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

Prematurely born infants are at risk of bleeding into the brain in the first few weeks of life. This is called intraventricular haemorrhage. The risk of this occurring is greatest to infants who are born less than 32 weeks gestation. Many potential therapies have been studied to determine if they might reduce the risk of this bleeding. One such therapy is a drug called Ethamsylate. It is not exactly known how this drug works, but it appears to reduce bleeding in other clinical situations, such as excessive menstrual bleeding and after some types of surgery.

A total of seven studies with 1410 preterm infants were included in this review. Most of these initial studies were conducted between 1980 and 1990. Preterm infants treated with ethamsylate had similar outcomes with respect to death and disability at the age of two years when compared to infants who were treated with a placebo. Infants born less than 35 weeks gestation appeared to have less intraventricular haemorrhage when treated with ethamsylate compared to controls, however this did not lead to improved developmental outcome in later childhood. There were no adverse effects noted with ethamsylate treatment.

Based on these results, routine use of ethamsylate for prematurely born infants to prevent intraventricular haemorrhage cannot be recommended. It is highly unlikely that any further trials will be conducted to explore this clinical question.

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.

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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.

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