Human neocortical development as a basis to understand mechanisms underlying neurodevelopmental disabilities in extremely preterm infants

Aim: Recent advances in perinatal and neonatal medicine have resulted in marked improvements in the survival rates of extremely preterm infants (born before 28 gestational weeks) around the world, and Japan is among the countries with the highest reported survival rates of extremely preterm infants. However, it remains a major concern that many survivors develop neurodevelopmental disabilities, including cognitive dysfunctions and neurodevelopmental disorders later in life. In order to understand the pathophysiological mechanisms underlying the neurodevelopmental disabilities observed in the survivors of extremely preterm births, we reviewed recently reported findings about the development of the human neocortex. Methods: First, we have summarized the current knowledge about the development of the neocortex, including recently reported human- and/or primate-specific developmental events. Next, we discussed the possible causal mechanisms underlying the development of neurodevelopmental disabilities in extremely preterm infants. Results: Around the birth of extremely preterm infants, neurogenesis and succeeding neuronal migrations are ongoing in the neocortex of human brain. Expansion and maturation of the subplate, which is thought to reflect the axonal wiring in the neocortex, is also prominent at this time. Conclusion: Brain injuries that occur around the birth of extremely preterm infants are presumed to affect the dynamic developmental events in the neocortex, such as neurogenesis, neuronal migrations and maturation of the subplate, which could underlie the neurodevelopmental disabilities that often develop subsequently in extremely preterm infants. These possibilities should be borne in mind while considering maternal and neonatal care to further improve the long-term outcomes of extremely preterm infants.