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NCT Number: NCT07424846

Xylitol and the Prevention of Periodontal Disease and Preterm Birth Trial

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.

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Key information

Conditions

Preterm Birth Communication Disorders Developmental Delay Female Urogenital Diseases and Pregnancy Complications Gingival Diseases Gingivitis Infections Learning Disabilities Low Birthweight Neonate Mental Disorders Mouth Diseases Nervous System Diseases Neurobehavioral Manifestations Neurodevelopmental Disorders Neurologic Manifestations Obstetric Labor Complications Obstetric Labor, Premature Pathological Conditions, Signs and Symptoms Periodontal Diseases Periodontitis Pregnancy Complications Premature Birth Signs and Symptoms Stomatognathic Diseases Urogenital Diseases

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Baylor College of Medicine Children's Foundation Malawi

Lilongwe, Malawi

Location status: Recruiting

Location contact

Joseph Mhango

CONTACT

[email protected]

+265 1 750 877

About this study

The hypothesis is that xylitol-containing chewing gum use compared to control (flavored gum base) during pregnancy, starting before 20 weeks' gestation, will lead to reduced risk of adverse pregnancy outcomes, namely preterm birth, as well as improved metrics of periodontal disease and improve neurodevelopmental outcomes of offspring at 2 years corrected gestational age, with most beneficial effect seen in those with 6.4 grams/day xylitol dose.

The study will utilize an individually randomized, placebo-controlled, double-blinded, phase II/III clinical trial with a 1:1:1 allocation ratio between xylitol-containing chewing gum (6.4 grams of xylitol/day), xylitol-containing chewing gum (2.1 grams of xylitol/day), and placebo (flavored gum base, sorbitol, 0 grams of xylitol/day).

Intervention (1st arm): Epic dental chewing gum (xylitol-containing chewing gum containing 1.06 grams xylitol/pellet). Participants will chew 6 Epic xylitol-containing chewing gum pellets each day (2 pellets three times daily in pre-made blister packs). Each participant will be instructed to chew 2 pieces of gum three times daily for 5 minutes each time starting at study entry (<20 weeks' gestation) and continuing until delivery.

Intervention (2nd arm): Epic dental chewing gum (xylitol-containing chewing gum containing 1.06 grams xylitol/pellet). Participants will chew 2 Epic xylitol-containing chewing gum pellets and 4 placebo gum pellets per day, representing 2 pellets three times daily in pre-made blister packs. Each participant will be instructed to chew 2 pieces of gum three times daily for 5 minutes each time starting at study entry (<20 weeks' gestation) and continuing until delivery.

Control: Flavored gum base (sorbitol) without xylitol, instructing the participants to chew 2 pieces of gum three times daily for 5 minutes each time, the same as the intervention, starting at study entry (<20 weeks' gestation) and continuing until delivery. These pellets will be non-xylitol placebo pellets of gum that otherwise taste and look the same as the intervention.

All gum will be pre-packaged into blister packs with the proper mix of Epic xylitol-containing chewing gum and/or placebo pellets to ensure the proper daily dose is administered per group the participant is randomized.

All patients who meet inclusion criteria will be approached without regard to race, ethnicity, parents' country of origin, or religious preferences.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Able to provide informed consent. For those under 18 years of age, an approval will additionally be sought from the parent or guardian
  • Less than 20 weeks' gestation (by best obstetric estimate)
  • At least 20 natural teeth
  • Planning to deliver at one of the health facilities within the XaPPP trial
  • Receiving antenatal obstetric care at one of the 8 health districts
  • Willing to chew two pieces of gum thrice daily for 5 minutes after the morning, day and evening meals throughout pregnancy
  • Willing to attend all study visits
  • Willing to provide biospecimens (oral, vaginal, placental, breast milk)
  • Willing to undergo at least two dental exams including oral microbiota sampling at study enrolment <20 weeks of pregnancy, 28-30 weeks of pregnancy, and 6-8 weeks after giving birth
  • Willing to have their child undergo follow up through at least 12 months after birth including neurodevelopmental examination(s)
  • Speaks Chichewa or English

All patients who meet inclusion criteria will be approached without regard to sex, race, ethnicity, parents' country of origin, or religious preferences.

Exclusion criteria

  • Those who upon screening and enrolment but dislike the taste of the gum and state they will not chew the gum throughout pregnancy
  • Gravidae with known or suspected non-viable pregnancy (including life threatening congenital anomalies such as cardiac, neurological or others)
  • Pregnant individual has a life-threatening diagnosis such as cancer requiring treatment during pregnancy
  • Pregnant women with a known or suspected morbidly adherent placenta (such as placenta accrete, increta and percreta)
  • Known allergy to xylitol

Treatment and study plan

Xylitol Chewing gum

Drug

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.

Sorbitol chewing gum

Other

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.

Primary outcomes

  1. Preterm Birth

    Time frame: delivery

    <37 weeks gestation

  2. Low birthweight offspring

    Time frame: at delivery

    <2500 gram birthweight of offspring

Secondary outcomes

  1. Neonatal mortality

    Time frame: first 28 days after delivery

    Death of neonate between birth-28 days after birth

  2. Infant Mortality

    Time frame: 1 year after birth

    Death of neonate between birth and 1 year after birth

  3. Neurodevelopmental Outcomes at 12 months

    Time frame: 1 year after birth

    Bayley Scales of Infant and Toddler Development. Standardized score range from 0-200 with 100 being the median and 15 points being 1 standard deviation. Higher scores represent better outcomes. Domains of cognitive, motor, and language will be assessed.

  4. Periodontitis

    Time frame: at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)

    Periodontitis will be defined as (a) interdental clinical attachment level (CAL) detectable at ≥ 2 non-adjacent teeth, or (b) buccal or oral CAL ≥ 3 mm with pocketing ≥ 2 teeth but the observed CAL cannot be ascribed to non-periodontitis-related causes.116 The sites with periodontitis should have CAL ≥ 1 mm and probing depth ≥ 4 mm, along with the presence of bleeding on probing (BOP).

  5. Gingivitis

    Time frame: at 28-30 weeks of pregnancy at 6-8 weeks postpartum (in the enrolled pregnant individuals)

    Gingivitis will be defined as having ≥50% of the sites with bleeding on probing (BOP) in a full-mouth examination. By selecting ≥50% with BOP, we are seeking to capture significant differences in gingival inflammation consistent with our previous trials.

Study contacts

Contact information is provided by the study sponsor or research team.

Greg Valentine, MD MED FAAP

CONTACT

[email protected]

2066167378 ext. (206) 543-3200

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Collaborators

  • Baylor College of Medicine
  • Baylor College of Medicine Children's Foundation

Registry information

Official study title

Xylitol and the Prevention of Periodontal Disease and Preterm Birth (XaPPP) Trial

Acronym: XaPPP

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Feb 20, 2026
Registry last updated
Aug 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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