Dear Editor,

Catterelli et al(1) suggest that early theophylline administration improves renal function during the first two days of life in very preterm infants with RDS. We are concerned that this very short term outcome could be over interpreted if the long-term outcome is not taken into consideration.

The inhibitory neuromodulator adenosine is neuroprotective against damage induced by cerebral ischemia.(2,3)Theophylline by antagonising the effect of adenosine could have a damaging effect on the brain.(3) The authors have shown that the effect of theophylline was increased urine output only on day 1 and infants not on theophylline, had a good urine output by day 2. This short term outcome of increased urine output may not be considered beneficial in view of the long term problems.

Other points which need further clarification include the definition of oliguria. This is still debatable and can range from 0.5-1ml/kg/hr on day1 and this need to be considered when interpreting the results.(4) Also, the actual fluid intake in each baby has not been mentioned. It is possible that the actual intake differs from the prescribed amount, taking into the fact the various practical problems encountered in the neonatal unit. (Delay in obtaining i.v access, replacement of long lines etc) Almost 85% of infants were noted to be on dopamine but the blood pressure aimed has not been mentioned. This is quite rare in our practice. We feel this is an important data which could influence the results.

The authors are to be commended for tackling an important issue in neonatology. They have confirmed the increased urine output on day1 with better creatinine clearance in preterm infants on theophylline. However, further studies are required to asses the long term safety profile of theophylline before implementing in clinical practice.

References:

1. A randomised, double blind, placebo controlled trial of the effect of theophylline in prevention of vasomotor nephropathy in very preterm neonates with respiratory distress syndrome D Cattarelli, M Spandrio, A Gasparoni, R Bottino, C Offer, and G Chirico Arch. Dis. Child. Fetal Neonatal Ed. 2006; 91: F80-F84

2. Neuroprotective effects of adenosine in cerebral ischemia: window of opportunity. SweeneyMI. Neurosci Biobehav Rev. 1997 Mar;21(2):207-17.

3. Methylxanthine therapy in premature infants: Sound practice, disaster, or fruitless byway? Barbara Schmidt Journal of Pediatrics, Volume 135, Issue 4, Pages 526-8

4. Text book of Neonatology by Rennie and Roberton 3rd edition.