Relationship between intake of artificial sweeteners and adverse pregnancy outcomes

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Oct 8 2024

Artificial sweetener (AS) consumption may cause complications in pregnancy; however, this association remains unclear.

Study: Artificial Sweetener and the Risk of Adverse Pregnancy Outcomes: A Mendelian Randomization Study. Image Credit: Tatjana Baibakova / Shutterstock.com

A recent study published in Nutrients utilizes Mendelian randomization (MR) to identify causal associations that may exist between AS exposure and pregnancy outcomes.

What are artificial sweeteners?

ASs or non-nutritive sweeteners are sugar substitutes with high sweetness but low energy content. The use of ASs may reduce the incidence of dental caries and obesity, thus making these sweeteners an attractive option for people with type 2 diabetes mellitus (T2DM).

Nevertheless, previous studies suggest an increased risk of T2DM with AS consumption. Some of the common ASs utilized throughout the world include aspartame, acesulfame, saccharin, and sucralose, all of which are used in a wide range of products, some of which include breads, pastries, and sodas.

Previous observational studies suggest an increased risk of adverse pregnancy outcomes (APOs) with AS consumption, including low birth weight, preterm delivery, and gestational diabetes. However, these associations have not been fully evaluated.

About 33% of pregnant women in the Randomized Control Trial of Low Glycemic Index Diet in Pregnancy to Prevent Recurrence of Macrosomia (ROLO) reported the consumption of ASs during each trimester, over 51% of whom continued to consume ASs when advised to maintain a low-glycemic index diet. In fact, pregnant women may be even more likely to use ASs than the general population.

The current study utilized MR, which employs genetic variants as the instrumental variables (IVs). MR studies assume that the IV is firmly associated with the exposure but not to potential confounding factors nor the outcome. Thus, the only effect on the outcome is through its effect on the exposure.

About the study

Previous animal research has indicated impaired glucose tolerance and weight gain in pregnancy with aspartame intake; however, these results were not observed in a meta-analysis of 24 human studies. Nevertheless, diet drink consumption has been associated with impaired glucose tolerance, weight gain, gestational diabetes, and pre-eclampsia.

The aim of the current study was to identify the presence and significance of causality in any observed associations between AS exposure and APOs. To this end, genome-wide association study (GWAS) data were obtained from the publicly available IEU Open GWAS Project. Multiple analytic methods were used to examine the presence and significance of correlations between AS intake and pregnancy outcomes.

A total of 41, 18, and 18 IVs were associated with ASs added to cereal, coffee, and tea, respectively. Univariable MR (UVMR) showed that AS intake in tea was associated with an increased risk of ectopic pregnancy.

However, after adjusting for maternal body mass index (BMI) values and the presence of type 2 diabetes mellitus, multivariable MR (MVMR) indicated that the intake of ASs with cereal was negatively associated with ectopic pregnancy. More specifically, the risk of an ectopic pregnancy was 67% lower in AS consumers as compared to non-consumers.

The risk of placenta previa was also reduced by 89% with AS intake in cereal. However, the risk of premature rupture of membranes (PROM) increased by 62% when ASs were used in coffee. Notably, consuming three cups or more of coffee every day in the first trimester is an independent risk factor for PROM, with a two-fold risk observed in these individuals as compared to those who drink less coffee.

Other adverse outcomes were not associated with AS consumption.

Conclusions

The current study is the first to systematically analyze causal associations between AS intake from several foods and beverages with APOs based on genetic variations. While avoiding the limitations of observational studies, the current study did not identify any evidence that AS intake causes gestational diabetes, weight gain in pregnancy, or pre-eclampsia.

Nevertheless, PROM was found to be more common with AS use during pregnancy. Ectopic pregnancy and placenta previa were found to be reduced with AS consumption. Adjusting for BMI and T2DM did not change this pattern, perhaps because these individuals are more likely to use ASs with their cereal.

Further research is needed to validate the causal associations identified in the current study.