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Temporising versus interventionist management (preterm and at term)

https://doi.org/10.1016/j.bpobgyn.2011.01.004Get rights and content

Pre-eclampsia has a strong association with adverse outcomes: high incidences at term, and low incidences of morbidity; low incidences remote from term, high incidences of morbidity. The ultimate cure for pre-eclampsia is delivery of the placenta, but gestational age at delivery has an effect on perinatal outcome. We review aspects of two contrasting management approaches, and their indication areas are described (i.e. a more interventionist approach of stabilization (with antihypertensive drugs if needed and corticosteroids for acceleration of fetal lung maturation) and delivery, compared with a more temporizing approach, that treats the symptoms until delivery is necessary. In general, the temporizing approach has been shown to be safe, but beyond 37 weeks gestational age, there is evidence for better outcomes after early delivery. Below that gestational age, trials are awaited that help determine the balance in individual cases, depending on severity of maternal disease and fetal condition.

Introduction

Hypertensive disorders of pregnancy (and pre-eclampsia specifically)1, 2, 3 remain a leading cause of maternal mortality internationally.4 The ultimate cure for pre-eclampsia is delivery of the placenta, although women may worsen (or new complications may develop) in the immediate postpartum period.5

The maternal syndrome of pre-eclampsia is associated with significant maternal morbidity, especially when the onset is below 32 weeks’ gestation.6, *7, *8 Potentially life-threatening conditions are rare but significant, and include placental abruption, eclampsia or other encephalopathies, stroke, pulmonary oedema, liver rupture, and renal insufficiency.

Fetal and neonatal consequences include stillbirth and complications of iatrogenic very preterm delivery. As such, they are strongly associated with gestational age at onset of pre-eclampsia, as well as severity of the maternal syndrome, which results in iatrogenic premature delivery and fetal growth restriction.*8, 9 Severe neonatal morbidity associated with very preterm delivery (i.e. retinopathy of prematurity, necrotising enterocolitis, respiratory distress syndrome, infectious morbidity and brain injury) may cause neonatal death or long-term morbidity (i.e. blindness, chronic lung disease, cerebral palsy or more subtle neurodevelopmental disabilities).10, 11, 12 In addition, intrauterine fetal growth restriction (IUGR) is commonly associated with early onset pre-eclampsia (before 34 weeks’).3 This IUGR is associated with compensatory physiological adaptation of blood flow (brain sparing) and, can ultimately lead to fetal death without delivery.13

On the basis of these observations, two contrasting management approaches have been developed for pre-eclampsia of early onset: a more interventionist approach of stabilisation (with antihypertensive treatment if needed and corticosteroids for acceleration of fetal lung maturation) and delivery, compared with a more temporising approach. Although such temporising management has long been called ‘expectant management’, this is a misnomer. ‘Expectant’ suggests a passive attitude from maternity-care providers. In reality, however, temporising management is active, requiring close maternal and fetal surveillance to determine the optimal timing of delivery, in addition to antihypertensive treatment (if needed) and antenatal corticosteroids used in an interventionist approach.

The relative maternal and perinatal benefits and risks of the interventionist compared with the temporising approaches are yet to be established. It must be assumed that prolongation of pregnancy associated with temporising care exposes the woman to further risk of complications, over and above that associated with the postpartum period (during which women often deteriorate).*14, 15, 16 On the other hand, it is probable that temporising management reduces neonatal morbidity and mortality.16, 17, 18, 19, *20, 21, 22

This review focuses on patient selection and the elements that together constitute temporising management of pre-eclampsia (Fig. 1) across gestational ages. It is based on available evidence from published meta-analyses (including Cochrane reviews), guidelines, and other relevant studies identified through a structured search of Medline until October 2010. The search was broad and the key words used among others (text word, MESH-term) were ‘pre-eclampsia or haemolysis elevated liver enzymes low platelets (HELLP) syndrome or fetal growth restriction’ and ‘management’; limits for English language, no limits for gestational age.

Section snippets

Acute symptom management

Maternal manifestations of pre-eclampsia show impressive variation between and within patients. Maternal expression ranges from isolated gestational hypertension, to pre-eclampsia, classically defined as gestational hypertension with proteinuria, with or without end-organ involvement such as eclampsia or the HELLP syndrome (haemolysis elevated liver enzymes low platelets).1, 2, 23 This broad definition of pre-eclampsia (which includes gestational hypertension without proteinuria but with

Treatment of severe hypertension

Severe hypertension (i.e. systolic blood pressure ≥ 160–170 mm Hg, diastolic blood pressure ≥ 110 mm Hg, or both) during pregnancy poses a serious threat to women and their babies. A direct statistical relationship exists between height of (systolic) blood pressure risk and risks of maternal complications, particularly stroke.27 The need for antihypertensive treatment is universally agreed at these blood pressure levels.28 A wide range of short-acting antihypertensive drugs is available for this

Treatment of non-severe hypertension

Non-severe hypertension during pregnancy (i.e. systolic blood pressure 140 to 160–170 mmHg, diastolic blood pressure 90–110 mmHg, or both) is common. In contrast to severe hypertension discussed above, the indications for antihypertensive therapy and target ranges for antihypertensive therapy vary widely across centres and between published guidelines.30 At the heart of this controversy are differences in anticipated effects. Antihypertensive drugs are often used in the belief that lowering blood

