The Effectiveness of interventions to prevent intraventricular haemorrhage in premature infants: A systematic review and network meta-analysis

BACKGROUND: Intraventricular haemorrhage (IVH) is a common problem in preterm infants, being a major cause of morbidity and mortality. Despite many randomised controlled trials comparing interventions to prevent IVH, the best prevention remains unclear. This study aims to review all the interventions which intended to reduce the incidence of IVH and compare them in a network meta-analysis. METHODS: A search on MEDLINE, EMBASE, Emcare, and CENTRAL was performed. Randomised controlled trials which evaluated neonatal interventions with a primary aim to reduce incidence of IVH in preterm infants were eligible. A surface under a cumulative ranking curve (SUCRA) was produced to indicate the intervention’s likelihood of being the most effective for preventing IVH. RESULTS: 40 studies were eligible, enrolling over 6760 infants. Twelve intervention groups were found, including delayed cord clamping, erythropoietin, ethamsylate, fresh frozen plasma, heparin, ibuprofen, indomethacin, magnesium, nursing interventions, sedation, tranexamic acid, and vitamin E. Vitamin E and indomethacin had the highest probability of being the best interventions to prevent IVH in premature infants, but interpretation of these results is difficult due to study limitations. CONCLUSION: Despite the impact of IVH, we were unable to identify a clearly beneficial treatment to reduce its incidence. Interpretation of the network meta-analysis was limited due to differences within studied populations, wide range of therapies trialled, and underlying advances in neonatal care between units, and over time. Although vitamin E and indomethacin appear to be promising candidates, contemporaneous trials of these, or novel agents, enrolling the most at-risk infants is needed urgently.