The case for establishing a Holocaust survivors cohort in Israel.

In this issue, Keinan-Boker summarises the main studies that have followed up offspring of women exposed to famine during pregnancy and calls for the establishment of a national cohort of Holocaust survivors and their offspring to study inter-generational effects. She suggests that the study would consolidate the fetal origins theory and lead to translational applications to deal with the inter-generational effects of the Holocaust. Barker suggested that alterations in the nutritional supply during critical stages of intra-uterine development permanently alter the structure and metabolism of fetal organs which he termed 'fetal programming' (now known as developmental origins of health and disease). The famine studies have played an important role in refining the hypothesis by allowing a 'quasi-experimental' setting that would otherwise have been impossible to recreate. The developmental origins hypothesis provides a framework to link genetic, environmental and social factors across the lifecourse and offers a primordial preventive strategy to prevent non-communicable disease. Although the famine studies have provided valuable information, the results from various studies are inconsistent. It is perhaps unsurprising given the problems with collecting and interpreting data from famine studies. Survival bias and information bias are key issues. With mortality rates being high, survivors may differ significantly from non-survivors in factors which influence disease development. Most of the data is at ecological level; a lack of individual-level data and poor records make it difficult to identify those affected and assess the severity of effect. Confounding is also possible due to the varying periods and degrees of food deprivation, physical punishment and mental stress undergone by famine survivors. Nonetheless, there would be value in setting up a cohort of Holocaust survivors and their offspring and Keinan-Boker correctly argues that they deserve special attention. National support is essential as the study may re-open old wounds. The study will need to be appropriately planned and resourced. If properly designed, it may provide further insight into the developmental origins hypothesis and suggest translational applications. It may also influence provision of support to women and children affected by man-made wars and famines that continue to happen across the world.