Prevention of Developmental Delay and Xylitol (PDDaX) Study

NCT05361122 | Recruiting

• 1 other identifier: STUDY00015305
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prematurity; Neurodevelopmental Disorders

Keywords

Xylitol; Oral Health; Pregnancy; Prematurity

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• Incidence of cognitive delay per specific KABC-II subdomain

  1 month (1-2 clinic visits)

• Incidence of executive function delay per specific EF Touch subdomains

  1 month (1-2 clinic visits)

• Incidence of social-emotional delay per specific SDQ subdomains

  1 month (1-2 clinic visits)

• Incidence of neurodevelopmental delay as per MDAT subdomains

  1 month (1-2 clinic visits)

Study Arms (4)

Xylitol-exposed formerly term children

EXPERIMENTAL

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

Non xylitol-exposed formerly term children

ACTIVE COMPARATOR

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

Xylitol-exposed formerly preterm children

EXPERIMENTAL

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

Non xylitol-exposed formerly preterm children

ACTIVE COMPARATOR

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

Interventions

Maternal Use of Xylitol Chewing Gum During Pregnancy DIETARY_SUPPLEMENT

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).

Xylitol-exposed formerly preterm children; Xylitol-exposed formerly term children

No Maternal Xylitol Chewing Gum Use During Pregnancy DIETARY_SUPPLEMENT

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

Non xylitol-exposed formerly preterm children; Non xylitol-exposed formerly term children

Eligibility Criteria

• Age: 4 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Baylor College of Medicine Children's Foundation-Malawi

Lilongwe, Malawi

RECRUITING

Related Publications (1)

• Valentine GC, Collett B, Wallie S, Mhango J, Engmann C, Sullivan E, Seferovic M, Willoughby M, Shayo B, Walson JL, Milgrom P, Aagaard K, Juul SE. 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. Trials. 2025 Nov 14;26(1):506. doi: 10.1186/s13063-025-09204-y.

  PMID: 41239527 DERIVED

MeSH Terms

Conditions

Premature Birth; Neurodevelopmental Disorders

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Mental Disorders

Study Officials

• Greg Valentine, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Greg Valentine, MD

CONTACT

(206) 543-3200; gcvalent@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: Psychologists and dentists will be blinded to the treatment status (xylitol or no xylitol use during pregnancy) of the mothers of the pediatric subjects.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor: Pediatrics

Model Details: We will enroll 1000 children aged 4-8 years of age. n=500 will be former term children and additional n=500 will be former preterm children. Half in each group (n=250) will be gestationally xylitol-exposed, and the other half (n=250) will not be xylitol-exposed.

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 4, 2022
• Study Start: April 4, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 27, 2025

Record last verified: 2025-03

Locations

MA (1)