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Background and PurposeSerum neurofilament light chain (sNfL) has recently emerged as a promising biomarker reflecting structural neuro-axonal damage in different neurological diseases. Our study aimed at assessing whether sNfL can predict the functional outcome in preterm infants who suffered from neonatal haemorrhagic brain injury.MethodsIn this prospective observational study, we used an ultrasensitive single-molecule array assay to measure serum and cerebrospinal fluid (CSF) concentrations of NfL in preterm infants diagnosed with intraventricular haemorrhage (IVH) in the first few days of life. We determined the temporal profile of serum and CSF NfL levels from first diagnosis of IVH until term equivalent age, their association with cerebral imaging markers, and with clinical and functional outcome until 2 years of age assessed by Bayley Scales of Infant Development. We fitted univariable and multivariable logistic regression models to determine risk factors for low motor and cognitive development. Longitudinal mixed effects models modelled NfL levels using cubic spline smoothers to track the trajectory over time.ResultsThe study included 48 infants born with less than 32 weeks of gestation. At the time point of IVH diagnosis, NfL median levels were 271.9 pg/mL (IQR 151.2–389.7), and strongly decreased until term equivalent age to 15.7 pg/mL (IQR 11.1–32.2). CSF values were 113-fold higher (IQR 40–211) than corresponding serum values. Additional cerebral infarction (n=23) but not post-haemorrhagic hydrocephalus with permanent external ventricular drainage (n=29) or other diseases independently determined sNfL levels. In multivariate logistic regression models, the only significant predictor of poor motor outcome at 2 years or death was sNfL level (p=0.02).There was a clear difference between the NfL trajectory for those with poor motor outcome at 1 year.ConclusionsThis study shows that early sNfL is an independent prognostic biomarker for motor functional outcome in preterm infants after IVH.Disclosure(s)Nothing to disclose

Background Endothelin-1 (ET-1) is a potent pulmonary vasoconstrictor, involved in lung injury and remodelling. ET-1 can be estimated by measuring its stable by-product, C-terminal pro-ET-1 (CT-proET-1), in plasma. Aims To investigate CT-proET-1 values in very preterm infants (gestational age Methods Prospective cross-sectional study of 391 CT-proET-1 measurements (fully automated immunoflorescent assay) from 267 very preterm infants. Measurements were performed at birth (n = 72 infants), on day of life (DOL) 2 (n = 89), on DOL 6 (n = 49), on DOL 28 (n = 106), and at PMA 36 (n = 75). Trial registration: ClinicalTrials.gov NCT01644981. Results CT-proET-1 values were (median) 151 pmol/L (IQR 118–186) at birth, peaked on DOL 2 (319 pmol/L (235–382)), and declined thereafter to 214 pmol/L (148–293) on DOL 6, 184 pmol/L (149–233) on DOL 28, and 150 pmol/L (118–188) at PMA 36. Infants with BPD had higher CT-proET-1 values on DOL 2 (p = 0.001), DOL 6 (p Conclusions The levels and the pattern of CT-proET-1 increase during the first week of life might serve as an early marker of BPD.

Background Preterm infants suffering from intraventricular haemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (EPO) aimed at preventing anaemia also improves long-term cognitive outcome in infants with IVH (Neubauer AP et al ., Annals Neurology, 2010). The recently completed first early high-dose EPO trial in very preterm infants did not raise any significant safety concerns (Fauchere J-C. et al ., ESPR Annual Meeting, 2012). Hypothesis : High-dose EPO improves long-term neurodevelopmental outcome in preterm infants with IVH. Methods Design: Double blind, 1:1 randomised clinical study in 11 perinatal centres (Germany and Switzerland). Patients : 120 very preterm (gestational age I°) diagnosed by cranial ultrasound during the first 4 days of life. Intervention : 5 intravenous applications of EPO (2000 U/kg) or placebo spread over 3 weeks. Primary objective : Neurodevelopmental outcome at 5 years of age (Kaufmann-ABC or Son-R). Secondary objectives : (1) safety; (2) MRI at term equivalent age to quantitatively analyse brain injury and growth; (3) psychomotor development at 2 years of age (BSID-III). Recruitment : March 2014 to February 2016. Results and conclusions Given the fact that long-term neurodevelopmental outcome cannot be reliably assessed until preschool age, the primary outcome of this study providing evidence as to whether high-dose EPO improves restitution of brain damage in preterm infants will not be reported before 2021. However, MRI data can be reported much earlier. (Funded by the Swiss National Science Foundation; Clinical Trials Registry: NCT02076373).

Background and aims Plasma concentrations of endothelin-1 (ET-1), a potent pulmonary vasoconstrictor with a short serum half-life, can be estimated by measuring its stable by-product, C-terminal pro-Endothelin-1 (CT-proET-1). To investigate the association between CT-proET-1, gestational age, and pulmonary morbidity in newborn infants. Methods A prospective cross-sectional study at two tertiary university hospitals was conducted. CT-proET-1 concentrations (pmol/L) were determined in plasma samples of 293 newborn infants (gestational age 24–41 weeks) at birth and on day 3 of life with BRAHMS KRYPTOR automated immunoflorescent assay. Results At birth, CT-proET-1 concentrations were unrelated to birth weight and gestational age. Venous umbilical cord CT-proET-1 concentrations were consistently higher than matched arterial ones (M 148 vs. 134 pmol/L, p S =0.745, p S 0.566, 0.658, and 0.819, respectively, for all p Conclusions In term and preterm newborn infants, pulmonary compromise is associated with increased concentrations of circulating CT-proET-1.