Prevention of seizures of eclampsia

Eclampsia, the occurrence of one or more convulsions (seizures), in association with pre-eclampsia, is a rare but serious complication, and can be decreased in frequency by anticonvulsant therapy. In pooled data, it was unequivocally shown that the use of magnesium sulphate for 24–48 h is the single most effective anticonvulsant drug, more than halving the risk of eclampsia compared with placebo or no therapy (relative risk [RR] 0.41, 95% confidence interval [CI] 0.29 to 0.58).34 Mild

Corticosteroids for haemolysis elevated liver enzymes low platelets syndrome

It has been suggested from observational studies that steroid treatment in HELLP syndrome may improve disordered maternal haematological and biochemical features. The controversy about steroid use for this purpose is based on uncertainty about whether steroids improve clinical maternal and perinatal outcomes. In a 2010 Cochrane review36, 11 trials (550 women) were identified that compared corticosteroids with placebo or no treatment. No significant difference was found in the risk of maternal

Corticosteroids for fetal lung maturation

After the publication of the randomised trial of Liggins and Howie in 1972,37 the introduction and widespread use of antenatal corticosteroids in severely preterm fetuses resulted in a drastic decrease in neonatal mortality and morbidity.38, 39 International guidelines now recognise the use of single course antenatal corticosteroids as standard care in pregnancies at imminent risk of preterm delivery at less than 34 weeks.38, 40, 41 Further information is required about the optimal

Pain

Maternal pain, such as headache, chest pain, or right-upper quadrant discomfort are considered to be non-specific markers of potential subclinical end-organ dysfunction of pre-eclampsia and, as such, they may be the best predictors for imminent maternal pathology.35 Their presence should prompt close maternal and fetal surveillance to detect the development of actual end-organ dysfunction. Under close observation, analgesic use is acceptable, and use of prophylactic magnesium sulphate for

Plasma volume expansion

Reports that diminished circulating plasma volume, reduced cardiac output and end-organ vasoconstriction are key features of pre-eclampsia or IUGR received interest as early as the 1970s.49, 50 It was hypothesised that a lower blood-pressure target combined with plasma-volume expansion might reduce the maternal and perinatal risks associated with pre-eclampsia. Numerous observational cohort studies documented beneficial effects for women with pre-eclampsia and fetuses with IUGR.51, 52, 53, 54,

Oliguria

Oliguria is commonly seen in women with severe pre-eclampsia, particularly after caesarean section. Oliguria is usually transient, lasting for hours to days. However, it creates clinical anxiety because it may be a marker of renal insufficiency and progressive renal failure. As such, close follow-up of renal function is required, by measuring serum creatinine looking for relative changes (and not just a value that is ‘abnormal’). Responding to transient oliguria with volume loading is not a

Timing of delivery

The ultimate cure for pre-eclampsia is delivery of the placenta, although women may worsen (or new complications may appear) in the immediate postpartum period, particularly the first 5 days.5

When considering the relative benefits and risks of the interventionist and temporising approaches to pre-eclampsia management, a number of assumptions are made. It is assumed that antenatal maternal risk will be decreased by an interventionist approach; postpartum maternal risk will be unaltered by an

Gestational age before 24 weeks

Pre-eclampsia, with onset before 24 weeks’ gestation is a rare but severe condition in pregnancy with few data to inform management. In the South African population, gestational age below 24 weeks uniformly resulted in fetal demise.70, 71 In a US tertiary care centre, gestational age below 24 weeks was associated with a grim fetal prognosis in those opting for temporising management.72 Despite obvious advances in neonatal intensive care, these older studies are consistent with more recent data

Gestational age between 24 and 34 weeks

Several large retrospective cohort studies from different settings (The Netherlands, South-Africa, France, Egypt and USA) have reported on the results from temporising management strategies.*7, *14, 15, 16, 19, *20, 21, 22, 53, 54, 70, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 Combined with data from two randomised-controlled trials,17, 18 a picture arises of a severe maternal condition with significant, but in general reversible, morbidity, as shown in Table 1. Interpretation of these data are

Gestational age after 34 weeks

Given the good perinatal outcomes in this gestational age category, no severe maternal disease or morbidity is considered to be acceptable. Yet, some minor neonatal morbidity may occur after early delivery, especially respiratory complications and need for neonatal intensive care.92, 93 If only perinatal outcomes are considered, for instance in chronic hypertension, the optimal trade-off between fetal risks (unanticipated stillbirth) and neonatal risks seems to be at 38–39 weeks.94 IUGR,

Mode of delivery

When a decision is made to pursue delivery at term gestational ages, vaginal delivery is a viable option if the maternal and fetal conditions allow it, although caesarean section rates are nonetheless high (14–19%).97 At lower gestational ages, rates of successful vaginal delivery are better than what might be expected: 69% between 32 and 34 weeks and 48% between 28 and 32 weeks. However, vaginal delivery is rarely achieved at less than 28 weeks (7%).98, 99

Conclusion

In women with pre-eclampsia, fetal and maternal interests are in conflict, with the best interests of the mother dictating delivery, but the best interests of the fetus without compromise dictating prolongation of pregnancy. The timing of delivery will depend on the balance of estimated risks of temporising management and immediate delivery. Here, the available evidence has been reviewed to suggest appropriate choices in individual women at different gestational ages and with different maternal

Conflict of interest

The authors have no financial and personal relationships to disclose with other people or organisations that could inappropriately influence (bias) the content of this article.

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