Elsevier

The Lancet

Volume 398, Issue 10297, 24–30 July 2021, Pages 341-354
The Lancet

Seminar
Pre-eclampsia

https://doi.org/10.1016/S0140-6736(20)32335-7Get rights and content

Summary

Pre-eclampsia is a multisystem pregnancy disorder characterised by variable degrees of placental malperfusion, with release of soluble factors into the circulation. These factors cause maternal vascular endothelial injury, which leads to hypertension and multi-organ injury. The placental disease can cause fetal growth restriction and stillbirth. Pre-eclampsia is a major cause of maternal and perinatal mortality and morbidity, especially in low-income and middle-income countries. Prophylactic low-dose aspirin can reduce the risk of preterm pre-eclampsia, but once pre-eclampsia has been diagnosed there are no curative treatments except for delivery, and no drugs have been shown to influence disease progression. Timing of delivery is planned to optimise fetal and maternal outcomes. Clinical trials have reported diagnostic and prognostic strategies that could improve fetal and maternal outcomes and have evaluated the optimal timing of birth in women with late preterm pre-eclampsia. Ongoing studies are evaluating the efficacy, dose, and timing of aspirin and calcium to prevent pre-eclampsia and are evaluating other drugs to control hypertension or ameliorate disease progression.

Introduction

Pre-eclampsia complicates about 3–5% of all pregnancies and is estimated to cause at least 42 000 maternal deaths annually.1, 2, 3 For every loss related to pre-eclampsia, at least 50–100 women have substantial morbidity.2, 4, 5 Low-income and middle-income countries (LMIC) have the highest burden of major complications because of scarce resources and poorer access to adequate obstetric care and family planning services than high-income countries.6, 7

Pre-eclampsia can present in many ways; it can be diagnosed after a woman presents with a seizure, breathlessness, severe epigastric pain, and massive placental abruption, or diagnosed at a routine antenatal consultation if a woman is asymptomatic but hypertensive.

Although keenly sought, no treatment has been found that affects disease progression. Current approaches to improving clinical outcomes in pre-eclampsia centre on prevention, prompt diagnosis, and stratification of care. If a woman diagnosed with pre-eclampsia is at an early gestation, the mainstay is expectant management with timing of birth planned to optimise maternal and fetal outcomes.

New trials and cohort studies have given insights into the prevention of pre-eclampsia, diagnostic and prognostic tools, and the optimal gestation to plan birth. This Seminar provides an update on the clinical management of pre-eclampsia. It focuses on evidence generated in the past 5 years and puts current findings into context as to how they could be used to improve clinical care and pregnancy outcomes.

Section snippets

Diagnosis and clinical definition

Pre-eclampsia is a progressive disease of pregnancy involving multiple organ systems. The clinical definition has evolved over time, from simply hypertension and proteinuria, to a broader classification that recognises the complex multi-organ system involvement caused by the disease. International guidelines agree that pre-eclampsia can be defined as new onset hypertension (systolic blood pressure sustained at ≥140 mm Hg or diastolic blood pressure sustained at ≥90 mm Hg, or both) with

Risk factors

Clinical risk factors for pre-eclampsia are summarised in table 1,21, 22 with the highest risk factors being history of pre-eclampsia (an 8-times increase in risk, although the risk might be lower for those with pre-eclampsia in a first pregnancy but not in subsequent pregnancy) and chronic hypertension (a 5-times increase in risk). A history of preterm pre-eclampsia carries the greatest risk of developing pre-eclampsia with around 25–30% of women experiencing recurrent disease.23, 24, 25, 26,

Pathogenesis of pre-eclampsia

In normal early pregnancy, the placenta remodels local uterine vasculature, setting up optimal conditions for nutrient and oxygen exchange throughout pregnancy. Extravillous placental trophoblast cells migrate through the inner third of the myometrium of the uterus and remove the smooth muscle from the maternal spiral arterioles,28 rendering the ends of the vessels unable to constrict. Consequently, the terminal part of the spiral arterioles remains wide open and the net result is a high

Predictive and diagnostic tools for pre-eclampsia

The two active strategies being pursued to decrease short-term and long-term adverse outcomes caused by pre-eclampsia are predicting who is at high risk of developing the disease (screening for pre-eclampsia), and using tests as diagnostic adjuncts to exclude the likelihood that a woman has pre-eclampsia.

Aspirin

Aspirin is the only preventive drug treatment for pre-eclampsia that is supported by strong evidence. A 2019 Cochrane review concluded there is high-quality evidence that low-dose aspirin taken daily from the end of the first trimester until 36 weeks' gestation reduces the risk of developing pre-eclampsia by around 18% (relative risk 0·82; 95% CI 0·77–0·82).64 The risk reduction for preterm pre-eclampsia is likely to be greater than for pre-eclampsia in general.65, 66

How aspirin prevents

Management of women with pre-eclampsia

Once diagnosed, pre-eclampsia is often a progressive condition and maternal organ function deteriorates with time. No drug has been discovered that clearly slows disease progression and the only option to stop the disease is to deliver the fetus and placenta. Therefore, the overall approach to management is to deliver the baby and placenta at term gestation, or, if preterm pre-eclampsia is diagnosed, to try expectant management of the pregnancy until a more advanced gestation is reached (figure

Long-term complications of pre-eclampsia

Large cohort studies and meta-analyses have established that pre-eclampsia confers an increased risk of major chronic diseases in later life including many cardiovascular complications.106, 107, 108, 109, 110 A 2017 systematic review including more than 6·4 million women showed that those with a history of pre-eclampsia have a 4-times greater risk of heart failure, a 2·5-times greater risk of coronary heart disease, a 1·8-times greater risk of stroke, and an overall 2·2-times greater risk of

Conclusion and future directions

The 2019 Maternal Mortality update from the WHO report125 illuminated the major contribution of pre-eclampsia and eclampsia to worldwide maternal deaths. There is much to be done to decrease the morbidity and mortality caused by this disease.

Most of the maternal deaths arising from pre-eclampsia occur in LMICs. There needs to be implementation research to determine how best to allocate scarce resources to save the greatest number of lives. Options might include improving access to antenatal

Search strategy and selection criteria

We searched PubMed and Cochrane Library from Jan 1, 2000, to April 30, 2020, with the search terms “pre-eclampsia” and “hypertensive disorders in pregnancy”. We cross-referenced these terms with: “pathophysiology”, “definition”, “guidelines”, “prediction”, “prevention”, “management”, “clinical trials”, “aspirin”, and “calcium”. We also searched for guidelines from international societies and clinical specialty colleges and limited our search to publications in English. We focused on

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