<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03786497</url>
  </required_header>
  <id_info>
    <org_study_id>PBSF_2020</org_study_id>
    <nct_id>NCT03786497</nct_id>
  </id_info>
  <brief_title>Protecting Brains and Saving Futures - the PBSF Protocol</brief_title>
  <acronym>PBSF</acronym>
  <official_title>Protecting Brains and Saving Futures - the PBSF Protocol: a Prospective Multicenter and Observational Study on the Use of Telemedicine for Neurocritical Care in High-risk Newborns in Brazil.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Protecting Brains Saving Futures</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Protecting Brains Saving Futures</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Multiple neonatal disorders are associated with risks of neurological injury.&#xD;
      Thus, management of these infants should involve a coordinated approach to permit early&#xD;
      diagnosis with improved clinical care. Such initiative involves the use of standardized&#xD;
      protocols, continuous and specialized brain monitoring with electroencephalography (EEG),&#xD;
      amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS), neuroimaging and&#xD;
      training. Brazil is a very large country with disparities in health care assessment; some&#xD;
      neonatal intensive care units (NICUs) are not well structured and trained to provide adequate&#xD;
      neurocritical care. However, the development and implementation of these neurocritical care&#xD;
      units requires high expertise and significant investment of time, manpower and equipment. In&#xD;
      order to reduce the existing gap, a unique advanced telemedicine model of neurocritical care&#xD;
      called Protecting Brains and Saving Futures (PBSF) protocol was developed and implemented in&#xD;
      some Brazilian NICUs.&#xD;
&#xD;
      Methods: A prospective observational cohort study will be conducted in 20 Brazilian NICUs&#xD;
      that have adopted the PBSF protocol. All infants receiving the protocol during January 2021&#xD;
      to December 2023 will be eligible. Ethical approval will be obtained from the participating&#xD;
      institutions. The primary objective is to describe the use of the PBSF protocol and clinical&#xD;
      outcomes, by center and over a 3 years period. The use of the PBSF protocol will be measured&#xD;
      by quantification of neuromonitoring, neuroimaging exams and sub-specialties consultation.&#xD;
      Clinical outcomes of interest after the protocol implementation are length of hospital stay,&#xD;
      detection of EEG seizures during hospitalization, use of anticonvulsants, inotropes, and&#xD;
      fluid resuscitation, death before hospital discharge, and referral of patients to high-risk&#xD;
      infant follow-up. These data will be also compared between infants with primarily neurologic&#xD;
      and primarily clinical diagnosis.&#xD;
&#xD;
      Discussion: The implementation of the PBSF protocol may provide adequate remote neurocritical&#xD;
      care in high-risk infants with optimization of clinical management and improved outcomes.&#xD;
      Data from this large, prospective, multicenter study are essential to determine whether&#xD;
      neonatal neurocritical units can improve outcomes. Finally, it may offer the necessary&#xD;
      framework for larger scale implementation and help in the development of studies of remote&#xD;
      neuromonitoring.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the&#xD;
      use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to&#xD;
      2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol&#xD;
      will increase over time with improvement of some specific short-term outcomes (see methods&#xD;
      below). Results of this study may provide the necessary background information for larger&#xD;
      studies and initiatives aiming to protect neonatal brains and save futures.&#xD;
&#xD;
      Study Design and Setting This will be a multicenter, prospective, observational study in a&#xD;
      cohort of high-risk neonates treated at 20 different NICU's in Brazil. The intended period of&#xD;
      patient recruitment and data collection will be 3 years (January 2021 to December 2023). The&#xD;
      study followed the precepts of good clinical practice and was approved by the Research Ethics&#xD;
      Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo. In addition, the&#xD;
      project has received formal authorization from the Clinical and Administrative Board of each&#xD;
      center. When selecting a participant, the principal investigator of the study or one of the&#xD;
      co-investigators will contact the parents or guardians and obtain informed consent. All data&#xD;
      will be treated anonymously and confidentially, and in no phase of the study any name, image,&#xD;
      or data that allows participants identification will be disclosed.&#xD;
&#xD;
      Participants In this cohort study, all the infants admitted to any of the 20 NICUs from birth&#xD;
      up to three months of life and receiving the PBSF protocol are eligible. Indications for the&#xD;
      use of the protocol are provided on Box 1. Patients with genetic syndromes or malformation&#xD;
      incompatible with life, or older than three months old will be excluded. Details on the PBSF&#xD;
      protocol are provided in supplemental material. Briefly, the protocol includes provision of&#xD;
      equipment and resources, connection between the associated NICU and the remote monitoring&#xD;
      center called the Central of Surveillance and Intelligence (CSI), training and teaching of&#xD;
      all health care professional team of each NICU, and customized multiparametric recordings of&#xD;
      biological signals of each patient monitoring. At the CSI, a team is available 24 hours a day&#xD;
      all year around, allowing for case discussions and simplified reports of brain monitoring&#xD;
      information on the patient monitor's display every 6 hours.&#xD;
&#xD;
      Variables Population demographics: gender, gestational age at birth, gestational age ≤ 32&#xD;
      weeks and &lt; 37 weeks, Apgar score at 1 min, 5 min and 10 min, birth weight, current weight,&#xD;
      inborn or outborn, use of antenatal steroids and magnesium sulfate, type of birth.&#xD;
&#xD;
      Primary diagnosis: seizure, anoxia/mild HIE, moderate or severe HIE/cooling, neurologic&#xD;
      abnormalities without specific diagnosis, congenital central nervous system (CNS) anomalies,&#xD;
      grade III or IV intraventricular hemorrhage (IVH) or hydrocephalus, periventricular&#xD;
      leukomalacia, meningitis, neural tube defects, stroke, cyanotic congenital heart defect&#xD;
      (CHD), prematurity, gestational age ≤ 32 weeks, meconium aspiration syndrome,&#xD;
      cardiorespiratory instability, necrotizing enterocolitis, metabolic disease, extracorporeal&#xD;
      membrane oxygenation (ECMO)/pre-ECMO and any other medical conditions not listed here.&#xD;
&#xD;
      For descriptive analysis of the 2 main outcomes (use of the PBSF protocol and clinical&#xD;
      outcomes) patients will be them divided into two groups accordingly to their primary&#xD;
      diagnosis: neurological or clinical.&#xD;
&#xD;
      Data sources / measurement Patient demographics, diagnosis and clinical outcomes will be&#xD;
      extracted from the medical charts of each patient enrolled and entered in the PBSF database.&#xD;
      The use of the PBSF protocol will be measured with the data collected by the CSI center&#xD;
      continuously. Details of these recordings are provided on Appendix 2.&#xD;
&#xD;
      Bias To address potential source of bias related to financial availability, the 2 main&#xD;
      outcomes of interest will be also adjusted based on the unit primary profile: private,&#xD;
      foundation or public.&#xD;
&#xD;
      Study size Based on our current experience, there are an average of 5 patients per month with&#xD;
      criteria for neurocritical care on each center, making a total of 3,240 eligible patients&#xD;
      during a three years period. Considering a 30% loss due to refusal to consent,&#xD;
      non-availability of the research team or missing data, we expect to recruit 2,268 infants&#xD;
      from all study centers (around 756 patients per year).&#xD;
&#xD;
      Statistical methods Categorical variables will be analyzed by descriptive statistics and&#xD;
      presented as number of valid cases and percentage (%). Numeric variables will be analyzed as&#xD;
      mean and standard deviation, median and interquartile ranges, or coefficient intervals.&#xD;
      Chi-square test (or Fisher's exact test) will be performed to analyze categorical variables&#xD;
      and the Student's t test, or Wilcoxon rank sum test will be used to check for significant&#xD;
      differences between the two groups. A p value of &lt;0.05 will be considered statistically&#xD;
      significant. The confidence interval considered will be 95%. Analysis of variability&#xD;
      (distribution) per site for each variable of the 2 main outcomes will also be performed.&#xD;
      ANOVA with post hoc Bonferroni will be used to compare outcomes over time, i.e. between years&#xD;
      1, 2 and 3 and Kaplan Meier curves will be generated to follow the evolution of outcomes over&#xD;
      time for the 2 groups of patients: neurologic and clinical.&#xD;
&#xD;
      Results Participants. A flow chart of all eligible and enrolled patients will be produced,&#xD;
      and the total number of patients will be reported, overall and per center.&#xD;
&#xD;
      Descriptive data Population demographics: male, n (%); gestational age at birth, weeks, mean&#xD;
      (SD); gestational age ≤ 32 wk, n(%); Gestational age &lt; 37 wk, n (%); Apgar score at 1 min, at&#xD;
      5 min, and at 10min, median (IQR); birth weight, grams, mean (SD); current weight, grams,&#xD;
      mean (SD); Inborn, n (%); use of antenatal steroids and magnesium sulfate, n (%); Caesarean,&#xD;
      n(%).&#xD;
&#xD;
      Primary outcomes:&#xD;
&#xD;
      Use of the PBSF protocol&#xD;
&#xD;
        1. Use of aEEG/EEG monitoring&#xD;
&#xD;
        2. Duration of aEEG/EEG monitoring&#xD;
&#xD;
        3. Number primary neurologic or medical patients with aEEG or EEG monitoring and the&#xD;
           duration of the monitoring (hours)&#xD;
&#xD;
        4. Number of primary neurologic or medical patients with NIRS monitoring and the duration&#xD;
           of the NIRS monitoring (hours)&#xD;
&#xD;
        5. Number of primary neurologic or medical patients with brain MRI, neurology consult, and&#xD;
           neurosurgery consult.&#xD;
&#xD;
        6. Number of clinical case discussions and videoconference meetings&#xD;
&#xD;
      Clinical outcomes&#xD;
&#xD;
        1. Length of hospital stay&#xD;
&#xD;
        2. Number of electroencephalographic seizures during hospitalization&#xD;
&#xD;
        3. Use and types of anticonvulsants administered&#xD;
&#xD;
        4. Number and types of anticonvulsants prescribed at discharge&#xD;
&#xD;
        5. Use and types of inotropes administered during NICU stay&#xD;
&#xD;
        6. Use and types of fluid resuscitation administered during NICU stay&#xD;
&#xD;
        7. Death before hospital discharge&#xD;
&#xD;
        8. Number of patients referred to neurology or neurosurgery&#xD;
&#xD;
        9. Number of patients referred to high-risk infant follow-up*&#xD;
&#xD;
      Secondary outcomes:&#xD;
&#xD;
      Use of the PBSF protocol&#xD;
&#xD;
        1. Number of remote communications between CSI and local team&#xD;
&#xD;
        2. Number of reports issued for aEEG / EEG exams with or without the use of NIRS&#xD;
&#xD;
        3. Number of patients who performed Therapeutic Hypothermia&#xD;
&#xD;
        4. Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and&#xD;
           alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and&#xD;
           cranial ultrasonography (cranial US) performed during hospitalization&#xD;
&#xD;
        5. Association of pathological brain monitoring findings with morbi-mortality and length of&#xD;
           hospital stay&#xD;
&#xD;
        6. Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia,&#xD;
           thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary&#xD;
           hypertension&#xD;
&#xD;
        7. Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor&#xD;
           positioning&#xD;
&#xD;
        8. Association of pathological brain monitoring findings with evaluation of&#xD;
           neurodevelopment by application of the Bayley test between 18 and 24 months of life&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 1, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>24 Months</target_duration>
  <primary_outcome>
    <measure>Applicability of telemedicine model for monitored infants</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Applicability of telemedicine model for recorded remote monitoring</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use of aEEG/EEG monitoring</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of aEEG/EEG monitoring</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of clinical case discussions and videoconference meetings</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of electroencephalographic seizures during hospitalization</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use and types of anticonvulsants administered</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number and types of anticonvulsants prescribed at discharge</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use and types of inotropes administered during NICU stay</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use and types of fluid resuscitation administered during NICU stay</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Death before hospital discharge</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients referred to neurology or neurosurgery</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients referred to high-risk infant follow-up</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of remote communications between CSI and local team</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of reports issued for aEEG / EEG exams with or without the use of NIRS</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients who performed Therapeutic Hypothermia</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life</measure>
    <time_frame>3 years period</time_frame>
    <description>Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).</description>
  </secondary_outcome>
  <enrollment type="Anticipated">2268</enrollment>
  <condition>Brain Injuries</condition>
  <condition>Congenital Heart Disease</condition>
  <condition>Newborn Morbidity</condition>
  <condition>Intraventricular Hemorrhage</condition>
  <condition>CNS Infection</condition>
  <condition>Neonatal Seizure</condition>
  <condition>Nosocomial Infection</condition>
  <condition>Hypoxic-Ischemic Encephalopathy</condition>
  <condition>Extreme Prematurity</condition>
  <condition>Brain Malformation</condition>
  <condition>Congenital Infection</condition>
  <condition>Neonatal Stroke</condition>
  <condition>Hemodynamic Instability</condition>
