Early Influences on Cardiovascular and Renal Development: the Generation R Study

Cardiovascular disease is common in the general population, affecting 40-60% of adults older than 60 years of age. Many lines of evidence indicate an important role of early life events in influencing later susceptibility to cardiovascular disease. Barker and Osmond demonstrated that areas of Britain with the highest neonatal mortality rates early in the 20th century also tended to have the highest rates of coronary heart disease many decades later.After this, observational studies showed that low birth weight and weight at one year were associated with an increased risk of later cardiovascular disease, especially in subjects who show a postnatal catch-up growth and become obese as adults. The most commonly studied risk factors for cardiovascular disease include blood pressure and total cholesterol levels. Several studies showed small but consistent effects. These observations resulted in the “fetal origins of adult disease” hypothesis. More recently, this hypothesis has been transformed to a more general “developmental plasticity hypothesis”, which suggests that an organism may develop in various ways, depending on the particular environment or setting. In this process, adverse environmental exposures in fetal and early postnatal life lead to adaptations that permanently program the fetus’ structure, physiology and metabolism. These adaptations may be beneficial in the short term but have adverse consequences at birth and in postnatal life, leading to both low birth weight and cardiovascular disease in adulthood. Thus, cardiovascular disease may at least partly originate in early fetal life.

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