Body mass index, prebiotic supplementation during pregnancy and gestational diabetes mellitus risk: an effect modification analysis from a randomised controlled trial

Prebiotic dietary supplementation has been shown to improve glucose homeostasis in type 2 diabetes patients. The aim of this analysis was to determine whether pre-pregnancy body mass index (BMI) modifies the effect of prebiotic supplementation from mid-pregnancy on reducing the risk of gestational diabetes mellitus (GDM). In a double-blinded, randomised controlled trial, pregnant women < 21 gestational weeks were randomly assigned (1:1) to consume daily prebiotics (14.2 g galacto-oligosaccharides and fructo-oligosaccharides) or placebo (8.7 g maltodextrin) powder. An effect modification analysis was performed to assess the heterogeneity of the effect of prebiotic supplementation in relation to pre-pregnancy BMI on GDM diagnosis. Between June 2016 and November 2021, 329 women were assigned to the prebiotic group (50.4%), and 323 (49.5%) were assigned to the placebo group. Overall, 288 of 652 women (44.2%) were classified as overweight/obese prior to pregnancy (BMI ≥ 25 kg/m2). The distribution was balanced, with 146/329 (44.4%) randomised to the prebiotics group and 142/323 (44.0%) in the placebo group. Pre-pregnancy BMI modified the effect of prebiotic supplementation, with the intervention reducing GDM rates in women with a BMI ≥ 25 kg/m2 (prebiotic group 11.0% vs. control group 21.8%; adjusted relative risk 0.50; 95% confidence interval (CI) 0.28 to 0.89) but not in women with a pre-pregnancy BMI < 25 kg/m2 (7.7–7% vs. 4.4%; adjusted relative risk 1.72; 95% CI 0.70 to 4.19; interaction p = 0.02). Pre-pregnancy BMI was found to modify the effect of prebiotic supplementation on GDM rates, with benefits observed in overweight and obese women. Our results highlight a target population for future randomised controlled trials to further investigate the effects of prebiotic supplementation during pregnancy on reducing the risk of GDM. Primary and secondary infant allergic disease outcomes of this randomised controlled trial have been previously published. The trial was registered with the Australian New Zealand Clinical Trial Registry: ACTRN12615001075572, https://www.anzctr.org.au/on13/10/2015.