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

• ClinicalTrials.gov Identifier: NCT02536352
• Recruitment Status: Completed
• First Posted: August 31, 2015
• Last Update Posted: November 5, 2019
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: August 27, 2015
• First Posted Date: August 31, 2015
• Last Update Posted Date: November 5, 2019
• Study Start Date: October 2015
• Actual Primary Completion Date: October 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 7, 2017)

Length of gestation [ Time Frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study ]

the length of gestation will be measured in weeks at time of delivery

• Original Primary Outcome Measures (submitted: August 28, 2015): Length of gestation [ Time Frame: Participants will be followed from the time of study enrollment until delivery, an expected average of 24 weeks ]

Current Secondary Outcome Measures (submitted: August 7, 2017)

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

Original Secondary Outcome Measures (submitted: August 28, 2015)

• Birth weight [ Time Frame: Participants will be followed from the time of study enrollment until delivery, an expected average of 24 weeks ]
• Birth length [ Time Frame: Participants will be followed from the time of study enrollment until delivery, an expected average of 24 weeks ]
• Preterm birth rate [ Time Frame: Participants will be followed from the time of study enrollment until delivery, an expected average of 24 weeks ]
• Preterm premature rupture of membranes (PPROM) rate [ Time Frame: Participants will be followed from the time of study enrollment until delivery, an expected average of 24 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other

Condition

• Preterm Birth
• Preterm Labor
• Bacteremia
• Preterm Premature Rupture of Fetal Membranes

Intervention

• 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.
• 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.

Study Arms

• Experimental: Fluoride prenatal vitamin
  Prenatal vitamin-mineral containing 3 mg fluoride
  Intervention: Drug: Prenatal vitamin-mineral containing 3 mg fluoride
• Active Comparator: Standard prenatal vitamin
  Prenatal vitamin-mineral containing 0 mg fluoride
  Intervention: Dietary Supplement: Prenatal vitamin-mineral containing 0 mg fluoride

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 4, 2019): 43
• Original Estimated Enrollment (submitted: August 28, 2015): 1300
• Actual Study Completion Date: October 1, 2019
• Actual Primary Completion Date: October 1, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02536352
• Other Study ID Numbers: IRB00038838
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Johns Hopkins University
• Original Responsible Party: Same as current
• Current Study Sponsor: Johns Hopkins University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Johns Hopkins University
• Verification Date: November 2019