Churchill, David and Duley, Lelia and Thornton, Jim and Jones, Leanne (2013) Interventionist versus expectant care for severe pre-eclampsia

1 Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks’ gestation (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. baby, there is insufficient evidence for reliable conclusions about the effects on stillbirth or death after delivery (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.69 to 1.71; four studies; 425 women). Babies whose mothers had been allocated to the interventionist group hadmore intraventricular haemorrhage (RR 1.82, 95%CI 1.06 to 3.14; one study; 262 women), more hyalinemembrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), require 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 in days (average mean difference (MD) -9.91, 95% CI -16.37 to -3.45; four studies; 425 women), more likely to be admitted to neonatal intensive care (RR 1.35, 95% CI 1.16 to 1.58) and have a longer stay in the neonatal intensive care unit (average MD 11.14 days, 95% CI 1.57 to 20.72 days; two studies; 125 women) than those allocated an expectant policy. Nevertheless, babies allocated to the interventionist policy were less likely to be small-for-gestational age (RR 0.30, 95% CI 0.14 to 0.65; two studies; 125 women). Women who had been allocated to the interventionist group were more likely to have a caesarean section (RR 1.09, 95% CI 1.01 to 1.18; four studies; 425 women) than those allocated an expectant policy. There were no statistically significant differences between the two strategies for any other outcomes. Authors’ conclusions This review suggests 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 is based on data from only four trials. Further large trials are needed to confirm or refute these findings and establish if this approach is safe for the mother. P L A I N L A N G U A G E S U M M A R Y Interventionist versus expectant care for severe pre-eclampsia before term 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, clotting system and cause neurological disturbances such as headache, visual disturbances, and exaggerated tendon reflexes. If the placenta is involved, this can cause growth restriction or reduced amniotic fluid, placing the baby at risk. 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, interventionist management, whilst others prefer to delay delivery until it is no longer possible to safely stabilise the woman’s condition, expectant management. This review included four 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 425 women were included in these four trials. Babies born to women allocated to an interventionist approach were more likely to experience adverse effects such as intraventricular haemorrhage and neonatal respiratory distress syndrome. They were also more likely to require admission to the neonatal intensive care unit and ventilation, have a longer stay in the neonatal unit and weigh less at birth than those babies born to women allocated to an expectant management approach. Women in the interventionist group were also more likely to require caesarean section for delivery. Delaying delivery may therefore be more beneficial for the baby. There are insufficient data, however, for reliable conclusions about the comparative effects on most outcomes for the mother and hence the maternal safety of an expectant approach. This evidence is based on data from only four small 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. B A C K G R O U N D Pre-eclampsia is a multisystem disorder that is usually associated with raised blood pressure and proteinuria, but can also involve the woman’s liver, kidneys, clotting system, or brain. If the placenta is involved this may lead to growth restriction or premature birth. Pre-eclampsia is a relatively common complication of pregnancy, and can occur at any time during the second half of pregnancy or in the first few weeks after delivery. Prediction models for adverse 2 Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks’ gestation (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. maternal outcome have been developed and validated in recent times (von Dadelszen 2011), but there is still a paucity of data to guide the clinician on the timing of delivery to ensure safety of both the mother and the baby in the long term. Pre-eclampsia is described in more detail in the generic protocol on interventions for treatment of pre-eclampsia and its consequences (Duley 2009). Description of the condition Hypertension in pregnancy is defined as a systolic blood pressure of 140 mmHg or more, and/or a diastolic pressure of 90 mmHg or more. To be diagnosed with pre-eclampsia the hypertension has to arise de novo after 20 weeks of pregnancy in combination with proteinuria defined as greater than 300 mg of total protein in a 24-hour urine collection (Davey 1988). Recently, proteinuria has been assessed using a spot urinemeasuring the protein to creatinine ratio. A protein: creatinine ratio of 30 mg/mmol correlates with a 