TY - JOUR
T1 - Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight
T2 - Genetic Evidence From a Mendelian Randomization Study
AU - Ardissino, Maddalena
AU - Slob, Eric A W
AU - Millar, Ophelia
AU - Reddy, Rohin K
AU - Lazzari, Laura
AU - Patel, Kiran Haresh Kumar
AU - Ryan, David
AU - Johnson, Mark R
AU - Gill, Dipender
AU - Ng, Fu Siong
N1 - Funding Information:
This study was supported by the British Heart Foundation (RG/16/3/32175 for F.S. Ng and RE/18/4/34215 for D. Gill) and the National Institute for Health Research (NIHR Academic Foundation Training Programme for MA, NIHR Clinical Lectureship for D. Gill, Imperial NIHR Biomedical Research Centre funding for F.S. Ng and K.H.K. Patel), and the George’s Academic Training Small Grant Fund (for D. Ryan).
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/1/4
Y1 - 2022/1/4
N2 - BACKGROUND: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight.METHODS: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight.RESULTS: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45-2.49]; P=3.23×10-6) and reduced birthweight (OR=0.83 [95% CI=0.79-0.86]; P=3.96×10-18), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44-1.94]; P=7.45×10-12; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04-1.19]; P=1.19×10-3), but not with reduced birthweight.CONCLUSIONS: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.
AB - BACKGROUND: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight.METHODS: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight.RESULTS: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45-2.49]; P=3.23×10-6) and reduced birthweight (OR=0.83 [95% CI=0.79-0.86]; P=3.96×10-18), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44-1.94]; P=7.45×10-12; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04-1.19]; P=1.19×10-3), but not with reduced birthweight.CONCLUSIONS: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.
UR - http://www.scopus.com/inward/record.url?scp=85124295708&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.121.18617
DO - 10.1161/HYPERTENSIONAHA.121.18617
M3 - Article
C2 - 35138876
VL - 79
SP - 588
EP - 598
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 3
ER -
