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Review
. 2021 May 5;77(5):1430-1441.
doi: 10.1161/HYPERTENSIONAHA.120.14781. Epub 2021 Mar 29.

Subtypes of Preeclampsia: Recognition and Determining Clinical Usefulness

James M Roberts  1 , Janet W Rich-Edwards  2   3 , Thomas F McElrath  4 , Lana Garmire  5 , Leslie Myatt  6 ; Global Pregnancy Collaboration
Affiliations
Review

Subtypes of Preeclampsia: Recognition and Determining Clinical Usefulness

James M Roberts et al. Hypertension. .

Abstract

The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of inflammation, oxidative and endoplasm reticulum stress, and angiogenic dysfunction. Yet, we have not progressed greatly toward clinically useful prediction nor had substantial success in prevention or treatment. One possibility is that the maternal syndrome may be reached through different pathophysiological pathways, that is, subtypes of preeclampsia, that in their specificity yield more clinical utility. For example, early and late onset preeclampsia are increasingly acknowledged as different pathophysiological processes leading to a common presentation. Other subtypes of preeclampsia are supported by disparate clinical outcomes, long-range prognosis, organ systems involved, and risk factors. These insights have been supplemented by discovery-driven methods, which cluster preeclampsia cases into groups indicating different pathophysiologies. In this presentation, we review likely subtypes based on current knowledge and suggest others. We present a consideration of the requirements for a clinically meaningful preeclampsia subtype. A useful subtype should (1) identify a specific pathophysiological pathway or (2) specifically indicate maternal or fetal outcome, (3) be recognizable in a clinically useful time frame, and (4) these results should be reproducible and generalizable (but at varying frequency) including in low resource settings. We recommend that the default consideration be that preeclampsia includes several subtypes rather than trying to force all cases into a single pathophysiological pathway. The recognition of subtypes and deciphering their different pathophysiologies will provide specific targets for prevention, prediction, and treatment directing personalized care.

Keywords: epidemiology; inflammation; prediction; preeclampsia; syndrome.

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Figures

Figure 1:
Figure 1:. Multiple Pathophysiological Pathways
The classic pathway to preeclampsia is considered as a unified pathophysiological pathway resulting in the preeclampsia syndrome. In this presentation we propose that several pathways can result in the common clinical presentation of preeclampsia.
Figure 2:
Figure 2:. PlGF measured longitudinally across pregnancy
PlGF was measured in 50 women who developed preeclampsia and 300 who did not. The data are arrayed in Panel A as mean and standard error of the mean (square and dashed line preeclampsia, circle and solid line control). In Panel B the same data are arrayed as a scatter plot, (preeclampsia black triangle, control gray circle) clearly indicating the heterogeneity of the data that is not evident in Panel A.
Figure 3:
Figure 3:. Increased information on adverse outcome determined by subtype
Panel A indicates the overall adverse outcome in women with or without preeclampsia. There is a slight to moderate increase in the adverse outcome in all women with preeclampsia. In panel B the circled area indicates that within these same women those within a specific cluster or subtype (formula image) manifest a greater difference in the proportional occurrence of the outcome.
See this image and copyright information in PMC

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