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Cerebral Metabolism in the Very Low Birth Weight Infant

  • Eugene M. Dempsey
Chapter

Abstract

The preterm brain undergoes significant structural and functional changes throughout the third trimester. These changes require a constant supply of energy which is provided predominantly in the form of glucose. Alterations in this natural process can result in lifelong consequences for the very low birth weight infant. In this chapter the reader is provided with an insight into some of the neuroimaging modalities available to assess structural and functional changes in the preterm brain as well as an insight into the assessment of cerebral glucose transport and glucose metabolism in the very low birth weight infant. A review is provided of the assessment of cerebral blood flow and cerebral oxygen consumption in the very low birth weight infant followed by some of the processes that may interfere with normal cerebral metabolism in the preterm very low birth weight infant. The preterm brain has low energy requirements which coupled with low cerebral blood flow, means that the immature brain has the ability to deal with many significant alterations in cerebral metabolism. However, despite these factors many conditions can disrupt normal metabolism and result in brain injury. The last 30 years have witnessed significant improvements in survival of extremely preterm infants; the focus has now shifted towards improved quality of life in survivors. A better understanding of normal cerebral metabolism will allow one to identify alterations in this process and hence direct intervention, with the ultimate goal being improved long-term neurodevelopmental outcome.

Keywords

Apparent Diffusion Coefficient Cerebral Blood Flow Preterm Infant Standardize Uptake Value Superior Vena Cava 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ABP

Arterial blood pressure

ADC

Apparent diffusion coefficient

AEEG

Amplitude integrated electroencephalogram

CBF

Cerebral blood flow

CBFV

Cerebral blood flow velocity

CMRglc

Cerebral glucose metabolism

CTXglc

Cerebral glucose transport

CVo2

Cerebral oxygen consumption

DI

Diffusion imaging

HIE

Hypoxic ischaemic encephalopathy

EEG

Electroencephalogram

MRI

Magnetic resonance imaging

MRS

Magnetic resonance spectroscopy

PET

Positron emission topography

VLBW

Very low birth weight (<1500 g)

