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UBC Theses and Dissertations

Impact of repeated invasive procedures during neonatal intensive care on brain microstructure, growth, neurodevelopment and behavior in children born very preterm Vinall, Jillian Frances


As part of their lifesaving care in the neonatal intensive care unit (NICU), infants born very preterm (between 24 and 32 weeks gestation), undergo frequent invasive procedures that induce pain and stress, during a period of rapid brain development. We examined whether repeated exposure to invasive procedures was associated with altered brain development, and thereby poorer neurodevelopmental and behavioral outcome in children born very preterm. We also explored whether parent interaction moderates long-term effects of invasive procedures on child behavior. Data were collected from two prospective cohorts of infants born ≤32 weeks gestation between February 2001–July 2004 and March 2006–January 2009. Neonatal data were recorded from birth to term-equivalent age. Infants in the 2006–2009 cohort were scanned sequentially, once near birth and again at term-equivalent age. Infants in the 2001–2004 cohort were followed-up at 18 months corrected age (CA), and again at 7.5 years of age, when they underwent an MRI. At 18 months CA, parents of the 2001–2004 cohort completed questionnaires and participated in a recorded play session with their child, from which the parent-child interaction was later coded. All statistical analyses were adjusted for known neonatal and clinical confounders. In a series of 4 studies, greater exposure to invasive procedures in the NICU was associated with slower postnatal body and head growth, and slower growth was associated with delayed cerebral cortical maturation. Among the preterm children exposed to a higher number of invasive procedures, more positive parental interaction was associated with fewer anxious/depressive behaviors reported at 18 months CA. Furthermore, greater exposure to invasive procedures was related to poorer white matter maturation at 7.5 years, and together these factors predicted lower IQ. Greater exposure to invasive procedures was associated with slower body and head growth, altered brain maturation and poorer outcomes, after adjustment for clinical confounders. It is necessary that pain management strategies be evaluated for the extent that they are brain protective, in order to minimize the long-term impact of ongoing pain/stress in the NICU. Furthermore, interventions should address the parent-child relationship in order to improve later outcomes.

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