Intrauterine growth restriction, brain-sparing effect, and neurotrophins.

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.

The varying patterns of neurotrophin changes in the perinatal period.

Neurotrophins (NTs), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 are of major importance in prenatal and postnatal brain development, due to their neuroprotective action. Developmental changes alter the neuronal responsiveness to certain NTs, which subsequently are variously expressed, to properly balance their action. The following study aimed at examining the pattern of perinatal changes of the four NTs--NGF, BDNF, NT-3, and NT-4 in 30 appropriate for gestational age (AGA) full-term fetuses and neonates by determining their circulating levels at characteristic time points. This study show a gradual decrease of circulating levels of the NTs, NT-3 and NT-4 from umbilical cord (UC) to neonates day 4 (N4), while circulating levels of NGF and BDNF present the opposite pattern: an increase from UC to N4. These patterns of perinatal changes differ according to their impact on the process of neuronal development and their reaction to perinatal stress. NT3 and NT4 have been documented to act at early stages of neuronal development and to decrease after hypoxia-ischemia, while NGF and BDNF to increase. Further studies should investigate these patterns in premature or full-term infants, presenting various pathological conditions in the perinatal period.