Impact of Short-Term Fluoride Supplementation in Pregnancy on the Maternal Microbiome, Pregnancy, and Neonatal Outcomes: A Pilot Randomized Controlled Trial.

Introduction This report presents secondary, exploratory analyses of a double-blind randomized trial originally designed to determine whether fluoride supplementation during pregnancy reduced preterm birth (PTB). The trial was terminated early because of enrollment difficulties and was not powered for its original clinical endpoint. We therefore examined whether randomized fluoride supplementation was associated with oral or vaginal microbiome composition and descriptively evaluated gestational and neonatal outcomes. Methodology In the original double-blind randomized controlled trial, pregnant participants at 10-20 weeks of gestation were assigned to a daily capsule containing 3 mg fluoride or an otherwise comparable prenatal vitamin. Of 319 screened individuals, 47 were eligible, and 30 participants completed follow-up through delivery. Maternal urine, oral swabs, and vaginal swabs were collected during the second and third trimesters and at delivery. The V3-V4 region of the bacterial 16S rRNA gene was sequenced from oral and vaginal specimens. The present secondary analyses compared microbiome composition and diversity by treatment assignment and descriptively examined gestational and neonatal outcomes. Results Urine fluoride concentration differed between groups at the second-trimester assessment but not at later assessments. No differences in vaginal microbiome richness or diversity were observed between treatment groups. Several oral taxa, including