ABSTRACT
BACKGROUND: A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. OBJECTIVE: To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. METHODS: From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. RESULTS: Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). CONCLUSIONS: The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.
Subject(s)
Asphyxia Neonatorum/metabolism , Asphyxia Neonatorum/physiopathology , Fetal Blood/metabolism , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/physiopathology , Australia , Biomarkers/metabolism , Cerebral Palsy/diagnosis , Child, Preschool , Electroencephalography , Female , Humans , Infant , Infant, Newborn , Language Development , Linear Models , Male , Metabolomics , ROC Curve , Severity of Illness IndexABSTRACT
OBJECTIVES: Metabolomics is defined as the comprehensive study of all low molecular weight biochemicals, (metabolites) present in an organism. Using a systems biology approach, metabolomics in umbilical cord blood (UCB) may offer insight into many perinatal disease processes by uniquely detecting rapid biochemical pathway alterations. In vitro haemolysis is a common technical problem affecting UCB sampling in the delivery room, and can hamper metabolomic analysis. The extent of metabolomic alteration which occurs in haemolysed samples is unknown. DESIGN AND METHODS: Visual haemolysis was designated by the laboratory technician using a standardised haemolysis index colour chart. The metabolomic profile of haemolysed and non-haemolysed UCB serum samples from 69 healthy term infants was compared using both (1)H-NMR and targeted DI and LC-MS/MS approach. RESULTS: We identified 43 metabolites that are significantly altered in visually haemolysed UCB samples, acylcarnitines (n=2), glycerophospholipids (n=23), sphingolipids (n=7), sugars (n=3), amino acids (n=4) and Krebs cycle intermediates (n=4). CONCLUSION: This information will be useful for researchers in the field of neonatal metabolomics to avoid false findings in the presence of haemolysis, to ensure reproducible and credible results.
Subject(s)
Fetal Blood/chemistry , Fetal Blood/metabolism , Hemolysis , Female , Humans , Infant, Newborn , Magnetic Resonance Spectroscopy , Male , Metabolomics , Pregnancy , Tandem Mass SpectrometryABSTRACT
OBJECTIVES: The need for early and accurate prediction of outcome in hypoxic-ischaemic encephalopathy (HIE) remains critical. We have previously demonstrated that Interleukin 16 (IL-16) is raised in the umbilical cord blood (UCB) of infants with moderate and severe HIE and has the potential to be developed as a predictive biomarker. Normal reference ranges for IL-16 in UCB have not been previously described. The aim of this study was to determine normative levels of IL-16 in full term neonates using UCB following uncomplicated deliveries and to examine the effect of labour on cord IL-16 values. DESIGN AND METHODS: Full term infants were recruited as part of an ongoing birth cohort study, the Cork BASELINE Birth Cohort Study. All had UCB drawn and bio-banked at -80°C, within 3hours of birth. Samples for this experiment were chosen from this population based cohort study to represent uncomplicated pre-labour caesarean sections and spontaneous vaginal deliveries. Analysis was performed on plasma EDTA, using ELISA Quantikine® (R&D Systems, Europe). RESULTS: Samples were analysed from 48 infants with two modes of delivery; spontaneous vaginal delivery (n=12 male, n=12 female) and elective caesarean section (n=12 male, n=12 female). The range of all samples was normally distributed between 87.0 and 114.6pg/ml. Overall mean (SD) for IL-16 was 102.9 (21.5) pg/ml. Levels were not affected by spontaneous vaginal delivery or gender. CONCLUSION: For the first time we have described the expected range of cord plasma IL-16 levels in healthy term infants following pre-labour and post-labour delivery.
