Mendelian Randomization Evidence Shows Maternal Blood Pressure During Pregnancy Linked to Adverse Perinatal Outcomes
Key Highlights:
- Higher genetically predicted maternal blood pressure was associated with increased risks of gestational diabetes, preterm birth, and neonatal intensive care unit admission.
- Elevated systolic and diastolic blood pressure were linked to reduced fetal growth, including higher odds of low birth weight and small-for-gestational-age infants.
- No causal association was observed between maternal blood pressure and miscarriage or stillbirth.
A wide-angled Mendelian randomization analysis published in BMC Medicine evaluated whether maternal blood pressure during pregnancy has a causal impact on pregnancy and perinatal outcomes. Using genetic instruments to reduce confounding and reverse causation, the investigators examined systolic and diastolic blood pressure in relation to 24 maternal and offspring outcomes, offering a comprehensive assessment beyond traditional observational studies.1
The researchers conducted a 2-sample Mendelian randomization study. They used genetic variants associated with systolic and diastolic blood pressure that were derived from large genome-wide association studies. These studies involved more than 1 million individuals of predominantly European ancestry. These variants were applied to pregnancy and perinatal outcome data from up to 714,899 women across multiple cohorts and biobanks. The primary analyses used inverse-variance weighted models scaled to a 10 mmHg increase in blood pressure, with extensive sensitivity analyses to account for pleiotropy, fetal genetic effects, and sample overlap.1
Study Findings
Higher genetically predicted maternal systolic blood pressure was associated with increased odds of several adverse outcomes, including gestational diabetes (odds ratio [OR], 1.11), induction of labor (OR, 1.11), low birth weight (OR, 1.33), small-for-gestational-age birth (OR, 1.16), preterm birth (OR, 1.12), and neonatal intensive care unit admission (OR, 1.11) per 10 mmHg increase. Conversely, higher systolic blood pressure was associated with lower odds of high birth weight, large-for-gestational-age birth, and post-term birth.
Results for diastolic blood pressure were broadly similar, though less precise. Importantly, the study did not find evidence that higher maternal blood pressure increased the risk of miscarriage or stillbirth. Sensitivity analyses generally supported the robustness of the findings, including analyses adjusted for fetal genotype.1
Clinical Implications
According to the study authors, these findings suggest that elevated maternal blood pressure contributes causally to shorter gestation and impaired fetal growth, as well as higher risks of gestational diabetes and neonatal intensive care unit admission. The results support the clinical importance of monitoring and managing blood pressure during pregnancy to reduce the burden of adverse perinatal outcomes, while indicating that such interventions are unlikely to influence miscarriage or stillbirth risk.1
Expert Commentary
“By using genetic information to better isolate cause and effect, our study helps clarify whether a mother’s blood pressure itself contributes to pregnancy and newborn complications,” Carolina Borges, PhD, Associate Professor in Aetiological Epidemiology at the University of Bristol and co-author of the study, said in a press release. “This matters for clinical care and public health, as it strengthens the evidence base needed to guide prevention, monitoring, and treatment strategies aimed at improving maternal and infant outcomes.”2
Reference
1. Morales-Berstein F, Gonçalves-Soares A, Yang Q, et al. Assessing the impact of maternal blood pressure during pregnancy on perinatal health: a wide-angled Mendelian randomization study. BMC Medicine. 2025;23:Article 4548. doi:10.1186/s12916-025-04548-3
2. Higher maternal blood pressure increases the risk of pregnancy complications, study concludes. News release. University of Bristol; January 14, 2026. Accessed January 14, 2026.