Programming by intrauterine deficiency

The concept of perinatal programming comprises the idea that adverse influences during sensitive developmental stages have a long-term impact on the physiology, structure and function of organs. Over the last decades there has been a growing body of evidence, both clinical and experimental that intrauterine deficiency adversely affects intrauterine and postnatal growth trajectories (e.g. catch-up growth) as well as physiological processes in the offspring. This article not only summarizes the causes and the clinical implications of intrauterine growth restriction but also emphasizes the need of translational studies using various animal models to unravel the underlying mechanisms in order to develop strategies for preventing the adverse effects of perinatal programming. Intrauterine deficiency, intrauterine growth restriction (IUGR) and small for gestational age (SGA) have been used interchangeably; however, exposure to reduced nutrient supply does not necessarily result in SGA and IUGR is more a symptom of intrauterine deficiency than the cause of intrauterine programming. The consequences of intrauterine programming are diverse, affecting a multitude of organs notably the kidneys, the lungs and the brain. Clinical and experimental studies have linked intrauterine deficiency and IUGR not only to cardiovascular diseases, such as arterial hypertension and cardiomyopathies and impaired renal function but also to neonatal chronic lung disease and bronchial asthma as well as altered neurocognitive functions in infancy and beyond. Of particular interest is the pathophysiological role of postnatal catchup growth, which is related to an altered body composition favoring adipose tissue and representing a risk factor for metabolic sequelae. Intrauterine deficiency coupled with postnatal catch-up growth highlights a dual mechanism by which long-term organ structure and function can be programmed: (1) a direct intrauterine-mediated programming effect by nutrient deficiency and (2) an indirect metabolic effect as a result of postnatal catch-up following reduced intrauterine nutrient supply