Xylitol and the Prevention of Periodontal Disease and Preterm Birth Trial

Summary

The ground-breaking Prevention of Prematurity and Xylitol (PPaX) cluster randomized controlled clinical trial was conducted in Lilongwe, Malawi and enrolled approximately 10,069 pregnant individuals seeking to evaluate the impact of xylitol-containing chewing gum compared to no chewing gum on reducing the occurrence of maternal periodontal disease, preterm birth, and low birthweight offspring. The premise of this study centers upon the numerous publications supporting a strong association between maternal periodontal disease and preterm birth. Given that xylitol-containing chewing gum is considered a prebiotic and known to reduce cariogenic and periodontopathic bacteria, the study evaluated and discovered a statistically significant reduction in maternal periodontal disease, preterm birth, and low birthweight offspring among pregnant individuals who chewed xylitol-containing chewing gum.

While PPaX demonstrated the efficacy of xylitol to reduce preterm birth (PTB), the study had important limitations: (a) PPaX was an unblinded cluster-randomized study with only 8 clusters, 4 with xylitol-containing chewing gum and 4 without any gum (not placebo-controlled); (b) PPaX used a suboptimal dose of 2 grams of xylitol daily which may have reduced the effectiveness of the intervention given that recent literature suggests 5-10 grams/day more effectively improve oral health; and (c) PPaX did not evaluate infant mortality nor early neurodevelopmental outcomes. Notably, reducing fetal exposure to periodontal disease (PD) as well as PTB may improve neurodevelopmental outcomes for offspring as both prematurity and fetal exposure to inflammation are well-documented risk factors for neurodevelopmental delay (NDD) and infant mortality.

The investigators will conduct a double-blind, placebo-controlled, individually randomized clinical trial with 3 arms among Malawian pregnant individuals (n=6000) at \<20 weeks of pregnancy with the co-primary outcomes being the incidence of PTB and low birthweight offspring. The 3 study arms (n=2000 each) will be (a) an optimized dose of xylitol-containing chewing gum (6.4 grams/day), (b) the PPaX trial xylitol dose (2.1 grams/day), or (c) flavored sorbitol gum base (placebo control). This trial overcomes the PPaX trial's limitations and will definitively answer whether xylitol prevents PTB in Malawi. The investigators will additionally collect biospecimens from a random sampling of the participants for biobanking for later analysis of inflammatory and microbiome alterations that may occur with xylitol exposure compared with placebo. The investigators hypothesize that pregnant individuals who chew xylitol-containing chewing gum will have a significant reduction in periodontal disease metrics at 28-30 weeks' gestation (e.g. bleeding on probing) as well as offspring with improved neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development 4th edition and reduced risk of adverse pregnancy outcomes including preterm birth.

Conditions

• Preterm Birth
• Low Birthweight Neonate
• Periodontitis
• Gingivitis
• Developmental Delay

Interventions

DRUG

Xylitol Chewing gum

Xylitol chewing gum (1 gram per pellet of gum). This is a dietary supplement, but clinicaltrials.gov requires us to identify it as a "drug" due to IND requirements.

OTHER

Sorbitol chewing gum

Sorbitol (non-xylitol) chewing gum. This is a dietary supplement, but clinicaltrials.gov requires us to identify it as a "drug" due to IND requirements.

Sponsors & Collaborators

• Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine Children's Foundation Malawi

  collaborator UNKNOWN

• University of Washington

  lead OTHER

Principal Investigators

• Greg Valentine · University of Washington

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-15

Primary Completion

2030-09-30

Completion

2030-09-30

FDA Drug

Yes