Elsevier

The Lancet

Volume 385, Issue 9986, 20–26 June 2015, Pages 2492-2501
The Lancet

Articles
Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial

https://doi.org/10.1016/S0140-6736(14)61998-XGet rights and content

Summary

Background

There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women.

Methods

We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792).

Findings

Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12–1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4–8·2; p=0·005). No maternal or perinatal deaths occurred.

Interpretation

For women with non-severe hypertensive disorders at 34–37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered.

Funding

ZonMw.

Introduction

Hypertensive disorders of pregnancy, such as gestational hypertension, pre-existing or chronic hypertension during pregnancy, pre-eclampsia, and superimposed pre-eclampsia,1 occur in roughly 10% of all pregnancies.2, 3 These disorders cause substantial maternal and neonatal morbidity and mortality worldwide.4, 5

Delivery of the placenta is the only definitive treatment for hypertensive disorders of pregnancy; it will stop progression and therefore has the potential to prevent adverse pregnancy outcomes. However, immediate delivery also has potential disadvantages. First, it can result in preterm or early term birth, which increases the risk of neonatal complications.6 Second, induction of labour might increase the risk of a need for caesarean section.7 Therefore, management of hypertensive disorders should be based on the balance between the risks of immediate delivery versus the risks of continuing the pregnancy. In severe pre-eclampsia before 34 weeks of gestation, delivery decreases the proportion of neonates born small for gestational age, while the effect on other neonatal morbidity and maternal outcomes is uncertain.8, 9, 10, 11 The first HYPITAT study showed that delivery reduces the risk of adverse maternal outcomes for women with mild gestational hypertension or pre-eclampsia beyond 37 weeks of gestation, without affecting neonatal outcomes or risk of caesarean section.12 However, for women at 34–37 weeks of gestation who have hypertensive disorders, little is known of the risks and benefits of immediate delivery versus continuing pregnancy.13 Dutch guidelines do not advise about timing of delivery for women with hypertensive disorders of pregnancy and both strategies are practised in Netherlands.14 Therefore, we investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes for women with hypertensive disorders between 34 and 37 weeks' gestation.

Section snippets

Study design and participants

We did an open-label, randomised controlled trial in seven academic hospitals and 44 non-academic hospitals in Netherlands.15 Women were eligible if they had gestational hypertension, pre-eclampsia, deteriorating pre-existing hypertension, or superimposed pre-eclampsia, and had a gestational age of 340/7 weeks up to and including 366/7 weeks (in Netherlands, gestational age is routinely measured by first trimester ultrasound).

We defined gestational hypertension as a diastolic blood pressure of

Results

Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate (figure 1). Of the 193 women who did not give informed consent to be randomly assigned, 176 gave informed consent for us to extract data from their medical files; 168 of them (95%) were monitored expectantly. 704 women gave informed consent to be randomly assigned and were allocated to immediate delivery (n=353) or expectant monitoring (n=351). One woman withdrew after being randomised to immediate delivery, which

Discussion

In our study population, immediate delivery led to fewer adverse maternal outcomes than expectant monitoring. But although the RR suggests a large effect, the fact that the absolute risk of adverse maternal outcomes was lower than assumed in our sample size calculation resulted in a difference that was not statistically significant. The effect of immediate delivery on maternal outcomes therefore remains uncertain. However, given the low absolute risk, the potential benefit of immediate delivery

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