Surfactant for pulmonary hemorrhage in neonates

In the late 1960's and 1970's, pulmonary hemorrhage (PH) occurred mainly in full term infants with severe pre-existing illness. The incidence of PH was quoted as 1.3 per 1,000 live births. In the older medical literature, the risk factors associated with PH included the severity of the associated illness, intrauterine growth restriction, patent ductus arteriosus (PDA), coagulopathy, and the need for assisted ventilation. Presently, PH occurs mainly in preterm ventilated infants with severe respiratory distress syndrome (RDS) who often have a PDA and have received surfactant. Currently, PH complicates the hospital course of 3-5% of preterm infants with RDS. Although not clear, the cause of PH is thought to be due to a rapid lowering of intrapulmonary pressure, which facilitates left to right shunting across a patent ductus arteriosus and an increase in pulmonary blood flow. Retrospective case reports and one prospective uncontrolled study that used surfactant for PH in neonates have shown promising results in treating PH.

To evaluate the effect of surfactant treatment compared to placebo or no intervention on mortality in neonates with pulmonary hemorrhage. In addition, the review will evaluate the effect of surfactant treatment on neonatal morbidities associated with PH compared to placebo or no intervention.

The following databases were searched in January 2008: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2007) and MEDLINE from 1966 and EMBASE from 1980 to the time of the full review using the OVID interface. The proceedings of the Annual Meetings of the Pediatric Academic Societies and the European Society of Pediatric Research published in Pediatric Research or electronically on their web sites were searched from 1994 to the time of the full review. Science citation index (Web of Science) was searched for authors quoting key references of observational studies.

Randomised or quasi-randomised controlled trials that evaluated the effect of surfactant in the treatment of PH in intubated term or preterm (< 37 weeks) neonates with PH. Infants were included up to 44 weeks postmenstrual age. Infants were included regardless of prior treatment with surfactant. The interventions studied were intratracheal instillation of surfactant (natural or synthetic, regardless of dose) vs. placebo or no intervention.

If studies were identified by the literature search, the planned analyses included calculation of the relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH) for dichotomous outcomes, and weighed mean difference (WMD) for continuous outcomes, with their 95% confidence intervals (CI). A fixed effects model would be used for meta-analyses. Heterogeneity tests, including the I- squared (I(2)) statistic, would be performed to assess the appropriateness of pooling the data and the results would be reported.

No trials were identified.

No randomized or quasi-randomized trials that evaluated the effect of surfactant in PH were identified. Therefore, no conclusions from such trials can be drawn. In view of the promising results from studies with less strict study designs than a randomized controlled trial, there is reason to conduct further trials of surfactant for the treatment of PH in neonates.