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Prognosis

This is mainly determined by the aetiology67,68. The prognosis after hypocalcaemic seizures
and in familial neonatal seizures is excellent. Symptomatic hypoglycaemia and meningitis have
a 50% chance of sequelae in the survivors47. In hypoxic ischaemic encephalopathy the
prognosis depends very much on the grade (overall 3050% normal), while CNS
malformations are generally associated with poor outcome. Very low birthweight infants with
clinical seizures have a higher incidence of impairment than preterm infants without seizures48.

There is increasing evidence that neonatal seizures have an adverse effect on
neurodevelopmental outcome, and predispose to cognitive, behavioural, or epileptic
complications in later life. In animal studies, seizures impair neurogenesis and derange
neuronal structure, function and connectivity leading to permanent effects on seizure
susceptibility, learning and memory49. Recent work has also shown how even a single seizure
in the neonatal period may lead to long-term neuro-developmental consequences50.

Undetected and untreated seizure activity increases the insult to the neonatal brain51. Seizures
add to the hypoxic-ischaemic insult in newborn animals, and the same may be true for
babies1,52.

More recently a clear association between the number of electrographic seizures and
subsequent mortality and morbidity has been shown14, illustrating the need for EEG monitoring
in neonatal seizures.

However, there is increasing concern about the potentially adverse effects of AEDs on the
developing nervous system. In animal models, phenobarbitone has been shown to cause
additional brain damage by increasing neuronal death (apoptosis)53,54. Better treatments for
neonatal seizures have been identified as a high priority for research by several international
expert groups, with emphasis on innovative strategies targeted specifically to the needs of
babies with the ultimate aim to improve long-term outcome.

References

1. MILLER SP, WEISS J, BARNWELL A et al. Seizure-associated brain injury in term newborns with perinatal
asphyxia. Neurology 2002; 58: 542-548.

2. DAVIS AS, HINTZ SR, VAN MEURS KP et al. Seizures in extremely low birth weight infants are associated
with adverse outcome. J Pediatr 2010; 157: 720-725.

3. BERG A, JALLON P, PREUX P. The epidemiology of seizure disorders in infancy and childhood: definitions and
classifications. In: O Dulac et al (Eds), Handbook of Clinical Neurology. Pediatric Neurology, Part 1 (3rd edition),
pp 381-398. Elsevier, Amsterdam, Netherlands, 2013.

4. MIZRAHI EM, KELLAWAY P. Diagnosis and Management of Neonatal Seizures (1st edition). Philadelphia,
Lippincott-Raven, 1998.

5. VASUDEVAN C, LEVENE M. Epidemiology and aetiology of neonatal seizures. Semin Fetal Neonatal Med
2013; 18(4): 185-191.

6. BEN ARI Y, HOLMES GL. Effects of seizures on developmental processes in the immature brain. Lancet Neurol
2006; 5: 1055-1063.

7. JENSEN FE. Neonatal seizures: an update on mechanisms and management. Clin Perinatol 2009; 36: 881-900.
8. MALONE A, RYAN CA, FITZGERALD A et al. Interobserver agreement in neonatal seizure identification.

Epilepsia 2009; 50: 2097-2101.
9. MURRAY DM, BOYLAN GB, ALI I et al. Defining the gap between electrographic seizure burden, clinical

expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed 2008; 93: F187-F191.
10. MIZRAHI EM, KELLAWAY P. Characterization and classification of neonatal seizures. Neurology 1987; 37:

1837-1844.
11. BOYLAN, GB, PRESSLER, RM, RENNIE JM et al. Outcome of electroclinical, subclinical and clinical seizures

in the newborn infant. Dev Med Child Neurol 1999; 41: 819-825.
12. MURRAY DM, BOYLAN GB, ALI I, RYAN CA, MURPHY BP, CONNOLLY S. Defining the gap between

electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal
Neonatal Ed 2008; 93: F187-F191.
13. WEINER SP, PAINTER MJ, GEVA D et al. Neonatal Seizures: Electroclinical dissociation. Pediatric Neurol