The Taiwan Birth Cohort Study (TBCS) is the first nationwide birth cohort database in Asia designed to establish national norms of children's development. Several challenges during database development and data analysis were identified. Challenges include sampling methods, instrument development and statistical approach to missing data. The purpose of this paper is to describe the pilot study underpinning the TBCS, testing of the TBCS developmental instrument and the resolution of methodological challenges. Bayesian analysis fill in missing data, three-step regression analysis for the investigation of mediating and moderating effect, the use of structural equation modeling in a large scale investigation, investigating direct and indirect effects, confounding factors and reciprocal relationships in children's development, and used latent growth model in longitudinal observations are described. The TBCS will provide ongoing longitudinal information regarding the predisposing and maintaining factors affecting the long term outcome of pediatric illnesses. (Contains 1 figure and 4 tables.)