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      Quantitative ultrasonographic examination of cerebral white matter by pixel brightness intensity as marker of middle-term neurodevelopment: a prospective observational study

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          Abstract

          Non-cystic white matter (WM) injury has become prevalent among preterm newborns and is associated with long-term neurodevelopmental impairment. Magnetic resonance is the gold-standard for diagnosis; however, cranial ultrasound (CUS) is more easily available but limited by subjective interpretation of images. To overcome this problem, we enrolled in a prospective observational study, patients with gestational age at birth < 32 weeks with normal CUS scans or grade 1 WM injury. Patients underwent CUS examinations at 0–7 days of life (T 0), 14–35 days of life (T 1), 37 0/7–41 6/7 weeks’ postmenstrual age (T 2), and 42 0/7–52 0/7 weeks’ postmenstrual age (T 3). The echogenicity of parieto-occipital periventricular WM relative to that of homolateral choroid plexus (RE CP) was calculated on parasagittal scans by means of pixel brightness intensity and its relationship with Bayley-III assessment at 12 months’ corrected age was evaluated. We demonstrated that: (1) Left RE CP values at T 1 negatively correlated with cognitive composite scores; (2) Right RE CP values at T 2 and T 3 negatively correlated with language composite scores; (3) Left RE CP values at T 1 and T 2 negatively correlated with motor composite scores. Thus, this technique may be used as screening method to early identify patients at risk of neurodevelopmental issues and promptly initiate preventive and therapeutic interventions.

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          Most cited references52

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          Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children.

          Sequelae of academic underachievement, behavioral problems, and poor executive function (EF) have been extensively reported for very preterm ( 0.51). Very preterm and/or VLBW children have moderate-to-severe deficits in academic achievement, attention problems, and internalizing behavioral problems and poor EF, which are adverse outcomes that were strongly correlated to their immaturity at birth. During transition to young adulthood these children continue to lag behind term-born peers.
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            Brain injury in premature neonates: A primary cerebral dysmaturation disorder?

            With advances in neonatal care, preterm neonates are surviving with an evolving constellation of motor and cognitive disabilities that appear to be related to widespread cellular maturational disturbances that target cerebral gray and white matter. Whereas preterm infants were previously at high risk for destructive brain lesions that resulted in cystic white matter injury and secondary cortical and subcortical gray matter degeneration, contemporary cohorts of preterm survivors commonly display less severe injury that does not appear to involve pronounced glial or neuronal loss. Nevertheless, these milder forms of injury are also associated with reduced cerebral growth. Recent human and experimental studies support that impaired cerebral growth is related to disparate responses in gray and white matter. Myelination disturbances in cerebral white matter are related to aberrant regeneration and repair responses to acute death of premyelinating late oligodendrocyte progenitors (preOLs). In response to preOL death, early oligodendrocyte progenitors rapidly proliferate and differentiate, but the regenerated preOLs fail to normally mature to myelinating cells required for white matter growth. Although immature neurons appear to be more resistant to cell death from hypoxia-ischemia than glia, they display widespread disturbances in maturation of their dendritic arbors, which further contribute to impaired cerebral growth. These complex and disparate responses of neurons and preOLs thus result in large numbers of cells that fail to fully mature during a critical window in development of neural circuitry. These recently recognized forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic directions centered on reversal of the processes that promote dysmaturation. © 2014 American Neurological Association.
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              Levels of neonatal care.

              (2012)
              Provision of risk-appropriate care for newborn infants and mothers was first proposed in 1976. This updated policy statement provides a review of data supporting evidence for a tiered provision of care and reaffirms the need for uniform, nationally applicable definitions and consistent standards of service for public health to improve neonatal outcomes. Facilities that provide hospital care for newborn infants should be classified on the basis of functional capabilities, and these facilities should be organized within a regionalized system of perinatal care.
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                Author and article information

                Contributors
                gianluigi.laccetta@uniroma1.it
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                5 October 2023
                5 October 2023
                2023
                : 13
                : 16816
                Affiliations
                [1 ]Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, ( https://ror.org/02be6w209) Rome, Italy
                [2 ]Department of Developmental and Social Psychology, Sapienza University of Rome, ( https://ror.org/02be6w209) Rome, Italy
                [3 ]Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Faculty of Medicine and Psychology, Sant’Andrea University Hospital, Sapienza University of Rome, ( https://ror.org/02be6w209) Rome, Italy
                Author information
                http://orcid.org/0000-0001-7807-2870
                Article
                44083
                10.1038/s41598-023-44083-w
                10556025
                37798394
                7900fe7d-d641-4521-b279-22cca76be832
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 March 2023
                : 3 October 2023
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                © Springer Nature Limited 2023

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                biomarkers,neurology
                Uncategorized
                biomarkers, neurology

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