a study done after the dutch hunger winter of 1944-1945 showed that undernutrition during the early stages of pregnancy are associated with hypomethylation of the insulin-like growth factor ii (igf2) gene even after six decades. these individuals had significantly lower methylation rates as compared to their same sex sibling who had not been conceived during the famine. a comparison was done with children conceived prior to the famine so that their mothers were nutrient deprived during the later stages of gestation; these children had normal methylation patterns. the igf2 stands for insulin-like growth factor ii; this gene is a key contributor in human growth and development. igf2 gene is also maternally imprinted meaning that the mother's gene is silenced. the mother's gene is typically methylated at the differentially methylated region (dmr); however, when hypomethylated, the gene is bi-allelically expressed. thus, individuals with lower methylation states likely lost some of the imprinting effect. similar results have been demonstrated in the nr3c1 and ppara genes of the offspring of rats fed on an isocaloric protein-deficient diet before starting pregnancy. this further implies that the undernutrition was the cause of the epigenetic changes. surprisingly, there was not a correlation between methylation states and birth weight. this displayed that birth weight may not be an adequate way to determine nutritional status during gestation. this study stressed that epigenetic effects vary depending on the timing of exposure and that early stages of mammalian development are crucial periods for establishing epigenetic marks. those exposed earlier in gestation had decreased methylation while those who were exposed at the end of gestation had relatively normal methylation levels. the offspring and descendants of mothers with hypomethylation were more likely to develop cardiovascular disease. epigenetic alterations that occur during embryogenesis and early fetal development have greater physiologic and metabolic effects because they are transmitted over more mitotic divisions. in other words, the epigenetic changes that occur earlier are more likely to persist in more cells.