A cluster randomized trial of xylitol chewing gum for prevention of preterm birth: The PPaX trial

Authors: VALENTINE, GREGORY - Baylor College Of Medicine; ANTONY, KATHLEEN - Baylor College Of Medicine; SANGI-HAGHPEYKAR, HALEH - Baylor College Of Medicine; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); CHIRWA, ROSE - Baylor College Of Medicine; PETRO, SAUKANI - Baylor College Of Medicine; DUMBA, MARY - Baylor College Of Medicine; NANTHURU, DEBORAH - Baylor College Of Medicine; SHOPE, CYNTHIA - Baylor College Of Medicine; MLOTHA-NAMARIKA, JESSE - Kamuzu Central Hospital; WILKINSON, JEFFREY - Baylor College Of Medicine; AAGAARD, JOSHUA - St Olaf College; AAGAARD, ELLEN - Baylor University; SEFEROVIC, MAXIM - Baylor College Of Medicine; LEVISON, JUDY - Baylor College Of Medicine; AAGAARD, KJERSTI - Baylor College Of Medicine

Submitted to: Med
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2024
Publication Date: 11/13/2024
Citation: Valentine, G.C., Antony, K.M., Sangi-Haghpeykar, H., Wood, A.C., Chirwa, R., Petro, S., Dumba, M., Nanthuru, D., Shope, C., Mlotha-Namarika, J., Wilkinson, J., Aagard, J., Aagard, E.J., Seferovic, M.D., Levison, J., Aagard, K. 2024. A cluster randomized trial of xylitol chewing gum for prevention of preterm birth: The PPaX trial. Med. https://doi.org/10.1016/j.medj.2024.10.016.
DOI: https://doi.org/10.1016/j.medj.2024.10.016

Interpretive Summary: Poor nutrition during pregnancy is a risk factor for maternal periodontal disease, which can lead to preterm and low-birthweight deliveries. Traditional treatments like dental cleaning during pregnancy have not demonstrated preventative benefit. Researchers in Houston tested whether chewing xylitol gum from before conception could help reduce maternal periodontal disease in a sample of women from Malawi. In a large study involving over 10,000 participants in various health centers, comparing those who received prenatal education plus xylitol gum with those who only received education, the study found that chewing xylitol gum led to fewer preterm births and babies with low-birthweight compared to the control group. Additionally, periodontal disease was significantly reduced in those who chewed xylitol gum. These results suggest that xylitol gum is an effective way to lower the risk of preterm and low-birthweight deliveries, as well as to improve oral health during pregnancy.

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