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

Pediatric Research (2024)Cite this article

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.

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Fig. 1
Fig. 2: Distribution of the biomolecules that are differently expressed between the two groups.
Fig. 3: Biomolecules correlated with the severity of the GM-IVH (Papile classification), R is the Spearman correlation coefficient.

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Data availability

Data is available and can be found in the supplementary tables.

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Acknowledgements

We thank Nathalie Mestre for data capture and monitoring. We thank the medical team and the midwives for their implication to this study. We thank the parents for consenting to have their child participate in this study. The promoter of the study is the Delegation for Clinical Research and Innovation of the Rouen University Hospital. This research received the favorable opinion of the ethical comity “Comité de Protection des Personnes”—CPP and the authorization of the “Agence Nationale de Sécurité du Medicament”—ANSM on 11/07/2014. This research is registered on the clinicaltrials.gov website with the identifier NCT02400853. The collection of biological samples carried out within the framework of this research was declared to the ANSM at the same time as the request for authorization of the research and will be declared at the end of the study to the Minister in charge of research and the Director of the Regional Health Agency.

Funding

This study received intramural financial support from the Rouen University Hospital.

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Authors and Affiliations

  1. Normandie Univ, UNIROUEN, INSERM U1245, CHU Rouen, Department of Neonatal Pediatrics, Intensive Care, and Neuropediatrics, 76000, Rouen, France

    Franklin Ducatez, Lenaig Abily-Donval, Charlotte Le Chatelier & Stéphane Marret

  2. Normandie Univ, UNIROUEN, INSERM U1245, CHU Rouen, Department of Metabolic Biochemistry, 76000, Rouen, France

    Franklin Ducatez, Abdellah Tebani, Sarah Snanoudj & Soumeya Bekri

  3. CHU Rouen, Department of Metabolic Biochemistry, 76000, Rouen, France

    Carine Pilon & Thomas Plichet

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  1. Franklin Ducatez
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Contributions

S.M., S.B., A.T. conceptualized and designed the research, and collected and analyzed data. S.M., A.T., S.B., and F.D. drafted the initial manuscript. F.D., C.P., T.P., S.S., L.A.D., C.L.C. acquired the data. F.D., A.T. performed the statistical analysis. All authors reviewed, revised, and approved the final manuscript.

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Correspondence to Stéphane Marret.

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Written parental consent was needed and obtained as soon as possible after birth following a clear explanation of the study.

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Ducatez, F., Tebani, A., Abily-Donval, L. et al. New insights and potential biomarkers for intraventricular hemorrhage in extremely premature infant, case-control study. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03111-9

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