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Is the use of prophylactic theophylline safe for the prevention of severe renal dysfunction in term and post-term neonates with perinatal asphyxia?

Journal of Perinatology volume 34, page 82 (2014)Cite this article

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We read with great interest the article by Al-Wassia et al.1 that reports the effect of prophylactic theophylline for the prevention of severe renal dysfunction in post-asphyxiated term and post-term infants. In their report,1 it is stated that prophylactic theophylline significantly reduce the incidence of severe renal dysfunction in neonates with perinatal asphyxia. However, we have some doubts that theophylline may cause proconvulsive activity, excitotoxicity and neurotoxicity in neonates.2 Hence, we would like to make some comments on their report.

First, theophylline is also known to be an additional risk factor for seizure exacerbation. Several potential mechanisms have been proposed that could explain the proconvulsive role of theophylline: (i) general decrease of seizure thresholds; (ii) inhibition of adenosine A1 receptor that normally suppress seizures by blocking the release of excitatory amino acids; (iii) inhibition of cerebral blood flow via adenosine antagonism; (iv) inhibition of 5′-nucleotidase and decrease in endogenous adenosine production; (v) inhibition of pyridoxal kinase, an enzyme needed for the synthesis of GABA; and (vi) a presumed direct inhibition of the GABA A receptor.2, 3 In addition, new findings suggest a role of free radicals in theophylline-induced seizures.2

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References

  1. Al-Wassia H, Alshaikh B, Sauve R . Prophylactic theophylline for the prevention of severe renal dysfunction in term and post-term neonates with perinatal asphyxia: a systematic review and meta-analysis of randomized controlled trials. J Perinatol 2013; 33: 271–277.

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  2. Boison D . Methylxanthines, seizures, and excitotoxicity. Handb Exp Pharmacol 2011; 200: 251–266.

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  3. Nakada T, Kwee IL, Lerner AM, Remler MP . Theophylline-induced seizures: clinical and pathophysiologic aspects. West J Med 1983; 138: 371–374.

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  5. Kulkarni C, Joseph T, David J . Influence of adenosine receptor antagonists, aminophylline and caffeine, on seizure protective ability of antiepileptic drugs in rats. Indian J Exp Biol 1991; 29: 751–754.

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Authors and Affiliations

  1. Department of Neonatology, Dr. Sami Ulus Maternity and Children Hospital, Ankara, Turkey

    M Aydin, N Hakan, A Zenciroglu & N Okumus

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  1. M Aydin
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  2. N Hakan
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  3. A Zenciroglu
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  4. N Okumus
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Correspondence to N Hakan.

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Aydin, M., Hakan, N., Zenciroglu, A. et al. Is the use of prophylactic theophylline safe for the prevention of severe renal dysfunction in term and post-term neonates with perinatal asphyxia?. J Perinatol 34, 82 (2014). https://doi.org/10.1038/jp.2013.123

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