New insights and potential biomarkers for intraventricular hemorrhage in extremely premature infant, case-control study

Abstract

Background: Despite advancements in neonatal care, germinal matrix-intraventricular hemorrhage impacts 20% of very preterm infants, exacerbating their neurological prognosis. Understanding its complex, multifactorial pathophysiology and rapid onset remains challenging. This study aims to link specific cord blood biomolecules at birth with post-natal germinal matrix-intraventricular hemorrhage onset.

Methods: A monocentric, prospective case-control study was conducted at Rouen University Hospital from 2015 to 2020. Premature newborns ( < 30 gestational age) were included and cord blood was sampled in the delivery room. A retrospective matching procedure was held in 2021 to select samples for proteomic and metabolomic analysis of 370 biomolecules.

Results: 26 patients with germinal matrix-intraventricular hemorrhage cases and 60 controls were included. Clinical differences were minimal, except for higher invasive ventilation rates in the germinal matrix-intraventricular hemorrhage group. Germinal matrix-intraventricular hemorrhage newborns exhibited lower phosphatidylcholine levels and elevated levels of four proteins: BOC cell adhesion-associated protein, placental growth factor, Leukocyte-associated immunoglobulin-like receptor 2, and tumor necrosis factor-related apoptosis-inducing ligand receptor 2.

Conclusion: This study identifies biomolecules that may be linked to subsequent germinal matrix-intraventricular hemorrhage, suggesting heightened vascular disruption risk as an independent factor. These results need further validation but could serve as early germinal matrix-intraventricular hemorrhage risk biomarkers for future evaluations.

Impact: Decrease in certain phosphatidylcholines and increase in four proteins in cord blood at birth may be linked to subsequent germinal matrix-intraventricular hemorrhage in premature newborns. The four proteins are BOC cell adhesion-associated protein, placental growth factor, leukocyte-associated immunoglobulin-like receptor 2, and TNF-related apoptosis-inducing ligand receptor 2. This biological imprint could point toward higher vascular disruption risk as an independent risk factor for this complication and with further validations, could be used for better stratification of premature newborns at birth.