Indian Pediatr 2009;46: 122-123
Neonatal Hypoglycemia: Role in Infantile
Senior Lecturer in Perinatal Neurology, Departments of
Paediatrics and Imaging Sciences, Imperial College, Hammersmith Hospital,
DuCane Rd, London W12 OHS, UK. E-mail: firstname.lastname@example.org
remains a significant cause of brain injury in newborn infants(1), as
highlighted by Udani, et al.(2) in this issue of Indian
Pediatrics. The authors recruited 100 consecutively presenting infants
with epilepsy, 83 of whom had brain imaging and/or a clear metabolic or
genetic diagnosis. The majority of the 83 infants had evidence of brain
injury of perinatal onset and in the largest subset of these, the injury
pattern suggested hypoglycemia as a cause. Genetic, metabolic and
documented postnatal causes constituted a much smaller group. Infants with
acute symptomatic seizures, those without available imaging and those with
uncertain age of epilepsy onset were not included; it would have been
informative to know the number of children excluded to have a better
understanding of how representative was the study cohort. It is somewhat
surprising that only eight children had imaging evidence of acute
perinatal hypoxia-ischemia; perhaps these are under-represented as their
difficulties had been known from birth and the cause of seizures was
Burns, et al.(3) recently reported on the
spectrum of neonatal MR imaging abnormalities in term-born infants having
symptomatic neonatal hypoglycemia; these included arterial territory
stroke, white matter change that was not confined solely to posterior
parietal and occipital lobes, focal hemorrhage and also a diffuse increase
in signal on T1-weighted imaging in the globus pallidum.
Of note is that the white matter findings associated
with neonatal hypoglycemia can be subtle such that they might not be
easily seen on imaging carried out after the neonatal period. In the
present study, 9 infants with hypoglycemia were not thought to have
typical imaging patterns and hence were not included in that etiological
category, potentially underestimating the contribution of hypoglycemia in
their cases, as also pointed out by Udani, et al.(2). On the other
hand, the injury pattern typically described in hypoglycemia is not
pathognomonic and it is a concern that etiology was based, for many
infants, solely on the imaging characteristics without confirmatory
biochemistry – this may have resulted in an overestimate of the
contribution of hypoglycemia to later epilepsy in some infants.
Typically, hypoglycemia does not affect the posterior
putamen and ventrolateral thalamic nuclei or the main motor tracts as is
seen with acute perinatal hypoxic-ischemic injury. The authors also found
a striking lack of severe spasticity and dystonia in the infants with
epilepsy following neonatal hypoglycemia. The more diffuse signal in the
globus pallidum is different. It has been reported by Barkovich, et al.(4)
and may be seen in a variety of conditions including mitochrondrial
problems, perhaps reflecting the effects of hypoglycemia on mitochrondrial
Interestingly, 9 children had stroke. Stroke has been
reported in preterm(6) and term(3) infants with hypoglycaemia. However,
the association was not explained in either of these studies. It is
possible, at least in the term infant, that the stroke affected feeding
resulting in secondary hypoglycemia.
Udani, et al.(2) compared the perinatal
characteristics of infants with hypoglycemic injury to those with epilepsy
due to developmental disorders arguing that these infants were least
likely to have immediate perinatal problems. However these infants are
also more perinatally vulnerable and have a higher risk of being small and
not feeding well, so this approach, though understandable, may have
underestimated the differences between the hypoglycemic group and normal
controls. Interestingly two-thirds of their infants were male; Burns,
et al.(3) also found more males compared to controls supporting the
observation in many domains of male vulnerability(7).
This study suggests that for infants presenting with
epilepsy in early childhood evidence for neonatal hypoglycemia should be
sought. Epilepsy of varying severity following hypoglycemia has been
reported by others(8,9) as have learning deficits including severe mental
retardation, microcephaly, visual impairments, behavioural problems, and
autistic spectrum behavior(8-12). Udani, et al.(2) highlight an
association with apraxia. Microcephaly and delay in visual maturation or
other visual abnormality are features that can be looked for early after
neonatal hypoglycemia and may serve as markers of later presenting
difficulties – most children do not have severe cerebral palsy and longer
term neuro-developmental follow up is needed to ensure the early detection
of the learning, behavioral and other difficulties that are not easy to
evaluate in the first months after birth.
Competing interests: None stated.
1. Rozance PJ, Hay WW. Hypoglycemia in newborn infants:
Features associated with adverse outcomes. Biol Neonate 2006; 90: 74-86.
2. Udani V, Munot P, Ursekar M, Gupta S. Neonatal
hypoglycemic brain injury - a common cause of infantile-onset remote
symptomatic epilepsy. Indian Pediatr 2009; 46: 127-132.
3. Burns CM, Rutherford MA, Boardman JP, Cowan FM.
Patterns of cerebral injury and neuro-developmental outcomes after
symptomatic neonatal hypoglycaemia. Pediatrics 2008; 122: 65-74.
4. Barkovich AJ, Ali FA, Rowley HA, Bass N. Imaging
patterns of neonatal hypoglycemia. AJNR Am J Neuroradiol 1998;19: 523-528
5. Ballesteros JR, Mishra OP, McGowan JE. Alterations
in cerebral mitochondria during acute hypoglycemia. Biol Neonate 2003; 84:
6. Benders MJ, Groenendaal F, Uiterwaal CS, Nikkels PG,
Bruinse HW, Nievelstein RA, et al. Maternal and infant
characteristics associated with perinatal arterial stroke in the preterm
infant. Stroke 2007; 38: 1759-1765.
7. Johnston MV, Hagberg H. Sex and the pathogenesis of
cerebral palsy. Dev Med Child Neurol 2007;49:74-78
8. Fluge G. Neurological findings at follow-up in
neonatal hypoglycaemia. Acta Paediatr Scand 1975; 64: 629-634.
9. Caraballo RH, Sakr D, Mozzi M, Guerrero A, Adi JN,
Cersosimo RO, et al. Symptomatic occipital lobe epilepsy following
neonatal hypoglycemia. Pediatr Neurol 2004; 31: 24-29.
10. Yalnizoglu D, Haliloglu G, Turanli G, Cila A, Topcu
M. Neurologic outcome in patients with MRI pattern of damage typical for
neonatal hypoglycaemia. Brain Dev 2007; 29: 285-292.
11. Tam EW, Widjaja E, Blaser SI, Macgregor DL, Satodia
P, Moore AM. Occipital lobe injury and cortical visual outcomes after
neonatal hypoglycemia. Pediatrics 2008; 122: 507-512.
12. Buitendijk S, de Vries LS, Groenendaal F, Toet MC. Cerebral damage
due to hypoglycaemia in otherwise healthy breast-fed term infants Ned
Tijdschr Geneeskd 2008; 152: 721-726.