Maternal Supplementation of Low Dose Fluoride Alleviates Adverse Perinatal Outcomes Following Exposure to Intrauterine Inflammation

Maternal periodontal disease has been linked to adverse pregnancy sequelae, including preterm birth (PTB); yet, root planing and scaling in pregnancy has not been associated with improved perinatal outcomes. Fluoride, a cariostatic agent, has been added to drinking water and dental products to prevent caries and improve dental health. The objective of this study was to explore the effects of fluoride supplementation using a mouse model of preterm birth and perinatal sequalae. Pregnant mice were fed low dose fluoride (LF(−)) or high dose fluoride (HF(−)) and given intrauterine injections of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). We found that LPS + LF(−) significantly increased livebirths, pup survival, and litter size compared to LPS alone. Moreover, offspring from the LPS + LF(−) group exhibited significantly improved neuromotor performance and more neurons compared to those from the LPS group. Additionally, LF(−) treatment on human umbilical vein endothelial cells (HUVECs) increased cell viability and decreased oxidative stress after treatment with LPS. Collectively, our data demonstrates that maternal LF(−) supplementation during pregnancy postpones the onset of PTB, acts to increase the liveborn rate and survival time of newborns, and reduces perinatal brain injury in cases of intrauterine inflammation.