Globally, 15 million preterm births occur annually, with the majority born in low- and middle-income countries.
Prematurity is a leading cause of both under-5 mortality and future neurodevelopmental delay. A long-
established link between periodontal disease and preterm birth exists, yet common dental interventions such as
scaling and planing fail to prevent preterm birth. Xylitol, a sugar substitute commonly found in gum products,
prevents caries and periodontitis with presumed dampening of local and systemic inflammation, a risk factor for
neurodevelopmental delay in offspring. We recently completed a cluster-randomized trial in Malawi designed to
test the efficacy of xylitol gums to prevent preterm birth and immediate neonatal outcomes. This follow-up study
proposal seeks to meaningfully advance our findings by evaluating if exposure to xylitol gum administered
preconception or during early pregnancy improves neurodevelopmental outcomes in offspring (up to 6 years of
age). Specifically, we will test the hypothesis by formally evaluating whether chewing xylitol gum prevents
adverse neurodevelopmental outcomes by leveraging subjects from the Prevention of Prematurity and Xylitol
(PPaX) Trial that enrolled 10,404 pregnant women in Malawi from 2015-2019.
The Specific Aims of the research are to: 1) Evaluate the sensitivity and specificity of the MDAT as compared
to the KABC-II neurodevelopment diagnostic tool in assessing neurodevelopmental delay of formerly term
children aged 4-6 years of age; 2) Evaluate the sensitivity and specificity of the MDAT as compared to the KABC-
II in assessing neurodevelopmental delay of formerly preterm children aged 4-6 years of age; 3) Determine the
impact of xylitol gum exposure during pregnancy on the neurodevelopmental outcomes of 200 sex-matched term
born children (100 controls, 100 xylitol) and 200 preterm born children (100 controls, 100 xylitol). Validating the
MDAT by comparing it to the KABC-II neurodevelopmental assessment in former preterm and term neonates in
Malawi will allow for more efficient, cost-effective studies in the future and build capacity in low-resourced settings
to identify children with neurodevelopmental delay more easily and provide more timely intervention. If xylitol use
during pregnancy is found to prevent neurodevelopmental delay in offspring, this low-cost solution will prove to
be a game-changer in preventing neurodevelopmental delay worldwide.
Proposed Career and Learning Objectives are to: 1) Attain advanced skills in epidemiology, study design, data
management, and analytic methods to correctly implement research focusing on evaluating neonatal outcomes
in settings of health disparities, and 2) Enhance skills in database development, scientific writing, presentations,
and grant preparation, and 3) Attain advanced skills, including neurodevelopmental test selection, examiner
training and oversight, test interpretation and knowledge needed to conduct rigorous neurodevelopmental
outcomes research. These skills will facilitate the applicant’s cutting-edge research on perinatal interventions to
improve neonatal health and future neurodevelopmental outcomes in the most vulnerable populations.