Ethamsylate for the prevention of morbidity and mortality in preterm or very low birth weight infants.

BACKGROUND: Ethamsylate decreases blood loss in certain clinical situations such as menorrhagia and following some surgical procedures. This potential to reduce bleeding has led to the hypothesis that it may have a role to play in reducing intraventricular haemorrhage in preterm infants. OBJECTIVES: To determine if ethamsylate, when compared to placebo or no treatment, reduces morbidity and/or mortality in preterm infants. SEARCH STRATEGY: We searched the Cochrane Neonatal Group Trials Register (24 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2009, Issue 2), MEDLINE and EMBASE (January 1966 to July 2009) and the Oxford Database of Perinatal Trials. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised trials comparing ethamsylate with placebo or no treatment. The initial search for trials enrolling infants born less than 32 weeks gestation was subsequently expanded to include trials enrolling preterm infants < 35 weeks gestation or < 2000 grams birth weight. Studies were included if they reported on outcomes of all children until death or discharge home. Data from reports of neurodevelopmental follow-up were only included if at least 80% of participants were followed up. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed trial quality and extracted data. We calculated relative risk (RR) and risk difference (RD) together with 95% confidence intervals (CI) and used a fixed-effect model for meta-analysis. MAIN RESULTS: Eight studies were identified but only seven trials enrolling 1410 preterm infants were located. There was no significant difference detected in neonatal mortality or neurodevelopmental outcome at two years between infants treated with ethamsylate and controls. Infants treated with ethamsylate had significantly less intraventricular haemorrhage than controls at < 31 weeks (typical RR 0.63, 95% CI 0.47 to 0.86) and < 35 weeks gestation (typical RR 0.77, 0.65 to 0.92). There was also a significant reduction in grade 3 and 4 intraventricular haemorrhage when all infants < 35 weeks gestation (typical RR 0.67, 95% CI 0.49 to 0.94) were analysed as a single group, but not for the group of infants < 32 weeks alone. There was a reduction in symptomatic patent ductus arteriosus at < 31 weeks gestation (typical RR 0.32, 95% CI 0.12 to 0.87). There were no adverse effects of ethamsylate identified from this systematic review. AUTHORS' CONCLUSIONS: Preterm infants treated with ethamsylate showed no reductions in mortality or neurodevelopmental impairment despite the reduction in any grade of intraventricular haemorrhage seen in infants < 35 weeks gestation.