PROJECT SUMMARY Dental caries is the most common chronic disease of childhood estimated to affect a quarter of U.S children ages 2-5 years. Widely accepted risk factors are a susceptible tooth, fermentable carbohydrates and caries bacteria. Given its multifactorial etiology, dental caries represents a complex chronic disease, with etiology comprising certain upstream factors that promote a favorable oral environment for dental caries susceptibility and progression. These upstream risk factors include prenatal smoking and pregnancy BMI. The prenatal period is a sensitive time for fetal growth and development. Development of the primary tooth germ commences at the end of the 5th week of gestation with mineralization starting at about the 13th week, and continuing throughout pregnancy to the end of the first year of life. Exposure to maternal lifestyle related factors during this critical period affects the health and wellbeing of the developing fetus as well as the quality (i.e. tooth calcification and mineralization) of the developing tooth. Specifically, maternal smoking during pregnancy (prenatal smoking) alters fetal blood flow and protein metabolism, and is associated with earlier tooth eruption times and developmental enamel defects. It has previously been reported that children whose mothers smoke during pregnancy had more teeth erupted at 1 and 2 years old compared to similarly aged children whose mothers did not smoke. Indeed, prematurely erupted and possibly hypoplastic teeth are exposed to frequent infant feedings and the associated oral environment longer and thus have more opportunity to be affected by dental caries. Similarly, it has been suggested that pregnancy weight likely affects dental caries development in the child, although the mechanism by which this happens is yet to be elucidated but likely involves host-microbiome interaction and episodes of pregnancy hyperglycemia and hyperinsulinemia, mechanisms by which pregnancy weight has been shown to be related to offspring obesity. Using data from the Avon longitudinal study of parents and children (ALSPAC), this proposal aims to independently investigate associations between prenatal smoking, quantity of cigarettes smoked and pregnancy weight on subsequent offspring dental caries experience. Furthermore, this proposal aims to assess whether there is a critical trimester of pregnancy where prenatal smoking caries the greatest risk of subsequent offspring dental caries experience.