  <condition>Extracorporeal Membrane Oxygenation Complication</condition>
  <condition>Inborn Errors of Metabolism</condition>
  <condition>Respiratory Complication</condition>
  <condition>Neonatal Death</condition>
  <eligibility>
    <study_pop>
      <textblock>
        This will be a multicenter, prospective, observational study in a cohort of high-risk&#xD;
        neonates treated at 20 different Neonatal Intensive Care Units in terciary hospitals in&#xD;
        Brazil.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        - Inclusion criteria:&#xD;
&#xD;
        In this cohort study, all the infants admitted to any of the 20 NICUs from birth up to&#xD;
        three months of life and receiving the PBSF protocol are eligible. Following are the&#xD;
        indications for use of the PBSF protocol in the participating centers&#xD;
&#xD;
          1. Extreme prematurity&#xD;
&#xD;
          2. Peri-intraventricular Hemorrhage&#xD;
&#xD;
          3. Hypoxic-ischemic encephalopathy (mild, moderate or severe)&#xD;
&#xD;
          4. Congenital heart disease&#xD;
&#xD;
          5. Neonatal stroke&#xD;
&#xD;
          6. Congenital infections&#xD;
&#xD;
          7. Nosocomial infections&#xD;
&#xD;
          8. Inborn errors of metabolism&#xD;
&#xD;
          9. Severe hemodynamic/ventilatory instability&#xD;
&#xD;
         10. Seizures&#xD;
&#xD;
         11. Brain malformations&#xD;
&#xD;
         12. CNS infection&#xD;
&#xD;
         13. ECMO&#xD;
&#xD;
               -  Exclusion criteria:&#xD;
&#xD;
        Patients with genetic syndromes or malformation incompatible with life, or older than three&#xD;
        months old will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>3 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guilherme M Sant'Anna, PhD</last_name>
    <role>Study Director</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gabriel FT Variane, MD</last_name>
    <phone>5511996243520</phone>
    <email>gabriel.variane@pbsf.com.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Daniela P Rodrigues, BSN, RN, CNS</last_name>
    <phone>5511983707307</phone>
    <email>daniela.rodrigues@pbsf.com.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Irmandade da Santa Casa de Misericórdia de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01221-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <contact>
      <last_name>Maurício Maralhães, MD</last_name>
      <phone>5511999330294</phone>
      <email>m-magalhaes@uol.com.br</email>
    </contact>
    <contact_backup>
      <last_name>Rafaela FR Pietrobom, MD</last_name>
      <phone>5511949724721</phone>
      <email>rafaela.fabri@pbsf.com.br</email>
    </contact_backup>
    <investigator>
      <last_name>Renato Gasperini, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Protecting Brains and Saving Futures - PBSF</name>
      <address>
        <city>São Paulo</city>
        <zip>01407-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <contact>
      <last_name>Gabriel FT Variane, MD</last_name>
      <phone>5511996243520</phone>
      <email>gabriel.variane@pbsf.com.br</email>
    </contact>
    <contact_backup>
      <last_name>Alexandre Netto, MD</last_name>
      <phone>+5511993284856</phone>
      <email>alexandre.netto@pbsf.com.br</email>
    </contact_backup>
    <investigator>
      <last_name>Daniela P Rodrigues, BSN, RN, CNS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>https://apps.who.int/iris/handle/10665/63857</url>
    <description>25. World Health Organization. A health telematics policy in support of WHO's Health-for-All Strategy for Global Health Development. Geneva (Switzerland); 1998.</description>
  </link>
  <link>
    <url>https://apps.who.int/iris/handle/10665/44497</url>
    <description>26. World Health Organization. Telemedicine: Opportunities and Development in Member States: Report on the second global survey on eHealth. Geneva (Switzerland); 2010.</description>
  </link>
  <link>
    <url>https://datasus.saude.gov.br/informacoes-de-saude-tabnet/</url>
    <description>30. Ministério da Saúde. DATASUS. [online] Tabnet. [accessed on Jan 10th 2018]</description>
  </link>
  <reference>
    <citation>Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.</citation>
    <PMID>20554402</PMID>
  </reference>
  <reference>
    <citation>Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5.</citation>
    <PMID>15752534</PMID>
  </reference>
  <reference>
    <citation>Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol. 2006 Jun;35(3):706-18. doi: 10.1093/ije/dyl043. Epub 2006 Mar 23.</citation>
    <PMID>16556647</PMID>
  </reference>
  <reference>
    <citation>Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991 May;25(2):135-48. doi: 10.1016/0378-3782(91)90191-5.</citation>
    <PMID>1713544</PMID>
  </reference>
  <reference>
    <citation>Robertson CMT. Long-term follow-up of term infants with perinatal asphyxia. In: Stevenson DK, Benitz WE, Sunshine P. Fetal and neonatal brain injury. 3. Ed. New York: Cambridge University; 2003. p.829-58.</citation>
  </reference>
  <reference>
    <citation>de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F220-4. doi: 10.1136/adc.2008.148205.</citation>
    <PMID>20444814</PMID>
  </reference>
  <reference>
    <citation>Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F380-7. doi: 10.1136/adc.2004.067520.</citation>
    <PMID>16113154</PMID>
  </reference>
  <reference>
    <citation>Blencowe H, Lee AC, Cousens S, Bahalim A, Narwal R, Zhong N, Chou D, Say L, Modi N, Katz J, Vos T, Marlow N, Lawn JE. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013 Dec;74 Suppl 1(Suppl 1):17-34. doi: 10.1038/pr.2013.204.</citation>
    <PMID>24366461</PMID>
  </reference>
  <reference>
    <citation>Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med. 2006 Dec;11(6):503-11. doi: 10.1016/j.siny.2006.07.011. Epub 2006 Oct 24.</citation>
    <PMID>17067863</PMID>
  </reference>
  <reference>
    <citation>Hellström-Westas L, Rosén I, de Vries LS, Greisen G. Amplitude-integrated EEG Classification and Interpretation in Preterm and Term Infants. NeoReviews. 2006;7(2):e76-87.</citation>
  </reference>
  <reference>
    <citation>Shah DK, Mackay MT, Lavery S, Watson S, Harvey AS, Zempel J, Mathur A, Inder TE. Accuracy of bedside electroencephalographic monitoring in comparison with simultaneous continuous conventional electroencephalography for seizure detection in term infants. Pediatrics. 2008 Jun;121(6):1146-54. doi: 10.1542/peds.2007-1839.</citation>
    <PMID>18519484</PMID>
  </reference>
  <reference>
    <citation>Mastrangelo M, Fiocchi I, Fontana P, Gorgone G, Lista G, Belcastro V. Acute neonatal encephalopathy and seizures recurrence: a combined aEEG/EEG study. Seizure. 2013 Nov;22(9):703-7. doi: 10.1016/j.seizure.2013.05.006. Epub 2013 May 29.</citation>
    <PMID>23725740</PMID>
  </reference>
  <reference>
    <citation>Shah DK, Zempel J, Barton T, Lukas K, Inder TE. Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury. Pediatr Res. 2010 Jan;67(1):102-6. doi: 10.1203/PDR.0b013e3181bf5914.</citation>
    <PMID>19745782</PMID>
  </reference>
  <reference>
    <citation>Payne ET, Zhao XY, Frndova H, McBain K, Sharma R, Hutchison JS, Hahn CD. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014 May;137(Pt 5):1429-38. doi: 10.1093/brain/awu042. Epub 2014 Mar 4.</citation>
    <PMID>24595203</PMID>
  </reference>
  <reference>
    <citation>van Rooij LG, Toet MC, van Huffelen AC, Groenendaal F, Laan W, Zecic A, de Haan TR, van Straaten IL, Vrancken S, van Wezel G, van der Sluijs J, Ter Horst H, Gavilanes D, Laroche S, Naulaers G, de Vries LS. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics. 2010 Feb;125(2):e358-66. doi: 10.1542/peds.2009-0136. Epub 2010 Jan 25.</citation>
    <PMID>20100767</PMID>
  </reference>
  <reference>
    <citation>Vesoulis ZA, Inder TE, Woodward LJ, Buse B, Vavasseur C, Mathur AM. Early electrographic seizures, brain injury, and neurodevelopmental risk in the very preterm infant. Pediatr Res. 2014 Apr;75(4):564-9. doi: 10.1038/pr.2013.245. Epub 2013 Dec 23.</citation>
    <PMID>24366515</PMID>
  </reference>
  <reference>
    <citation>Srinivasakumar P, Zempel J, Trivedi S, Wallendorf M, Rao R, Smith B, Inder T, Mathur AM. Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial. Pediatrics. 2015 Nov;136(5):e1302-9. doi: 10.1542/peds.2014-3777. Epub 2015 Oct 19.</citation>
    <PMID>26482675</PMID>
  </reference>
  <reference>
    <citation>Hellstrom-Westas L, Rosen I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed. 1995 Jan;72(1):F34-8. doi: 10.1136/fn.72.1.f34.</citation>
    <PMID>7743282</PMID>
  </reference>
  <reference>
    <citation>Thoresen M, Hellstrom-Westas L, Liu X, de Vries LS. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics. 2010 Jul;126(1):e131-9. doi: 10.1542/peds.2009-2938. Epub 2010 Jun 21.</citation>
    <PMID>20566612</PMID>
  </reference>
  <reference>
    <citation>van Rooij LG, Toet MC, Osredkar D, van Huffelen AC, Groenendaal F, de Vries LS. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed. 2005 May;90(3):F245-51. doi: 10.1136/adc.2004.064964.</citation>
    <PMID>15846017</PMID>
  </reference>
  <reference>
    <citation>Del Rio R, Ochoa C, Alarcon A, Arnaez J, Blanco D, Garcia-Alix A. Amplitude Integrated Electroencephalogram as a Prognostic Tool in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review. PLoS One. 2016 Nov 1;11(11):e0165744. doi: 10.1371/journal.pone.0165744. eCollection 2016.</citation>
    <PMID>27802300</PMID>
  </reference>
  <reference>
    <citation>van Bel F, Lemmers P, Naulaers G. Monitoring neonatal regional cerebral oxygen saturation in clinical practice: value and pitfalls. Neonatology. 2008;94(4):237-44. doi: 10.1159/000151642. Epub 2008 Sep 11.</citation>
    <PMID>18784420</PMID>
  </reference>
  <reference>
    <citation>Alderliesten T, De Vis JB, Lemmers PM, Hendrikse J, Groenendaal F, van Bel F, Benders MJ, Petersen ET. Brain oxygen saturation assessment in neonates using T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy. J Cereb Blood Flow Metab. 2017 Mar;37(3):902-913. doi: 10.1177/0271678X16647737. Epub 2016 Jul 20.</citation>
    <PMID>27151900</PMID>
  </reference>
  <reference>
    <citation>Chock VY, Rose LA, Mante JV, Punn R. Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatr Res. 2016 Nov;80(5):675-680. doi: 10.1038/pr.2016.148. Epub 2016 Sep 7.</citation>
    <PMID>27603562</PMID>
  </reference>
  <reference>
    <citation>Hall RW, Hall-Barrow J, Garcia-Rill E. Neonatal regionalization through telemedicine using a community-based research and education core facility. Ethn Dis. 2010 Winter;20(1 Suppl 1):S1-136-40.</citation>
    <PMID>20521402</PMID>
  </reference>
  <reference>
    <citation>Burke BL Jr, Hall RW; SECTION ON TELEHEALTH CARE. Telemedicine: Pediatric Applications. Pediatrics. 2015 Jul;136(1):e293-308. doi: 10.1542/peds.2015-1517.</citation>
    <PMID>26122813</PMID>
  </reference>
  <reference>
    <citation>McConnochie K, Wood N, Herendeen N, ten Hoopen C, Denk L, Neuderfer J. Integrating telemedicine in urban pediatric primary care: provider perspectives and performance. Telemed J E Health. 2010 Apr;16(3):280-8. doi: 10.1089/tmj.2009.0112.</citation>
    <PMID>20406114</PMID>
  </reference>
  <reference>
    <citation>Variane GF, Cunha LM, Pinto P, Brandao P, Mascaretti RS, Magalhaes M, Sant'Anna GM. Therapeutic Hypothermia in Brazil: A MultiProfessional National Survey. Am J Perinatol. 2019 Sep;36(11):1150-1156. doi: 10.1055/s-0038-1676052. Epub 2018 Dec 15.</citation>
    <PMID>30553235</PMID>
  </reference>
  <reference>
    <citation>Triulzi F, Parazzini C, Righini A. Patterns of damage in the mature neonatal brain. Pediatr Radiol. 2006 Jul;36(7):608-20. doi: 10.1007/s00247-006-0203-5. Epub 2006 May 18.</citation>
    <PMID>16770665</PMID>
  </reference>
  <reference>
    <citation>Ferriero DM. Neonatal brain injury. N Engl J Med. 2004 Nov 4;351(19):1985-95. doi: 10.1056/NEJMra041996. No abstract available.</citation>
    <PMID>15525724</PMID>
  </reference>
  <reference>
    <citation>Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.</citation>
    <PMID>29095433</PMID>
  </reference>
  <reference>
    <citation>Abend NS, Wusthoff CJ, Goldberg EM, Dlugos DJ. Electrographic seizures and status epilepticus in critically ill children and neonates with encephalopathy. Lancet Neurol. 2013 Dec;12(12):1170-9. doi: 10.1016/S1474-4422(13)70246-1.</citation>
    <PMID>24229615</PMID>
  </reference>
  <reference>
    <citation>Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008 May;93(3):F187-91. doi: 10.1136/adc.2005.086314. Epub 2007 Jul 11.</citation>
    <PMID>17626147</PMID>
  </reference>
  <reference>
    <citation>Burnett AC, Cheong JLY, Doyle LW. Biological and Social Influences on the Neurodevelopmental Outcomes of Preterm Infants. Clin Perinatol. 2018 Sep;45(3):485-500. doi: 10.1016/j.clp.2018.05.005.</citation>
    <PMID>30144851</PMID>
  </reference>
  <reference>
    <citation>Joseph RM, O'Shea TM, Allred EN, Heeren T, Hirtz D, Jara H, Leviton A, Kuban KC; ELGAN Study Investigators. Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns. Pediatrics. 2016 Apr;137(4):e20154343. doi: 10.1542/peds.2015-4343. Epub 2016 Mar 22.</citation>
    <PMID>27006473</PMID>
  </reference>
  <reference>
    <citation>Cheong JL, Doyle LW, Burnett AC, Lee KJ, Walsh JM, Potter CR, Treyvaud K, Thompson DK, Olsen JE, Anderson PJ, Spittle AJ. Association Between Moderate and Late Preterm Birth and Neurodevelopment and Social-Emotional Development at Age 2 Years. JAMA Pediatr. 2017 Apr 3;171(4):e164805. doi: 10.1001/jamapediatrics.2016.4805. Epub 2017 Apr 3.</citation>
    <PMID>28152144</PMID>
  </reference>
  <reference>
    <citation>Bosi G, Garani G, Scorrano M, Calzolari E; IMER Working Party. Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry. J Pediatr. 2003 Jun;142(6):690-8. doi: 10.1067/mpd.2003.243. Erratum In: J Pediatr. 2003 Oct;143(4):531.</citation>
    <PMID>12838199</PMID>
  </reference>
  <reference>
    <citation>Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.</citation>
    <PMID>12084585</PMID>
  </reference>
  <reference>
    <citation>Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH Jr, Li J, Smith SE, Bellinger DC, Mahle WT; American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation. 2012 Aug 28;126(9):1143-72. doi: 10.1161/CIR.0b013e318265ee8a. Epub 2012 Jul 30.</citation>
    <PMID>22851541</PMID>
  </reference>
  <reference>
    <citation>Dimitropoulos A, McQuillen PS, Sethi V, Moosa A, Chau V, Xu D, Brant R, Azakie A, Campbell A, Barkovich AJ, Poskitt KJ, Miller SP. Brain injury and development in newborns with critical congenital heart disease. Neurology. 2013 Jul 16;81(3):241-8. doi: 10.1212/WNL.0b013e31829bfdcf. Epub 2013 Jun 14.</citation>
    <PMID>23771484</PMID>
  </reference>
  <reference>
    <citation>Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurologic status of newborns with congenital heart defects before open heart surgery. Pediatrics. 1999 Feb;103(2):402-8. doi: 10.1542/peds.103.2.402.</citation>
    <PMID>9925832</PMID>
  </reference>
  <reference>
    <citation>Gunn JK, Beca J, Hunt RW, Olischar M, Shekerdemian LS. Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease. Intensive Care Med. 2012 Sep;38(9):1539-47. doi: 10.1007/s00134-012-2608-y. Epub 2012 Jun 1.</citation>
