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.
The National Academy of Medicine (NAM), previously known as the Institute of Medicine, recommends a daily intake of 3 mg of fluoride for women aged 14 to 50. The NAM also notes that most research indicates that a daily intake of 10 mg for 10 or more years is necessary to produce clinical signs of mild skeletal fluorosis; thus, the upper intake limit is regarded as 10 mg/day29. The Food and Drug Administration has also stated that 10 mg/day is the upper intake limit29. While fluoride has been linked to certain negative health outcomes, this has occurred only at extremely high doses30. The role of low dose fluoride (LF–) on pregnancy outcomes, although recommended by the NAM, has not been very well explored.
- 29. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes & Food and Nutrition Board Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride CHAPTER 6. In Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride 190–249, https://doi.org/10.1111/j.1753-4887.2004.tb00011.x (1997).
- Perumal, E., Paul, V., Govindarajan, V. & Panneerselvam, L. A brief review on experimental fluorosis. Toxicology Letters 223, 236–251 (2013).
Affiliation of the Authors:
All the authors, Bei Jia, Lu Zong, Ji Yeon Lee, Jun Lei, Yan Zhu, Han Xie, Julia L. Clemens, Mia C. Feller, Quan Na, Jie Dong, Michael W. McLane, Kimberly Jones-Beatty, and Irina Burd, are identified with
Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.