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Neonatal hypoglycemia and its effects on the immature brain. September 4, 2003. Objectives:. To discuss the definition of neonatal hypoglycemia and the pathophysiology of hypoglycemia and its effects on the neonatal brain.
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September 4, 2003.
Difficulty in determining a significant definition of neonatal hypoglycemia.
How do we define significant hypoglycemia?
Koh et al.
A survey of 36 pediatric textbooks and 178 pediatric consultants produced a range from 1-4 mmol/L
Koh TTHG, Eyre HA, Aynsley-Green A. Neonatal hypoglycemia: the controversy regarding definition. Arch Dis Child 1988;63:1386-8.
Cornblath M, Mawdon JM, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. May 2000, 105(5).
Lucas A, Morley R, Cole TH. Adverse neurodevelopmental outcome of moderate neonatal hypoglycemia. BMJ 1988, 297:831-8
Hypoglycemia at less than 2.6 mmol/L occurred in 433 of 661 preterm infants studied. Strong correlation was found between the number of days with recorded hypoglycemia and reduced mental and motor development scores at 18 months.
Duvanel CB, Fawer C-L, Cotting J, et al. Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational age preterm infants. J Petiatr 1999, 134;492-8.
73% of the 85 SGA preterm newborns tested had hypoglycemia at < 2.6 mmol/L. Strong correlation was found between recurrent episodes of hypoglycemia and persistent neurodevelopmental and physical growth deficits at 5 years of age.
What level of hypoglycemia will impact on long term neurodevelopmental outcome?
Many such studies are difficult to perform in human subjects, thus much of this work has been done on laboratory animals.
The neonatal brain differs with adult brains with the following mechanisms providing increased resistance to brain injury:
Pryds O, Greisen G, Friis-Hansen B. Compensatory incrase of CBF in preterm infants during hypoglycemia. Acta Paediatr Scand 1988, 77:632-7.
Human infants can increase CBF by 200% above normal when blood glucose falls < 1.6 mmol/L
Mujsce DJ, Christensen MA, Vannucci RC. Regional cerebral blood flow and glucose utilization during hypoglycemia in newborn dogs. Am J Physiol 1989, 256:H1859-66.
Similar findings in newborn dogs with glucose concentrations at 1.0 mmol/L. CBF increased 170% in white matter to 250% in the thalamus.
Vannucci RC, Nardis EE, Vannucci SJ, et al. Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs. Am J Physiol. 1981, 240:R192-9.
Vannuci RC, Nardis EE, Vannucci SJ, et al. Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs. Am J Physiol 1981, 240:R192-9
Similar investigations showed high energy phosphate (phosphocreatine and ATP) reserves reamined within normal during hypoglycemia in newborn dogs.
Hypoglycemia is more deleterious when superimposed on hypoxia-ischemia or seizures, according to animal studies.
Vannucci RC, Vannucci SJ. Cerebral carbohydrate metabolism during hypoglycemia and anoxia in newborn rats. Ann Neurol 1978, 4:73-9.
In newborn rat pups subjected to anoxia, normoglycemic pups survived 10x longer than hypoglycemic ones.
Young RS, Cowan BE, Petrof OA. In vivo 31P and in vitro 1H nuclear magnetic resonance study of hypoglycemia during neonatal seizure. Ann Neurol 1987, 22:622-8.
31P NMR studies showed significant depletion of high-energy phosphate stores when seizures occurred in conjunction with hypoglycemia as compared to without.
Anderson JM, Milner RDG, Strich SJ. Effects of neonatal hypoglycemia on the nervous system: a pathological study. J Neurol Neurosurg Psychiatry 1967, 30:295-310.
Banker BQ. The neuropathological effects of anoxia and hypoglycemia in the newborn. Dev Med Child Neurol 1967, 9:544-550.
Spar HA, Lewine JD, Orrison WW. Neonatal hypoglycemia: CT and MR findings. AJNR 1994, 15:1477-1478.
Symptomatic hypoglycemia is associated with parieto-occipital white matter abnormalities, as well as abnormal signals in the deep grey matter structures of the thalamus and basal ganglia.
CT image source: Yager JY. Hypoglycemic injury to the immature brain. Clinics in Perinatology 2002, 29:651-674.
Lucas A, Morley R, Cole TG. Adverse neurodevelopmental outcome of moderate neonatal hypoglycemia. BMH 1988, 297:1304-8.
Multi-center study of 661 preterm infants weighing < 1850 g, with outcomes determined at 18 months of age.
Reduced mental and motor developmental scores were found to be related to increasing number of days with glucose levels < 2.6 mmol/L.
Relative risk for neurodevelopmental impairment was 3.5x greater in infants with blood glucose < 2.6 mmol/L for > 5 days.
Vannucci RC & Vannucci SJ. Hypoglycemic brain injury. Semin Neonatol 2001, 6:147-155.
Yager JY. Hypoglycemic injury to the immature brain. Clinics in Perinatology. 2002, 29:651-674.