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PO-0474 Impact Of Glutamate Transporter Haplotypes And Clinical Course On Functional Brain Networks In Preterm Infants
  1. A Smith-Collins1,
  2. A Heep1,
  3. RA Kauppinen2,
  4. A Váradi3,
  5. S Rajatileka3,
  6. E Molnár4,
  7. K Luyt1
  1. 1Neonatal Neuroscience, University of Bristol, Bristol, UK
  2. 2Clinical Research and Imaging Centre, University of Bristol, Bristol, UK
  3. 3Centre for Research in Biosciences, University of the West of England, Bristol, UK
  4. 4School of Physiology and Pharmacology, University of Bristol, Bristol, UK

Abstract

Reducing adverse neurodevelopmental outcomes associated with preterm birth is a major challenge facing neonatal medicine, as abnormalities engendered during the perinatal period have lifelong implications. The pathological mechanisms leading to abnormal neurodevelopment in preterm infants involve several pathways. Many direct and indirect effects of preterm birth on neural development occur at the micro structural or neurochemical level, meaning that current methods for assessing neurological injury in preterm infants provide only limited mechanistic and prognostic information. A promising alternative approach is the use of resting state functional MRI (rs-fMRI) to infer integration of neural activity across brain regions (functional connectivity (FC)). Adults who were born preterm show persistent differences in FC, and early detection of such changes offers potential insights into the pathophysiology of preterm brain injury. These functional changes may be influenced by both neonatal course and underlying susceptibilities to abnormal development, including genetic factors.

We utilised rapid multiband sequence rs-fMRI acquisition at 3 Tesla, to characterise functional brain connectivity in 30 infants born at <32 weeks gestation, scanned at term. DNA was extracted and sequenced for EAAT2 glutamate transporter haplotypes associated with adverse preterm neurodevelopmental outcomes. Using a multivariate model we identified dissociable and interacting influences of demographic, genetic and clinical variables on functional infant brain networks. We are the first to describe the influence of genetic variability in cerebral glutamate homeostasis on neonatal brain connectivity. We discuss the impact on understanding preterm brain injury, and the potential for predicting neurodevelopmental outcome by non-invasive measurement of functional brain connectivity.

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