Abstract
Background: Neurofilament light chain (NfL) is a highly promising biomarker of neuroaxonal injury that has mainly been studied in adult neurodegenerative disease. Its involvement in neonatal disease remains largely unknown. Our aim was to establish NfL plasma concentrations in preterm and term infants in the first week of life.Methods: Plasma NfL was measured by single molecule array immunoassay in two neonatal cohorts: cohort 1 contained 203 term and preterm infants, median gestational age (GA) 37.9 weeks (interquartile range [IQR] 31.9–39.4), in whom venous and arterial umbilical cord blood was sampled at birth and venous blood at day of life (DOL) 3; cohort 2 contained 98 preterm infants, median GA 29.3 weeks (IQR 26.9–30.6), in whom venous blood was sampled at DOL 7.Results: Median NfL concentrations in venous blood increased significantly from birth (18.2 pg/mL [IQR 12.8–30.8, cohort 1]) to DOL 3 (50.9 pg/mL [41.3–100, cohort 1]) and DOL 7 (126 pg/mL [78.8–225, cohort 2]) (p < 0.001). In both cohorts NfL correlated inversely with birth weight (BW, Spearman's rho −0.403, p < 0.001, cohort 1; R −0.525, p < 0.001, cohort 2) and GA (R −0.271, p < 0.001, cohort 1; R −0.487, p < 0.001, cohort 2). Additional significant correlations were found for maternal age at delivery, preeclampsia, delivery mode, 5-min Apgar, duration of oxygen supplementation, sepsis, and brain damage (intraventricular hemorrhage or periventricular leukomalacia). Multivariable logistic regression analysis identified the independent predictors of NfL in cohort 1 as BW (beta = −0.297, p = 0.003), delivery mode (beta = 0.237, p = 0.001) and preeclampsia (beta = 0.183, p = 0.022) and in cohort 2 as BW (beta = −0.385, p = 0.001) and brain damage (beta = 0.222, p = 0.015).Conclusion: Neonatal NfL levels correlate inversely with maturity and BW, increase during the first days of life, and relate to brain injury factors such as intraventricular hemorrhage and periventricular leukomalacia, and also to vaginal delivery.
Highlights
As direct access to the central nervous system (CNS) is almost impossible, neuronal biomarkers have been investigated for decades in order to improve early diagnostics, monitor disease progression and optimize care
Nf light chain (NfL) levels were significantly higher in very preterm infants than in the moderate preterm and term (MPT) group at birth, but not at day of life (DOL) 3
Levels increased significantly from birth to DOL 3 in both the very preterm and MPT groups, and from DOL 3 to DOL 7 in the very preterm group (Table 2). This increase was confirmed in cohort 1 when comparing paired samples from same infants (MPT group n = 16, very preterm group n = 11) at birth and DOL 3
Summary
As direct access to the central nervous system (CNS) is almost impossible, neuronal biomarkers have been investigated for decades in order to improve early diagnostics, monitor disease progression and optimize care. Neurofilaments (Nf) are highly specific major neuronal scaffolding proteins comprising 4 subunits: the triplet of Nf light chain (NfL), Nf medium chain, and Nf heavy chain (NfH), and α-internexin in the CNS, or peripherin in the peripheral nervous system [1]. Recent advances using highly sensitive single molecule array (Simoa) immunoassay have improved NfL detection, in peripheral blood, making it a promising and readily accessible biomarker for neuroaxonal injury [7]. Whereas, circulating Nf has been extensively characterized in adults and older children with neurologic disease, data in infants and newborns are sparse. Plasma NfH in newborns with hypoxic-ischemic encephalopathy (HIE) was higher than in healthy neonates [9, 10]. Neurofilament light chain (NfL) is a highly promising biomarker of neuroaxonal injury that has mainly been studied in adult neurodegenerative disease. Our aim was to establish NfL plasma concentrations in preterm and term infants in the first week of life
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