Procedural pain and brain development in premature newborns

Authors

  • Susanne Brummelte PhD,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Ruth E. Grunau PhD,

    Corresponding author
    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
    • Developmental Neurosciences and Child Health, Child and Family Research Institute, Department of Pediatrics, University of British Columbia, F605B–4480 Oak Street, Vancouver, BC V6H 3V4, Canada
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  • Vann Chau MD,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Kenneth J. Poskitt MDCM,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
    3. Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada
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  • Rollin Brant PhD,

    1. Department of Biostatistics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Jillian Vinall BA,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Ayala Gover MD,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Anne R. Synnes MDCM,

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Steven P. Miller MDCM

    1. Developmental Neurosciences and Child Health, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract

Objective:

Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants.

Methods:

Infants born very preterm (N = 86; 24–32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.

Results:

After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (β = −0.0002, p = 0.028) and reduced subcortical gray matter NAA/choline (β = −0.0006, p = 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.

Interpretation:

Early procedural pain in very preterm infants may contribute to impaired brain development. ANN NEUROL 2012;

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