    <PMID>22653373</PMID>
  </reference>
  <reference>
    <citation>Gunn JK, Beca J, Penny DJ, Horton SB, d'Udekem YA, Brizard CP, Finucane K, Olischar M, Hunt RW, Shekerdemian LS. Amplitude-integrated electroencephalography and brain injury in infants undergoing Norwood-type operations. Ann Thorac Surg. 2012 Jan;93(1):170-6. doi: 10.1016/j.athoracsur.2011.08.014. Epub 2011 Nov 9.</citation>
    <PMID>22075220</PMID>
  </reference>
  <reference>
    <citation>Toso PA, Gonzalez AJ, Perez ME, Kattan J, Fabres JG, Tapia JL, Gonzalez HS. Clinical utility of early amplitude integrated EEG in monitoring term newborns at risk of neurological injury. J Pediatr (Rio J). 2014 Mar-Apr;90(2):143-8. doi: 10.1016/j.jped.2013.07.004. Epub 2013 Oct 30.</citation>
    <PMID>24184304</PMID>
  </reference>
  <reference>
    <citation>Shah NA, Wusthoff CJ. How to use: amplitude-integrated EEG (aEEG). Arch Dis Child Educ Pract Ed. 2015 Apr;100(2):75-81. doi: 10.1136/archdischild-2013-305676. Epub 2014 Jul 17.</citation>
    <PMID>25035312</PMID>
  </reference>
  <reference>
    <citation>Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854. Erratum In: N Engl J Med. 2010 Mar 18;362(11):1056.</citation>
    <PMID>19797281</PMID>
  </reference>
  <reference>
    <citation>Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.</citation>
    <PMID>15721471</PMID>
  </reference>
  <reference>
    <citation>Simbruner G, Mittal RA, Rohlmann F, Muche R; neo.nEURO.network Trial Participants. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010 Oct;126(4):e771-8. doi: 10.1542/peds.2009-2441. Epub 2010 Sep 20.</citation>
    <PMID>20855387</PMID>
  </reference>
  <reference>
    <citation>Skranes JH, Lohaugen G, Schumacher EM, Osredkar D, Server A, Cowan FM, Stiris T, Fugelseth D, Thoresen M. Amplitude-Integrated Electroencephalography Improves the Identification of Infants with Encephalopathy for Therapeutic Hypothermia and Predicts Neurodevelopmental Outcomes at 2 Years of Age. J Pediatr. 2017 Aug;187:34-42. doi: 10.1016/j.jpeds.2017.04.041. Epub 2017 May 23.</citation>
    <PMID>28549636</PMID>
  </reference>
  <reference>
    <citation>Sarkar S, Barks JD, Donn SM. Should amplitude-integrated electroencephalography be used to identify infants suitable for hypothermic neuroprotection? J Perinatol. 2008 Feb;28(2):117-22. doi: 10.1038/sj.jp.7211882. Epub 2007 Nov 15.</citation>
    <PMID>18004390</PMID>
  </reference>
  <reference>
    <citation>Chandrasekaran M, Chaban B, Montaldo P, Thayyil S. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a meta-analysis. J Perinatol. 2017 Jun;37(6):684-689. doi: 10.1038/jp.2017.14. Epub 2017 Mar 2.</citation>
    <PMID>28252661</PMID>
  </reference>
  <reference>
    <citation>Ancora G, Maranella E, Grandi S, Sbravati F, Coccolini E, Savini S, Faldella G. Early predictors of short term neurodevelopmental outcome in asphyxiated cooled infants. A combined brain amplitude integrated electroencephalography and near infrared spectroscopy study. Brain Dev. 2013 Jan;35(1):26-31. doi: 10.1016/j.braindev.2011.09.008. Epub 2011 Nov 13.</citation>
    <PMID>22082686</PMID>
  </reference>
  <reference>
    <citation>Jain SV, Pagano L, Gillam-Krakauer M, Slaughter JC, Pruthi S, Engelhardt B. Cerebral regional oxygen saturation trends in infants with hypoxic-ischemic encephalopathy. Early Hum Dev. 2017 Oct;113:55-61. doi: 10.1016/j.earlhumdev.2017.07.008. Epub 2017 Aug 1.</citation>
    <PMID>28772198</PMID>
  </reference>
  <reference>
    <citation>Lemmers PM, Zwanenburg RJ, Benders MJ, de Vries LS, Groenendaal F, van Bel F, Toet MC. Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value? Pediatr Res. 2013 Aug;74(2):180-5. doi: 10.1038/pr.2013.84. Epub 2013 May 31.</citation>
    <PMID>23728382</PMID>
  </reference>
  <reference>
    <citation>Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R, Stewart J, Volpe J, Bourgeois B, du Plessis AJ. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics. 2006 Apr;117(4):1270-80. doi: 10.1542/peds.2005-1178.</citation>
    <PMID>16585324</PMID>
  </reference>
  <reference>
    <citation>Hellstrom-Westas L, Rosen I, Svenningsen NW. Cerebral function monitoring during the first week of life in extremely small low birthweight (ESLBW) infants. Neuropediatrics. 1991 Feb;22(1):27-32. doi: 10.1055/s-2008-1071411.</citation>
    <PMID>2038424</PMID>
  </reference>
  <reference>
    <citation>Wikstrom S, Pupp IH, Rosen I, Norman E, Fellman V, Ley D, Hellstrom-Westas L. Early single-channel aEEG/EEG predicts outcome in very preterm infants. Acta Paediatr. 2012 Jul;101(7):719-26. doi: 10.1111/j.1651-2227.2012.02677.x. Epub 2012 Apr 24.</citation>
    <PMID>22530996</PMID>
  </reference>
  <reference>
    <citation>Soubasi V, Mitsakis K, Sarafidis K, Griva M, Nakas CT, Drossou V. Early abnormal amplitude-integrated electroencephalography (aEEG) is associated with adverse short-term outcome in premature infants. Eur J Paediatr Neurol. 2012 Nov;16(6):625-30. doi: 10.1016/j.ejpn.2012.02.008. Epub 2012 Mar 15.</citation>
    <PMID>22425390</PMID>
  </reference>
  <reference>
    <citation>Klebermass K, Olischar M, Waldhoer T, Fuiko R, Pollak A, Weninger M. Amplitude-integrated EEG pattern predicts further outcome in preterm infants. Pediatr Res. 2011 Jul;70(1):102-8. doi: 10.1203/PDR.0b013e31821ba200.</citation>
    <PMID>21436758</PMID>
  </reference>
  <reference>
    <citation>Variane GFT, Magalhaes M, Gasperine R, Alves HCBR, Scoppetta TLPD, Figueredo RJG, Rodrigues FPM, Netto A, Mimica MJ, Gallacci CB. Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury. J Pediatr (Rio J). 2017 Sep-Oct;93(5):460-466. doi: 10.1016/j.jped.2016.12.003. Epub 2017 Feb 23.</citation>
    <PMID>28238681</PMID>
  </reference>
  <reference>
    <citation>Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Franz AR, Fumagalli M, Gluud C, Grevstad B, Hagmann C, Lemmers P, van Oeveren W, Pichler G, Plomgaard AM, Riera J, Sanchez L, Winkel P, Wolf M, Greisen G. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015 Jan 5;350:g7635. doi: 10.1136/bmj.g7635.</citation>
    <PMID>25569128</PMID>
  </reference>
  <reference>
    <citation>Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics. 2008 Jan;121(1):142-7. doi: 10.1542/peds.2007-0925.</citation>
    <PMID>18166568</PMID>
  </reference>
  <reference>
    <citation>Underwood MA, Milstein JM, Sherman MP. Near-infrared spectroscopy as a screening tool for patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2007;91(2):134-9. doi: 10.1159/000097131. Epub 2006 Nov 20.</citation>
    <PMID>17344664</PMID>
  </reference>
  <reference>
    <citation>Olischar M, Shany E, Aygun C, Azzopardi D, Hunt RW, Toet MC, Hamosh A, de Vries LS, Hellstrom-Westas L, Theda C. Amplitude-integrated electroencephalography in newborns with inborn errors of metabolism. Neonatology. 2012;102(3):203-11. doi: 10.1159/000339567. Epub 2012 Jul 12.</citation>
    <PMID>22797054</PMID>
  </reference>
  <reference>
    <citation>Helderman JB, Welch CD, Leng X, O'Shea TM. Sepsis-associated electroencephalographic changes in extremely low gestational age neonates. Early Hum Dev. 2010 Aug;86(8):509-13. doi: 10.1016/j.earlhumdev.2010.06.006. Epub 2010 Aug 12.</citation>
    <PMID>20708356</PMID>
  </reference>
  <reference>
    <citation>ter Horst HJ, Mud M, Roofthooft MT, Bos AF. Amplitude integrated electroencephalographic activity in infants with congenital heart disease before surgery. Early Hum Dev. 2010 Dec;86(12):759-64. doi: 10.1016/j.earlhumdev.2010.08.028.</citation>
    <PMID>20970264</PMID>
  </reference>
  <reference>
    <citation>Latal B, Wohlrab G, Brotschi B, Beck I, Knirsch W, Bernet V. Postoperative Amplitude-Integrated Electroencephalography Predicts Four-Year Neurodevelopmental Outcome in Children with Complex Congenital Heart Disease. J Pediatr. 2016 Nov;178:55-60.e1. doi: 10.1016/j.jpeds.2016.06.050. Epub 2016 Jul 22.</citation>
    <PMID>27453368</PMID>
  </reference>
  <reference>
    <citation>Dodge-Khatami J, Gottschalk U, Eulenburg C, Wendt U, Schnegg C, Rebel M, Reichenspurner H, Dodge-Khatami A. Prognostic value of perioperative near-infrared spectroscopy during neonatal and infant congenital heart surgery for adverse in-hospital clinical events. World J Pediatr Congenit Heart Surg. 2012 Apr 1;3(2):221-8. doi: 10.1177/2150135111426298.</citation>
    <PMID>23804778</PMID>
  </reference>
  <reference>
    <citation>Colasacco C, Worthen M, Peterson B, Lamberti J, Spear R. Near-infrared spectroscopy monitoring to predict postoperative renal insufficiency following repair of congenital heart disease. World J Pediatr Congenit Heart Surg. 2011 Oct 1;2(4):536-40. doi: 10.1177/2150135111411932.</citation>
    <PMID>23804464</PMID>
  </reference>
  <reference>
    <citation>Hoffman GM, Ghanayem NS, Scott JP, Tweddell JS, Mitchell ME, Mussatto KA. Postoperative Cerebral and Somatic Near-Infrared Spectroscopy Saturations and Outcome in Hypoplastic Left Heart Syndrome. Ann Thorac Surg. 2017 May;103(5):1527-1535. doi: 10.1016/j.athoracsur.2016.09.100. Epub 2016 Dec 21.</citation>
    <PMID>28012642</PMID>
  </reference>
  <reference>
    <citation>Clair MP, Rambaud J, Flahault A, Guedj R, Guilbert J, Guellec I, Durandy A, Demoulin M, Jean S, Mitanchez D, Chalard F, Sileo C, Carbajal R, Renolleau S, Leger PL. Prognostic value of cerebral tissue oxygen saturation during neonatal extracorporeal membrane oxygenation. PLoS One. 2017 Mar 9;12(3):e0172991. doi: 10.1371/journal.pone.0172991. eCollection 2017.</citation>
    <PMID>28278259</PMID>
  </reference>
  <reference>
    <citation>Sood BG, McLaughlin K, Cortez J. Near-infrared spectroscopy: applications in neonates. Semin Fetal Neonatal Med. 2015 Jun;20(3):164-72. doi: 10.1016/j.siny.2015.03.008. Epub 2015 Apr 29.</citation>
    <PMID>25934116</PMID>
  </reference>
  <reference>
    <citation>Johnson BA, Hoffman GM, Tweddell JS, Cava JR, Basir M, Mitchell ME, Scanlon MC, Mussatto KA, Ghanayem NS. Near-infrared spectroscopy in neonates before palliation of hypoplastic left heart syndrome. Ann Thorac Surg. 2009 Feb;87(2):571-7; discussion 577-9. doi: 10.1016/j.athoracsur.2008.10.043.</citation>
    <PMID>19161781</PMID>
  </reference>
  <reference>
    <citation>Hanson SJ, Berens RJ, Havens PL, Kim MK, Hoffman GM. Effect of volume resuscitation on regional perfusion in dehydrated pediatric patients as measured by two-site near-infrared spectroscopy. Pediatr Emerg Care. 2009 Mar;25(3):150-3. doi: 10.1097/PEC.0b013e31819a7f60.</citation>
    <PMID>19262423</PMID>
  </reference>
  <reference>
    <citation>Pichler G, Holler N, Baik-Schneditz N, Schwaberger B, Mileder L, Stadler J, Avian A, Pansy J, Urlesberger B. Avoiding Arterial Hypotension in Preterm Neonates (AHIP)-A Single Center Randomised Controlled Study Investigating Simultaneous Near Infrared Spectroscopy Measurements of Cerebral and Peripheral Regional Tissue Oxygenation and Dedicated Interventions. Front Pediatr. 2018 Feb 1;6:15. doi: 10.3389/fped.2018.00015. eCollection 2018.</citation>
    <PMID>29450194</PMID>
  </reference>
  <reference>
    <citation>Variane GFT, Chock VY, Netto A, Pietrobom RFR, Van Meurs KP. Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology. Front Pediatr. 2020 Jan 21;7:560. doi: 10.3389/fped.2019.00560. eCollection 2019.</citation>
    <PMID>32039117</PMID>
  </reference>
  <reference>
    <citation>Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8(3):e58834. doi: 10.1371/journal.pone.0058834. Epub 2013 Mar 19.</citation>
    <PMID>23527034</PMID>
  </reference>
  <reference>
    <citation>Frenkel N, Friger M, Meledin I, Berger I, Marks K, Bassan H, Shany E. Neonatal seizure recognition--comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings. Clin Neurophysiol. 2011 Jun;122(6):1091-7. doi: 10.1016/j.clinph.2010.09.028. Epub 2011 Jan 7.</citation>
    <PMID>21216190</PMID>
  </reference>
  <reference>
    <citation>Rakshasbhuvankar A, Paul S, Nagarajan L, Ghosh S, Rao S. Amplitude-integrated EEG for detection of neonatal seizures: a systematic review. Seizure. 2015 Dec;33:90-8. doi: 10.1016/j.seizure.2015.09.014. Epub 2015 Sep 26.</citation>
    <PMID>26456517</PMID>
  </reference>
  <reference>
    <citation>Udeh C, Udeh B, Rahman N, Canfield C, Campbell J, Hata JS. Telemedicine/Virtual ICU: Where Are We and Where Are We Going? Methodist Debakey Cardiovasc J. 2018 Apr-Jun;14(2):126-133. doi: 10.14797/mdcj-14-2-126.</citation>
    <PMID>29977469</PMID>
  </reference>
  <reference>
    <citation>Kahn JM, Le TQ, Barnato AE, Hravnak M, Kuza CC, Pike F, Angus DC. ICU Telemedicine and Critical Care Mortality: A National Effectiveness Study. Med Care. 2016 Mar;54(3):319-25. doi: 10.1097/MLR.0000000000000485.</citation>
    <PMID>26765148</PMID>
  </reference>
  <reference>
    <citation>Maldonado JM, Marques AB, Cruz A. Telemedicine: challenges to dissemination in Brazil. Cad Saude Publica. 2016 Nov 3;32Suppl 2(Suppl 2):e00155615. doi: 10.1590/0102-311X00155615. English, Portuguese.</citation>
    <PMID>27828681</PMID>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>November 11, 2020</last_update_submitted>
  <last_update_submitted_qc>November 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Protecting Brains Saving Futures</investigator_affiliation>
    <investigator_full_name>Dr Gabriel Variane</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </responsible_party>
  <keyword>Newborn</keyword>
  <keyword>Neonatal Neurocritical Care Units</keyword>
  <keyword>Neonatal Brain Monitoring</keyword>
  <keyword>Brain Injury</keyword>
  <keyword>Neuroprotection</keyword>
  <keyword>Telemedicine</keyword>
  <keyword>Electroencephalography</keyword>
  <keyword>Amplitude-Integrated Electroencephalography</keyword>
  <keyword>Near Infrared Spectroscopy</keyword>
  <keyword>Neurodevelopmental Problems</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Cross Infection</mesh_term>
    <mesh_term>Central Nervous System Infections</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</mesh_term>
    <mesh_term>Perinatal Death</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
    <mesh_term>Metabolism, Inborn Errors</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03786497
org study id: PBSF_2020
nct id: NCT03786497
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Multiple neonatal disorders are associated with risks of neurological injury.
      Thus, management of these infants should involve a coordinated approach to permit early
      diagnosis with improved clinical care. Such initiative involves the use of standardized
      protocols, continuous and specialized brain monitoring with electroencephalography (EEG),
      amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS), neuroimaging and
      training. Brazil is a very large country with disparities in health care assessment; some
      neonatal intensive care units (NICUs) are not well structured and trained to provide adequate
      neurocritical care. However, the development and implementation of these neurocritical care
      units requires high expertise and significant investment of time, manpower and equipment. In
      order to reduce the existing gap, a unique advanced telemedicine model of neurocritical care
      called Protecting Brains and Saving Futures (PBSF) protocol was developed and implemented in
      some Brazilian NICUs.

