Clinical trial NCT02536352: Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being
Official title: Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Preterm Birth
Preterm Labor
Bacteremia
Preterm Premature Rupture of Fetal Membranes
Keywords: Fluoride Supplementation
Prenatal Vitamin
Pregnancy Nutrition
Prenatal Nutrition
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2015-08-31
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to determine whether fluoride supplementation during pregnancy is effective in extending the length of gestation and improving overall perinatal well-being.

Detailed description: The Centers for Disease Control and Prevention (CDC) reports that preterm birth affected about 1 in 10 infants born in the United States in 2015. These statistics emphasize the significance of implementing a safe and effective therapy into routine clinical care aimed at reducing the rate of preterm birth. There has been evidence to suggest that fluoride supplementation to women during pregnancy can provide other medical benefits, in addition to a reduction in dental caries.

Fluoride is recognized by the Food and Nutrition Board (F\&NB) of the American Academy of Sciences and the Food \& Drug Administration (FDA) as an essential ion due to its association with a reduction in dental caries.

Upon entering the body, fluoride is taken up into the bones/calcified tissues, and excreted by the kidneys. When supplied during pregnancy in small aliquots, as with water fluoridation, the fluoride is likely taken up in the mother's bones and excreted by her kidneys so rapidly, that the fetus is denied a meaningful amount of fluoride, unless it is supplied in a pulse dose by supplement. The Institute of Medicine's Food and Nutrition Board recommends 3 mg/day for Adequate Intake in pregnancy and deems 10 mg/day as the Upper Limit.

After several papers elucidating an association between poor dentition, periodontal disease, and preterm birth, subsequent RCT's of regular periodontal scaling and treatment during pregnancy are still inconclusive in regards to preterm birth.

The investigators hypothesize that fluoride supplementation during pregnancy may have a beneficial effect on the natural microbiome of the maternal oral cavity and genital tract, capable of protecting against transient bacteremia and ascending infection, respectively, which are known antecedents to both preterm labor and preterm premature rupture of membranes. The research team predicts that the testing and analysis of specimens collected will demonstrate microbiome changes toward a more favorable profile not associated with preterm birth.

The proposed randomized, double-blinded, placebo-controlled clinical trial aims to confirm the efficacy of fluoride supplementation in pregnancy to extend length of gestation and increase overall perinatal well-being, and to confirm transplacental transfer of supplemental fluoride. This research may also identify other beneficial maternal and neonatal outcomes associated with the administration of fluoride during the perinatal period by attempting to characterize and compare the microbiomes of the maternal oral cavity and genital tracts between supplemented and unsupplemented gravidas.

Eligibility criteria: Inclusion Criteria:

* Women who are between 10-20 weeks gestational age at the time of recruitment
* Delivery at Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center

Exclusion Criteria:

* Use of prescription strength, high dose fluoride products (greater than 0.76% of fluoride), prescribed by a dental professional (toothpastes, mouthwashes, topical treatments). All over-the-counter toothpaste and mouthwash products are acceptable to use.
* Occupational exposure to fluoride.
* The daily amount of fluoride ingested should not exceed 10 mg/day, according to the Institute of Medicine and the FDA. Any participants consuming amounts of fluoride close to 10 mg/day will be excluded.

Primary outcomes:
measure: Length of gestation
timeFrame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Secondary outcomes:
measure: Birth weight
timeFrame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
measure: Birth length
timeFrame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
measure: Preterm birth
timeFrame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
measure: Preterm premature rupture of membranes (PPROM)
timeFrame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Irina Burd, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leverett DH, Adair SM, Vaughan BW, Proskin HM, Moss ME. Randomized clinical trial of the effect of prenatal fluoride supplements in preventing dental caries. Caries Res. 1997;31(3):174-9. doi: 10.1159/000262394.
citation: Srinivas SK, Sammel MD, Stamilio DM, Clothier B, Jeffcoat MK, Parry S, Macones GA, Elovitz MA, Metlay J. Periodontal disease and adverse pregnancy outcomes: is there an association? Am J Obstet Gynecol. 2009 May;200(5):497.e1-8. doi: 10.1016/j.ajog.2009.03.003.
citation: Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); 1997. Available from http://www.ncbi.nlm.nih.gov/books/NBK109825/
citation: Iheozor-Ejiofor Z, Middleton P, Esposito M, Glenny AM. Treating periodontal disease for preventing adverse birth outcomes in pregnant women. Cochrane Database Syst Rev. 2017 Jun 12;6(6):CD005297. doi: 10.1002/14651858.CD005297.pub3.