Melbourne School of Psychological Sciences - Theses
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ItemThe neuroendocrine system following preterm birth and its effects on cognitive and brain development at age 7( 2012)Preterm birth is associated with a well-defined pattern of neurodevelopmental impairments which include a range of cognitive deficits, as well as structural brain abnormalities. Further, preterm infants are known to have a transiently altered neuroendocrine system during the first weeks of postnatal life. Although recent studies have focused on characterising long-term neurobehavioural deficits, few have examined potential mechanisms that may, at least partly, explain these poorer outcomes. This study aimed to address this shortcoming by focusing on the postnatal neuroendocrine system and its association with neurodevelopmental outcomes at age 7 in a group of children born very preterm. Postnatal concentrations of three hormones, free thyroxine, cortisol, and growth hormone, were examined using both direct hypothesis testing and exploratory hypothesis-generating approaches. Three direct hypotheses were proposed following review of the literature. Firstly, it was hypothesised that lower postnatal free thyroxine concentrations would be associated with poorer performances on measures of intellect, attention, and visuoperceptual abilities, as well as reductions in grey and white matter volumes at age 7 in children born very preterm. Secondly, it was hypothesised that higher postnatal cortisol concentrations would be associated with poorer performances on tasks of new learning and memory and volumetric reductions in the hippocampi at age 7 in children born very preterm. The final hypothesis predicted that elevated postnatal growth hormone concentrations would be related to deficits in attention and executive functioning and reductions in the prefrontal brain volumes at age 7 in children born very preterm. The current study investigated 83 children born very preterm (gestational age <30 weeks and/or birth weight <1250g), born between June 2002 and December 2003 in Melbourne, Victoria. During the neonatal period, hormone analysis was conducted over eight time points during the first 42 days of life (cord, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, and Day 42) to characterise the hormone profiles associated with preterm birth. At age 7, the children participated in a cognitive assessment and an MRI scan. A broad neuropsychological battery that assessed six domains of cognition, namely intellect, language, visuoperceptual reasoning, memory, attention and executive functioning, and processing speed, was used to characterise the cognitive profiles of this group of children. MRI imaging analysis was conducted using Freesurfer (v 5.1.0) to obtain cortical and subcortical brain volumes. The results did not confirm the direct hypotheses, although some interesting and novel findings arose. Firstly, elevated free thyroxine concentrations were related to poorer processing speed performances. A similar relationship was observed with elevated cortisol concentrations and decrements in processing speed. Lastly, elevated cortisol concentrations were related to volumetric reductions in subcortical regions, particularly the basal ganglia. Possible explanations for these findings were reviewed, though more research is required to confirm these relationships. Using a critical illness theory of endocrinology, it was concluded that the hormone profile exhibited by this cohort of children born very preterm during the early postnatal period, namely low concentrations of free thyroxine, and elevated concentrations of cortisol and growth hormone, reflected a transient reaction to acute critical illness. Moreover, given the adaptive nature of this acute illness phase, it was concluded that this postnatal hormone profile did not explain the diffuse nature of the neurodevelopmental impairments common to the preterm population.