Clinical trial NCT02333227: Saving Lives at Birth: Primary Prevention of Periodontal Disease in Relation to Preterm Birth in Malawi
Official title: Saving Lives at Birth: Primary Prevention of Periodontal Disease in Relation to Preterm Birth in Malawi (Prevention of Prematurity and Xylitol)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preterm Birth
Periodontal Disease
Caries, Dental
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2015-01-07
Enrollment: 10069
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The hypothesis of the investigators' project is that comprehensive primary preterm birth prevention, inclusive of maternal oral health with xylitol chewing gum (the intervention), will reduce the rate of periodontal disease and caries, preterm birth prevalence, and neonatal mortality.

Detailed description: Significance and Impact: Adverse birth outcomes related to the length of gestation (preterm birth) are recognized as one of the most significant disorders in maternal-child health at a global scale. In the developed world, the preterm birth rate approximates 7%. In Malawi, the investigators have recently demonstrated that this rate more than triples to approximate 26.1%. Of the 4 million newborn deaths annually, nearly 1/3 (27%) are directly attributable to prematurity with another 36% secondary to related opportunistic infections (sepsis, pneumonia, gastrointestinal). 75% of the 4 million deaths occur within the first week of life, with the vast majority occurring in the first 48 hours. For those that do survive, there are persistent and lifelong risks due to stunted growth, chronic infection, retinopathy of prematurity, and bronchopulmonary dysplasia. The link between maternal oral health (periodontal disease in particular) and risk of preterm birth has been demonstrated across all populations (rural and urban, in both industrialized and developing regions) studied to date. However, in multiple randomized controlled trials treatment of active periodontal disease with scaling and planning during pregnancy has failed to demonstrate a significant benefit in preventing preterm birth.

Why would maternal oral health impact preterm birth? In rodents, subcutaneous inoculations with periodontal pathogens cause dose-dependent decreases in pup weights, and elicit inflammatory responses that can trigger preterm birth when present in amniotic fluid. Periodontitis (defined as a destructive inflammation of the periodontium) has a prevalence of 30% or greater in women of child bearing age. By definition, it involves microbial infiltration of the periodontium, which stimulates a chronic inflammatory response, recurrent bacteremia, and the production of cytokines and prostaglandins which trigger risk of preterm birth. It is the same production of prostaglandins which are felt to mediate the risk of preterm birth. So if the investigators know that there is biologic evidence that periodontitis is related to preterm birth, but treating active periodontitis does not reduce these morbidities, is it possible that preventing periodontitis might prevent preterm birth and low birth weight? If so, what are the least expensive efficacious preventative measures? The investigators' overarching hypothesis is that comprehensive primary preterm birth prevention, inclusive of maternal oral health with xylitol chewing gum (the intervention), will reduce the rate of periodontal disease and caries, preterm birth prevalence, and neonatal mortality.

Eligibility criteria: Inclusion Criteria:

1. Enrollment at \<20 weeks gestation by best obstetrical estimate, or
2. Enrollment post partum with an anticipated next pregnancy within 18 months, or
3. Enrollment preconception with an anticipated pregnancy within 18 months (preconception); and
4. Cognitively aware enough to participate in the study
5. \>18 years of age (in Malawi, constitutes a legal adult and capacity to consent for study)
6. Willing to participate in the study
7. Willing to undergo at least two periodontal exams
8. Willing to chew 1 piece of xylitol gum for 10 minutes after the morning and evening meal (intervention sites)
9. Anticipating to remain within the region for 18 months

Exclusion Criteria:

1. \>20 weeks gestation by best obstetrical estimate
2. Post partum and not anticipating another pregnancy within 18 months
3. Preconception and not anticipating another pregnancy within 18 months
4. Not cognitively aware enough to participate in the study
5. Not willing to undergo at least two periodontal exams
6. \<18 years of age
7. Not willing to chew 1 piece of xylitol gum for 10 minutes after the morning and evening meal (intervention sites)
8. Anticipating a move outside of the region within 18 months

Primary outcomes:
measure: Rate of Preterm Birth
timeFrame: Conception to date of delivery, <37 weeks gestation
measure: Number of Infants <2500 Grams
timeFrame: Date of delivery to 1 week postnatal
Secondary outcomes:
measure: Number of Infants With Adverse Neonatal Composite Morbidity and Mortality
timeFrame: Date of delivery to 28 days postnatal
measure: Number of Participants With Periodontal Disease
timeFrame: During pregnancy, up to 2 dental visits performed during pregnancy (approximately 37-40 weeks if term) to evaluate dental outcomes
measure: Number of Participants With Dental Caries
timeFrame: During pregnancy, up to 2 dental visits performed during pregnancy (approximately 37-40 weeks if term) to evaluate dental outcomes
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Kjersti Aagaard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: