The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

BackgroundSurvival 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.MethodsTwenty-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.ResultsThe 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.ConclusionOur data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome

The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

Funding Information: This study was funded by the Karolinska Institutet, the University Hospital of Iceland and the Swedish Society for Medical Research, the Swedish Brain Foundation (FO2019-0087 and FO2019-0006), Strategic Research Area Neuroscience (StratNeuro), Ehrling-Person Family Foundation, Axel Tielmans, Freemasons Children’s House, the Swedish National Heart and Lung (20180505) Foundations, the Swedish Research Council (2019-01157), and the Stockholm County Council (20190400). KJ received funding from the Swiss National Science Foundation (Postdoc Mobility Fellowship, P400PM_194474. The funders did not participate in the design or conduct of the study. Publisher Copyright: Copyright © 2022 Leifsdottir, Jost, Siljehav, Thelin, Lassarén, Nilsson, Haraldsson, Eksborg and Herlenius.Background: 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. Methods: 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. Results: 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. Conclusion: Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.Peer reviewe

Treating very preterm European infants with inhaled nitric oxide increased in-hospital mortality but did not affect neurodevelopment at 5 years of age

Aim: We examined the outcomes of using inhaled nitric oxide (iNO) to treat very preterm born (VPT) infants across Europe. Methods: This was a sub-study of the Screening to Improve Health in Very Preterm Infants in Europe research. It focused on all infants born between 22 + 0 and 31 + 6 weeks/days of gestation from 2011 to 2012, in 19 regions in 11 European countries. We studied 7268 infants admitted to neonatal care and 5 years later, we followed up the outcomes of 103 who had received iNO treatment. They were compared with 3502 propensity score-matched controls of the same age who did not receive treatment. Results: All countries used iNO and 292/7268 (4.0%) infants received this treatment, ranging from 1.2% in the UK to 10.5% in France. There were also large regional variations within some countries. Infants treated with iNO faced higher in-hospital mortality than matched controls (odds ratio 2.03, 95% confidence interval 1.33–3.09). The 5-year follow-up analysis of 103 survivors showed no increased risk of neurodevelopmental impairment after iNO treatment. Conclusion: iNO was used for VPT patients in all 11 countries. In-hospital mortality was increased in infants treated with iNO, but long-term neurodevelopmental outcomes were not affected in 103 5-year-old survivors

The early educational environment at five years of age in a European cohort of children born very preterm: challenges and opportunities for research

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