Smoking-Associated DNA Methylation and Offspring Caries Experience: Findings from the GUSTO Study

Area of Science:

• Environmental Epidemiology
• Genetics and Epigenetics
• Pediatric Dentistry

Background:

• Self-reported smoking during pregnancy is prone to measurement errors, potentially biasing associations with offspring caries.
• A previously identified DNA methylation (DNAm) signature linked to prenatal smoking requires further validation regarding its association with offspring caries.
• Gestational smoking exposure can be indexed through self-report and plasma cotinine, offering alternative measures to assess its impact on child health.

Purpose of the Study:

• To evaluate the association between a prenatal smoking-associated DNAm signature and offspring caries experience.
• To assess whether gestational smoking, indexed by self-report and plasma cotinine, is linked to offspring caries.
• To investigate the relationship between a weighted DNAm risk score (wMRS_DNAm) and the count of tooth surface caries in children.

Main Methods:

• Utilized the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort (n=577 mother-child dyads).
• Assessed gestational smoking via questionnaires and plasma cotinine, DNAm from umbilical cord tissue, and child dental caries at age 3 years.
• Employed zero-inflated Poisson regression to analyze the association between wMRS_DNAm and caries experience, adjusting for covariates.

Main Results:

• Each additional interquartile range (IQR) of wMRS_DNAm was associated with a 20% higher adjusted caries risk (RR=1.20, 95% CI [1.10, 1.31]).
• Mothers who smoked during gestation (self-report/cotinine) had children with higher adjusted caries risk (RR=1.31, 95% CI [1.11, 1.55] for light smoking).
• A DNAm risk score derived from umbilical cord DNA showed a positive association with greater offspring caries experience.

Conclusions:

• Findings corroborate a link between prenatal smoking exposure and increased offspring caries.
• Maternal smoking-associated DNAm risk scores are novelly associated with greater offspring caries experience.
• These results underscore the importance of smoking cessation support during pregnancy for improving child oral health.