      Methods: A prospective observational cohort study will be conducted in 20 Brazilian NICUs
      that have adopted the PBSF protocol. All infants receiving the protocol during January 2021
      to December 2023 will be eligible. Ethical approval will be obtained from the participating
      institutions. The primary objective is to describe the use of the PBSF protocol and clinical
      outcomes, by center and over a 3 years period. The use of the PBSF protocol will be measured
      by quantification of neuromonitoring, neuroimaging exams and sub-specialties consultation.
      Clinical outcomes of interest after the protocol implementation are length of hospital stay,
      detection of EEG seizures during hospitalization, use of anticonvulsants, inotropes, and
      fluid resuscitation, death before hospital discharge, and referral of patients to high-risk
      infant follow-up. These data will be also compared between infants with primarily neurologic
      and primarily clinical diagnosis.

      Discussion: The implementation of the PBSF protocol may provide adequate remote neurocritical
      care in high-risk infants with optimization of clinical management and improved outcomes.
      Data from this large, prospective, multicenter study are essential to determine whether
      neonatal neurocritical units can improve outcomes. Finally, it may offer the necessary
      framework for larger scale implementation and help in the development of studies of remote
      neuromonitoring.
METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the
      use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to
      2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol
      will increase over time with improvement of some specific short-term outcomes (see methods
      below). Results of this study may provide the necessary background information for larger
      studies and initiatives aiming to protect neonatal brains and save futures.

