Preterm birth and early life developmentthe influence of neuropsychology, brain and social factors

Abstract

Preterm birth (PB) alters brain development influenced by neurological damage, environmental circumstances, and the timing of their occurrence. Based on weeks of gestation, there are newborns considered moderate and late preterm (MLPT) who are born between 32 to 36 weeks of gestation. This group is of increasing interest as it comprises more than 84% of all PBs. However, there is a paucity of research converging neurodevelopmental outcomes in well-characterized samples in terms of clinical manifestations at birth, which would allow researchers to assess the effect of PB per se and brain injury on cognition and cerebral development. Especially, considering that only a small percentage of MLPT children present a profile of developmental difficulties close in phenotype to those born at a lower gestational age. Nevertheless, the existing neurodevelopmental consequences may contribute to lower education, employment status and income during adulthood in this population, leading to decreased well-being and poorer mental and physical health. Aside from the presence or absence of neonatal brain injury, some environmental factors may also place PB at even greater risk for adverse long-term development. This thesis is composed of six studies and analyzes PB taking into account different degrees of neonatal immaturity, with the first two studies focusing on childhood and the following four on adolescence and young adulthood. More specifically, it addresses the impact of PB on the neuropsychological profiles of preterm born children, adolescents and young adults according to their clinical manifestations at birth. On the other hand, it assesses the potential role of early life environmental factors on cognitive development, such as socioeconomic status, parental bonding, and adverse childhood experiences. In turn, a systematic review and meta-analysis is conducted with the aim of gaining insight into the long-term neurodevelopmental outcomes of MLPT adults in relation to cognitive functioning and psychiatric disorders. Finally, it studies the brain after PB at different developmental stages, with special emphasis on the hippocampus and amygdala taking into account the importance of both structures on cognition and social-emotional outcomes. These studies mentioned here provide different neuropsychological profiles and brain indicators in the prognosis of short- and long-term development of PB. For instance, children, adolescents, and young adults born prematurely, with or without neonatal brain injury, continued to lag behind their full-term peers in a variety of cognitive domains. However, the effects of MLPT on psychiatric illnesses are frequently small during adolescence and adulthood, even none regarding social-emotional problems at different developmental stages. At brain level, in the absence of neonatal brain injury, differences in normative structural brain development and regional white matter microstructure were found during young adulthood. Moreover, increased functional connectivity was also displayed in brain areas related to social-emotional outcomes. Although much work remains to be done regarding the inclusion of neuropsychological and brain adverse outcomes in PB care, the present thesis suggests that the use of standardized long-term follow-up may be potentially useful, even at a lower risk for developing negative developmental consequences, without ignoring the impact of different environmental factors during the first years of life.