Maternal hypertensive traits and adverse outcome in pregnancy: a Mendelian randomization study
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Author(s)
Type
Journal Article
Abstract
Introduction
Hypertensive disorders of pregnancy are associated with adverse feto-maternal outcomes. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of component hypertensive indices on multiple adverse pregnancy outcomes using Mendelian randomization (MR).
Methods
Uncorrelated (r2<0.001) genome-wide significant (p<5x10-8) single-nucleotide polymorphisms associated with SBP, diastolic blood pressure (DBP) and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of pre-eclampsia or eclampsia, preterm birth, placental abruption and hemorrhage in early pregnancy were extracted from summary statistics of genome-wide association studies in the FinnGen cohort. Two-sample, inverse-variance weighted MR formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically-predicted hypertensive index.
Results
Higher genetically-predicted SBP associated with higher odds of pre-eclampsia or eclampsia (OR 1.81, 95% confidence interval (CI) 1.68–1.96, p=5.45x10-49), preterm birth (OR 1.09 95%CI 1.03–1.16, p=0.005) and placental abruption (OR 1.33, 95%CI 1.05–1.68, p=0.016). Higher genetically-predicted DBP was associated with pre-eclampsia or eclampsia (OR 2.54, 95%CI 2.21–2.92, p=5.35x10-40). Higher genetically-predicted PP was associated with pre-eclampsia or eclampsia (OR 1.68, 95%CI 1.47–1.92, p=1.9×10-14) and preterm birth (OR 1.18, 95%CI 1.06–1.30, p= 0.002).
Conclusion
This study provides genetic evidence to support causal associations of SBP, DBP and PP on multiple adverse outcomes of pregnancy. SBP and PP were associated with the broadest range of adverse outcomes, suggesting that optimized management of blood pressure, particularly SBP, is a key priority to improve feto-maternal health.
Hypertensive disorders of pregnancy are associated with adverse feto-maternal outcomes. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of component hypertensive indices on multiple adverse pregnancy outcomes using Mendelian randomization (MR).
Methods
Uncorrelated (r2<0.001) genome-wide significant (p<5x10-8) single-nucleotide polymorphisms associated with SBP, diastolic blood pressure (DBP) and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of pre-eclampsia or eclampsia, preterm birth, placental abruption and hemorrhage in early pregnancy were extracted from summary statistics of genome-wide association studies in the FinnGen cohort. Two-sample, inverse-variance weighted MR formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically-predicted hypertensive index.
Results
Higher genetically-predicted SBP associated with higher odds of pre-eclampsia or eclampsia (OR 1.81, 95% confidence interval (CI) 1.68–1.96, p=5.45x10-49), preterm birth (OR 1.09 95%CI 1.03–1.16, p=0.005) and placental abruption (OR 1.33, 95%CI 1.05–1.68, p=0.016). Higher genetically-predicted DBP was associated with pre-eclampsia or eclampsia (OR 2.54, 95%CI 2.21–2.92, p=5.35x10-40). Higher genetically-predicted PP was associated with pre-eclampsia or eclampsia (OR 1.68, 95%CI 1.47–1.92, p=1.9×10-14) and preterm birth (OR 1.18, 95%CI 1.06–1.30, p= 0.002).
Conclusion
This study provides genetic evidence to support causal associations of SBP, DBP and PP on multiple adverse outcomes of pregnancy. SBP and PP were associated with the broadest range of adverse outcomes, suggesting that optimized management of blood pressure, particularly SBP, is a key priority to improve feto-maternal health.
Date Issued
2023-09
Date Acceptance
2023-05-24
Citation
Journal of Hypertension, 2023, 41 (9), pp.1438-1445
ISSN
0263-6352
Publisher
Lippincott, Williams & Wilkins
Start Page
1438
End Page
1445
Journal / Book Title
Journal of Hypertension
Volume
41
Issue
9
Copyright Statement
Copyright © 2023 The Author(s). Published by Wolters
Kluwer Health, Inc. This is an open access article distributed under the Creative
Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Kluwer Health, Inc. This is an open access article distributed under the Creative
Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://journals.lww.com/jhypertension/fulltext/2023/09000/maternal_hypertensive_traits_and_adverse_outcome.9.aspx
Publication Status
Published
Date Publish Online
2023-09