The vulnerable developing brain.

D uring healthy pregnancy, appropriate levels of fetal nutrition and oxygenation are indispensable for the optimal growth and development of the fetal organs. In pregnancy complicated by decreased nutrient and oxygen delivery to the fetus, current dogma is that the growth and development of key organs, such as the brain, are “spared” at the expense of nonessential organs served by peripheral vascular beds, for instance the kidneys, pancreas, and skeletal muscle. The article by Antonow-Schlorke et al. in PNAS (1) challenges this concept and shows that the developing brain is more vulnerable than previously thought, even to moderate reductions in maternal nutrition during early pregnancy. The study is particularly relevant because it was undertaken in nonhuman primates rather than in rodents. In contrast to primates, including the human, in rodent species many stages of brain development continue to occur after birth. The concept of fetal brain sparing in adverse pregnancy is based on overwhelming evidence obtained from epidemiological studies in humans and experimental studies in animals, which have revealed that malnourished or hypoxic pregnancy yields disproportionately growth-retarded offspring (2, 3). The “thrifty phenotype” baby has an increased head diameter to body length or weight ratio, with a reduced ponderal index, being thin for its length. In experimental animals, asymmetric intrauterine growth restriction is also represented by increased fetal brain weight relative to body weight or an increase in the fetal brain to liver weight ratio (4, 5).