Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT06329596

Microbiome Alterations With Xylitol (MAX) in Pregnancy

The purpose of this study is to understand if chewing xylitol-gum initiated before 20 weeks of pregnancy and continued until delivery affects the bacteria that are found in the oral and vaginal cavities, signs of inflammation within the gingiva of the oral cavity, the health of the tissues in the mouth (clinical parameters of periodontal disease) and placentae, and the bacteria in the mouth and gut of newborns among pregnant individuals in Malawi. In addition, we will evaluate the impact of xylitol-containing chewing gum use during pregnancy on the offsprings neurodevelopment at approximately 6- and 18-months corrected age.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Dysbiosis Gingival Diseases Gingivitis Infections Inflammation Gum Microbioata Mouth Diseases Neurodevelopmental Changes (Childhood, Ageing) Pathologic Processes Pathological Conditions, Signs and Symptoms Periodontal Diseases Placenta-mediated Pregnancy Complications Stomatognathic Diseases

Age range

12 year–60 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Area 25 Health Center

Lilongwe, Malawi

About this study

After consenting to the study, pregnant participants who have a singleton gestation and are <20 weeks' gestation will be randomised into either the intervention arm ( 6.36grams of daily xylitol; Epic dental gum, 1.06 grams Xylitol per piece of gum; chew two pieces for 5 minutes after meals, thrice a day) or the placebo control arm (Sorbitol Gum base; Epic sorbitol-containing gum, 0 grams/day of xylitol; chew two pieces for 5 minutes after meals, thrice a day) by randomly picking from a group of opaque, sealed envelopes containing group allocation. The participants will also undergo a dental assessment and sampling, and vaginal sampling at enrolment, 28- 30 weeks of pregnancy, at birth - 48 hours and 4-6 weeks after birth. In addition, placental and breastmilk specimens will be obtained at the time of delivery, and stored in a biobank for future analyses. The investigators will also obtain oral and meconium (and stool at 4-6 weeks) samples of their newborns at birth and 4-6 weeks after birth. Furthermore, at 6- and 18-months corrected age, the infants will undergo neurodevelopmental assessments using the the Hammersmith Infant Neurologic Exam (HINE), Developmental Assessment of Young Children 2nd Edition (DAY-C), and Malawi Development Assessment Tool (MDAT). The assessments will be done by two community health workers trained in these methods and will be compared to assessments by a paediatric neurologist.

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, consent will additionally be sought from the parent or guardian.
  • A singleton at <20 weeks' gestation (based on ultrasound or best obstetric measurement)
  • Planning to deliver at Area 25 health center.
  • Willing to chew two pieces of gum thrice daily for 5 minutes after the morning, day and evening meals throughout pregnancy.
  • Willing to undergo at least two dental exams including oral microbiota sampling at study enrolment <20 weeks of pregnancy, 28-30 weeks, at delivery/within 48 hours and 4-6 weeks after giving birth.
  • Willing to have at least two vaginal sampling at study enrolment <20 weeks of pregnancy, 28-30 weeks, at delivery/within 48 hours and 4-6 weeks after giving birth.
  • Able to speak Chichewa or English.
  • Cognitively aware enough to be able to participate in the study.
  • Willing to consent to all required aspects of protocol including allowing collection of placenta specimens, infant oral swab and meconium/stool sampling at birth/within 48 hours and 4-6 weeks after.

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).

Treatment and study plan

Xylitol gum

Dietary Supplement

Two pieces of xylitol gum after meals, thrice a day.

Other names: Epic Xylitol gum

Sorbitol gum

Dietary Supplement

Two pieces of sorbitol gum after meals, thrice a day.

Primary outcomes

  1. Periodontal disease at 28-30 weeks of pregnancy

    Time frame: Enrolment and 28-30 weeks of pregnancy.

    The investigators will create scaled periodontal disease score comprising of sum of scores for gingival bleeding (+1 if bleeding was present, per tooth), gingival pockets (+1 for pockets of 4-5 mm and +2 for 6 mm or deeper, per tooth), and loss of attachment (+1 for 4-5 mm loss, +2 for 6-8 mm, +3 for 9-11 mm, and +4 for 12 mm or more, per tooth with values recorded for index teeth) divided by the number of teeth present will be created for every dental visit. A score of >0 will indicate presence of periodontal disease. The investigators will compare periodontal disease status at 28-30 weeks of pregnancy to that at enrolment.