References

  1. Abrams RM, Ito M, Frisinger JE, Patlak CS, Pettigrew KD, Kennedy C. Local cerebral glucose utilization in fetal and neonatal sheep. Am J Physiol. 1984;246:R608–18.PubMedGoogle Scholar
  2. Adelson PD, Nemoto E, Scheuer M, Painter M, Morgan J, Yonas H. Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report. Epilepsia. 1999;40:1484–9.PubMedCrossRefGoogle Scholar
  3. Altman DI, Perlman JM, Volpe JJ, Powers WJ. Cerebral oxygen metabolism in newborns. Pediatrics. 1993;92:99–104.PubMedGoogle Scholar
  4. Altman DI, Powers WJ, Perlman JM, Herscovitch P, Volpe SL, Volpe JJ. Cerebral blood flow requirement for brain viability in newborn infants is lower than in adults. Ann Neurol. 1988;24:218–26.PubMedCrossRefGoogle Scholar
  5. Auer RN. Hypoglycemic brain damage. Metab Brain Dis. 2004;19:169–75.PubMedCrossRefGoogle Scholar
  6. Augustine EM, Spielman DM, Barnes PD, Sutcliffe TL, Dermon JD, Mirmiran M, Clayton DB, Ariagno RL. Can magnetic resonance spectroscopy predict neurodevelopmental outcome in very low birth weight preterm infants? J Perinatol. 2008;28:611–8.PubMedCrossRefGoogle Scholar
  7. Barkovich AJ. Normal development. In Pediatric neuroimaging. Philadelphia, PA: Lippincott Williams & Wilkins, PA; 2000. p. 13–69.Google Scholar
  8. Bartha AI, Foster-Barber A, Miller SP, Vigneron DB, Glidden DV, Barkovich AJ, Ferriero DM. Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome. Pediatr Res. 2004;56:960–6.PubMedCrossRefGoogle Scholar
  9. Biagioni E, Frisone MF, Laroche S, Kapetanakis BA, Ricci D, Adeyi-Obe M, Lewis H, Kennea N, Cioni G, Cowan F, Rutherford M, Azzopardi D, Mercuri E. Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants. Clin Neurophysiol. 2007;118:53–9.PubMedCrossRefGoogle Scholar
  10. Blennow M, Hagberg H, Ingvar M, Zeman J, Wang YS, Lagercrantz H. Neurochemical and biophysical assessment of neonatal hypoxic-ischemic encephalopathy. Semin Perinatol. 1994;18:30–5.PubMedGoogle Scholar
  11. Boylan GB, Young K, Panerai RB, Rennie JM, Evans DH. Dynamic cerebral autoregulation in sick newborn infants. Pediatr Res. 2000;48:12–7.PubMedCrossRefGoogle Scholar
  12. Busija DW, Leffler CW. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs. Am J Physiol. 1987;253:H869–73.PubMedGoogle Scholar
  13. Cappellini M, Rapisardi G, Cioni ML, Fonda C. Acute hypoxic encephalopathy in the full-term newborn: correlation between magnetic resonance spectroscopy and neurological evaluation at short and long term. Radiol Med. 2002;104:332–40.PubMedGoogle Scholar
  14. Chugani HT. Positron emission tomography scanning: applications in newborns. Clin Perinatol. 1993;20:395–409.PubMedGoogle Scholar
  15. Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. 2000;105:1141–5.PubMedCrossRefGoogle Scholar
  16. Cremer JE. Substrate utilization and brain development. J Cereb Blood Flow Metab. 1982;2:394–407.PubMedCrossRefGoogle Scholar
  17. Dinneen S, GerichJ, Rizza R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N Engl J Med. 1992;327:707–13.PubMedCrossRefGoogle Scholar
  18. Evans N, Kluckow M, Simmons M, Osborn D. Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Arch Dis Child Fetal Neonatal Ed. 2002;87:F181–4.PubMedCrossRefGoogle Scholar
  19. Evans D, Levene M. Neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 1998;78:F70–5.PubMedCrossRefGoogle Scholar
  20. Greisen G. Cerebral blood flow in preterm infants during the first week of life. Acta Paediatr Scand. 1986;75:43–51.PubMedCrossRefGoogle Scholar
  21. Hanaoka S, Takashima S, Morooka K. Study of the maturation of the child’s brain using 31P-MRS. Pediatr Neurol 1998;18:305–10.PubMedCrossRefGoogle Scholar
  22. Hanrahan JD, Sargentoni J, Azzopardi D, Manji K, Cowan FM, Rutherford MA, Cox IJ, Bell JD, Bryant DJ, Edwards AD. Cerebral metabolism within 18 hours of birth asphyxia: a proton magnetic resonance spectroscopy study. Pediatr Res. 1996:39;584–90.PubMedCrossRefGoogle Scholar
  23. Hatzidaki E, Giahnakis E, Maraka S, Korakaki E, Manoura A, Saitakis E, Papamastoraki I, Margari KM, Giannakopoulou C. Risk factors for periventricular leukomalacia. Acta Obstet Gynecol Scand. 2009;88:110–5.PubMedCrossRefGoogle Scholar
  24. Hellmann J, Vannucci RC, Nardis EE. Blood-brain barrier permeability to lactic acid in the newborn dog: lactate as a cerebral metabolic fuel. Pediatr Res 1982;16:40–4.PubMedCrossRefGoogle Scholar
  25. Huppi PS, Fusch C, Boesch C, Burri R, Bossi E, Amato M, Herschkowitz N. Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue. Pediatr Res. 1995;37:145–50.PubMedCrossRefGoogle Scholar
  26. Huppi PS, Warfield S, Kikinis R, Barnes PD, Zientara GP, Jolesz FA, Tsuji MK, Volpe JJ. Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann Neurol. 1998;43:224–35.PubMedCrossRefGoogle Scholar
