Early life serum neurofilament dynamics predict neurodevelopmental outcome of preterm infants

J Neurol. 2021 Jul;268(7):2570-2577. doi: 10.1007/s00415-021-10429-5. Epub 2021 Feb 10.

Abstract

Background and purpose: 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). We fitted univariate and multivariate logistic regression models to determine risk factors for poor motor and cognitive development.

Results: The 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.

Conclusions: Serum neurofilament light chain dynamics in the first weeks of life predict motor outcome in preterm infants with PIVH.

Keywords: Biomarker; Brain damage; Children; Neurodevelopment; Neurofilament.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Biomarkers
  • Humans
  • Hydrocephalus*
  • Infant, Newborn
  • Infant, Premature
  • Intermediate Filaments*
  • Neurofilament Proteins
  • Prospective Studies

Substances

  • Biomarkers
  • Neurofilament Proteins