Assessing the impact of maternal blood pressure during pregnancy on perinatal health: a wide-angled Mendelian

Fernanda Morales-Berstein^1,2, Ana Gonçalves-Soares^3,4, Qian Yang^3,4,5,6

¹MRC Integrative Epidemiology Unit at the University of Bristol, Augustine's Courtyard, Orchard Lane, Bristol, BS1 5DS, UK. fernanda.moralesberstein@bristol.ac.uk.

|January 13, 2026

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 randomization (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 meta-analyses of genome-wide association studies involving predominantly European ancestry individuals for SBP/DBP (N = 1,028,980), and pregnancy and perinatal outcomes (N = 74,368-714,899). 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 (SGA), preterm birth (PTB), and neonatal intensive care unit (NICU) admission (OR ranging from 1.11 [95% CI 1.02 to 1.20] for NICU admission to 1.33 [1.26 to 1.41] for LBW); while decreasing the odds of high birth weight (HBW), large-for-gestational age (LGA), 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. The results for maternal DBP were similar to the 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 neonatal intensive care unit admission. This and other emerging evidence highlight the value of interventions aimed at controlling blood pressure in the population to reduce the burden of adverse pregnancy outcomes.

Keywords:

ALSPAC BiB FinnGen Maternal blood pressure Mendelian randomization MoBa Perinatal outcomes UK Biobank

Frequently Asked Questions

According to the study's authors, elevated maternal blood pressure reduces fetal growth, as evidenced by a 10 mmHg increase in Systolic Blood Pressure (SBP) resulting in an Odds Ratio (OR) of 1.33 for Low Birth Weight (LBW).

Based on this study's findings, a genetically predicted 10 mmHg rise in maternal Systolic Blood Pressure (SBP) increases the odds of Neonatal Intensive Care Unit (NICU) admission with an Odds Ratio (OR) of 1.11.

The researchers used the Inverse-Variance Weighted (IVW) method to combine genetic association data from over one million individuals, enabling the estimation of causal effects of blood pressure on sixteen primary pregnancy outcomes.

The findings indicate that the causal influence of maternal blood pressure does not extend to all adverse events, as the researchers found no evidence linking genetically predicted higher Systolic Blood Pressure (SBP) to miscarriage or stillbirth.

The study's authors propose that interventions aimed at controlling blood pressure in the general population are valuable for reducing the overall burden of adverse pregnancy outcomes.

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