Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Maddalena Ardissino, Eric A W Slob, Ophelia Millar, Rohin K Reddy, Laura Lazzari, Kiran Haresh Kumar Patel, David Ryan, Mark R Johnson, Dipender Gill, Fu Siong Ng

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19 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)588-598
Number of pages11
Issue number3
Publication statusPublished - 4 Jan 2022

Bibliographical note

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.


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