Objectives: To determine the relation between several potential risk factors and the risk of having a newborn with one or more congenital anomalies. Participants: Data on 1,594,380 registered newborns from the Netherlands Perinatal Registry database were analysed. Logistic regression models were used to estimate the risk of having a newborn with anomalies. Results: All studied risk factors were significantly related to the risk of having a newborn with anomalies. The highest adjusted risks were observed for preexisting maternal diabetes (OR=2.0) and maternal epilepsy (OR=2.1). For maternal diabetes the risk was especially elevated in the cardiovascular system and for maternal epilepsy in the central nervous system. High maternal age, IVF/ICSI pregnancy, male gender and plurality were also strongly related to the risk of having a newborn with anomalies. The PARs were especially high for male gender, primiparity, high maternal age and non-Western ethnicity (respectively 18.4, 5.0, 2.5 and 1.7). The PARs for maternal diabetes, epilepsy and IVF/ICSI were very small as the prevalence of these risk factors in the general population is very low. In total 30% of the registered anomalies could be ascribed to the studied risk factors. Conclusions: Strategies for primary prevention of congenital anomalies should focus on different risk factors depending on the approach used. For a highrisk group approach existing maternal morbidity such as diabetes and epilepsy are important factors. For a public health approach, however, factors such as high maternal age, primiparity and ethnicity are more important to focus on, for example in preconception counselling.