      Study Design and Setting This will be a multicenter, prospective, observational study in a
      cohort of high-risk neonates treated at 20 different NICU's in Brazil. The intended period of
      patient recruitment and data collection will be 3 years (January 2021 to December 2023). The
      study followed the precepts of good clinical practice and was approved by the Research Ethics
      Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo. In addition, the
      project has received formal authorization from the Clinical and Administrative Board of each
      center. When selecting a participant, the principal investigator of the study or one of the
      co-investigators will contact the parents or guardians and obtain informed consent. All data
      will be treated anonymously and confidentially, and in no phase of the study any name, image,
      or data that allows participants identification will be disclosed.

      Participants In this cohort study, all the infants admitted to any of the 20 NICUs from birth
      up to three months of life and receiving the PBSF protocol are eligible. Indications for the
      use of the protocol are provided on Box 1. Patients with genetic syndromes or malformation
      incompatible with life, or older than three months old will be excluded. Details on the PBSF
      protocol are provided in supplemental material. Briefly, the protocol includes provision of
      equipment and resources, connection between the associated NICU and the remote monitoring
      center called the Central of Surveillance and Intelligence (CSI), training and teaching of
      all health care professional team of each NICU, and customized multiparametric recordings of
      biological signals of each patient monitoring. At the CSI, a team is available 24 hours a day
      all year around, allowing for case discussions and simplified reports of brain monitoring
      information on the patient monitor's display every 6 hours.

