Investigation of clusters of adverse reproductive outcomes, an overview.

Clusters of adverse reproductive outcomes are reported with increasing frequency to public health services, but it is likely that only a minority of clusters are caused by a common environmental teratogen or mutagen. Many guidelines and protocols have been developed for the investigation and the management of chronic disease clusters and can be applied to the study of adverse reproductive outcomes. Cluster investigation normally follows four successive phases: (i) the generation of one or more etiologic hypotheses, (ii) the confirmation of the hypotheses, (iii) an intervention aimed at reducing any dangerous exposure, and (iv) the evaluation of the effect of the intervention. However, each situation is unique and there is no standard recipe for conducting the epidemiologic investigation at each successive phase, for choosing the appropriate statistical technique and for communicating with interested parties. In order to minimize both the risk of pursuing a worthless investigation and the risk of ignoring a real excess of cases caused by an adverse environmental factor, it is imperative to rely on a team of specialists with expertise in epidemiology, statistics, toxicology, embryology, and communication.