PMID- 33566157 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20220531 IS - 1432-1459 (Electronic) IS - 0340-5354 (Print) IS - 0340-5354 (Linking) VI - 268 IP - 7 DP - 2021 Jul TI - Early life serum neurofilament dynamics predict neurodevelopmental outcome of preterm infants. PG - 2570-2577 LID - 10.1007/s00415-021-10429-5 [doi] AB - 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. FAU - Goeral, Katharina AU - Goeral K AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Hauck, Annalisa AU - Hauck A AD - Division of Neonatology, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland. FAU - Atkinson, Andrew AU - Atkinson A AD - Division of Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), Basel, Switzerland. FAU - Wagner, Michael B AU - Wagner MB AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Pimpel, Birgit AU - Pimpel B AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Fuiko, Renate AU - Fuiko R AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Klebermass-Schrehof, Katrin AU - Klebermass-Schrehof K AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Leppert, David AU - Leppert D AD - Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Kuhle, Jens AU - Kuhle J AD - Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Berger, Angelika AU - Berger A AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Olischar, Monika AU - Olischar M AD - Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University Vienna, Vienna, Austria. FAU - Wellmann, Sven AU - Wellmann S AUID- ORCID: 0000-0001-9230-6266 AD - Division of Neonatology, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland. sven.wellmann@ukr.de. AD - Division of Neonatology, Campus Hospital St. Hedwig, University Children's Hospital Regensburg (KUNO), University of Regensburg, Steinmetzstr 1-3, 93049, Regensburg, Germany. sven.wellmann@ukr.de. LA - eng GR - 320030_160221/Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung/ GR - 320030 not_169848/Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung/ PT - Journal Article PT - Observational Study DEP - 20210210 PL - Germany TA - J Neurol JT - Journal of neurology JID - 0423161 RN - 0 (Biomarkers) RN - 0 (Neurofilament Proteins) SB - IM MH - Adolescent MH - Biomarkers MH - Humans MH - *Hydrocephalus MH - Infant, Newborn MH - Infant, Premature MH - *Intermediate Filaments MH - Neurofilament Proteins MH - Prospective Studies PMC - PMC8217001 OTO - NOTNLM OT - Biomarker OT - Brain damage OT - Children OT - Neurodevelopment OT - Neurofilament COIS- JK has advised and/or received speaker fees, research & travel support from ECTRIMS, Swiss MS Society, University of Basel, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Roche & Teva. AB received speaker fees, research support, travel support and/or served on advisory boards by Abbvie, Chiesi, Pfizer, Schulke, Milupa, Nestle, MCA Scientific Events, and the Anniversary Fund of the Osterreichische Nationalbank. All other authors listed report no disclosures. EDAT- 2021/02/11 06:00 MHDA- 2021/06/24 06:00 PMCR- 2021/02/10 CRDT- 2021/02/10 12:11 PHST- 2020/10/31 00:00 [received] PHST- 2021/01/27 00:00 [accepted] PHST- 2021/01/23 00:00 [revised] PHST- 2021/02/11 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2021/02/10 12:11 [entrez] PHST- 2021/02/10 00:00 [pmc-release] AID - 10.1007/s00415-021-10429-5 [pii] AID - 10429 [pii] AID - 10.1007/s00415-021-10429-5 [doi] PST - ppublish SO - J Neurol. 2021 Jul;268(7):2570-2577. doi: 10.1007/s00415-021-10429-5. Epub 2021 Feb 10.