      Variables Population demographics: gender, gestational age at birth, gestational age ≤ 32
      weeks and < 37 weeks, Apgar score at 1 min, 5 min and 10 min, birth weight, current weight,
      inborn or outborn, use of antenatal steroids and magnesium sulfate, type of birth.

      Primary diagnosis: seizure, anoxia/mild HIE, moderate or severe HIE/cooling, neurologic
      abnormalities without specific diagnosis, congenital central nervous system (CNS) anomalies,
      grade III or IV intraventricular hemorrhage (IVH) or hydrocephalus, periventricular
      leukomalacia, meningitis, neural tube defects, stroke, cyanotic congenital heart defect
      (CHD), prematurity, gestational age ≤ 32 weeks, meconium aspiration syndrome,
      cardiorespiratory instability, necrotizing enterocolitis, metabolic disease, extracorporeal
      membrane oxygenation (ECMO)/pre-ECMO and any other medical conditions not listed here.

      For descriptive analysis of the 2 main outcomes (use of the PBSF protocol and clinical
      outcomes) patients will be them divided into two groups accordingly to their primary
      diagnosis: neurological or clinical.

      Data sources / measurement Patient demographics, diagnosis and clinical outcomes will be
      extracted from the medical charts of each patient enrolled and entered in the PBSF database.
      The use of the PBSF protocol will be measured with the data collected by the CSI center
      continuously. Details of these recordings are provided on Appendix 2.

      Bias To address potential source of bias related to financial availability, the 2 main
      outcomes of interest will be also adjusted based on the unit primary profile: private,
      foundation or public.

      Study size Based on our current experience, there are an average of 5 patients per month with
      criteria for neurocritical care on each center, making a total of 3,240 eligible patients
      during a three years period. Considering a 30% loss due to refusal to consent,
      non-availability of the research team or missing data, we expect to recruit 2,268 infants
      from all study centers (around 756 patients per year).

      Statistical methods Categorical variables will be analyzed by descriptive statistics and
      presented as number of valid cases and percentage (%). Numeric variables will be analyzed as
      mean and standard deviation, median and interquartile ranges, or coefficient intervals.
      Chi-square test (or Fisher's exact test) will be performed to analyze categorical variables
      and the Student's t test, or Wilcoxon rank sum test will be used to check for significant
      differences between the two groups. A p value of <0.05 will be considered statistically
      significant. The confidence interval considered will be 95%. Analysis of variability
      (distribution) per site for each variable of the 2 main outcomes will also be performed.
      ANOVA with post hoc Bonferroni will be used to compare outcomes over time, i.e. between years
      1, 2 and 3 and Kaplan Meier curves will be generated to follow the evolution of outcomes over
      time for the 2 groups of patients: neurologic and clinical.

      Results Participants. A flow chart of all eligible and enrolled patients will be produced,
      and the total number of patients will be reported, overall and per center.

