Intrauterine growth restriction, brain-sparing effect, and neurotrophins

Abstract

Intrauterine growth restriction (IUGR) is failure of the fetus to achieve his or her intrinsic growth potential, due to anatomical/functional diseases or disorders in the feto-placental-maternal unit. Growth restriction successfully balances reduced oxygen delivery and consumption; however, chronic hypoxia is responsible for fetal blood flow redistribution to cardinal organs (brain, myocardium, and adrenal glands), the so-called brain-sparing effect. The neurotrophin family comprises four structurally related molecules: the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the neurotrophin-4 (NT-4). By exerting neuroprotection, neurotrophins are critical for pre- and postnatal brain development. Based on the assumption that the brain-sparing effect might be activated in full-term IUGR infants, we hypothesized that circulating neurotrophin levels should not differ between IUGR and appropriate for gestational age (AGA) infants. Indeed, we found that in both groups, circulating NT-3, NT-4, and BDNF levels do not differ, and this finding could possibly be attributed to the activation of the brain-sparing effect. In contrast, NGF levels were higher in the AGA compared to the IUGR group. However, only NGF levels positively correlated with the customized centile and the birth weight of the infants, and both of them were lower in the IUGR group.