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Comparison of the effects of theophylline and caffeine on serum erythropoietin concentration in premature infants


Theophylline administration has been shown to attenuate erythropoietin (EP) production in adults; the effect of caffeine is not known. Our aim was to determine whether caffeine and theophylline had similar effects on EP production in the premature newborn. If caffeine was found to have a greater effect, this would influence prescribing habits. Fifty preterm infants (mean gestational age 28 weeks) who had clinically significant apnoea were randomized to receive theophylline (4 mg/kg then 2 mg/kg twice daily) or caffeine (10 mg/kg then 2.5 mg/kg once daily). The methylxanthines were continued at least until discharge from the NICU and the dosage altered to keep the levels within the therapeutic range. As an assessment of EP production, serum EP concentrations were measured. Blood for EP, haemoglobin, reticulocyte count, theophylline and caffeine levels was obtained prior to treatment and at least during weeks 3 and 7. There was no significant difference in the mean EP level in the two groups taken prior to treatment at a median age of 2 days of life. There were similar falls in haematocrit and haemoglobin in the two groups during the study period compared to pre-treatment values. At that time, however, the median reticulocyte count was higher in the caffeine compared to the theophylline treated infants (P < 0.05). This was associated with a rise compared to baseline (median 10.0–0.2 mU/ml) in the mean EP levels in the caffeine group and a decrease from a median of 10.1 to 8.3 mU/ml in the theophylline group, but the EP levels in the two groups at week 7 did not differ significantly.


These results suggest that caffeine does not have a greater impact than theophylline on EP production.

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Correspondence to S. Fang or R. A. Sherwood or H. R. Gamsu or J. T. Marsden or T. J. Peters or A. Greenough.

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Fang, S., Sherwood, R.A., Gamsu, H.R. et al. Comparison of the effects of theophylline and caffeine on serum erythropoietin concentration in premature infants. Eur J Pediatr 157, 406–409 (1998). https://doi.org/10.1007/s004310050840

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Key words

  • Methylxanthines
  • Prematurity
  • Erythropoietin