      Descriptive data Population demographics: male, n (%); gestational age at birth, weeks, mean
      (SD); gestational age ≤ 32 wk, n(%); Gestational age < 37 wk, n (%); Apgar score at 1 min, at
      5 min, and at 10min, median (IQR); birth weight, grams, mean (SD); current weight, grams,
      mean (SD); Inborn, n (%); use of antenatal steroids and magnesium sulfate, n (%); Caesarean,
      n(%).

      Primary outcomes:

      Use of the PBSF protocol

        1. Use of aEEG/EEG monitoring

        2. Duration of aEEG/EEG monitoring

        3. Number primary neurologic or medical patients with aEEG or EEG monitoring and the
           duration of the monitoring (hours)

        4. Number of primary neurologic or medical patients with NIRS monitoring and the duration
           of the NIRS monitoring (hours)

        5. Number of primary neurologic or medical patients with brain MRI, neurology consult, and
           neurosurgery consult.

        6. Number of clinical case discussions and videoconference meetings

      Clinical outcomes

        1. Length of hospital stay

        2. Number of electroencephalographic seizures during hospitalization

        3. Use and types of anticonvulsants administered

        4. Number and types of anticonvulsants prescribed at discharge

        5. Use and types of inotropes administered during NICU stay

        6. Use and types of fluid resuscitation administered during NICU stay

        7. Death before hospital discharge

        8. Number of patients referred to neurology or neurosurgery

        9. Number of patients referred to high-risk infant follow-up*

      Secondary outcomes:

      Use of the PBSF protocol

        1. Number of remote communications between CSI and local team

        2. Number of reports issued for aEEG / EEG exams with or without the use of NIRS

        3. Number of patients who performed Therapeutic Hypothermia

        4. Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and
           alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and
           cranial ultrasonography (cranial US) performed during hospitalization

        5. Association of pathological brain monitoring findings with morbi-mortality and length of
           hospital stay

        6. Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia,
           thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary
           hypertension

