Developmental Origins of Health and Disease

Abstract

At first glance, it may seem implausible that your mother's exposure to stress or toxins while she was pregnant with you, how she fed you when you were an infant, or how fast you grew during childhood can determine your risk for chronic disease as an adult. Mounting evidence, however, indicates that events occurring in the earliest stages of human development — even before birth — may influence the occurrence of diabetes, cardiovascular disease, asthma, cancers, osteoporosis, and neuropsychiatric disorders. More than 40 years ago, Widdowson and McCance 1 discovered that rat pups that were undernourished during the three weeks of lactation gained weight more slowly over their lifetime than control pups did, even though they had access to ad libitum diets after weaning. In contrast, an identical duration of an energy deficit between 9 and 12 weeks of age had only a short-term effect on weight gain. These experiments showed not only that an environmental insult in early life could have long-term, irreversible consequences, but also that the insult must occur during a critical period in development to have maximal effect. In the years since, investigators have induced such developmental programming of adverse health outcomes in many animal species with the use of diverse interventions, ranging from the modification of the maternal (or even the grandmaternal) diet to the prenatal administration of glucocorticoid hormones, ligation of the uterine artery, experimentally produced anemia, and alteration of postnatal growth. 2 These perturbations can result in the adverse development of organs or organ systems directly or in adaptive responses that may be beneficial in the short term but deleterious in the long run. Because such experiments in animals involve environmental changes, they do not address purely genetic influences, but epigenetic processes may play a key role in the mechanisms underlying these phenomena. 2