Abstract – Background: The prevalence of enamel defects in the first permanent molars among children in Western Australia is higher than that reported for some European countries. The cause(s) of the defects, both white diffuse opacities and demarcated opacities, with or without hypoplasia, continue to be investigated. A recent review identified childhood illnesses and exposure to environmental toxins as putative causal factors for the occurrence of demarcated opacities (usually in association with hypoplasia). Diffuse opacities have been reported to be associated with exposure to the antibiotic amoxicillin, adjusted for otitis media and fluoride. The aim of this study was to examine the possible risk factors for enamel defects in the first permanent molars among children in Western Australia.Methods: Children attending pre-primary schools (1999–2000 year of birth) in metropolitan Perth, Western Australia, were invited to participate in the study. In 2005, before the child’s first permanent molars had erupted, parents completed a questionnaire about the mother’s health during pregnancy, and their child’s health for the first 3 years. The first permanent molars were classified for type and extent of enamel defects using the modified Developmental Defects of Enamel (DDE) index. Caries experience and the presence of enamel defects on the deciduous molars and canines were also recorded using the WHO criteria. Bivariate, multinomial logistic and logistic regression analyses were used to test the factors for their influence on the occurrence of the enamel defects.Results: Five hundred and fifty children were examined for the occurrence of enamel defects on the first permanent molars. Multinomial logistic regression indicated that neonatal health conditions, prematurity (OR 2.75) and other health conditions (OR 2.40) were significant risk factors for the occurrence of diffuse enamel defects. Infection during the neonatal period was a strong risk factor for the occurrence of demarcated enamel defects (OR 6.88). Increased deciduous tooth caries experience increased the risk of demarcated enamel defects by 10% (OR 1.10) and living further from a heavy industrial area increased the risk of diffuse enamel defects nearly twofold (OR 1.93).Conclusions: Neonatal health factors were found to be important risk factors for the occurrence of enamel defects in first permanent molars. The effects of residential location and the association between deciduous tooth caries experience and enamel defects require further investigations.