Congenital heart diseases (CHD) have become the most common of all birth defects in recent decades. It is a serious disease with a high burden of clinical treatments but the causes remain unclear. At present there are no effective primary prevention measures. Based on our previous studies of community-based micronutrient interventions to prevent preterm birth, low birth weight and neonatal mortality, the present study will be conducted in high risk areas of CHD in China and focus on an in-depth analysis of epidemiological characteristics of CHD, the identification of specific risk factors and the investigation of the impact of periconceptional deficiency of micronutrients on the occurrence of CHD by a range of approaches including cross-sectional and case-control studies,nutritional and molecular epidemiological studies assisted with meta analysis and a focus group study. Further, a large-scale community-based trial with three interventions, the first randomized controlled intervention study targeted on CHD primary prevention registered in the international clinic trial registry, will be conducted among periconceptional women. The three intervention arms will be iron/folic acid, multiple micronutrients containing iron/folic, and folic acid only (as control). Simultaneously a basic intervention will delivered in each of the treatment arms to control potential risk factor exposures. The study aims to verify the preventive effect of periconceptional iron and/or multiple micronutrient supplements on CHD occurrence using a randomized trial study design to control for potential risk factors. The relationship of CHD with polymorphism of susceptible genes, nutrients and active elements will be clarified. The mechanisms by which multiple micronutrients containing iron/folic acid play roles in preventing CHD will also be explored at the population and molecular levels. This project has the potential to establish the first model of primary prevention against CHD.