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Pre-eclampsia

Nature Reviews Disease Primers volume 9, Article number: 8 (2023) Cite this article

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An Author Correction to this article was published on 03 July 2023

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Abstract

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only ‘cure’ for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

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Fig. 1: Organs affected by pre-eclampsia.
Fig. 2: Syncytiotrophoblast stress is driven by dysfunctional placental perfusion.
Fig. 3: Algorithms to screen for pre-eclampsia in first, second and third trimesters.
Fig. 4: Treatment algorithm for pregnancies presenting with hypertension.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia

    Evdokia Dimitriadis, Wei Zhou, Clare Whitehead & Ellen Menkhorst

  2. Gynaecology Research Centre, Royal Women’s Hospital, Melbourne, Victoria, Australia

    Evdokia Dimitriadis, Wei Zhou & Ellen Menkhorst

  3. Women’s and Newborn, Monash Health, Melbourne, Victoria, Australia

    Daniel L. Rolnik

  4. Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia

    Daniel L. Rolnik

  5. Research Division, Instituto Nacional de Perinatologia, Mexico City, Mexico

    Guadalupe Estrada-Gutierrez

  6. Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan

    Kaori Koga

  7. Department of Reproductive Medicine, Chiba University, Chiba, Japan

    Kaori Koga

  8. Departamento de Obstetrícia e Giencologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil

    Rossana P. V. Francisco

  9. Fetal Medicine Unit, Royal Women’s Hospital, Melbourne, Victoria, Australia

    Clare Whitehead

  10. Obstetric Research Group Ingham Institute, South Western Sydney Local Health District and Western Sydney University, Sydney, New South Wales, Australia

    Jon Hyett

  11. Maternal Fetal Medicine Unit, Gold Coast University Hospital and School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia

    Fabricio da Silva Costa

  12. Fetal Medicine Foundation, London, UK

    Kypros Nicolaides

  13. Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK

    Kypros Nicolaides

Authors
  1. Evdokia Dimitriadis
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  2. Daniel L. Rolnik
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  3. Wei Zhou
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  4. Guadalupe Estrada-Gutierrez
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  5. Kaori Koga
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  6. Rossana P. V. Francisco
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  7. Clare Whitehead
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  8. Jon Hyett
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  9. Fabricio da Silva Costa
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  10. Kypros Nicolaides
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  11. Ellen Menkhorst
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Contributions

Introduction (E.M.); Epidemiology (E.M., D.L.R. and C.W); Mechanisms/pathophysiology (E.D., E.M., W.Z. and G.E.-G.); Diagnosis, screening and prevention (D.L.R., F.d.S.C., J.H. and K.N.); Management (D.L.R., K.K., R.P.V.F. and J.H.); Quality of life (W.Z. and F.d.S.C.); Outlook (E.D.); Overview of Primer (E.M. and E.D.)

Corresponding author

Correspondence to Ellen Menkhorst.

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Competing interests

F.d.S.C. has Research Funding from ThermoFisher for an angiogenic marker study (sFLT1/PGF). The other authors declare no competing interests.

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Peer review information

Nature Reviews Disease Primers thanks M. K. Santillan; S. R. Hansson; R. Dechend; P. Nunes, who co-reviewed with V. C. Sandrim; E. Toivonen, who co-reviewed with H. M. Laivuori; and the other, anonymous, reviewer for their contribution to the peer review of this work.

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Glossary

Anticardiolipin antibodies

Auto-antibodies found in antiphospholipid syndrome.

Antiphospholipid syndrome

Autoimmune disease characterized by recurring thromboses, recurrent pregnancy loss and thrombocytopenia.

Chorionicity

The number of placentas in a pregnancy.

Cytotrophoblasts

Trophoblast progenitor stem cells located interior to the syncytiotrophoblast in placental villus and in cell columns that anchor placental villus to the decidua.

Decidua

The modified endometrial layer during pregnancy into which the placenta is anchored.

Extravillous trophoblasts

Differentiated cytotrophoblasts that invade from cell columns into the decidua and engraft maternal spiral arteries.

Lupus anticoagulant

Immunoglobulin that binds to phospholipids and increases the risk of developing thromboses.

Placental malperfusion

Reduced maternal blood flow to the intervillous space of the placenta.

Primiparity

Term used to describe a first pregnancy and/or to have given birth only once.

Syncytiotrophoblast

Multinucleated, continuous trophoblast that covers the entire surface of the placental villus and is in direct contact with maternal blood.

Trophoblast

Non-embryonic fetal cells derived from the trophectoderm of the blastocyst.

Uterine spiral arteries

Small arteries that supply blood to the endometrium of the uterus during the menstrual cycle and the intervillus space of the placenta during pregnancy.

Zygosity

Genetic similarity of fetuses in multifetal pregnancies.

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Dimitriadis, E., Rolnik, D.L., Zhou, W. et al. Pre-eclampsia. Nat Rev Dis Primers 9, 8 (2023). https://doi.org/10.1038/s41572-023-00417-6

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