Treatment for Post-hemorrhagic Ventricular Dilatation: A Multiple-Treatment Meta-Analysis

Abstract

Objective: To perform a systematic review and multiple-treatment meta-analysis for the treatment of premature infants with post-hemorrhagic ventricular dilatation (PHVD), to prevent death or long-term neuro-disability. Design/Method: A systematic review was performed using PubMed, EMBASE, and the Cochrane Library. A free-word search was performed to identify likely relevant literature intervention trials of PHVD in preterm infants. Initially, network mapping was performed followed by performing a Bayesian random-effects model using the Markov chain Monte Carlo method. Areas under the cumulative ranking curve (SUCRA) were calculated as a measure of the probability that each intervention was likely to be the 1st, 2nd, 3rd, etc. best therapy. Primary outcome measure was death or moderate or severe neurodevelopmental outcome at or beyond 12 months of corrected age. Results: Ten different trials were identified, enrolling 700 individuals (449 for the primary outcome). Seven intervention categories were identified, and of the 15 possible pair comparisons, 6 have been studied directly. In the multiple-treatment meta-analysis, no comparison reached conventional levels of statistical significance. Drainage Irrigation and Fibrinolytic Therapy (DRIFT) had the highest probability of being the best treatment for the primary outcome (82.1%), followed by CSF removal (10.8%), conservative management (6.7%), and then diuretic therapy (0.4%). Conclusions: PHVD is a significant cause of death and disability in developed countries, yet few therapeutic options have so far been trialed. While new therapies are urgently needed for these infants, at present, NMA shows that DRIFT appears to be the most likely candidate to improve outcomes after sIVH.

Global incidence proportion of intraventricular haemorrhage of prematurity: a meta-analysis of studies published 2010–2020

“…Most studies reporting VPS rates only evaluated patients who received neurosurgical consultation or intervention, which limits comparison across studies because treatment thresholds vary 38. Previous meta-analyses have compared outcomes by surgical treatment modality,39–41 but the current study is the first to report pooled estimates of shunting of all infants diagnosed with IVH regardless of need for treatment.…”

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

“…The quality of every included study was assessed by SLY with respect to selection (randomisation and concealment bias), measurement (performance bias, blinding of radiologist), attrition (loss to follow-up) and reporting bias, based on the Cochrane Handbook for Systematic Reviews (31) and previous studies (11). A study's risk of bias was assessed as low, high, or unclear.…”

“…(5,6) These can lead to long-term adverse outcomes such as cerebral palsy, developmental delay, visual, hearing impairment, (7)(8)(9), and death, (10) meaning that IVH and its complications are one of the leading causes of neurological disability and mortality for premature infants. (2,8,11) Preventative strategies have been based on the pathogenesis of IVH, which is predominantly due to the immaturity and fragility of the germinal matrix vasculature. (3,12) Disturbances of cerebral blood flow and impaired cerebral autoregulation can damage fragile blood vessels in the germinal matrix, causing them to bleed.…”

Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion

“…These results represented the most marked improvement in cognition and survival with any intervention after IVH and PHVD. A study that used network meta-analysis methodology to evaluate the outcome of ten different trials for PHVD also demonstrated that DRIFT is the most efficacious and the most likely treatment to improve outcomes [44]. Despite this, however, the DRIFT technique has not been widely adopted and has not changed standard practice due to the resource-intensive nature of the treatment and the potential risks of secondary haemorrhage.…”

“…Further research into the direct management of intraventricular blood and its breakdown products is required. Despite the incidence and developmental impact of IVH and PHVD, only about 700 infants have been enrolled into intervention trials, and fewer than 500 have had long-term developmental measures reported [44]. The role of surgical and medical therapies in removing the blood and reducing its toxicity on the developing brain requires robust evaluation and may hold the potential to further improve developmental outcomes in premature neonates with IVH.…”