The Prevention of Developmental Delay and Xylitol (PDDaX) trial: study protocol of a nested cohort follow-up from the PPaX (Prevention of Prematurity and Xylitol) trial examining neurodevelopmental outcomes among offspring at 4-8 years of age in Malawi.

Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2006-

Xylitol*/administration & dosage ; Xylitol*/adverse effects ; Child Development*/drug effects ; Developmental Disabilities*/prevention & control ; Premature Birth*/prevention & control; Malawi/epidemiology ; Humans ; Child, Preschool ; Child ; Female ; Pregnancy ; Prospective Studies ; Randomized Controlled Trials as Topic ; Male ; Chewing Gum ; Infant, Newborn ; Infant, Premature

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.
(© 2025. The Author(s).)

Declarations. Ethics approval and consent to participate {24}: The PDDaX trial was conducted after IRB, and ethics approvals were obtained by the Malawi NHSRC (Protocol 22/07/1950), Baylor College of Medicine (H-52314), and the University of Washington (STUDY00015305). All participants must provide consent to participate in the PDDaX trial. Consent for publication {32}: This study will be conducted in accordance with the following publication and data sharing policies and regulations. All participants consent to having their data published, and the data will be de-identified. Competing interests {28}: The independence of this study from any actual or perceived influence is critical. Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation in the design and conduct of this trial. The study leadership in conjunction with the Thrasher Research Fund, NIH, the UW, BCM, and BCMCF has established policies and procedures for all study group members to disclose all conflicts of interest and will establish a mechanism for the management of all reported dualities of interest. Financial conflict of interest attestations will be completed prior to the trial initiation.

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K23 HD105929 United States HD NICHD NIH HHS; K23HD105929 National Institute of Child Health and Human Development

Keywords: Development; Global health; Inflammation; Neurodevelopment; Prematurity; Xylitol

ClinicalTrials.gov NCT05361122

VCQ006KQ1E (Xylitol)
0 (Chewing Gum)

Date Created: 20251114 Date Completed: 20251115 Latest Revision: 20251215

20260130

PMC12619221

10.1186/s13063-025-09204-y

41239527