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.

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.

Psychologists and dentists will be blinded to the treatment status (xylitol or no xylitol use during pregnancy) of the mothers of the pediatric subjects.

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)

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)

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)

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)

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).

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

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

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

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

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

sequential processing (working memory), simultaneous processing (visual processing), planning ability (fluid reasoning), and learning ability (long-term memory and retrieval)

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")

Emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior

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