Saving Lives at Birth: Primary Prevention of Periodontal Disease in Relation to Preterm Birth in Malawi (PPaX)

Saving Lives at Birth: Primary Prevention of Periodontal Disease in Relation to Preterm Birth in Malawi (Prevention of Prematurity and Xylitol)

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.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Periodontal Disease; Caries, Dental
• Intervention / Treatment: Dietary supplement: Xylitol gum

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.

• Study Type: Interventional
• Enrollment (Actual): 10069
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Cluster of sites not receiving xylitol gum. This is a cluster randomized trial, whereby 4 sites will not receive the intervention of xylitol gum in the prepregnancy and early pregnancy interval.
Experimental: Xylitol; Cluster of sites receiving xylitol gum.	Dietary supplement: Xylitol gum; This is a cluster randomized trial, whereby 4 sites will receive the intervention of xylitol gum in the prepregnancy and early pregnancy interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Preterm Birth	This is a co-primary outcome: Measure rate of preterm birth <37 weeks gestation, as defined by best obstetrical estimate based upon last menstrual period correlated with fundal height at entry to prenatal care or ultrasound, when available; all sites have access to referral for ultrasound.	Conception to date of delivery, <37 weeks gestation
Number of Infants <2500 Grams	This is a co-primary outcome: Measured weight at delivery to determine the rate of <2500 gram infants.	Date of delivery to 1 week postnatal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Infants With Adverse Neonatal Composite Morbidity and Mortality	Additive or singular composite neonatal morbidity up to 28 days of age. Composite neonatal morbidity and mortality outcomes are defined as: neonatal death, miscarriage <28 weeks, stillbirth (fresh or macerated), neonatal sepsis, neonatal respiratory distress, neonatal seizures, feeding problems, fever, hypothermia, Apgar score <7 at 5 minutes after birth, referral to other hospital or neonatal intensive care unit (NICU)	Date of delivery to 28 days postnatal
Number of Participants With Periodontal Disease	We will measure the prevalence of periodontal disease among gravidae. We will use standardized World Health Organization (WHO) oral health forms and disease scoring.	During pregnancy, up to 2 dental visits performed during pregnancy (approximately 37-40 weeks if term) to evaluate dental outcomes
Number of Participants With Dental Caries	We will measure the prevalence of dental caries among gravidae. We will use standardized World Health Organization (WHO) oral health forms and disease scoring.	During pregnancy, up to 2 dental visits performed during pregnancy (approximately 37-40 weeks if term) to evaluate dental outcomes

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Kjersti Aagaard, M.D., Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimated): January 7, 2015

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Tooth Demineralization; Tooth Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Dental Caries; Periodontal Diseases
• Other Study ID Numbers: NHSRC # 1030; H-35933 (Other Identifier: Baylor College of Medicine)