Artificial Sweetener and the Risk of Adverse Pregnancy Outcomes: a Mendelian Randomization Study

Background: The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. Methods/Objectives: A mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association studies summary data from public datasets. Inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable mendelian randomization enrolling body mass index, type 2 diabetes mellitus and fasting glucose was employed to further validate the consistency and robustness of results. Results: The intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR=1.821 (1.118 - 2.967), p=0.016] in univariable MR. The intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR=0.361 (0.145 - 0.895), p=0.028] and premature rupture of membranes [OR=0.116 (0.019 - 0.704), p=0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR=1.617 (1.042 - 2.510), p=0.032] adjusting for body mass index and type 2 diabetes mellitus in multivariable MR. No causal relationship was identified between the intake of artificial sweetener and the other adverse pregnancy outcomes. Conclusions: The consumption of artificial sweeteners during pregnancy warrants careful consideration.