Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ≈340–370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury.
Blüml S, Wisnowski JL, Nelson MD, Paquette L, Gilles FH, et al.. (2012) Metabolic Maturation of the Human Brain From Birth Through Adolescence: Insights From In Vivo Magnetic Resonance Spectroscopy. Cereb Cortex.
Pouwels PJ, Brockmann K, Kruse B, Wilken B, Wick M, et al. (1999) Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatr Res 46: 474–485.
Dyet LE, Kennea N, Counsell SJ, Maalouf EF, Ajayi-Obe M, et al. (2006) Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics 118: 536–548.
Miller SP, Ferriero DM, Leonard C, Piecuch R, Glidden DV, et al. (2005) Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr 147: 609–616.
Hintz SR, Kendrick DE, Wilson-Costello DE, Das A, Bell EF, et al. (2011) Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks' gestational age. Pediatrics 127: 62–70.
Kinney HC, Brody BA, Kloman AS, Gilles FH (1988) Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants. J Neuropathol Exp Neurol 47: 217–234.
Hüppi PS, Maier SE, Peled S, Zientara GP, Barnes PD, et al. (1998) Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Pediatr Res 44: 584–590.
Giménez M, Miranda MJ, Born AP, Nagy Z, Rostrup E, et al. (2008) Accelerated cerebral white matter development in preterm infants: a voxel-based morphometry study with diffusion tensor MR imaging. Neuroimage 41: 728–734.
Wisnowski J, L, Bluml S, Lisa P, Zelinski E, Nelson M, D, et al (2013) Altered Glutamatergic Metabolism Associated with Punctate White Matter Lesions In Preterm Infants. PLOS ONE 8(2): e56880 doi: 10.1371/journal.pone.0056880.
Folkerth RD, Haynes RL, Borenstein NS, Belliveau RA, Trachtenberg F, et al. (2004) Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. J Neuropathol Exp Neurol 63: 990–999.
Kreis R, Hofmann L, Kuhlmann B, Boesch C, Bossi E, et al. (2002) Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 48: 949–958.
Matsumae M, Kurita D, Atsumi H, Haida M, Sato O, et al. (2001) Sequential changes in MR water proton relaxation time detect the process of rat brain myelination during maturation. Mech Ageing Dev 122: 1281–1291.
Sulyok E, Nyúl Z, Bogner P, Berényi E, Repa I, et al. (2001) Brain water and proton magnetic resonance relaxation in preterm and term rabbit pups: their relation to tissue hyaluronan. Biol Neonate 79: 67–72.