Methodological issues in the study of rare exposures and rare outcomes in perinatal epidemiology

Epidemiologic study of rare exposures and rare outcomes is complicated. For perinatal epidemiology, a prospective cohort study design is preferred for reproductive outcomes with incidences of at least 5%. Case-control studies are generally used to investigate rare outcomes with incidences from 5 per 1000 to less than 1 per 1000. However, obtaining data on large numbers of rare cases can be difficult. The use of nested case-control designs or nested prospective studies may be particularly useful in perinatal epidemiology.