Very preterm birth has become more frequent during the past decades due to progress in reproductive medicine, more frequent indicated preterm births due to maternal illnesses, and increasing maternal age. Moreover, survival rates of very preterm children have increased due to improved neonatal management. However, very preterm-born children, adolescents, and young adults are at increased risk for poor cognitive function and socio-emotional problems, which is of growing public health concern. Very premature birth has been studied to unravel consequences of a nonoptimal environment during a developmental period which under normal circumstances would be the last trimester of fetal development. For very preterm children, this developmental period partly occurs outside the womb, which leads to major distress for the immature newborn. For the cerebral cortex, the last trimester of pregnancy is a particularly sensitive period during which cortical folding takes place and the volume increases 4fold. During this period, even minor insults may cascade into disturbances of brain development. The most frequent complication after very preterm birth is related to insufficient functioning of the lungs, which may lead to hypoxic-ischemic incidences and damage to nervous tissue. This review presents evidence for long-term sequels of very premature birth regarding neurocognitive, academic, socio-emotional, and mental health development. Then it discusses possible underlying mechanisms including alterations in brain development, programming of the hypothalamic-pituitary-adrenal axis and circadian rhythmicity, as well as affected parent-child interaction patterns in families with very preterm children. Finally, intervention approaches to improve outcomes after very preterm birth are discussed and directions for future research presented.
DNA methylation and brain dysmaturation in preterm infants
