Prevention of Developmental Delay and Xylitol (PDDaX) Study

The goals of this study are to: evaluate and validate the low-cost, transportable, easily-administered Malawi Developmental Assessment Tool (MDAT) for neurodevelopmental assessment of children aged 4-8 years old in Malawi, as compared to the gold-standard yet more cumbersome and costly Kaufman Assessment Battery for Children-II (KABC-II) among (1) n=500 formerly preterm children and (2) n=500 formerly term children.

Additionally, we will evaluate the effects of gestational xylitol exposure compared to a lack of gestational xylitol exposure on neurodevelopmental outcomes of children aged 4-8 years old in Malawi through the following four neurodevelopmental tests: (3) KABC-II (cognitive outcomes), (4) EF Touch (executive functions), (5) Strengths and Difficulties Questionnaire (social-emotional outcomes), and (6) MDAT (motor and cognitive outcomes).

The researchers will leverage subjects who completed the parent Prevention of Prematurity and Xylitol Trial, which enrolled 10069 pregnant individuals in Malawi and demonstrated a significant 24% reduction in incidence of preterm birth and low birthweight offspring in gravidae who chewed xylitol-containing chewing gum compared to those who did not. By ensuring that these offspring did not have higher rates of neurodevelopmental impairment, the study will promote promising multi-center international and domestic trial evaluating the impact of xylitol-containing chewing gum use and optimal dosage during pregnancy.

Study Overview

• Status: Recruiting
• Conditions: Neurodevelopmental Disorders; Prematurity
• Intervention / Treatment: Dietary supplement: Maternal Use of Xylitol Chewing Gum During Pregnancy; Dietary supplement: No Maternal Xylitol Chewing Gum Use During Pregnancy

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Greg Valentine, MD; Phone Number: (206) 543-3200; Email: gcvalent@uw.edu

Study Locations

• Malawi
  • Lilongwe, Malawi
    • Recruiting
    • Baylor College of Medicine Children's Foundation-Malawi
    • Contact: Phoebe Nyasulu; Email: pnyasulu@baylor-malawi.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Child born during the PPaX trial
• Enrollment age between 4-8 years old
• Parental or legal guardian consent obtained
• Willing to undergo 3 neurodevelopmental tests
• Willing to travel to BCMF for neurodevelopmental assessment
• Assent by the pediatric subject for participation in the study

Exclusion Criteria:

• Parent or legal guardian cognitively unable to provide consent
• Child unwilling to provide assent to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xylitol-exposed formerly term children; n=250 formerly term children born during the PPaX trial who were born to gravidae in the interventional arm (received xylitol chewing gum but had access to a dentist and received prenatal counseling)	Dietary supplement: Maternal Use of Xylitol Chewing Gum During Pregnancy; There are no current interventions within this follow-up study. However, the mothers enrolled in the parent PPaX trial received xylitol-containing chewing gum (1 gram per stick of gum and instructed to chew 1-2 sticks of gum twice daily for a total dose of 2-4 grams/day of xylitol throughout pregnancy starting pre-conception or at <20 weeks gestation).
Active Comparator: Non xylitol-exposed formerly term children; n=250 formerly term children born during the PPaX trial who were born to gravidae in the active comparator arm (no xylitol chewing gum but had access to a dentist and received prenatal counseling)	Dietary supplement: No Maternal Xylitol Chewing Gum Use During Pregnancy; There are no current interventions within this follow-up study. Children born to mothers who received access to a dentist and prenatal education (oral health, prevention of preterm birth) are in the active comparator group
Experimental: Xylitol-exposed formerly preterm children; n=250 formerly preterm children born during the PPaX trial who were born to gravidae in the interventional arm (received xylitol chewing gum but had access to a dentist and received prenatal counseling)	Dietary supplement: Maternal Use of Xylitol Chewing Gum During Pregnancy; There are no current interventions within this follow-up study. However, the mothers enrolled in the parent PPaX trial received xylitol-containing chewing gum (1 gram per stick of gum and instructed to chew 1-2 sticks of gum twice daily for a total dose of 2-4 grams/day of xylitol throughout pregnancy starting pre-conception or at <20 weeks gestation).
Active Comparator: Non xylitol-exposed formerly preterm children; n=250 formerly preterm children born during the PPaX trial who were born to gravidae in the active comparator arm (no xylitol chewing gum but had access to a dentist and received prenatal counseling)	Dietary supplement: No Maternal Xylitol Chewing Gum Use During Pregnancy; There are no current interventions within this follow-up study. Children born to mothers who received access to a dentist and prenatal education (oral health, prevention of preterm birth) are in the active comparator group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of the MDAT in Former Preterm Children	compared to the KABC-II	1 month (1-2 clinic visits)
Validation of the MDAT in Former Term Children	compared to the KABC-II	1 month (1-2 clinic visits)
KABC-II mental processing index	In n=500 former term and n=500 former preterm children aged 4-8 years old with half of each being gestationally xylitol exposed vs not exposed	1 month (1-2 clinic visits)
EF Touch composite score	In n=500 former term and n=500 former preterm children aged 4-8 years old with half of each being gestationally xylitol exposed vs not exposed	1 month (1-2 clinic visits)
SDQ composite	In n=500 former term and n=500 former preterm children aged 4-8 years old with half of each being gestationally xylitol exposed vs not exposed	1 month (1-2 clinic visits)
MDAT composite neurodevelopmental outcome	In n=500 former term and n=500 former preterm children aged 4-8 years old with half of each being gestationally xylitol exposed vs not exposed	1 month (1-2 clinic visits)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cognitive delay per specific KABC-II subdomain	sequential processing (working memory), simultaneous processing (visual processing), planning ability (fluid reasoning), and learning ability (long-term memory and retrieval)	1 month (1-2 clinic visits)
Incidence of executive function delay per specific EF Touch subdomains	processing speed ("Bubbles"), visual spatial working memory ability ("Farmer"), working memory ("Pick the Picture" and "Houses"), inhibitory motor control ("Pig", "Silly Sounds Game", and "Arrows"), and Flexible thinking ("Something's the Same")	1 month (1-2 clinic visits)
Incidence of social-emotional delay per specific SDQ subdomains	Emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior	1 month (1-2 clinic visits)
Incidence of neurodevelopmental delay as per MDAT subdomains	Gross motor, fine motor, social, and language	1 month (1-2 clinic visits)

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Greg Valentine, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; Oral Health; Prematurity; Xylitol
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Neurodevelopmental Disorders
• Other Study ID Numbers: STUDY00015305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No