Search

Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants.Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured.The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development.Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.

Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes.We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF.Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE.Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.

INTRODUCTION Extremely low birth weight (ELBW) children (birth weight ≤1000 g) are at risk of adverse neurodevelopmental outcome. The objectives of this study were to determine the prevalence of developmental disorders and disabilities among ELBW children born in Iceland during a 25 year period and to assess which clinical factors predict disability among these children. MATERIAL AND METHODS A retrospective study of all ELBW children born in Iceland 1988-2012 and discharged alive. The study group was found in the Children´s Hospital of Iceland NICU registry. Information was gathered from the NICU registry, the children´s and their mothers´ medical records and the State Diagnostic and Counselling Centre database. RESULTS Of 189 children 45 (24%) had developmental disorders, 13 (7%) had mild disorders and 32 (17%) had major disorders (disability) at 3-6 years. Risk factors for disability were multiple birth (RR 2.21; 95% CI: 1.19-4.09), Apgar < 5 after one minute (RR 2.40; 95% CI: 1.14-5.07), the initiation of enteral feeding more than four days after birth (RR 2.14; 95% CI: 1.11-4.11), full enteral feeding achieved after more then 21 days (RR 2.15; 95% CI: 1.11-4.15), neonatal pneumonia (RR 3.61; 95% CI: 1.98-6.57) and PVL (RR 4.84; 95% CI: 2.81-8.34). CONCLUSION The majority of ELBW children do not have major developmental disorders. The rate of disability in this study is similar to other studies. The study probably underestimates the rate of mild developmental disorders in the Icelandic population. Risk factors for disability in this study are comparable to previous studies.

Aims: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors.Methods: All infants with gestational age < 27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age, Images were analysed using a previously established scoring system for grey and white matter abnormalities.Results: No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk index for Babies (CRIB 11) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities.Conclusion: The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing.

Aim Acute anoxic exposure rapidly increases prostaglandin E2 (PGE2) production and release in neonatal mice brains. We hypothesize that PGE2 is released in human cerebrospinal fluid (CSF) during perinatal asphyxia and that it might be used as a biomarker for perinatal asphyxia. Methods In full-term infants with lumbar puncture performed within 72 h of birth (n = 35), CSF was analysed for prostaglandin E2 metabolite (PGEM) using an enzyme immunoassay. Term infants with suspected but unverified infections were used as controls (n = 11). Hypoxic–ischaemic encephalopathy (HIE) was classified as mild, moderate or severe (HIE I-III). Neurological assessment of surviving patients was performed at 18 months of age. Results Prostaglandin E2 metabolite levels correlated to a low Apgar score at 5 min (p

Acute anoxic exposure rapidly increases prostaglandin E2 (PGE2 ) production and release in neonatal mice brains. We hypothesize that PGE2 is released in human cerebrospinal fluid (CSF) during perinatal asphyxia and that it might be used as a biomarker for perinatal asphyxia.In full-term infants with lumbar puncture performed within 72 h of birth (n = 35), CSF was analysed for prostaglandin E2 metabolite (PGEM) using an enzyme immunoassay. Term infants with suspected but unverified infections were used as controls (n = 11). Hypoxic-ischaemic encephalopathy (HIE) was classified as mild, moderate or severe (HIE I-III). Neurological assessment of surviving patients was performed at 18 months of age.Prostaglandin E2 metabolite levels correlated to a low Apgar score at 5 min (p 0.01) and 10 min (p 0.01), a low pH (p 0.001) and HIE score (p 0.05). The HIE-III cases (n = 7) had significantly higher PGEM levels compared with both controls and the HIE-I group (n = 8). Irrespective of HIE grade, patients with adverse or fatal outcome had higher PGEM values compared with controls and asphyxiated infants with normal outcome (p 0.05).PGE2 is released during anoxic events in newborn infants, and PGEM may be useful as a biomarker for estimating degree of insult and predicting long-term outcome after perinatal asphyxia.

Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors.All infants with gestational age27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age. Images were analysed using a previously established scoring system for grey and white matter abnormalities.No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities.The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing.

ObjectiveTo determine whether infection, with associated eicosanoid release, is a main cause of respiratory disruption in neonates, by measuring levels of prostaglandin E2 (PGE2) and its metabolite (PGEM) in cerebrospinal fluid (CSF).Study designOf 59 eligible infants, 25 preterm infants (mean gestational age, 28 ± 0.5 weeks) and 22 full-term infants (mean gestational age, 40 ± 0.5 weeks) from a level 3 neonatal intensive care unit and the general maternity neonatal ward were enrolled prospectively. Infants with a condition that can cause secondary apnea were excluded. Cardiorespiratory disturbances, such as apnea, bradycardia, and desaturation (ABD) events, were quantified. All infants were subjected to standard laboratory analysis of blood and CSF concentrations of biomarkers, including PGE2 and PGEM, within 24 hours of lumbar puncture, which were correlated with ABD events and culture-verified infections.ResultsPGEM levels were highest in infants with culture-verified sepsis and meningitis (P

Top of pageAbstract Aim/ subject: Magnetic resonance imaging (MRI) has contributed to the understanding of brain damage in infants with extremely low gestational age (ELGA

149 Increased Concentrations of IL-6 and Fas-Ligand in Cerebrospinal Fluid Obtained from Newborn Infants Following Cerebral Hypoxic-Ischaemic Injury

Activation of the cerebral cortex after administration or unpleasant smells in newborn infants in intensive care unit: A functional Near Infrared Spectroscopy preliminary study