The Prevention of Developmental Delay and Xylitol (PDDaX) trial

Abstract

BACKGROUND: We recently conducted the cluster-randomized, Prevention of Prematurity and Xylitol (PPaX) trial which demonstrated a significant reduction in the occurrence of delivery of preterm and low birthweight deliveries from mothers who used twice-daily xylitol-containing chewing gum in pregnancy as compared to active control among n = 10,069 enrolled pregnant participants in Lilongwe, Malawi. We seek to determine the neurodevelopmental outcomes, including any benefits or harm, of a nested cohort of n = 1000 children delivered among participants of the PPaX trial.

METHODS: The Prevention of Developmental Delay and Xylitol (PDDaX) trial is a prospective, nested cohort study of 1000 randomly selected 4-8-year-old children born to gravid participants who completed the parent PPaX trial. We will assess the neurodevelopmental outcomes of the 1000 children at 4-8 years of age and evaluate any differences in neurodevelopmental outcomes related to xylitol exposure or lack thereof by assessing children's (a) cognition, (b) executive functioning, (c) social-emotional development, (d) gross motor skills, (e) fine motor skills, and (f) language. These neurodevelopmental outcomes will be assessed via the Kaufman Assessment Battery for Children-2nd Edition (KABC-II), the EF Touch, the Strengths and Difficulties Questionnaire, the Malawi Developmental Assessment Tool, the Anchor Items in Measuring Early Childhood Development, and the International Development and Early Learning Assessment. The primary outcome will be the overall cognitive score, as determined by the KABC-II mental processing index. All children will also undergo hearing, vision, and comprehensive oral health examinations. Investigators from the participating sites developed and approved the research question and protocol. Each site obtained its own institutional review board and ethics approval. Patient recruitment started in July 2022 and will continue through 2027.

DISCUSSION: Xylitol-containing chewing gum reduces the risk of delivery of a preterm or low birthweight neonate and neonatal demise. It also reduces gingival inflammation in gravidae. The findings from the PDDaX follow-up study will explore whether there are any long-lasting risks or benefits to offspring exposed to xylitol during gestation. If either benefit or lack of benefit (but no harm) occurs to offspring, then xylitol-containing chewing gum has strong potential to change obstetric-related care for individuals in Malawi and similar settings.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05361122. Registered on April 27 2022.