Impact of multiple obesity metrics on hypertensive disorders of pregnancy: a meta-analysis and Mendelian randomisation study

Background The relationships between various obesity measures and hypertensive disorders of pregnancy (HDP) remain inadequately explored, and their causal links are not well understood. This study aims to clarify these associations and investigate the mediating role of triglycerides. Methods We conducted a comprehensive meta-analysis of observational studies alongside Mendelian randomisation (MR) analysis to assess the impact of 10 obesity measures on HDP risk. Additionally, we evaluated the mediating effect of triglycerides. Results Our meta-analysis revealed significant associations between maternal prepregnancy overweight/obesity and increased risks of gestational hypertension (GH) (overweight: OR=1.98, 95% CI 1.83 to 2.15; obesity: OR=3.77, 95% CI 3.45 to 4.13) and pre-eclampsia (overweight: OR=1.78, 95% CI 1.67 to 1.90; obesity: OR=3.46, 95% CI 3.16 to 3.79). Higher maternal waist circumference (WC) was also linked to increased pre-eclampsia risk (OR=1.45, 95% CI 1.14 to 1.83). MR analyses indicated that each 1-SD increase in genetically predicted obesity measures (whole body fat mass, body fat percentage, trunk fat mass, trunk fat percentage, body mass index, WC, hip circumference) was associated with higher risks of GH and pre-eclampsia. Triglycerides mediated 4.3%–14.1% of the total genetic effect of these obesity measures on GH and pre-eclampsia risks. Conclusions This study demonstrates that various obesity measures are causally linked to increased HDP risk and highlights the mediating role of triglycerides. These findings could inform clinical practices and public health strategies aimed at reducing HDP through targeted obesity and triglyceride management.