe pre-eclampsia was the main adverse outcome for both maternal groups, affecting 287 (64%) women in the planned delivery group compared with 334 (74%) women in the expectant management group (aRR 0.86, 95% CI 0.79 to 0.94). There were no strokes, low incidence of other complications and one death that was thought to be unrelated to the trial.
  • Total maternal and infant costs were lower in the planned delivery group compared with the expectant management group, with an adjusted cost saving of £1,478 (95% CI £2,354 to £605).

What does current guidance say on this issue?

Recent NICE guidance on the diagnosis and management of hypertension in pregnancy recommends that women diagnosed before 34 weeks should be monitored until they reach 37 weeks unless the condition worsens. Intravenous magnesium sulphate and a course of antenatal corticosteroids should be offered in line with the NICE guideline on preterm labour and birth.

The advice for women between 34 and 37 weeks is the same, but in addition, it states that if considering a planned birth, it is important to take into account the woman's and baby's condition. A course of antenatal corticosteroids should be considered, in line with the NICE guideline on preterm labour and birth. At 37 weeks and above birth should be initiated within 24 to 48 hours.

What are the implications?

The results of this trial suggest that early planned delivery for late pre-term pre-eclampsia is better for the mother and does no harm to the baby, though at the cost of more admissions to the neonatal unit. If, as the authors of the trial suggest, alternative care strategies such as transitional care to enable mother and child to stay together, then this disadvantage could be minimised. Further long-term results are awaited.

Citation and Funding

Chappell LC, Brocklehurst P, Green ME et al. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet. 2019;394:1181-90.

This project was funded by the NIHR Health Technology Assessment Programme (project number 12/25/03).

Bibliography

NHS website. Pre-eclampsia. London: Department of Health and Social Care; updated 2018.

NICE. Hypertension in pregnancy: diagnosis and management. NG133. London: National Institute for Health and Care Excellence; 2019.

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Care Excellence; updated 2019.

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

Published on 28 August 2019

Lucy C Chappell, Peter Brocklehurst, Marcus E Green, Rachael Hunter, Pollyanna Hardy, Edmund Juszczak, Louise Linsell, Virginia Chiocchia,Melanie Greenland, Anna Placzek, John Townend, Neil Marlow, Jane Sandall, Andrew Shennan, on behalf of the PHOENIX Study Group

The Lancet , 2019

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 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 noninferiority 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 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. 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.

Expert commentary

Pre-eclampsia carries risks to both mother and baby, but the only curative treatment is delivery, which also carries risks to the baby if the pregnancy has not yet reached term. The PHOENIX trial included women who were between 34 and 37 weeks, i.e. mildly pre-term, and compared a policy of delivery within 48 hours, with waiting until delivery was mandated by worsening maternal or foetal condition.

The immediate delivery policy reduced a composite of maternal adverse outcomes but increased a similar composite of adverse baby outcomes. The authors’ suggestion that the trade-off should be discussed with women to allow shared decision making is surely correct.

Jim Thornton, Professor of Obstetrics and Gynaecology, School of Clinical Sciences, University of Nottingham

The commentator declares no conflicting interests