Interventionist versus expectant care for severe pre-eclampsia before term

What is the issue?

Women who develop pre-eclampsia (high blood pressure and protein in the urine) before 34 weeks of pregnancy (early onset) are at risk of severe complications, and even death. These involve the woman's liver, kidneys, and clotting system, and cause neurological disturbances, such as headache, visual disturbances, and fits. If the placenta is involved, this can cause growth restriction or reduced amniotic fluid, placing the baby at risk.

Why is this important?

The only known cure for pre-eclampsia is delivery of the baby. Being born too early can in itself have problems for the baby, even with the administration of corticosteroids 24 to 48 hours beforehand, to help mature the lungs. Some hospitals follow a policy of early delivery, within 24 to 48 hours, called interventionist management, whilst others prefer to delay delivery until it is no longer possible to safely stabilise the woman's condition, called expectant management.

What evidence did we find?

We searched for evidence in November 2017 and identified six randomised trials. This review included six trials that randomly assigned women to a policy of interventionist management or expectant management when presenting with severe pre-eclampsia before 34 weeks of pregnancy. A total of 748 women were included in these six trials. Babies born to women allocated to an interventionist approach were probably more likely to experience adverse effects such as bleeding in the brain (intraventricular haemorrhage). They may also have been more likely to require ventilation, have a longer stay in the neonatal unit, have a lower gestation at birth in days, and weigh less at birth than those babies born to women allocated to an expectant management approach. There was insufficient evidence for reliable conclusions about the effects on perinatal deaths. Babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care.

There were no maternal deaths in the two studies that reported this outcome. The evidence was very low-quality for the outcome of fits or convulsions (eclampsia), or of fluid in the lungs (pulmonary oedema), and so it was uncertain whether interventionist care made any clear difference to the mothers' health. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for a severe form of pre-eclampsia, which affects the liver and blood clotting, called HELLP syndrome, which stands for haemolysis (breakdown of red blood cells), elevated liver enzymes (a sign of liver damage), and low platelets (platelets help the blood to clot). None of the studies reported on the incidence of stroke in the mother. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the caesarean section rate.

What does this mean?

In the absence of an over-riding maternal or fetal indication for immediate delivery, delay may be more beneficial for the baby. However, there were insufficient data to enable us to draw reliable conclusions about the comparative effects on most outcomes for the mother, and hence the maternal safety of an expectant approach.

This evidence was based on data from only six trials. Further large trials with long-term follow-up of the children are needed to confirm or refute whether expectant care is better than early delivery for women who suffer from severe pre-eclampsia before 34 weeks of pregnancy.

Authors' conclusions: 

This review suggested that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence was based on data from only six trials. Further large, high-quality trials are needed to confirm or refute these findings, and establish if this approach is safe for the mother.

Read the full abstract...
Background: 

Severe pre-eclampsia can cause significant mortality and morbidity for both mother and child, particularly when it occurs remote from term, between 24 and 34 weeks' gestation. The only known cure for this disease is delivery. Some obstetricians advocate early delivery to ensure that the development of serious maternal complications, such as eclampsia (fits) and kidney failure are prevented. Others prefer a more expectant approach, delaying delivery in an attempt to reduce the mortality and morbidity for the child that is associated with being born too early.

Objectives: 

To evaluate the comparative benefits and risks of a policy of early delivery by induction of labour or by caesarean section, after sufficient time has elapsed to administer corticosteroids, and allow them to take effect; with a policy of delaying delivery (expectant care) for women with severe pre-eclampsia between 24 and 34 weeks' gestation.

Search strategy: 

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) on 27 November 2017, and reference lists of retrieved studies.

Selection criteria: 

Randomised trials comparing the two intervention strategies for women with early onset, severe pre-eclampsia. Trials reported in an abstract were eligible for inclusion, as were cluster-trial designs. We excluded quasi-randomised trials.

Data collection and analysis: 

Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We assessed the quality of the evidence for specified outcomes using the GRADE approach.

Main results: 

We included six trials, with a total of 748 women in this review. All trials included women in whom there was no overriding indication for immediate delivery in the fetal or maternal interest. Half of the trials were at low risk of bias for methods of randomisation and allocation concealment; and four trials were at low risk for selective reporting. For most other domains, risk of bias was unclear. There were insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. Two studies reported on maternal deaths; neither study reported any deaths (two studies; 320 women; low-quality evidence). It was uncertain whether interventionist care reduced eclampsia (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.06 to 15.58; two studies; 359 women) or pulmonary oedema (RR 0.45, 95% CI 0.07 to 3.00; two studies; 415 women), because the quality of the evidence for these outcomes was very low. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome (RR 1.09, 95% CI 0.62 to 1.91; two studies; 359 women; low-quality evidence). No study reported on stroke. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the incidence of caesarean section (average RR 1.01, 95% CI 0.91 to 1.12; six studies; 745 women; Heterogeneity: Tau² = 0.01; I² = 63%).

For the baby, there was insufficient evidence to draw reliable conclusions about the effects on perinatal deaths (RR 1.11, 95% CI 0.62 to 1.99; three studies; 343 women; low-quality evidence). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.94, 95% CI 1.15 to 3.29; two studies; 537 women; moderate-quality evidence), more respiratory distress caused by hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), required more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women), and were more likely to have a lower gestation at birth (mean difference (MD) -9.91 days, 95% CI -16.37 to -3.45 days; four studies; 425 women; Heterogeneity: Tau² = 31.74; I² = 76%). However, babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care (average RR 1.19, 95% CI 0.89 to 1.60; three studies; 400 infants; Heterogeneity: Tau² = 0.05; I² = 84%). Babies born to mothers in the interventionist groups were more likely to have a longer stay in the neonatal intensive care unit (MD 7.38 days, 95% CI -0.45 to 15.20 days; three studies; 400 women; Heterogeneity: Tau² = 40.93, I² = 85%) and were less likely to be small-for-gestational age (RR 0.38, 95% CI 0.24 to 0.61; three studies; 400 women). There were no clear differences between the two strategies for any other outcomes.

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