Secondary outcomes

  1. Periodontal disease at 6 weeks postpartum

    Time frame: Enrolment and 6 weeks postpartum

    The investigators will create scaled periodontal disease score comprising of sum of scores for gingival bleeding (+1 if bleeding was present, per tooth), gingival pockets (+1 for pockets of 4-5 mm and +2 for 6 mm or deeper, per tooth), and loss of attachment (+1 for 4-5 mm loss, +2 for 6-8 mm, +3 for 9-11 mm, and +4 for 12 mm or more, per tooth with values recorded for index teeth) divided by the number of teeth present will be created for every dental visit. A score of >0 will indicate presence of periodontal disease. The investigators will compare periodontal disease status at 6 weeks postpartum to that at enrolment.

  2. Alterations in the maternal oral microbiome communities

    Time frame: Enrolment and at 28-30 weeks, delivery and 4-6 weeks after

    Using 16S rRNA sequencing to assess strain level changes in sub gingival plaque composition within and between those exposed to xylitol and placebo gum using exact amplicon sequence variants.

  3. Alterations in the maternal vaginal microbiome communities

    Time frame: Enrolment and at 28-30 weeks, delivery and 4-6 weeks after

    Using 16S rRNA sequencing to assess strain level changes in the vaginal microbiome at the vaginal introitus and posterior fornix. The investigators will compare compositional differences between sites in relationship to treatment

  4. Inflammatory mediator changes in the maternal gingival crevicular fluid compared to changes in the placenta.

    Time frame: Enrolment and at 28-30 weeks, and at delivery

    The investigators will assess changes in local oral inflammation associated with xylitol exposure or not by evaluating the gingival crevicular fluid using a 10-plex pro inflammatory cytokine panel.

  5. Alterations within the infants' oral microbiome communities

    Time frame: 4-6 weeks

    The investigators will us 16S rRNA sequencing to assess strain level changes within the oral swabs of the infants born during the MAX trial and assess changes in the composition within and between those exposed to xylitol and placebo gum.

  6. Alterations within the infants' gut microbiome communities

    Time frame: 4-6 weeks

    The investigators will use 16S rRNA sequencing to assess strain level changes in the stool/meconium samples from the infants' gut microbiome and assess compositional changes within and between those exposed to xylitol and placebo gum.

  7. To determine the impact of chewing xylitol-containing gum (6.4 grams/day) vs placebo gum in pregnancy on neurodevelopmental outcomes of offspring at 6 and 18 months

    Time frame: At 6- and 18- months of corrected age.

    We will use the MDAT z-score as a primary outcome. Secondary outcomes include DAYC-2 raw score and HINE optimality scores and asymmetries. Relevant descriptive statistics, and non-parametric tests will be used in analysis.

  8. To determine whether the addition of the DAYC-2 and HINE to the MDAT at 6 months of age improves the predictive validity for any NDD (1 SD below normative score on any MDAT domain), identified on the MDAT, DAYC-2 and/or HINE at 18 months corrected age.

    Time frame: 6- and 18-months of corrected age

    We will utilise logistic regression to establish a predictive model for addition of the DAYC-2 and HINE to MDAT for NDD at 18 months corrected age.

  9. (Exploratory) To assess the intra-class correlation between an intensively trained Community Health Workers (CHW) in administering the MDAT, DAYC-2, and HINE as compared to a gold-standard examiner (Malawi-based Pediatric Neurologist).

    Time frame: 6- and 18-months corrected age.

    We will use standard measures including Cronbach's alpha coefficient to compare all assessments between CHW and the gold standard examiner and generate a Bland-Altman plot. We will use the results of this exploratory aim to inform a power calculation for a planned future large investigation to determine how many assessments are needed by two examiners to assess the reliability of CHW exams.

Sponsors and collaborators

Lead sponsor

Baylor College of Medicine

Other

Collaborators

  • Baylor College of Medicine Children's Foundation
  • Cure Within Reach
  • Fogarty International Center of the National Institute of Health
  • Thrasher Medical Research Foundation
  • University of Washington

Registry information

Official study title

Periodontal Disease and Alterations in the Oral and Vaginal Microbiome Communities Among Gravidae Chewing Xylitol-gum in Malawi: Microbiome Alterations With Xylitol (MAX) in Pregnancy Trial.

Acronym: MAX

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Mar 26, 2024
Registry last updated
Mar 10, 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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.