The SPRING trial aimed to prevent gestational diabetes through supplementation with probiotics. This was proven not to be successful with 18.4% (38 of 207) of women in the probiotics arm developing gestational diabetes vs. 12.3 % (25 of 204) women in the placebo arm (P=0.10) (1). SPRING was not powered for detecting potential differences in rates of preeclampsia but we reported that 9.2% (19 of 207) women in the probiotics arm and 4.9% (10 of 204) women in the placebo arm developed preeclampsia (P=0.09).
There are no randomized controlled trials of probiotics in the development of preeclampsia. We therefore conducted a meta-analysis of the association between probiotics and preeclampsia in all randomized controlled trials of probiotics to prevent gestational diabetes.
Of the seven RCTs, four reported on preeclampsia incidence. Each individual study showed higher incidence of preeclampsia in the probiotics group. Of the 472 women in the probiotics group in the meta-analysis, 31 developed preeclampsia (6.6%) compared with 17 out of 483 women (3.5%) in the placebo group. The risk ratio for preeclampsia in women supplemented with probiotics was 1.85 [95% CI 1.04, 3.29].
Despite evidence for the beneficial effects of Lactobacilli and Bifidobacteria-based probiotics on gut wall barrier function, immune regulation and metabolic regulation (2), unexpected interactions between the probiotics and the host occur within pregnancy increasing the risk for the development of preeclampsia. These results suggest that probiotics may have detrimental outcomes and that their classification as Generally Recognized As Safe (GRAS) should be reconsidered.