Assessing the impact of maternal blood pressure during pregnancy on perinatal health: A wide-angled Mendelian randomization study
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Background
Observational studies link high blood pressure in pregnancy to numerous adverse pregnancy and perinatal outcomes; however, findings may be affected by residual confounding or reverse causation. This study aimed to assess the causal effect of blood pressure during pregnancy on a range of pregnancy and perinatal outcomes.
Methods
We performed two-sample Mendelian randomisation (MR) to assess the effect of systolic and diastolic blood pressure (SBP/DBP) during pregnancy on 16 primary and eight secondary adverse pregnancy and perinatal outcomes. We obtained genetic association data from large-scale metanalyses of genome-wide association studies involving predominantly European ancestry individuals for SBP/DBP (N=1,028,980), and pregnancy and perinatal outcomes (N=77,285–934,566). We used inverse-variance weighted (IVW) MR for main analyses and MR-Egger, weighted median, weighted mode, multivariable MR, and IVW adjusted for fetal genetic effects for sensitivity analyses.
Results
A 10 mmHg higher genetically predicted maternal SBP increased the odds of gestational diabetes, induction of labour, low birth weight (LBW), small-for-gestational age, preterm birth (PTB), and neonatal intensive care unit (NICU) admission [OR ranging from 1.09 (95% CI: 1.04 to 1.14) for PTB to 1.33 (1.26 to 1.41) for LBW]; while decreasing the odds of high birth weight (HBW), large-for-gestational age, and post-term birth [OR ranging from 0.76 (0.69 to 0.83) for HBW to 0.94 (0.90 to 0.99) for post-term birth]. We did not find evidence that genetically predicted higher maternal SBP was related to miscarriage or stillbirth. Results for maternal DBP were similar to results for SBP. Overall, the main results were consistent across sensitivity analyses accounting for pleiotropic instruments and fetal genetic effects.
Conclusions
Higher maternal blood pressure reduces gestation duration and fetal growth, and increases the risks of induction of labour, gestational diabetes and NICU admission. This and other emerging evidence highlight the value of interventions to control maternal blood pressure during pregnancy to reduce the burden of adverse pregnancy outcomes.
