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 pre-eclampsia or eclampsia, and low fetal birthweight.
Methods: Uncorrelated single nucleotide polymorphisms associated systolic blood pressure, body mass index, type 2 diabetes mellitus, 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 two-sample Mendelian randomization study was performed with primary outcome of pre-eclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight.
Results: Higher genetically-predicted systolic blood pressure was associated increased risk of PET [odds ratio (OR) per 1-SD systolic blood pressure increase 1.90 (95% confidence interval (CI)1.45-2.49;p=3.23x10-6 and reduced birthweight (OR=0.83; 95%CI=0.79-0.86;p=3.96x10-18), 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=7.45x10-12; and OR per logOR increase type 2 diabetes=1.11 95%CI=1.04-1.19p;=1.19x10-3), but not with reduced birthweight.
Conclusions: Our results provide evidence for causal effects of systolic blood pressure, body mass index and type 2 diabetes on PET, and identify that systolic blood pressure 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.