Intraventricular hemorrhage and high-frequency ventilation: a meta-analysis of prospective clinical trials.

ABSTRACT

OBJECTIVE: The association between high-frequency ventilation (HFV) and intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) has been debated. PURPOSE: To determine if premature neonates treated with HFV are at greater risk for developing IVH and/or PVL than neonates treated with conventional ventilation, we completed a meta-analysis of all prospective randomized control trials comparing HFV and conventional ventilation in the management of respiratory distress syndrome. METHODS: The meta-analysis included nine studies comparing HFV and conventional ventilation in the management of preterm neonates. To summarize the data, we calculated the difference in absolute risk for IVH and PVL between neonates treated with HFV and those treated with standard ventilation. These differences were combined to determine an overall difference in the absolute risk and its confidence interval. We examined the effect of estimated gestational age, birth weight, surfactant, and age at study entry on the results. Because one trial (HIFI study) was much larger than the other studies, it dominated the analysis, so we evaluated the data with and without including data from the HIFI trial. RESULTS: The occurrences of IVH and PVL ranged from 14% to 47% and 5% to 16%, respectively. This variation may be explained by the difference in the populations of neonates treated. The meta-analysis showed that use of HFV was associated with an increased risk of PVL (odds ratio = 1.7 with a confidence interval of 1.06 to 2.74), but not IVH or severe (> or = grade 3) IVH. When the results of the HIFI study were excluded, there were no differences between HFV and conventional ventilation in the occurrence of IVH or PVL. CONCLUSIONS: The association between HFV and adverse neurologic outcomes is primarily influenced by the results of the HIFI trial. Meta-analysis of more recent studies does not confirm the findings of the HIFI trial and suggests that HFV is not associated with increased occurrence of IVH or PVL.