  27. Jakobsen J, Schmidt JF, Waldemar G, Paulson OB. The acute effect of dilevalol on cerebral blood flow and oxygen consumption in normotensive humans. J Cardiovasc Pharmacol. 1990;15:574–8.PubMedCrossRefGoogle Scholar
  28. Jones MD, Jr, Burd LI, Makowski EL, Meschia G, Battaglia FC. Cerebral metabolism in sheep: a comparative study of the adult, the lamb, and the fetus. Am J Physiol 1975;229:235–9.PubMedGoogle Scholar
  29. Kesler SR, Ment LR, Vohr B, Pajot SK, Schneider KC, Katz KH, Ebbitt TB, Duncan CC, Makuch RW, Reiss AL. Volumetric analysis of regional cerebral development in preterm children. Pediatr Neurol. 2004;31:318–25.PubMedCrossRefGoogle Scholar
  30. Kidokoro H, Okumura A, Hayakawa F, Kato T, Maruyama K, Kubota T, Suzuki M, Natsume J, Watanabe K, Kojima S. Chronologic changes in neonatal EEG findings in periventricular leukomalacia. Pediatrics. 2009;124:e468–75.PubMedCrossRefGoogle Scholar
  31. Kimura H, Fujii Y, Itoh S, Matsuda T, Iwasaki T, Maeda M, Konishi Y, Ishii Y. Metabolic alterations in the neonate and infant brain during development: evaluation with proton MR spectroscopy. Radiology. 1995;194:483–9.PubMedGoogle Scholar
  32. Kissack CM, Garr R, Wardle SP, Weindling AM. Cerebral fractional oxygen extraction in very low birth weight infants is high when there is low left ventricular output and hypocarbia but is unaffected by hypotension. Pediatr Res. 2004a;55:400–5.PubMedCrossRefGoogle Scholar
  33. Kissack CM, Garr R, Wardle SP, Weindling AM. Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia. Pediatr Res. 2004b;56:111–6.PubMedCrossRefGoogle Scholar
  34. Kissack CM, Garr R, Wardle SP, Weindling AM. Cerebral fractional oxygen extraction is inversely correlated with oxygen delivery in the sick, newborn, preterm infant. J Cereb Blood Flow Metab. 2005;25:545–53.PubMedCrossRefGoogle Scholar
  35. Klingberg T, Vaidya CJ, Gabrieli JD, Moseley ME, Hedehus M. Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study. Neuroreport. 1999;10:2817–21.PubMedCrossRefGoogle Scholar
  36. Lipton P. Ischemic cell death in brain neurons. Physiol Rev. 1999;79:1431–568.PubMedGoogle Scholar
  37. Lou HC, Skov H, Pedersen H. Low cerebral blood flow: a risk factor in the neonate. J Pediatr. 1979;95:606–9.PubMedCrossRefGoogle Scholar
  38. Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988;297:1304–8.PubMedCrossRefGoogle Scholar
  39. Maunu J, Parkkola R, Rikalainen H, Lehtonen L, Haataja L, Lapinleimu H. Brain and ventricles in very low birth weight infants at term: a comparison among head circumference, ultrasound, and magnetic resonance imaging. Pediatrics. 2009;123:617–26.PubMedCrossRefGoogle Scholar
  40. McGowan JE, Chen L, Gao D, Trush M, Wei C. Increased mitochondrial reactive oxygen species production in newborn brain during hypoglycemia. Neurosci Lett. 2006;399:111–4.PubMedCrossRefGoogle Scholar
  41. Meek JH, Tyszczuk L, Elwell CE, Wyatt JS. Cerebral blood flow increases over the first three days of life in extremely preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1998;78:F33–7.PubMedCrossRefGoogle Scholar
  42. Ment LR, Kesler S, Vohr B, Katz KH, Baumgartner H, Schneider KC, Delancy S, Silbereis J, Duncan CC, Constable RT, Makuch RW, Reiss AL. Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence. Pediatrics. 2009;123:503–11.PubMedCrossRefGoogle Scholar
  43. Montassir H, Maegaki Y, Ohno K, Ogura K. Long term prognosis of symptomatic occipital lobe epilepsy secondary to neonatal hypoglycemia. Epilepsy Res. 2010;88:93–9.PubMedCrossRefGoogle Scholar
  44. Moran M, Miletin J, Pichova K, Dempsey EM. Cerebral tissue oxygenation index and superior vena cava blood flow in the very low birth weight infant. Acta Paediatr. 2009;98:43–6.PubMedCrossRefGoogle Scholar
  45. Mujsce DJ, Christensen MA, Vannucci RC. Regional cerebral blood flow and glucose utilization during hypoglycemia in newborn dogs. Am J Physiol. 1989;256:H1659–66.PubMedGoogle Scholar
  46. Musson RE, Batty R, Mordekar SR, Wilkinson ID, Griffiths PD, Connolly DJ. Diffusion-weighted imaging and magnetic resonance spectroscopy findings in a case of neonatal hypoglycaemia. Dev Med Child Neurol. 2009;51:653–4.PubMedCrossRefGoogle Scholar
  47. Nagy Z, Ashburner J, Andersson J, Jbabdi S, Draganski B, Skare S, Bohm B, Smedler AC, Forssberg H, Lagercrantz H. Structural correlates of preterm birth in the adolescent brain. Pediatrics. 2009;124:e964–72.PubMedCrossRefGoogle Scholar
  48. Naulaers G, Morren G, Van Huffel S, Casaer P, Devlieger H. Cerebral tissue oxygenation index in very premature infants. Arch Dis Child Fetal Neonatal Ed. 2002;87:F189–92.PubMedCrossRefGoogle Scholar
