Maternal hypertensive traits and adverse outcome in pregnancy: A Mendelian randomization study

Maddalena Ardissino; Rohin K. Reddy; Eric A.W. Slob; Jack Griffiths; Joanna Girling; Fu Siong Ng

doi:10.1097/HJH.0000000000003486

Maternal hypertensive traits and adverse outcome in pregnancy: A Mendelian randomization study

Maddalena Ardissino, Rohin K. Reddy, Eric A.W. Slob, Jack Griffiths, Joanna Girling, Fu Siong Ng^*

^*Corresponding author for this work

Applied Economics

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

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.

Methods:

Uncorrelated (r² < 0.001) genome-wide significant (P < 5 × 10⁻⁸) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia 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 Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.

Results:

Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68–1.96, P = 5.45 × 10⁻⁴⁹], 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 preeclampsia or eclampsia (OR 2.54, 95% CI 2.21–2.92, P = 5.35 × 10⁻⁴⁰). Higher genetically predicted PP was associated with preeclampsia 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.

Original language	English
Pages (from-to)	1438-1445
Number of pages	8
Journal	Journal of Hypertension
Volume	41
Issue number	9
DOIs	https://doi.org/10.1097/HJH.0000000000003486
Publication status	Published - 1 Sept 2023

Bibliographical note

Funding Information:
This study was supported by Imperial National Institute for Health Research (NIHR) Biomedical Research Centre for RKR, NIHR Academic Clinical Fellowship for M.A., NIHR Cambridge Biomedical Research Centre BRC-1215-20014 for S.B., Imperial NIHR Biomedical Research Centre funding for F.S.N.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

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@article{55897216e240488f8c7e33e2df65597a,

title = "Maternal hypertensive traits and adverse outcome in pregnancy: A Mendelian randomization study",

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.Methods: Uncorrelated (r2 < 0.001) genome-wide significant (P < 5 × 10−8) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia 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 Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.Results: Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68–1.96, P = 5.45 × 10−49], 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 preeclampsia or eclampsia (OR 2.54, 95% CI 2.21–2.92, P = 5.35 × 10−40). Higher genetically predicted PP was associated with preeclampsia 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.",

author = "Maddalena Ardissino and Reddy, {Rohin K.} and Slob, {Eric A.W.} and Jack Griffiths and Joanna Girling and Ng, {Fu Siong}",

note = "Funding Information: This study was supported by Imperial National Institute for Health Research (NIHR) Biomedical Research Centre for RKR, NIHR Academic Clinical Fellowship for M.A., NIHR Cambridge Biomedical Research Centre BRC-1215-20014 for S.B., Imperial NIHR Biomedical Research Centre funding for F.S.N. Publisher Copyright: {\textcopyright} 2023 Lippincott Williams and Wilkins. All rights reserved.",

year = "2023",

month = sep,

day = "1",

doi = "10.1097/HJH.0000000000003486",

language = "English",

volume = "41",

pages = "1438--1445",

journal = "Journal of Hypertension",

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publisher = "Lippincott Williams & Wilkins",

number = "9",

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T1 - Maternal hypertensive traits and adverse outcome in pregnancy

T2 - A Mendelian randomization study

AU - Ardissino, Maddalena

AU - Reddy, Rohin K.

AU - Slob, Eric A.W.

AU - Griffiths, Jack

AU - Girling, Joanna

AU - Ng, Fu Siong

N1 - Funding Information: This study was supported by Imperial National Institute for Health Research (NIHR) Biomedical Research Centre for RKR, NIHR Academic Clinical Fellowship for M.A., NIHR Cambridge Biomedical Research Centre BRC-1215-20014 for S.B., Imperial NIHR Biomedical Research Centre funding for F.S.N. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.

PY - 2023/9/1

Y1 - 2023/9/1

N2 - 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.Methods: Uncorrelated (r2 < 0.001) genome-wide significant (P < 5 × 10−8) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia 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 Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.Results: Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68–1.96, P = 5.45 × 10−49], 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 preeclampsia or eclampsia (OR 2.54, 95% CI 2.21–2.92, P = 5.35 × 10−40). Higher genetically predicted PP was associated with preeclampsia 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.

AB - 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.Methods: Uncorrelated (r2 < 0.001) genome-wide significant (P < 5 × 10−8) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia 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 Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.Results: Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68–1.96, P = 5.45 × 10−49], 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 preeclampsia or eclampsia (OR 2.54, 95% CI 2.21–2.92, P = 5.35 × 10−40). Higher genetically predicted PP was associated with preeclampsia 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.

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DO - 10.1097/HJH.0000000000003486

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AN - SCOPUS:85166733877

SN - 0263-6352

VL - 41

SP - 1438

EP - 1445

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 9

ER -

Maternal hypertensive traits and adverse outcome in pregnancy: A Mendelian randomization study

Abstract

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