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Published on: January 26, 2024
Clinical and Molecular Differences of Hypertensive Disorders During Pregnancy
Mariko Horii1,2,3, Robert Morey1,2,3, Jennifer N Chousal1,2,3
1Department of Pathology (M.H., R.M., J.N.C., M.M., O.A.), University of California San Diego, La Jolla.
Insights
Hypertensive disorders of pregnancy, including preeclampsia, are distinct conditions from gestational hypertension, not simply stages of severity. Maternal vascular malperfusion differentiates preeclampsia subtypes, suggesting early pregnancy divergence.
Area of Science:
- Obstetrics and Gynecology
- Perinatal Medicine
- Reproductive Biology
Background:
- Hypertensive disorders of pregnancy (HDP) encompass chronic hypertension (cHTN), gestational hypertension (gHTN), preeclampsia, and superimposed preeclampsia (siPE).
- Limited comparative studies exist on the detailed clinical and molecular characteristics differentiating HDP subtypes.
- This study evaluates HDP subtypes using clinical, placental histopathologic, and molecular data.
Purpose of the Study:
- To compare the clinical, placental histopathologic, and molecular characteristics of different hypertensive disorders of pregnancy subtypes.
- To investigate potential molecular distinctions and relationships between HDP subtypes.
- To determine if preeclampsia represents an advanced stage of other hypertensive disorders or a distinct condition.
Main Methods:
- Utilized a 10-year pregnancy cohort with clinical data, placental pathology, and placental tissue RNA-sequencing.
- Employed a nested case-control design for comparative analysis.
- Applied current ACOG criteria for clinical diagnosis and the Amsterdam consensus statement for placental examination.
Main Results:
- Chronic hypertension and gestational hypertension showed normal placental pathology, unlike preeclampsia and siPE, which were enriched in maternal vascular malperfusion.
- RNA-sequencing revealed distinct gene expression signatures and pathway activations across HDP subgroups.
- No molecular evidence supported preeclampsia as an advanced stage of other hypertensive disorders; instead, distinct pathophysiological conditions were identified. Preeclampsia and siPE shared gene expression profiles when maternal vascular malperfusion was present.
Conclusions:
- Maternal vascular malperfusion is a key differentiator for pregnancies progressing to preeclampsia and siPE.
- The cascade to preeclampsia/siPE may diverge early in pregnancy from gHTN/cHTN, potentially linked to early gestation events.
- Placental histopathologic evaluation is crucial for understanding the etiology of HDP.
Background:
Hypertensive disorders of pregnancy (HDP) comprise a spectrum of 4 subtypes: chronic hypertension (cHTN), gestational hypertension (gHTN), preeclampsia (PE), and superimposed preeclampsia (siPE). Although often characterized as a spectrum of disease severity, there have been limited comparative studies of detailed clinical and molecular characteristics of these disorders. We hereby evaluate HDP subtypes using clinical, placental histopathologic, and molecular data to compare similarities and differences between HDP subtypes.
Methods:
We used data from an over 10-year-long pregnancy cohort with detailed clinical and placental pathology, as well as placental tissue RNA-sequencing, to compare findings between HDP subtypes using a nested case-control design. Clinical diagnosis was based on current ACOG criteria, and placental gross and histological examination was based on the Amsterdam consensus statement.
Results:
Clinical data analysis showed cHTN and gHTN to be more likely to have normal placental pathology, while PE and siPE were more enriched in maternal vascular malperfusion. RNA-seq showed distinct gene expression signatures and pathway activation across HDP subgroups. We could not identify any molecular evidence that preeclampsia (PE or siPE) was an advanced stage of hypertensive disorder (gHTN or cHTN), but rather identified distinct gene expression profiles between these entities, suggesting preeclampsia (PE or siPE) and hypertension (gHTN or cHTN) are distinct pathophysiological conditions. Finally, we found that, in the presence of maternal vascular malperfusion, PE and siPE share significant gene expression profiles and pathway activation.
Conclusions:
Our findings suggest that maternal vascular malperfusion specifically differentiates pregnancies that progress to PE and siPE. Maternal vascular malperfusion is thought to initiate in early gestation, indicating the cascade to PE/siPE may be differentiated from gHTN/cHTN early in pregnancy. Incorporating placental histopathologic evaluation is an essential future avenue in probing the etiology of HDP.
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