Newest Results from the Early vs. Late Ventricular Intervention Study (ELVIS) in Preterm Infants with Posthemorrhagic Ventricular Dilation

By: Rebecca A. Dorner, MD MHS
Neonatology Fellow
Johns Hopkins Hospital

The randomized controlled ELVIS trial seeks to answer the question whether earlier or later neurosurgical interventions for preterm infants with posthemorrhagic ventricular dilation are better. In this study, intervention was defined as cerebral spinal fluid tapping by lumbar puncture (maximum of 3), followed by taps from a ventricular reservoir, all before a ventriculoperitoneal (VP) shunt. Early intervention was defined as intervention at a smaller ventricle size cutoff (ventricular index (VI) >97% and anterior horn width (AHW) >6 mm), in comparison to a larger ventricular size (VI>97% + 4 mm and AHW >10 mm).

The first paper¹ from the study group analyzed results from 126 infants <34 weeks with grade III/IV intraventricular hemorrhage who participated in the trial from 2006-2016. Randomization to the study groups was at day 9 of life (median). The first intervention took place on day 10 (median) in the early intervention group versus day 15 in the late intervention group. They found that there was no significant difference in rates of the combined outcome of VP shunt or death in infants treated at a low versus high threshold. Shunt incidence was 19% (median) in the early intervention group versus 23% (median) in the late intervention group. Not surprisingly, infants with intervention in the low threshold group had more interventions as their first procedure was earlier.

The newest paper,² recently published in the Journal of Pediatrics, is an additional analysis of the magnetic resonance imaging (MRI) results from this study. Babies’ MRI results at term age were given a brain injury score (Kidokoro Global Brain Abnormality Score) and ventricle sizes were measured too. This analysis found that infants in the earlier intervention/smaller ventricle size cutoff group had less brain abnormalities overall, and specifically less myelination delay, less thinning of the corpus callosum, less lateral ventricle dilation, and improved white and gray matter subscores. On these term age MRIs ventricle sizes were also lower in the smaller ventricle size cutoff groups.

The authors suggest that although the study failed to demonstrate a further reduction in the need for a VP shunt at the lower threshold, the need for VP shunt placement for both study groups is the lowest reported so far.  Smaller ventricle volumes and lower brain abnormality scores in the MRI studies might indicate the possible beneficial effects of earlier intervention in preterm infants with posthemorrhagic ventricular dilation. However, we still do not know if these improvements in MRI scores will translate to the most important results, lower rates of neurodevelopmental impairments in the future. It is important to wait for these results, as pointed out by Dr. Raye-Ann deRegnier in “The Editors’ Perspectives,” as the interventions (lumbar puncture, reservoir, VP shunt) themselves also have important complications.

 

1. de Vries LS, Groenendaal F, Liem KD,  Heep A, Brouwer AJ,  van ‘t Verlaat E, et al. Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed, 104: F70-F75, 2019.
2. Cizmeci MN, Khalili N, Claessens NHP, Groenendaal F, Liem KD, Heep A, et al. Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial. J Pediatr 208:191-197.e192, 2019