Oral Lacticaseibacillus rhamnosus GG Exposure During Pregnancy and Effects on Maternal Inflammatory Response—A Blinded, Pilot Randomized, Placebo‐Controlled Study

Problem This study aimed to investigate whether Lacticaseibacillus rhamnosus GG intake during pregnancy influences maternal cytokine levels and lymphocyte subpopulations. Method Pregnant women were categorized into three groups: those with a history of spontaneous preterm delivery (PTD) ( n = 40), those with a history of preeclampsia ( n = 40), and nulliparous or parous women without a history of PTD or preeclampsia ( n = 40). Participants were randomized to receive either L. rhamnosus GG or a placebo. Maternal blood samples were collected at baseline before gestational week 19 (visit 1) and around gestational weeks 25 and 35 (visits 2 and 3). The primary outcome was the change in tumor necrosis factor‐alpha (TNF‐α) levels in monocytes after stimulation of maternal blood with Escherichia coli lipopolysaccharide (LPS). Secondary outcomes included lymphocyte subpopulation analysis and changes in TNF‐α, interleukin (IL)‐10, and IL‐12 levels after stimulation with E. coli LPS, Lactobacillus paracasei , or Pseudomonas aeruginosa . Results In the intention‐to‐treat analysis, no significant differences in TNF‐α levels were observed. However, a sensitivity analysis excluding participants with fever or recent antibiotic use ( n = 27) revealed a significant decrease in TNF‐α levels in the intervention group at visit 2 compared to an increase in the placebo group (mean difference −11785 cells/mL, 95% CI: −22459 to −1287, p = 0.03). Secondary analyses showed lower total lymphocyte, T‐cell, IL‐10, and IL‐12 levels at visit 2 and higher IL‐10 and IL‐12 levels at visit 3 in the intervention group. Conclusions Although L. rhamnosus GG did not significantly affect TNF‐α levels, its influence on lymphocyte and cytokine levels warrants further investigation through larger trials.