Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being

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.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Bacteremia; Preterm Labor; Preterm Premature Rupture of Fetal Membranes
• Intervention / Treatment: Drug: Prenatal vitamin-mineral containing 3 mg fluoride; Dietary supplement: Prenatal vitamin-mineral containing 0 mg fluoride

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.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluoride prenatal vitamin; Prenatal vitamin-mineral containing 3 mg fluoride	Drug: Prenatal vitamin-mineral containing 3 mg fluoride; Prenatal vitamin-mineral containing 3 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery.
Active Comparator: Standard prenatal vitamin; Prenatal vitamin-mineral containing 0 mg fluoride	Dietary supplement: Prenatal vitamin-mineral containing 0 mg fluoride; Prenatal vitamin-mineral containing 0 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of gestation	the length of gestation will be measured in weeks at time of delivery	Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight	Birth weight will be measured in grams and pounds	Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Birth length	birth length will be measured in inches	Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm birth	Preterm birth will be measured in weeks at time of delivery	Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm premature rupture of membranes (PPROM)	PPROM will be measured in weeks at time of PPROM	Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Irina Burd, M.D., Ph.D., Johns Hopkins University

Publications and helpful links

General Publications

• 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.
• 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.
• 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/
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): August 31, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Fluoride Supplementation; Prenatal Vitamin; Pregnancy Nutrition; Prenatal Nutrition
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Wounds and Injuries; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Pregnancy Complications; Obstetric Labor Complications; Rupture; Premature Birth; Bacteremia; Obstetric Labor, Premature; Fetal Membranes, Premature Rupture; Physiological Effects of Drugs; Protective Agents; Micronutrients; Cariostatic Agents; Fluorides; Vitamins
• Other Study ID Numbers: IRB00038838

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No