The origin of congenital heart defects and the epigenetic programming of the healthy child

Birth defects are a global burden affecting 7% of births worldwide. Congenital heart defects (CHD) are the most common congenital malformation with approximately 1 million children born each year. It is not only the most frequent group of birth defects in human, but also the leading cause of infant morbidity in the Western world. Although the mortality of CHD has decreased in the last 20 years, the burden for the child, family, society, health care and insurances is enormous. Also in adulthood having a CHD, even when mild, has a substantial negative impact on societal perspectives.Patients with CHD are more likely to have a lower education, are more often unemployed and less likely to be in a relationship. Decades of animal and human studies made it clear that the vast majority of birth defects have a multifactorial origin, with contributions from genetic and environmental factors. Already in 1965 gene environment interactions factors have been recognized as the "Principle of Teratology" by Wilson and Warkany. This is also true for CHD, in which 80-90% seems to result from complex interactions between subtle genetic variations and periconception maternal characteristics and environmental exposures. The periconception environment comprises not only the external milieu of the pregnant woman, but also includes her metabolic, endocrine, immunological and vascular state as an internal environment for the developing embryo, foetus and placenta.