Could we detect intraventricular hemorrhage before it happens?

Germinal matrix intraventricular hemorrhage (IVH) is a serious complication of extremely preterm birth. 1 Its effects can be devastating, with high risks of death and severe neurodevelopmental disability, mainly after higher grade of hemorrhage. 2,3IVH most often occurs in the early hours or days after birth. 2,4Infants with IVH can be detected non-invasively on serial cranial ultrasounds, but by definition after it is present. 5A predictive biomarker is vital to help develop preventative strategies for IVH.There is growing evidence that useful biological signals can be detected.For example, a small single-center prospective study of urine samples collected from preterm infants with IVH (n = 7) and without IVH (n = 11), analyzed with targeted liquid chromatographytandem mass spectrometry, 6 showed that 20 of the 40 metabolites assessed were significantly different between the groups.The altered profile suggested a shift toward anaerobic metabolism and mitochondrial dysfunction, likely associated with hypoxia-ischemia and hypoperfusion.However, infants in the IVH group had lower gestational age that the controls, leaving the possibility that some of the changes may have been due to immaturity.In this issue, Ducatez et al. conducted a study of highthroughput assessment of cord blood in a prospective casecontrol study of 26 patients with germinal matrix-IVH and 60 control premature newborns at Rouen University Hospital from 2015 to 2020.This study reported that IVH was associated with upregulation of leukocyte-associated immunoglobulin-like receptor 2 (LAIR-2), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), placental growth factor (PGF), and Brother of CDO (BOC) cell adhesion associated protein. 7There was also a decrease of medium-chain long acylcarnitine C10:1 and 21 different phosphatidylcholines in infants with IVH.The reader should consider some limitations of these findings, particularly that it is vital to replicate the underlying observation.The study had a small sample size, including only 26 infants with variable IVH severities.Further, there was potential confounding, in that a higher proportion of babies with IVH required invasive positive pressure ventilation compared with controls (48% vs. 5.3%), and after adjusting for this, there was no significant association.This study excluded infants with IVH on early cranial ultrasound, supporting that these biomolecular changes might be useful prognostic markers for the risk of a particular infant to develop IVH.Further analysis of early and late onset IVH and sampling at different times is now needed to provide insight into how these proteins and metabolites change over time with IVH.