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      Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls

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          Abstract

          Objective

          Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls.

          Methods

          We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting).

          Results

          Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (β = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (β = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (β = -1.5; 95%CI = -2.95, -0.05; p = 0.04).

          Conclusion

          CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

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          Most cited references66

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          Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses.

          G*Power is a free power analysis program for a variety of statistical tests. We present extensions and improvements of the version introduced by Faul, Erdfelder, Lang, and Buchner (2007) in the domain of correlation and regression analyses. In the new version, we have added procedures to analyze the power of tests based on (1) single-sample tetrachoric correlations, (2) comparisons of dependent correlations, (3) bivariate linear regression, (4) multiple linear regression based on the random predictor model, (5) logistic regression, and (6) Poisson regression. We describe these new features and provide a brief introduction to their scope and handling.
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            Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association.

            The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population. A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD. Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation throughout childhood may enhance identification of significant deficits, allowing for appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning.
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              Abnormal brain development in newborns with congenital heart disease.

              Congenital heart disease in newborns is associated with global impairment in development. We characterized brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. We studied 41 term newborns with congenital heart disease--29 who had transposition of the great arteries and 12 who had single-ventricle physiology--with the use of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before cardiac surgery. We calculated the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). We compared these findings with those in 16 control newborns of a similar gestational age. As compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero. Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysis
                Role: Methodology
                Role: InvestigationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 May 2021
                2021
                : 16
                : 5
                : e0251255
                Affiliations
                [1 ] Institute for the Developing Mind, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [2 ] Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
                [3 ] Division of Cardiology, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [4 ] Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
                [5 ] University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [6 ] Department of Pediatric Radiology, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [7 ] Department of Preventive Medicine, Southern California Clinical and Translational Science Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
                [8 ] Division of Neonatology, Department of Pediatrics, Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [9 ] Division of Cardiothoracic Surgery, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [10 ] Institute for Nursing and Interprofessional Research, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
                [11 ] School of Nursing, University of California, Los Angeles, Los Angeles, California, United States of America
                [12 ] Lurie Children’s Hospital of Chicago, Anesthesiology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
                [13 ] Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
                Kobe University Graduate School of Medicine School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-3429-6415
                Article
                PONE-D-20-29114
                10.1371/journal.pone.0251255
                8109808
                33970937
                31330783-f8de-4cc0-a1ec-dc2b9db18d6c
                © 2021 Tran et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 September 2020
                : 22 April 2021
                Page count
                Figures: 4, Tables: 7, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000867, Robert Wood Johnson Foundation;
                Award ID: Future of Nursing Scholars Award
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100012400, Sigma Theta Tau International;
                Award ID: University of California, Los Angeles,Gamma Tau Chapter
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100006108, National Center for Advancing Translational Sciences;
                Award ID: UL1TR0001855
                Award Recipient :
                Funded by: Children's Hospital Los Angeles
                Award ID: Clinical Services Research Grant
                Award Recipient :
                NT received research grants from the Robert Wood Johnson Foundation; University of California, Los Angeles, Sigma Theta Tau, Gamma Tau Chapter; Children’s Hospital Los Angeles Clinical Services Research Grant; and by grant UL1TR001855 from the National Center for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Elements
                Oxygen
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Coronary Heart Disease
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                Cardiology
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