Developmental origins of health and disease theory in cardiology.

Numerous epidemiological and animal studies disclosed that birth weight is inversely associated with the incidence of the lifestyle-related disorders in adult life, such as cardiovascular disease, diabetes, and /or chronic kidney disease. Lower birth weight occurs in numerous undesired intrauterine environments including malnutrition, smoking, alcohol consumption, or stress.　The Developmental Origin of Health and Disease (DOHaD) theory is based on the concept that the origins of lifestyle-related disease is formed at the time of fertilization, embryonic, fetal, and neonatal stages by the interrelation between genes and the environments (nutrition, stress, or environmental chemicals). Adult disease develops after delivery facing to abnormal environments such as over-nutrition, much stress, or lack of exercise. Disease develops through these two insults. This concept was first proposed as the "Barker Hypothesis." David Barker had discovered the relation between the lower birth weight and the higher prevalence of ischemic heart disease mortality. Previous epidemiologic studies have found the people exposed to famine during early life had higher risks of cardiovascular diseases in adulthood. Yet, the exact mechanisms that permanently change the structure, physiology, and endocrine status of an individual across their lifespan following altered growth during fetal life are not entirely clear. Epidemiological studies including prospective cohort and observational analysis of the people exposed to malnutrition during fetal or infancy have disclosed the strong relation between the lower birth weight and the higher cardiovascular risks in adults. Recent progress of epigenetic studies unveiled strong genetic association. Hormonal regulation and epigenetic modifications have an important role for proper organ development and physiological functions. The molecular mechanism of predisposition is supposed to be the epigenetics modifications.　Their dysregulation is related to the acquisition of the disease-susceptible trait. In this review, we overview the concept of DOHaD and introduce related clinical and basic research.