Xylitol and the prevention of periodontal disease and preterm birth (xappp) trial - preterm birth (PTB) is the leading cause of under-5-year-old mortality and neurodevelopmental impairment worldwide…

The National Institute of Child Health and Human Development awarded the University of Washington $1,145,282 on September 12, 2025, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct the Xylitol and the Prevention of Periodontal Disease and Preterm Birth (XaPPP) Trial.

The trial is a double-blinded, three-arm, placebo-controlled study designed to test whether xylitol-containing chewing gum reduces preterm birth and maternal periodontal disease in pregnant individuals. The study will enroll 6,000 pregnant Malawian participants and addresses limitations of a prior cluster-randomized trial (PPAX Trial) by implementing individual randomization, placebo control, optimized xylitol dosing of 5–10 grams daily, and blinding. Xylitol is a naturally occurring sugar alcohol that acts as a prebiotic to inhibit periodontopathic bacteria growth and reduce pro-inflammatory responses; preterm birth remains the leading cause of under-five-year-old mortality and neurodevelopmental impairment worldwide.

Performance is based in Seattle, Washington. The period of performance runs through August 31, 2030. The University of Washington's Office of Sponsored Programs administers the award as the prime recipient.

Baylor College of Medicine Children's Foundation Malawi is a sub-recipient, providing services in support of the trial.

Xylitol and the prevention of periodontal disease and preterm birth (xappp) trial - preterm birth (PTB) is the leading cause of under-5-year-old mortality and neurodevelopmental impairment worldwide and affects between 5-29% of pregnancies. Periodontal disease (PD), including either gingivitis or periodontitis, is a risk factor for PTB. Unfortunately, PTB and PD disproportionately occur in many low- and middle-income countries where access to physicians and dentists is limited. Using a novel inexpensive and non- invasive treatment approach, we recently completed a cluster-randomized trial in malawi entitled the prevention of prematurity and xylitol (ppax) trial in which we demonstrated that use of xylitol-containing chewing GUM significantly reduced clinical metrics of maternal periodontal disease (p=0.03) and the occurrence of PTB (xylitol 12.6% VS control 16.5%, ARR 0.76, 95% CI 0.59-0.99). Xylitol is a naturally occurring sugar alcohol found in several chewing GUM products and is a prebiotic, known to prevent the growth of periodontopathic bacteria and dampen the pro-inflammatory cascade. As infection and inflammation are risk factors for PTB, xylitol may be a novel, inexpensive innovation that improves maternal and offspring outcomes. While the results of the ppax trial are promising, we propose to conduct a double-blinded, 3-arm, placebo- controlled trial to address the ppax trial's limitations and prove the results are reproducible. Ppax trial limitations included: (a) lack of blinding, (b) lack of placebo control, (c) lack of optimized xylitol dosing based on recent evidence that 5-10 grams of xylitol/day is best for oral health benefit, (d) and lack of individual randomization (ppax was cluster randomized with only 8 clusters). These limitations inflate the risk of spurious findings. The proposed individually randomized trial will enroll n=6000 malawian pregnant individuals at…