Hypoxia, fetal growth and developmental origins of health and disease

T he compelling evidence linking small size at birth with later cardiovascular disease, obtained from epidemiological studies of human populations of more than a dozen countries,(1) has clearly renewed and amplified a clinical and scientific interest into the determinants of fetal growth, birth weight and the development of cardiovascular function and dysfunction before and after birth. As early as the 1950s Penrose(2) highlighted that an important determinant of birth weight was the quality of the intrauterine environment, being twice as great a determinant of the rate of fetal growth than the maternal or fetal genotype. Studies of birth weights of relatives(2) together with strong evidence from animal cross-breeding experiments (3,4) have clearly supported this contention. One of the great qualifiers of the fetal environment is the maternal nutritional status during pregnancy. As such, the reciprocal association between low birth weight and increased risk of high blood pressure in adulthood, as first described by Barker,(1) has literally exploded a new field of research investigating the effects of maternofetal nutrition on fetal growth, birth weight and subsequent cardiovascular disease. However, the fetus nourishes itself also with oxygen, and in contrast to the international effort which is assessing the effects of maternofetal under-nutrition on early development, the effects of maternofetal under-oxygenation on fetal growth, birth weight and subsequent increased risk of disease have been little addressed. Here, evidence is presented, which supports the concept that fetal hypoxia alone may provide a candidate prenatal stimulus contributing to fetal growth restriction and the developmental origins of cardiovascular health and disease.