24-hour protein excretion of greater than 300 mg in 24 hours (Morris 2012). This method of estimating the amount of protein being excreted has several advantages over the 24-hour urine collection and has been endorsed in a Royal College of Obstetricians and Gynaecologists (RCOG) Pre-eclampsia study group consensus statement (RCOG 2003). However, pre-eclampsia is a multisystem disorder and the diagnosis of hypertension and proteinuria is considered to be too restrictive for clinical practice. Clinicians are all too aware that the disease can present in several ways and it is necessary to be vigilant when assessing women with symptoms and signs that are strongly associated with the disease. This has led to a widening of the definition for clinical purposes, to include the following: de novo hypertension after 20weeks’ gestation and new onset of one of the following: a) proteinuria as defined above; b) renal insufficiency (creatinine > 0.09 mmol/L, or oliguria; c) liver disease (raised transaminases and/or severe right upper quadrant or epigastric pain); d) neurological problems, convulsions (eclampsia), hyper-reflexia with clonus (involuntary muscular contractions), severe headaches, persistent visual disturbances (scotoma); e) haematological disturbances: thrombocytopenia (reduced numbers of platelets), disseminated intravascular coagulation, haemolysis; or f ) fetal growth restriction (Brown 2001). There is no widely accepted definition of severe pre-eclampsia (Duley 2009). Nevertheless, the features described above in combination with the early onset of the disease between 24 and 34 weeks’ gestation, would be considered by most clinicians to represent severe pre-eclampsia. We therefore did not further define nor categorise “severity”. Description of the intervention Within clinical practice, some units advocate early delivery, which has been referred to as ’aggressive management’ (Sibai 1984), but in this review the term ’interventionist’ is preferred. This means delivery by either induction of labour or caesarean section after corticosteroids have been given to improve fetal lung maturation, which in practice is after 24 to 48 hours (Crowley 1996). Others prefer to give corticosteroids, stabilise the woman’s condition and then, if possible, aim to delay delivery. This is usually known as ’expectant management’ (Derham 1989). The greatest dilemma in when to deliver is balancing the risks to mother and baby when the pregnancy is somewhere between 24 to 34 weeks. Early delivery resulting in a very premature baby could lead to more neonatal complications such as respiratory distress syndrome (difficulty in breathing and oxygenation), intraventricular haemorrhage (bleeding into the cavities of the brain) and necrotising enterocolitis (bleeding into the wall of the bowel due to a lack of oxygen). Conversely, delaying delivery in an attempt to allow fetal maturation could place the mother in jeopardy and at risk of multisystem organ failure as outlined above. It also prolongs the time that a fetus is in a potentially hostile in utero environment. This in turn will continue to adversely affect the growth of the fetus and may result in an intrauterine death, from severe hypoxia or an acute event such as an abruption. Although the precise cut offs for gestational age will vary with different settings, before 24 weeks the child has little chance of survival. After 34 weeks the prognosis improves with nearly 100 per cent survival. Between 24 and 34 weeks mortality decreases with increasing gestational age, but especially below 28 weeks there is also considerable risk of survival with severe disability. A structured review of observational studies found that expectant care for severe pre-eclampsia was associated with a prolongation of the pregnancy by between one and two weeks with better outcomes for babies and low risks for the mother. There were fewer neonatal deaths and complications of prematurity (Magee 2009). Why it is important to do this review This difficult clinical dilemma occurs relatively frequently in large units, and currently decisions are based mainly upon personal experience rather than good evidence. There is a great need for reliable data to help inform this decision-making. Other aspects of care forwomenwith severe pre-eclampsia are dealt with in other reviews. These include drugs for lowering very high blood pressure (Duley 2006), prophylactic anticonvulsants (Duley 2010) and plasma volume expansion (Duley 1999b). Prevention of pre-eclampsia is covered by reviews of calcium supplementation (Hofmeyr 2010), antiplatelets (Duley 2007), salt intake (Duley 1999a; Duley 2005) and magnesium supplementation (Makrides 2001). O B J E C T I V E S To evaluate the comparative benefits and risks of a policy of early delivery by induction of labour or by caesarean section after suf3 Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks’ gestation (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ficient 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.