Prenatal origins of adult disease.

PURPOSE OF REVIEW: Human epidemiological and animal studies show that many chronic adult conditions have their antecedents in compromised fetal and early postnatal development. Developmental programming is defined as the response by the developing mammalian organism to a specific challenge during a critical time window that alters the trajectory of development with resulting persistent effects on phenotype. Mammals pass more biological milestones before birth than any other time in their lives. Each individual's phenotype is influenced by the developmental environment as much as their genes. A better understanding is required of gene-environment interactions leading to adult disease.

RECENT FINDINGS: During development, there are critical periods of vulnerability to suboptimal conditions when programming may permanently modify disease susceptibility. Programming involves structural changes in important organs; altered cell number, imbalance in distribution of different cell types within the organ, and altered blood supply or receptor numbers. Compensatory efforts by the fetus may carry a price. Effects of programming may pass across generations by mechanisms that do not necessarily involve structural gene changes. Programming often has different effects in males and females.

SUMMARY: Developmental programming shows that epigenetic factors play major roles in development of phenotype and predisposition to disease in later life.