  49. Nguyen The Tich S, Anderson PJ, Shimony JS, Hunt RW, Doyle LW, Inder TE. A novel quantitative simple brain metric using MR imaging for preterm infants. AJNR Am J Neuroradiol. 2009;30:125–31.PubMedCrossRefGoogle Scholar
  50. Osborn DA, Evans N, Kluckow M, Bowen JR, Rieger I. Low superior vena cava flow and effect of inotropes on neurodevelopment to 3 years in preterm infants. Pediatrics 2007;120:372–80.PubMedCrossRefGoogle Scholar
  51. Patel J, Marks K, Roberts I, Azzopardi D, Edwards AD. Measurement of cerebral blood flow in newborn infants using near infrared spectroscopy with indocyanine green. Pediatr Res. 1998;43:34–9.PubMedCrossRefGoogle Scholar
  52. Perlman JM. White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome. Early Hum Dev. 1998;53:99–120.PubMedCrossRefGoogle Scholar
  53. Perlman JM, Volpe JJ. Seizures in the preterm infant: effects on cerebral blood flow velocity, intracranial pressure, and arterial blood pressure. J Pediatr. 1983;102:288–93.PubMedCrossRefGoogle Scholar
  54. Powers WJ, Rosenbaum JL, Dence CS, Markham J, Videen TO. Cerebral glucose transport and metabolism in preterm human infants. J Cereb Blood Flow Metab. 1998;18:632–8.PubMedCrossRefGoogle Scholar
  55. Pryds O, Greisen G, Friis-Hansen B. Compensatory increase of CBF in preterm infants during hypoglycaemia. Acta Paediatr Scand. 1988;77:632–7.PubMedCrossRefGoogle Scholar
  56. Rademaker KJ, Rijpert M, Uiterwaal CS, Lieftink AF, van Bel F, Grobbee DE, de Vries LS, Groenendaal F. Neonatal hydrocortisone treatment related to 1H-MRS of the hippocampus and short-term memory at school age in preterm born children. Pediatr Res. 2006;59:309–13.PubMedCrossRefGoogle Scholar
  57. Rozance PJ, Hay WW. Hypoglycemia in newborn infants: features associated with adverse outcomes. Biol Neonate. 2006;90:74–86.PubMedCrossRefGoogle Scholar
  58. Shi Y, Jin RB, Zhao JN, Tang SF, Li HQ, Li TY. Brain positron emission tomography in preterm and term newborn infants. Early Hum Dev. 2009;85:429–32.PubMedCrossRefGoogle Scholar
  59. Skov L, Pryds O, Greisen G, Lou H. Estimation of cerebral venous saturation in newborn infants by near infrared spectroscopy. Pediatr Res. 1993;33:52–5.PubMedCrossRefGoogle Scholar
  60. Thorngren-Jerneck K, Ohlsson T, Sandell A, Erlandsson K, Strand SE, Ryding E, Svenningsen NW. Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy. Pediatr Res. 2001;49:495–501.PubMedCrossRefGoogle Scholar
  61. Tsuji M, Saul JP, du Plessis A, Eichenwald E, Sobh J, Crocker R, Volpe JJ. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics. 2000;106:625–32.PubMedCrossRefGoogle Scholar
  62. Vannucci RC, Mujsce DJ. Effect of glucose on perinatal hypoxic-ischemic brain damage. Biol Neonate. 1992;62:215–24.PubMedCrossRefGoogle Scholar
  63. Vannucci RC, Vannucci SJ. Cerebral carbohydrate metabolism during hypoglycemia and anoxia in newborn rats. Ann Neurol. 1978;4:73–9.PubMedCrossRefGoogle Scholar
  64. Vannucci SJ, Maher F, Simpson IA. Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 1997;21:2–21.PubMedCrossRefGoogle Scholar
  65. van Wezel-Meijler G, Steggerda SJ, Leijser LM. Cranial ultrasonography in neonates: role and limitations. Semin Perinatol. 2000;34:28–38.CrossRefGoogle Scholar
  66. Vigneron DB, Barkovich AJ, Noworolski SM, von dem Bussche M, Henry RG, Lu Y, Partridge JC, Gregory G, Ferriero DM. Three-dimensional proton MR spectroscopic imaging of premature and term neonates. AJNR Am J Neuroradiol. 2001;22:1424–33.PubMedGoogle Scholar
  67. Volpe J. Neurology of the newborn. 5th ed. Philadelphia, PA: Saunders; 2008.Google Scholar
  68. Volpe JJ, Herscovitch P, Perlman JM, Kreusser KL, Raichle ME. Positron emission tomography in the asphyxiated term newborn: parasagittal impairment of cerebral blood flow. Ann Neurol. 1985;17:287–96.PubMedCrossRefGoogle Scholar
  69. Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med. 2006;355:685–94.PubMedCrossRefGoogle Scholar
  70. Young RS, Petroff OA, Chen B, Gore JC, Aquila WJ. Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study. Pediatr Res. 1991;29:191–5.PubMedCrossRefGoogle Scholar
  71. Yoxall CW, Weindling AM. Measurement of cerebral oxygen consumption in the human neonate using near infrared spectroscopy: cerebral oxygen consumption increases with advancing gestational age. Pediatr Res. 1998;44:283–90.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Pediatrics and Child HealthUniversity College CorkCorkIreland
  2. 2.Department of NeonatologyNeonatal Research Centre, Cork University Maternity HospitalCorkIreland

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