Birth defects are a major public health issue in China. A key to prevention of birth defects is to identify the causes of the defects. Recently the prevention of birth defects has achieved certain success, but causes of many defects are still unknown and thus prevention enters into bottleneck. Few studies use birth defects as the primary outcome partly due to their rarity, and there is a lack of “mega” birth cohort studies. Therefore, we will establish a birth cohort of 500,000 pregnant women. The participants will be recruited from 41 hospitals in 22 provinces and cities covering most areas of China. The maternal demographic information, clinical information and biological samples will be collected during pregnancy. This study aims to investigate the risk factors of major birth defects and establish a teratogenic risk database. In addition, an assessment system that can evaluate the risk level of birth defect, a risk monitoring system and an implementation plan in early pregnancy will be developed in order to further reduce the risk of birth defects. Currently, we have recruited nearly 70,000 participants and collected their biological samples. Some of the baseline data will be presented in this talk.