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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Bakris G, Sauter ER, Hussey JL, Fisher JW, Gaber AO, Winsett R (1990) Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplantation. N Engl J Med 323:86–90
Bechensteen AG, Halvorsen S, Hågå P, Cotes PM, Liestø lK (1996) Erythropoietin (Epo), protein and iron supplementation and the prevention of anaemia of prematurity: effects on serum immunoreactive Epo, growth and protein and iron metabolism. Acta Paediatr 85:490–495
Bonati M, Latini R, Marra G, et al (1981) Theophylline metabolism during the first month of life and development. Pediatr Res 15:304–308
Brown MS, Phibbs RH, Garcia JF (1983) Postnatal changes in erythropoietin levels in untransfused premature infants. J Pediatr 103:612–617
Christensen RD, Hunter DD, Goodell H, Rothstein G (1992) Evaluation of the mechanism causing anemia in infants with bronchopulmonary dysplasia. J Pediatr 120:593–598
Davi MJ, Sankaran K, Simons KJ, Simons FE, Seshia MM, Rigatto H (1978) Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. J Pediatr 92:91–95
Forestier F, Daffos F, Catherine N, Renard M, Andreux J-P (1991) Developmental hematopoiesis in normal human fetal blood. Blood 77:2360–2363
Gurney CW, Wackman N, Filmanowicz E (1961) Studies on erythopoiesis XVII. Some quantitative aspects of the erythropoietic response to erythropoietin. Blood 17:531–546
Howell J, Clozel M, Aranda JV (1981) Adverse effects of caffeine and theophylline in the newborn infant. Semin per-inatol 5:359–369
Humbert JR, Abelson H, Hathaway WE (1975) Poly-cythaemia in small for gestational age infants. J Pediatr 75:812–819
O’Brien RT, Pearson HA (1971) Physiologic anaemia of the newborn. J Pediatr 79:132–138
Ruth V, Fyhrquist F, Clemons G, Raivio KO (1988) Cord plasma vasopressin, erythropoietin and hypoxanthine as indices of asphyxia as birth. Pediatr Res 24:490–494
Sattin A, Rall TW (1970) The effect of adenosine and adenosine nucleotides on the cyclic adenosine 3′,5′ phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol 6:13
Schulman I (1959) Anemia of prematurity. J Pediatr 59:663–666
Shannon DC, Gotay F, Stein IM, Rogers MC, Todres ID, Moylan FM (1975) Prevention of apnea and bradycardia in low birthweight infants. Pediatrics 55:589–594
Sims ME, Rangasamy R, Lee S, Chung H, Cohen J, Walther FJ (1989) Comparative evaluation of caffeine and theophylline for weaning premature infants from the ventilator. Am J Perinatol 6:72–75
Soubasi V, Kremenopoulos G, Diamandi E, Tsantali C, Tsakiris D (1993) In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study. Pediatr Res 34:675–679
Spivak JL (1989) The mechanism of action of erythropoietin. Int J Cell Cloning 4:139–166
Stockman JA (1977) Anemia of prematurity. Clin Perinatol 4:239–257
Stockman JA, Graeber JE, Clark DA, McClellan K, Garcia JF, Kavey REW (1984) Anemia of prematurity: determinants of the erythropoietin response. J Pediatr 105:786–792
Trippenbach T (1983) Effects of drugs on the respiratory control system in the perinatal period and during postnatal development. Pharmacol Ther 20:307–314
Ueno M, Brookins J, Beckman B, Fisher JW (1988) A1 and A2 adenosine receptor regulation of erythropoietin production. Life Sci 43:229–237
Wardrop CAJ, Holland BM, Veale KEA, Jones JG, Gray OP (1978) Non-physiologic anemia of prematurity. Arch Dis Child 53:855–860
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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