Serum brain injury biomarkers are gestationally and post-natally regulated in non-brain injured neonates

Abstract

Objective: To determine the association of gestational age (GA) and day of life (DOL) with the circulating serum concentration of six brain injury-associated biomarkers in non-brain injured neonates born between 23–41 weeks’ GA. Methods: In a multicenter prospective observational cohort study, serum CNS-insult, inflammatory and trophic proteins concentrations were measured daily in the first 7 DOL. Results: 3232 serum samples were analyzed from 745 enrollees, median GA 32.3 weeks. BDNF increased 3.7% and IL-8 increased 8.9% each week of gestation. VEGF, IL-6, and IL-10 showed no relationship with GA. VEGF increased 10.8% and IL-8 18.9%, each DOL. IL-6 decreased by 15.8% each DOL. IL-10 decreased by 81.4% each DOL for DOL 0–3. BDNF did not change with DOL. Only 49.67% of samples had detectable GFAP and 33.15% had detectable NRGN. The odds of having detectable GFAP and NRGN increased by 53% and 11%, respectively, each week after 36 weeks’ GA. The odds of having detectable GFAP and NRGN decreased by 15% and 8%, respectively, each DOL. Conclusion: BDNF and IL-8 serum concentrations vary with GA. VEGF and interleukin concentrations are dynamic in the first week of life, suggesting circulating levels should be adjusted for GA and DOL for clinically relevant assessment of brain injury.

The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

“…It has also been shown to have trophical effects on neural progenitor cells ( 53 ). Serum VEGF concentrations of preterm infants are dynamic the first week of life ( 54 ). Recently the administration of VEGFC was shown to improve neurological repair following traumatic brain injury in a rat model through modulating microglial activation ( 52 ).…”

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions

“…In neonates without brain injury born between 23-and 41-weeks of gestation, there is a significant gestation-dependent increase in serum BDNF levels (3.7%) and IL-8 levels (8.9%) for every week of gestation [261]. However, BDNF concentrations do not show any association with the first 7 days of life (DOL), while IL-8 levels increase with each DOL by 18.9% [261].…”

“…In neonates without brain injury born between 23-and 41-weeks of gestation, there is a significant gestation-dependent increase in serum BDNF levels (3.7%) and IL-8 levels (8.9%) for every week of gestation [261]. However, BDNF concentrations do not show any association with the first 7 days of life (DOL), while IL-8 levels increase with each DOL by 18.9% [261]. Additionally, BDNF concentrations exhibit a remarkable increase with age, with a progressive and significant ascent from an average of 740 pg/mL in very preterm control infants to nearly 5500 pg/mL in adults [211].…”