Effects of vaginal microbiota transfer on social–emotional and neurodevelopment in cesarean‐born infants: 12‐month follow‐up of a pilot randomized clinical trial

INTRODUCTION: To evaluate the effects of vaginal microbiota transfer (VMT) on social-emotional development and to assess whether neurodevelopmental benefits observed at 6 months persist at 12 months in cesarean-born infants. MATERIAL AND METHODS: This 12-month follow-up study extended a prior randomized, placebo-controlled trial at a tertiary hospital in southern China. Cesarean-born infants were randomly assigned in a 1:1 ratio to receive maternal vaginal fluid (VMT group) or sterile saline-soaked gauze (Con group) immediately after delivery. Vaginally delivered mother-infant dyads served as a natural reference group (VD group). The primary endpoint of the original trial was infant neurodevelopment at 6 months. In this follow-up, social-emotion and neurodevelopment at 12 months were assessed using the Ages and Stages Questionnaires: Social-Emotional, Second Edition (ASQ:SE-2) and Third Edition (ASQ-3). Lower ASQ:SE-2 scores indicate better social-emotion skills, while higher ASQ-3 scores indicate better neurodevelopmental performance. This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000031326. RESULTS: A total of 210 mother-infant dyads were enrolled (VMT, Con, VD: n = 70 each) from December 10, 2020, to November 11, 2022. Infants in the VMT group had significantly lower ASQ:SE-2 total scores than those in the Con group (31.01% decrease; mean difference [MD]: -9.24; 95% confidence interval [95% CI]: -16.04 to -2.45), with improvements in self-regulation, social communication, and interaction with people. The VMT group also had higher ASQ-3 scores in the personal-social subdomain (MD: 4.65; 95% CI: 0.15 to 9.15), but no significant difference in total ASQ-3 scores (MD: 8.90; 95% CI, -2.9 to 20.70). No significant differences were found between the VMT and VD groups. The VMT group had a lower prevalence of social-emotional risk (adjusted RR: 0.39 [95% CI, 0.19 to 0.80]) than the Con group. CONCLUSIONS: This pilot randomized clinical trial suggests that VMT may be associated with improved social-emotional development at 12 months in cesarean-born infants, although the neurodevelopmental benefits observed earlier appear to diminish over time. Given the small sample size and exploratory nature, the findings should be interpreted with caution. Larger, multi-center randomized controlled trials with longer follow-up are needed to confirm these results and further evaluate the VMT's effectiveness.