Indomethacin has long been the standard treatment for patent ductus arteriosus (PDA) in premature infants but there is concern that it may impair renal function and cerebral perfusion. Evidence is now accumulating that ibuprofen could offer an equally effective and safe option.

Investigators from Belgium and the USA have reported a meta-analysis of randomised trials comparing treatment with ibuprofen and indomethacin in premature infants with PDA3. Eight trials involving a total of 503 infants were included. Overall, the two drugs were similarly effective in closing PDA and there were no significant differences in re-opening rates or mortality. Ibuprofen, however, had

substantially less impact on renal function, with a significantly smaller rise in serum creatinine (weighted mean difference*, WMD, 0.56; CI95% 0.37-0.76) and a smaller

reduction in urine output (WMD 0.50, CI95% 0.29-0.71). In the two trials reporting effects on cerebral blood flow, ibuprofen was associated with significantly less reduction than indomethacin (WMD 1.72, CI95%1.03-2.42). There was a higher risk of intravascular haemorrhage with indomethacin but no significant differences in the need for additional treatment, surgical ligation, ventilation or use of surfactant.

This study has recently been updated to include another randomised trial, increasing the number of infants involved to 566, and the new analysis has confirmed the original findings4.

Recent clinical trials have compared early prophylaxis with ibuprofen with placebo in premature infants (<28 - 30 weeks). Ibuprofen increased the proportion of premature infants with closure of PDA after 3 days (84% vs. 60% with placebo; relative risk 1.40, CI95% 1.23 - 1.59)5; and reduced the need for surgical ligation (9% vs. 0%, p=0.03)6. It did not significantly affect the risk of intraventricular haemorrhage or death, and adverse events included pulmonary hypertension (3/65 vs. 0/65 with placebo6) and transient renal effects.

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