Elsevier

The Lancet

Volume 376, Issue 9741, 21–27 August 2010, Pages 631-644
The Lancet

Seminar
Pre-eclampsia

https://doi.org/10.1016/S0140-6736(10)60279-6Get rights and content

Summary

Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease. Predisposing cardiovascular or metabolic risks for endothelial dysfunction, as part of an exaggerated systemic inflammatory response, might dominate in the origins of late onset pre-eclampsia. Because the multifactorial pathogenesis of different pre-eclampsia phenotypes has not been fully elucidated, prevention and prediction are still not possible, and symptomatic clinical management should be mainly directed to prevent maternal morbidity (eg, eclampsia) and mortality. Expectant management of women with early onset disease to improve perinatal outcome should not preclude timely delivery—the only definitive cure. Pre-eclampsia foretells raised rates of cardiovascular and metabolic disease in later life, which could be reason for subsequent lifestyle education and intervention.

Introduction

Complicating 2–8% of pregnancies, pre-eclampsia, along with the other hypertensive disorders of pregnancy, is a major contributor to maternal mortality worldwide.1, 2 In Latin America and the Caribbean, hypertensive disorders are responsible for almost 26% of maternal deaths, whereas in Africa and Asia they contribute to 9% of deaths. Although maternal mortality is much lower in high-income countries than in developing countries, 16% of maternal deaths can be assigned to hypertensive disorders.1 The incidence of pre-eclampsia has risen in the USA.3, 4 This finding might be related to an increased prevalence of predisposing disorders, such as chronic hypertension, diabetes, and obesity.3 Some ethnic groups (eg, African-American and Filipino women5, 6) and low socioeconomic status are associated with a heightened risk.7 Furthermore, severe pre-eclampsia is a major cause of severe maternal morbidity (eg, stroke and liver rupture) and adverse perinatal outcomes, such as prematurity and intrauterine growth restriction.2 Although the generalised seizures of eclampsia complicate 2–3 cases per 10 000 births in Europe, eclampsia is 10–30 times more common in developing countries than in high-income countries.2

Other hypertensive disorders in pregnancy are pre-existing hypertension and gestational hypertension. Pre-eclampsia is generally defined as new hypertension (diastolic blood pressure of ≥90 mm Hg) and substantial proteinuria (≥300 mg in 24 h) at or after 20 weeks' gestation.8 However, how best to define the maternal syndrome of pre-eclampsia, and how to differentiate mild from severe disease is being debated.9, 10, 11, 12 Table 1 shows recent classification frameworks, evolving from previous work of the American College of Obstetricians and Gynecologists13 and the International Society for the Study of Hypertension in Pregnancy.14 The main differences between the classification systems are: (1) inclusion or exclusion of complicated non-proteinuric gestational hypertension as pre-eclampsia; (2) differentiation between clinical and research definitions in the Australasian guideline; (3) use of early-onset pre-eclampsia as a severity criterion in Canada (<34 weeks) and the USA (<35 weeks); (4) clinical importance of assessing white-coat hypertension; and (5) definition of severe hypertension. Although perinatal risks have long been recognised to be highest remote from term, the 20-fold increase in maternal mortality that is associated with pre-eclampsia arising at less than 32 weeks (compared with that at ≥37 weeks)15 seems not to have been, emphasising the importance of early-onset pre-eclampsia as a severity criterion. The debate between setting the systolic blood pressure definition of severe hypertension at either 160 mm Hg or 170 mm Hg needs to be resolved because of rising concerns about lethal maternal stroke risks at the lower threshold for blood pressure.16, 17 None of these classification systems seems to have been independently assessed for the ability to identify women and fetuses at heightened risk of the adverse events that make pre-eclampsia so important.

Section snippets

Pathogenesis

Although the cause of pre-eclampsia remains largely unknown, the leading hypotheses strongly rely on disturbed placental function in early pregnancy (figure). Impaired remodelling of the spiral artery has especially been considered as an early, but not necessarily the primary, defect causing pre-eclampsia.19 Remodellingis a multistep process20 in which the first decidua-associated step should be initiated around implantation. Disturbances at this stage could increase risk of pre-eclampsia, and

Screening

Table 2 shows factors that can easily be measured at the first prenatal appointment and that increase the likelihood of pre-eclampsia in any pregnancy.8, 55 In risk assessments done after 20 weeks' gestation, attention should be paid to the possible onset of pre-eclampsia by identification of any of the following signs and symptoms: new hypertension, new proteinuria, symptoms of headache, visual disturbance, epigastric pain, vomiting, reduced fetal movements, and an infant that is small for

Prediction

Early prediction of pre-eclampsia would allow for close surveillance and preventive strategies. Many tests have been assessed for their relation to placental perfusion, vascular resistance, and placental products, including tests for Down's serum screening analytes and hormones, renal and endothelial dysfunction, oxidative stress, and fetal-derived products. Of 27 tests reviewed by Meads and colleagues,63 only a few reached specificities above 90%. These were body-mass index of 34 kg/m2 or

Clinical presentation

Maternal organ systems that are susceptible to excessive inflammation and endothelial damage are the CNS, lungs, liver, kidneys, systemic vasculature, coagulation, and the heart—the placenta and fetus are also at risk. The more organ systems that are affected, the more maternal and perinatal complications arise. Clinicians should take caution not to undervalue clinical signs and symptoms in (severe) pre-eclampsia (table 1) because they can be non-specific (eg, nausea and vomiting). Caregivers

Management

For women with pre-eclampsia, dependent on severity, review at day assessment units or admission to hospital is indicated according to local guidelines.56 Table 3 and panel 2 show our suggested management paradigms according to gestational age at presentation. Although we recognise that there is no universally accepted standard of care, which is dependent on local facilities, we believe that risk reduction for women with pre-eclampsia needs a series of strategies—namely standardised assessment

Preconception care and future health

Women at high risk for pre-eclampsia, including those with a history of the disease or other complications in their obstetric history, should be offered preconception care by obstetricians with experience in management of the disorder. If present, severity of chronic hypertension, diabetes, connective tissue, or renal disease should be assessed and pharmacological treatment adjusted for safety in pregnancy. Risks of occurrence and recurrence (10% for previous mild disease and up to 40% for

Perspectives

Although genetic contributions to the risk of pre-eclampsia are recognised by familial clustering of this disorder, underlying mechanisms remain uncertain.136 Maternal constitutional and environmental risk factors for pre-eclampsia could be implicated by interference with the epigenetic programming of the gametes, placenta, and fetus.137 Derangements in genomic imprinting in placental tissue, resulting in disturbed paternal versus maternal gene expression, have additionally been suggested to

Search strategy and selection criteria

We searched PubMed and the Cochrane Library with the search terms “pre-eclampsia” and “hypertension and pregnancy”, and cross-referenced them with the following terms: “epidemiology”, “definition”, “aetiology”, “pathophysiology”, “prediction”, “prevention”, “management”, “clinical trials”, “preconception care”, and “thrombophilia”. We mainly restricted our search to studies done in human beings. We largely selected publications from the past 5 years, but did not exclude commonly

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