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  • Review Article
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Pre-eclampsia part 1: current understanding of its pathophysiology

Key Points

  • Diagnosis of pre-eclampsia is based on new-onset hypertension and proteinuria at ≥20 weeks of gestation or, in the absence of proteinuria, hypertension together with evidence of systemic disease

  • Genetic and environmental factors are thought to create conditions leading to defective deep placentation; the injured placenta then releases factors into the maternal circulation that induce pre-eclampsia

  • Pre-eclampsia is characterized by multiple aetiologies and pathogenetic mechanisms, a long subclinical phase, fetal involvement, adaptive clinical manifestations and gene–environment interactions

  • An imbalance between angiogenic and antiangiogenic factors has emerged as a central pathogenetic mechanism in pre-eclampsia

  • An antiangiogenic state can also be observed in conditions other than pre-eclampsia, including intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction

  • The severity and timing of the antiangiogenic state, as well as maternal susceptibility, might determine the clinical presentation of pre-eclampsia

Abstract

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia.

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Figure 1: An experiment supporting the concept that hypertension in pregnancy represents a uteroplacental response to ischaemia.
Figure 2: Failure of physiological transformation of the spiral arteries is implicated in pre-eclampsia.
Figure 3: Transformed and nontransformed spiral arteries in the myometrium.
Figure 4: Integrated model of the complex pathophysiology of pre-eclampsia.

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Acknowledgements

The authors' research is supported partly by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Department of Health and Human Services (NICHD/NIH/DHHS) and partly with Federal funding from the NICHD and NIH under contract no. HHSN275201300006C.

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Chaiworapongsa, T., Chaemsaithong, P., Yeo, L. et al. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 10, 466–480 (2014). https://doi.org/10.1038/nrneph.2014.102

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