Abstract
Background and purposeTo determine whether neurofilament light chain (NfL), a promising serum and cerebrospinal fluid (CSF) biomarker of neuroaxonal damage, predicts functional outcome in preterm infants with neonatal brain injury.MethodsOur prospective observational study used a sensitive single-molecule array assay to measure serum and CSF NfL concentrations in preterm infants with moderate to severe peri/intraventricular hemorrhage (PIVH). We determined temporal serum and CSF NfL profiles from the initial diagnosis of PIVH until term-equivalent age and their association with clinical and neurodevelopmental outcome until 2 years of age assessed by Bayley Scales of Infant Development (3rd edition). We fitted univariate and multivariate logistic regression models to determine risk factors for poor motor and cognitive development.ResultsThe study included 48 infants born at < 32 weeks of gestation. Median serum NfL (sNfL) at PIVH diagnosis was 251 pg/mL [interquartile range (IQR) 139–379], decreasing markedly until term-equivalent age to 15.7 pg/mL (IQR 11.1–33.5). CSF NfL was on average 113-fold higher (IQR 40–211) than corresponding sNfL values. Additional cerebral infarction (n = 25)-but not post-hemorrhagic hydrocephalus requiring external ventricular drainage (n = 29) nor any other impairment-was independently associated with sNfL. Multivariate logistic regression models identified sNfL as an independent predictor of poor motor outcome or death at 1 and 2 years.ConclusionsSerum neurofilament light chain dynamics in the first weeks of life predict motor outcome in preterm infants with PIVH.
Highlights
One in ten infants are born preterm worldwide [1]
Our study investigated the role of neuroaxonal damage protein neurofilament light chain (NfL) in serum and cerebrospinal fluid (CSF) in predicting neurodevelopmental outcome in preterm infants with severe brain damage, namely intraventricular hemorrhage or periventricular infarction, in the first days of life
Our main findings were that (1) serum NfL (sNfL) levels depend on maturity, birth weight, postnatal age at measurement and brain damage severity, (2) sNfL levels are higher in infants with the composite outcome of poor motor skills or death at 1 and 2 years of age, and (3) sNfL is an independent predictor of motor but not cognitive outcome
Summary
One in ten infants are born preterm worldwide [1]. Despite steadily increasing survival rates, long-term neurodevelopmental outcome remains worrying, due mainly to brainJournal of Neurology (2021) 268:2570–2577 damage, peri/intraventricular hemorrhage (PIVH) [2,3], diagnosed in the first few days of life by cerebral ultrasound (cUS) and graded using the classification by Papile et al [4] revisited by Volpe [5]. To determine whether neurofilament light chain (NfL), a promising serum and cerebrospinal fluid (CSF) biomarker of neuroaxonal damage, predicts functional outcome in preterm infants with neonatal brain injury. Methods Our prospective observational study used a sensitive single-molecule array assay to measure serum and CSF NfL concentrations in preterm infants with moderate to severe peri/intraventricular hemorrhage (PIVH). We determined temporal serum and CSF NfL profiles from the initial diagnosis of PIVH until term-equivalent age and their association with clinical and neurodevelopmental outcome until 2 years of age assessed by Bayley Scales of Infant Development (3rd edition). Multivariate logistic regression models identified sNfL as an independent predictor of poor motor outcome or death at 1 and 2 years.
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