A Cluster Randomized Trial of Xylitol Chewing Gum for Prevention of Preterm Birth: The PPaX Trial

Authors

• Gregory C Valentine
• Kathleen M Antony
• Haleh Sangi-Haghpeykar
• Alexis C Wood
• Rose Chirwa
• Saukani Petro
• Mary Dumba
• Deborah Nanthuru
• Cynthia Shope
• Jesse Mlotha-Namarika
• Jeffrey Wilkinson
• Joshua Aagaard
• Ellen J Aagaard
• Maxim D Seferovic
• Judy Levison
• Peter Kazembe
• Kjersti M Aagaard

Language

English

Publication Date

4-11-2025

Journal

Med

DOI

10.1016/j.medj.2024.10.016

PMID

39541971

Abstract

Background: Maternal periodontal disease is associated with preterm and low-birthweight deliveries, but randomized trials of likely efficacious treatments (e.g., dental scaling and root planing) during pregnancy have not reduced these adverse outcomes. As an alternative, we hypothesized that periconception initiation of xylitol chewing gum would reduce the occurrence of preterm or low-birthweight deliveries among a historical high-prevalence population in Malawi.

Methods: We conducted an open-label, parallel-enrollment, matched-pair, cluster-randomized, controlled clinical trial across eight health centers (sites) in and around Lilongwe, Malawi. Sites were paired by anticipated delivery volume and randomized to prenatal and oral health education alone (active control) or with twice-daily xylitol chewing gum (intervention) throughout the periconception and antenatal periods. For the primary prevention of preterm (< 37 weeks) and low-birthweight (< 2,500 g) deliveries (co-primary outcomes), comparison by allocation group was performed using generalized linear mixed models for each outcome as a fixed factor and the site(s) as a random factor.

Findings: 10,069 participants were enrolled (n = 4,549 at intervention sites, n = 5,520 at active control sites), with >95% available for analyses. Initiation of xylitol chewing gum resulted in significant reductions in the co-primary outcomes: preterm birth (12.6% [549/4,349] vs. 16.5% [878/5,321]; relative risk [RR] 0.76, 95% confidence interval [CI] 0.57-0.99) and < 2,500-g neonates (8.9% [385/4,305] vs. 12.9% [679/5,260]; RR 0.70, 95% CI 0.49-0.99). Xylitol chewing gum use also led to fewer neonatal demises (0.2% [8/4,305] vs. 0.4% [22/5,260]; RR 0.41, 95% CI 0.19-0.89).

Conclusions: Periconception initiation and ongoing use of xylitol chewing gum significantly reduced the occurrence of preterm and low-birthweight deliveries in Malawi.

Funding: E.W. Al Thrasher Foundation (to K.A.) and USAID Saving Lives at Birth Grand Challenges Grant AID-OAA-G-11-00062 (to K.A.). Additional financial and in-kind support was graciously provided by Texas Children's Hospital and Baylor Foundation Malawi.

Keywords

Humans, Chewing Gum, Female, Xylitol, Pregnancy, Premature Birth, Adult, Malawi, Infant, Newborn, Periodontal Diseases, Young Adult, Infant, Low Birth Weight, Prenatal Care, Sweetening Agents, Translation to population health, low birthweight, oral health, periodontal disease, prebiotics, pregnancy, preterm birth, prevention of preterm birth, xylitol

Published Open-Access

yes

Recommended Citation

Valentine, Gregory C; Antony, Kathleen M; Sangi-Haghpeykar, Haleh; et al., "A Cluster Randomized Trial of Xylitol Chewing Gum for Prevention of Preterm Birth: The PPaX Trial" (2025). Children’s Nutrition Research Center Staff Publications. 378.
https://digitalcommons.library.tmc.edu/staff_pub/378