461 - Cord Blood Brain Injury Biomarkers are Associated with Intraventricular Hemorrhage Severity in Very Low Birth Weight Infants

Poster Number: 461
Publication Number: 461.342

Julie Nogee, Johns Hopkins University School of Medicine, Lutherville-Timonium, MD, United States; Dhananjay Vaidya, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Aylin Tekes, Johns Hopkins Hospital, Baltimore, MD, United States; Sandra Brooks, Johns Hopkins All Children’s Hospital, St Petersburg, FL, United States; Raul Chavez-Valdez, Johns Hopkins Children's Center, Catosnville, MD, United States; Ernie Graham, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Frances Northington, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Allen Everett, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Background: Intraventricular hemorrhage (IVH) occurs in 25-30% of infants born less than 1500g (VLBW) in the first days of life. While neonatal intensive care unit (NICU) survivorship is increasing, infants with moderate to severe IVH remain at high risk of neurodevelopmental impairment. There are no reliable biomarkers to stratify VLBW infants at high risk for IVH outside of common clinical associations such as gestational age and birth weight. Brain specific proteins and brain injury related proteins have been examined as biomarkers in adult brain injury, but their association with IVH is unknown.

Objective: To determine the association between cord blood brain injury biomarkers and the development of moderate to severe IVH.

Design/Methods: In this prospective observational cohort of VLBW infants in the NICU at Johns Hopkins Children’s Center (2009 - 2019), IVH was identified on standard head ultrasound screening interpreted by pediatric neuroradiologists using the modified Papile classification. Moderate to severe IVH was defined as Grades 2-3 and periventricular hemorrhagic infarction (PVHI). Biomarkers from cord blood remnant serum were measured simultaneously via a custom multiplex ELISA for BDNF, IL-6, IL-8, IL-10, and VEGF, and a separate custom duplex ELISA for GFAP and NRGN. All analyses were performed using Stata 15.1.

Results: We identified 798 VLBW infants in the cohort, of which 29% had IVH (50% Grade 1, 16% Grade 2, 18% Grade 3, 16% PVHI). The median birth weight was 1010g and gestational age 28 weeks. The cohort was 49% male, 54% Black, and 30% White. Cord blood levels of BDNF, IL-6, IL-8, IL-10, and VEGF were obtained for 436 infants, and levels of GFAP and NRGN were obtained for 442 infants. Moderate to severe IVH was associated with higher median levels of IL-6, IL-8, IL-10, and GFAP (Table 1). Additionally, we observed higher median levels of IL-6, IL-8, and IL 10 with greater severity of IVH (Figure 1). Conclusion(s): Biomarkers previously described in adult brain injury show a perinatal association with neonatal brain injury. IL-6, IL-8, IL-10 and GFAP may be useful for predicting moderate to severe IVH and may assist in optimizing patient selection for novel IVH prevention therapeutics.
Table 1. Cord blood biomarkers mild vs moderate to severe IVHCord blood biomarker levels in ng/mL given as median and 25th to 75th percentile range for no/mild IVH (Grade 1) vs. moderate to severe IVH (Grades 2-3 and PVHI). P value by Kruskal-Wallis test is reported. Brain-Derived Neurotrophic Factor (BDNF), Interleukins 6, 8, and 10, Vascular Endothelial Growth Factor (VEGF), Glial Fibrillary Acidic Protein (GFAP), and Neurogranin (NRGN). The lower limit of detection for NRGN was 0.010.
Figure 1. Cord blood biomarkers relative to IVH gradeBox-plot of the biomarkers for increasing severity of IVH. Lower and upper box boundaries 25th and 75th percentiles respectively, line inside box median, lower and upper error lines minimum and maximum values respectively. P value by Kruskal-Wallis test is reported with *=0.049, **=0.001, ***= < 0.001.