Morphology and function of the brain in correlation to levels of stress hormones, reading ability and cognitive function in 12 years old children with low birth weight.

Due to an improved neonatal intensive care prematurely born infants survive at lower gestational ages. Even though most of them survive without any obvious functional disability, cognitive impairment has been shown to be more common than previously thought. As many as 50% of children without functional disabilities have cognitive impairments which can affect their performance in school. It is important to learn more about brain development in premature infants in order to be able to identify children at risk for later cognitive impairments. It is equally important to look for relationships to prenatal risk factors in order to improve the neonatal intensive care. In this study we will examine the impact of being born with very low birth weight by studying brain structures relevant for reading and memory with both MRI and fMRI. We will also relate the above to possible disturbances in cortisol levels and to possibly stressful neonatal events.

• Staff:

Nina Nelson , Associate professon		Principal investigator		Department of Pediatrics
Ingemar Lejon , Associate professor				Department of Pediatrics
Maria Engström , Associate professor				CMIV/Radiology
Thomas Karlsson , Associate professor				CMIV/Behavioral sciences and learning
Hans Knutsson , Professor				CMIV/ IMT
Mats Andersson , Ph D				CMIV/IMT
Helene van Ettinger-Veenstra , Ph D student				CMIV/Radiology
Carin Widén , Pediatrician				Departments of pediatrics

• Former Staff:

• Project Description:

Due to an improved neonatal intensive care prematurely born infants survive at
lower gestational ages. In Sweden, 90% of infants with birth weight < 1500 g survive. Most of them (90%) survive without any functional disability. Cognitive impairment is though much more common. As many as 50% of children without functional disabilities has been shown to have cognitive impairments which can affect their performance in school.

Sick vulnerable premature infants are exposed to a lot of stressful moments during their newborn period. As a response to stress in general, the activation of hypothalamic pituitary adrenal (HPA axis) helps to maintain homeostasis in a challenging environment which is beneficial in the short run. However, sustained activation of this neuroendocrine system due to chronic or repeated stress exposure can result in “wear and tear” and disease related consequences.
Chronic stress in premature infants affects the level of cortisol which in turn can influence regions in the brain important for cognitive functioning, especially the hippocampus. Stress early in life may therefore be a risk factor for later cognitive impairment and learning difficulties. Longitudinal research in animal models indicates that stress early in life can have effects on the HPA axis activity that persist into adulthood.

Earlier volumetric studies with MRI of preterm children have shown significant changes in several brain regions, for example the hippocampus area which play an important role in cognitive functions, compared to controls.
Even diffusion tension imaging (DTI) studies have shown decreases in fractional anisotropy (FA) in premature children compared with control subjects. These changes in FA occurred in subjects who also differed significantly from controls in their frontal, temporal, parietal and deep white matter volumes.

We know from our own previous follow up study of prematurely born infants in the south-east region of Sweden born 1998-99, that these children are in risk of lower reading skill at 8 years old but with some later catch up compared to term controls. It has been shown with fMRI that children born prematurely develop auxiliary or alternative systems for neural processing of common language tasks.

The aims of this study is to determine quantitative changes in the brain of preterm adolescents and to assess neural mechanism underlying reading and memory skills with MRI and fMRI. The aim is also to establish associations between MRI-findings, reading and memory skills, cortisol levels and perinatal risk factors.

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