PROPHYLACTIC INDOMETHACIN - SYSTEMATIC REVIEW AND METAANALYSIS

Aims-To examine the effectiveness of prophylactic intravenous indometh acin in reducing the mortality and morbidity associated with patent du ctus arteriosus and intraventricular haemorrhage in infants weighing l ess than 1750 g at birth. Method-A Literature search from 1980 onwards was made of three databases: Medline; Embase; and the Oxford Database of Perinatal Trials. Using strict criteria applied to randomised cont rolled trials only, two observers independently selected 14 studies fo r inclusion in the review. The methodological quality of each study wa s assessed independently by two observers using explicit criteria. Dat a on relevant outcome measures were extracted on two separate occasion s. Where appropriate, the results of individual trials were combined u sing metaanalysis techniques to provide a pooled estimate of effect. R esults-There is a trend towards reduced neonatal mortality in infants receiving prophylactic indomethacin, pooled estimate of risk differenc e -0.025 (95% confidence interval (CI) -0.061, 0.010). The incidence o f symptomatic patent ductus arteriosus is significantly reduced in tre ated infants, pooled estimate of risk difference -0.217 (95% CI -0.275 , -0.160), but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin significantly reduces the inciden ce of grades 3 and 4 intraventricular haemorrhage in treated infants, pooled estimate of risk difference -0.039 (95% CI -0.066, -0.011). How ever, there is no sound evidence assessing the long term effect of pro phylaxis on neurodevelopmental outcome. Although there is a trend in t reated infants towards an increased incidence of necrotising enterocol itis, pooled estimate of risk difference 0.015 (95% CI -0.002, 0.033), and some evidence that treatment may transiently impair renal functio n, there is no evidence that haemostasis is disturbed. Conclusion-Prop hylactic treatment with indomethacin has several immediate benefits. H owever, more data are needed on the incidence of possible adverse effe cts and neurodevelopmental outcomes before routine use of this therapy can be recommended.