Association of sleep traits with risk of adverse pregnancy outcomes: a Mendelian randomisation analysis

Abstract

Background: The aims of this study are to investigate the causal relationships between sleep traits and the risk of gestational diabetes mellitus (GDM), preterm birth, and foetal growth restriction (FGR). Methods: This two-sample Mendelian Randomisation (MR) study was conducted from May to June 2024 to investigate the associations between seven sleep traits and GDM, preterm birth, and FGR. The study utilised data from large-scale genome-wide association study datasets, and specifically focused on individuals of European descent. The main analysis employed inverse-variance-weighted MR, with sensitivity analyses conducted to mitigate potential pleiotropy-induced biases. Additionally, multivariable MR analysis was conducted to adjust for potential confounding factors. Results: Genetically predicted excessive daytime sleepiness (OR 13.67; 95% CI, 1.03–180.59; p = 0.047) and sleep apnoea (OR 1.29; 95% CI, 1.00–1.65; p = 0.049) were found to be associated with a higher risk of GDM. No sleep trait was associated with either preterm birth or FGR. These results were robust across various sensitivity analyses. In the multivariable MR analysis, adjusting for body mass index (BMI) and smoking, the genetically instrumented excessive daytime sleepiness (OR 14.58; 95% CI 1.67–127.36; p = 0.015) and sleep apnoea (OR 1.30; 95% CI 1.02–1.64; p = 0.030) were consistently associated with an increased GDM risk. Conclusions: This study suggests a causal relationship between both excessive daytime sleepiness and sleep apnoea to the development of GDM. Excessive daytime sleepiness and sleep apnoea demonstrate promise as potentially preventable risk factors for GDM.