title: Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants.
abstract: BACKGROUND
  Persistent patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Prostaglandin synthetase inhibitors such as indomethacin promote PDA closure but also have potential side effects. The effect of the prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA would be exposed to indomethacin, warrants particular scrutiny.
  
  
  OBJECTIVE
  To determine the effect of prophylactic indomethacin on mortality and morbidity in preterm infants.
  
  
  METHODS
  The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 5, 2010), MEDLINE, EMBASE and CINAHL (until April 2010), conference proceedings, and previous reviews.
  
  
  METHODS
  Randomised or quasi-randomised controlled trials that compared prophylactic indomethacin versus placebo or no drug in preterm infants.
  
  
  METHODS
  The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two review authors.
  
  
  RESULTS
  Nineteen eligible trials in which 2872 infants participated were identified. Most participants were very low birth weight, but the largest single trial restricted participation to extremely low birth weight infants (N = 1202). The trials were generally of good quality.The incidence of symptomatic PDA [typical relative risk (RR) 0.44, 95% confidence interval (CI) 0.38 to 0.50] and PDA surgical ligation (typical RR 0.51, 95% CI 0.37,0.71) was significantly lower in treated infants. Prophylactic indomethacin also significantly reduced the incidence of severe intraventricular haemorrhage (typical RR 0.66, 95% CI 0.53 to 0.82). Meta-analyses found no evidence of an effect on mortality (typical RR 0.96, 95% CI 0.81 to 1.12) or on a composite of death or severe neurodevelopmental disability assessed at 18 to 36 months old (typical RR 1.02, 95% CI 0.90, 1.15).
  
  
  CONCLUSIONS
  Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment.
authors.affiliation: Women & Child Health, Ninewells Hospital and Medical School, Dundee, Scotland, UK, DD1 9SY.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Fowlie
authors.forename: Peter G
authors.initials: PG
authors.lastname: Davis
authors.forename: William
authors.initials: W
authors.lastname: McGuire
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002543:Cerebral Hemorrhage / Q000401:mortality / Q000517:prevention & control; D004374:Ductus Arteriosus, Patent / Q000517:prevention & control*; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000401:mortality*; D019102:Infant, Very Low Birth Weight; D007275:Injections, Intravenous; D016032:Randomized Controlled Trials as Topic
chemical_list: D002317:Cardiovascular Agents; D007213:Indomethacin