        7. Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor
           positioning

        8. Association of pathological brain monitoring findings with evaluation of
           neurodevelopment by application of the Bayley test between 18 and 24 months of life
observational model: Cohort
time perspective: Prospective
measure: Applicability of telemedicine model for monitored infants
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Applicability of telemedicine model for recorded remote monitoring
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Use of aEEG/EEG monitoring
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Duration of aEEG/EEG monitoring
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours)
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours)
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult.
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of clinical case discussions and videoconference meetings
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Length of hospital stay
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of electroencephalographic seizures during hospitalization
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Use and types of anticonvulsants administered
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number and types of anticonvulsants prescribed at discharge
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Use and types of inotropes administered during NICU stay
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Use and types of fluid resuscitation administered during NICU stay
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Death before hospital discharge
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of patients referred to neurology or neurosurgery
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of patients referred to high-risk infant follow-up
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of remote communications between CSI and local team
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of reports issued for aEEG / EEG exams with or without the use of NIRS
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Number of patients who performed Therapeutic Hypothermia
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
measure: Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life
time frame: 3 years period
description: Each outcome for all sites together will be also compared for changes over time from Year 1 (2021) to Year 3 (2023).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 3 Months
healthy volunteers: No
last name: Guilherme M Sant'Anna, PhD
role: Study Director
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Gabriel FT Variane, MD
phone: 5511996243520
email: gabriel.variane@pbsf.com.br
last name: Daniela P Rodrigues, BSN, RN, CNS
phone: 5511983707307
email: daniela.rodrigues@pbsf.com.br
facility: 
contact: 
contact backup: 
investigator: 
facility: 
contact: 
contact backup: 
investigator: 
country: Brazil
url: https://apps.who.int/iris/handle/10665/63857
description: 25. World Health Organization. A health telematics policy in support of WHO's Health-for-All Strategy for Global Health Development. Geneva (Switzerland); 1998.
url: https://apps.who.int/iris/handle/10665/44497
description: 26. World Health Organization. Telemedicine: Opportunities and Development in Member States: Report on the second global survey on eHealth. Geneva (Switzerland); 2010.
url: https://datasus.saude.gov.br/informacoes-de-saude-tabnet/
description: 30. Ministério da Saúde. DATASUS. [online] Tabnet. [accessed on Jan 10th 2018]
citation: Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.
PMID: 20554402
citation: Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5.
PMID: 15752534
citation: Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol. 2006 Jun;35(3):706-18. doi: 10.1093/ije/dyl043. Epub 2006 Mar 23.
PMID: 16556647
citation: Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991 May;25(2):135-48. doi: 10.1016/0378-3782(91)90191-5.
PMID: 1713544
citation: Robertson CMT. Long-term follow-up of term infants with perinatal asphyxia. In: Stevenson DK, Benitz WE, Sunshine P. Fetal and neonatal brain injury. 3. Ed. New York: Cambridge University; 2003. p.829-58.
citation: de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F220-4. doi: 10.1136/adc.2008.148205.
PMID: 20444814
citation: Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F380-7. doi: 10.1136/adc.2004.067520.
PMID: 16113154
citation: Blencowe H, Lee AC, Cousens S, Bahalim A, Narwal R, Zhong N, Chou D, Say L, Modi N, Katz J, Vos T, Marlow N, Lawn JE. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013 Dec;74 Suppl 1(Suppl 1):17-34. doi: 10.1038/pr.2013.204.
PMID: 24366461
citation: Hellstrom-Westas L, Rosen I. Continuous brain-function monitoring: state of the art in clinical practice. Semin Fetal Neonatal Med. 2006 Dec;11(6):503-11. doi: 10.1016/j.siny.2006.07.011. Epub 2006 Oct 24.
PMID: 17067863
citation: Hellström-Westas L, Rosén I, de Vries LS, Greisen G. Amplitude-integrated EEG Classification and Interpretation in Preterm and Term Infants. NeoReviews. 2006;7(2):e76-87.
citation: Shah DK, Mackay MT, Lavery S, Watson S, Harvey AS, Zempel J, Mathur A, Inder TE. Accuracy of bedside electroencephalographic monitoring in comparison with simultaneous continuous conventional electroencephalography for seizure detection in term infants. Pediatrics. 2008 Jun;121(6):1146-54. doi: 10.1542/peds.2007-1839.
PMID: 18519484
citation: Mastrangelo M, Fiocchi I, Fontana P, Gorgone G, Lista G, Belcastro V. Acute neonatal encephalopathy and seizures recurrence: a combined aEEG/EEG study. Seizure. 2013 Nov;22(9):703-7. doi: 10.1016/j.seizure.2013.05.006. Epub 2013 May 29.
PMID: 23725740
citation: Shah DK, Zempel J, Barton T, Lukas K, Inder TE. Electrographic seizures in preterm infants during the first week of life are associated with cerebral injury. Pediatr Res. 2010 Jan;67(1):102-6. doi: 10.1203/PDR.0b013e3181bf5914.
PMID: 19745782
citation: Payne ET, Zhao XY, Frndova H, McBain K, Sharma R, Hutchison JS, Hahn CD. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014 May;137(Pt 5):1429-38. doi: 10.1093/brain/awu042. Epub 2014 Mar 4.
PMID: 24595203
citation: van Rooij LG, Toet MC, van Huffelen AC, Groenendaal F, Laan W, Zecic A, de Haan TR, van Straaten IL, Vrancken S, van Wezel G, van der Sluijs J, Ter Horst H, Gavilanes D, Laroche S, Naulaers G, de Vries LS. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics. 2010 Feb;125(2):e358-66. doi: 10.1542/peds.2009-0136. Epub 2010 Jan 25.
PMID: 20100767
citation: Vesoulis ZA, Inder TE, Woodward LJ, Buse B, Vavasseur C, Mathur AM. Early electrographic seizures, brain injury, and neurodevelopmental risk in the very preterm infant. Pediatr Res. 2014 Apr;75(4):564-9. doi: 10.1038/pr.2013.245. Epub 2013 Dec 23.
PMID: 24366515
citation: Srinivasakumar P, Zempel J, Trivedi S, Wallendorf M, Rao R, Smith B, Inder T, Mathur AM. Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial. Pediatrics. 2015 Nov;136(5):e1302-9. doi: 10.1542/peds.2014-3777. Epub 2015 Oct 19.
PMID: 26482675
citation: Hellstrom-Westas L, Rosen I, Svenningsen NW. Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. Arch Dis Child Fetal Neonatal Ed. 1995 Jan;72(1):F34-8. doi: 10.1136/fn.72.1.f34.
PMID: 7743282
citation: Thoresen M, Hellstrom-Westas L, Liu X, de Vries LS. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with asphyxia. Pediatrics. 2010 Jul;126(1):e131-9. doi: 10.1542/peds.2009-2938. Epub 2010 Jun 21.
PMID: 20566612
citation: van Rooij LG, Toet MC, Osredkar D, van Huffelen AC, Groenendaal F, de Vries LS. Recovery of amplitude integrated electroencephalographic background patterns within 24 hours of perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed. 2005 May;90(3):F245-51. doi: 10.1136/adc.2004.064964.
PMID: 15846017
citation: Del Rio R, Ochoa C, Alarcon A, Arnaez J, Blanco D, Garcia-Alix A. Amplitude Integrated Electroencephalogram as a Prognostic Tool in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review. PLoS One. 2016 Nov 1;11(11):e0165744. doi: 10.1371/journal.pone.0165744. eCollection 2016.
PMID: 27802300
citation: van Bel F, Lemmers P, Naulaers G. Monitoring neonatal regional cerebral oxygen saturation in clinical practice: value and pitfalls. Neonatology. 2008;94(4):237-44. doi: 10.1159/000151642. Epub 2008 Sep 11.
PMID: 18784420
citation: Alderliesten T, De Vis JB, Lemmers PM, Hendrikse J, Groenendaal F, van Bel F, Benders MJ, Petersen ET. Brain oxygen saturation assessment in neonates using T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy. J Cereb Blood Flow Metab. 2017 Mar;37(3):902-913. doi: 10.1177/0271678X16647737. Epub 2016 Jul 20.
PMID: 27151900
citation: Chock VY, Rose LA, Mante JV, Punn R. Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatr Res. 2016 Nov;80(5):675-680. doi: 10.1038/pr.2016.148. Epub 2016 Sep 7.
PMID: 27603562
citation: Hall RW, Hall-Barrow J, Garcia-Rill E. Neonatal regionalization through telemedicine using a community-based research and education core facility. Ethn Dis. 2010 Winter;20(1 Suppl 1):S1-136-40.
PMID: 20521402
citation: Burke BL Jr, Hall RW; SECTION ON TELEHEALTH CARE. Telemedicine: Pediatric Applications. Pediatrics. 2015 Jul;136(1):e293-308. doi: 10.1542/peds.2015-1517.
PMID: 26122813
citation: McConnochie K, Wood N, Herendeen N, ten Hoopen C, Denk L, Neuderfer J. Integrating telemedicine in urban pediatric primary care: provider perspectives and performance. Telemed J E Health. 2010 Apr;16(3):280-8. doi: 10.1089/tmj.2009.0112.
PMID: 20406114
citation: Variane GF, Cunha LM, Pinto P, Brandao P, Mascaretti RS, Magalhaes M, Sant'Anna GM. Therapeutic Hypothermia in Brazil: A MultiProfessional National Survey. Am J Perinatol. 2019 Sep;36(11):1150-1156. doi: 10.1055/s-0038-1676052. Epub 2018 Dec 15.
PMID: 30553235
citation: Triulzi F, Parazzini C, Righini A. Patterns of damage in the mature neonatal brain. Pediatr Radiol. 2006 Jul;36(7):608-20. doi: 10.1007/s00247-006-0203-5. Epub 2006 May 18.
PMID: 16770665
citation: Ferriero DM. Neonatal brain injury. N Engl J Med. 2004 Nov 4;351(19):1985-95. doi: 10.1056/NEJMra041996. No abstract available.
PMID: 15525724
citation: Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.
PMID: 29095433
citation: Abend NS, Wusthoff CJ, Goldberg EM, Dlugos DJ. Electrographic seizures and status epilepticus in critically ill children and neonates with encephalopathy. Lancet Neurol. 2013 Dec;12(12):1170-9. doi: 10.1016/S1474-4422(13)70246-1.
PMID: 24229615
citation: Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2008 May;93(3):F187-91. doi: 10.1136/adc.2005.086314. Epub 2007 Jul 11.
PMID: 17626147
citation: Burnett AC, Cheong JLY, Doyle LW. Biological and Social Influences on the Neurodevelopmental Outcomes of Preterm Infants. Clin Perinatol. 2018 Sep;45(3):485-500. doi: 10.1016/j.clp.2018.05.005.
PMID: 30144851
citation: Joseph RM, O'Shea TM, Allred EN, Heeren T, Hirtz D, Jara H, Leviton A, Kuban KC; ELGAN Study Investigators. Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns. Pediatrics. 2016 Apr;137(4):e20154343. doi: 10.1542/peds.2015-4343. Epub 2016 Mar 22.
PMID: 27006473
citation: Cheong JL, Doyle LW, Burnett AC, Lee KJ, Walsh JM, Potter CR, Treyvaud K, Thompson DK, Olsen JE, Anderson PJ, Spittle AJ. Association Between Moderate and Late Preterm Birth and Neurodevelopment and Social-Emotional Development at Age 2 Years. JAMA Pediatr. 2017 Apr 3;171(4):e164805. doi: 10.1001/jamapediatrics.2016.4805. Epub 2017 Apr 3.
PMID: 28152144
citation: Bosi G, Garani G, Scorrano M, Calzolari E; IMER Working Party. Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry. J Pediatr. 2003 Jun;142(6):690-8. doi: 10.1067/mpd.2003.243. Erratum In: J Pediatr. 2003 Oct;143(4):531.
PMID: 12838199
citation: Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.
PMID: 12084585
citation: Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH Jr, Li J, Smith SE, Bellinger DC, Mahle WT; American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation. 2012 Aug 28;126(9):1143-72. doi: 10.1161/CIR.0b013e318265ee8a. Epub 2012 Jul 30.
PMID: 22851541
citation: Dimitropoulos A, McQuillen PS, Sethi V, Moosa A, Chau V, Xu D, Brant R, Azakie A, Campbell A, Barkovich AJ, Poskitt KJ, Miller SP. Brain injury and development in newborns with critical congenital heart disease. Neurology. 2013 Jul 16;81(3):241-8. doi: 10.1212/WNL.0b013e31829bfdcf. Epub 2013 Jun 14.
PMID: 23771484
citation: Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurologic status of newborns with congenital heart defects before open heart surgery. Pediatrics. 1999 Feb;103(2):402-8. doi: 10.1542/peds.103.2.402.
PMID: 9925832
citation: Gunn JK, Beca J, Hunt RW, Olischar M, Shekerdemian LS. Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease. Intensive Care Med. 2012 Sep;38(9):1539-47. doi: 10.1007/s00134-012-2608-y. Epub 2012 Jun 1.
PMID: 22653373
citation: Gunn JK, Beca J, Penny DJ, Horton SB, d'Udekem YA, Brizard CP, Finucane K, Olischar M, Hunt RW, Shekerdemian LS. Amplitude-integrated electroencephalography and brain injury in infants undergoing Norwood-type operations. Ann Thorac Surg. 2012 Jan;93(1):170-6. doi: 10.1016/j.athoracsur.2011.08.014. Epub 2011 Nov 9.
PMID: 22075220
citation: Toso PA, Gonzalez AJ, Perez ME, Kattan J, Fabres JG, Tapia JL, Gonzalez HS. Clinical utility of early amplitude integrated EEG in monitoring term newborns at risk of neurological injury. J Pediatr (Rio J). 2014 Mar-Apr;90(2):143-8. doi: 10.1016/j.jped.2013.07.004. Epub 2013 Oct 30.
PMID: 24184304
citation: Shah NA, Wusthoff CJ. How to use: amplitude-integrated EEG (aEEG). Arch Dis Child Educ Pract Ed. 2015 Apr;100(2):75-81. doi: 10.1136/archdischild-2013-305676. Epub 2014 Jul 17.
PMID: 25035312
citation: Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854. Erratum In: N Engl J Med. 2010 Mar 18;362(11):1056.
PMID: 19797281
citation: Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70. doi: 10.1016/S0140-6736(05)17946-X.
PMID: 15721471
citation: Simbruner G, Mittal RA, Rohlmann F, Muche R; neo.nEURO.network Trial Participants. Systemic hypothermia after neonatal encephalopathy: outcomes of neo.nEURO.network RCT. Pediatrics. 2010 Oct;126(4):e771-8. doi: 10.1542/peds.2009-2441. Epub 2010 Sep 20.
PMID: 20855387
citation: Skranes JH, Lohaugen G, Schumacher EM, Osredkar D, Server A, Cowan FM, Stiris T, Fugelseth D, Thoresen M. Amplitude-Integrated Electroencephalography Improves the Identification of Infants with Encephalopathy for Therapeutic Hypothermia and Predicts Neurodevelopmental Outcomes at 2 Years of Age. J Pediatr. 2017 Aug;187:34-42. doi: 10.1016/j.jpeds.2017.04.041. Epub 2017 May 23.
PMID: 28549636
citation: Sarkar S, Barks JD, Donn SM. Should amplitude-integrated electroencephalography be used to identify infants suitable for hypothermic neuroprotection? J Perinatol. 2008 Feb;28(2):117-22. doi: 10.1038/sj.jp.7211882. Epub 2007 Nov 15.
PMID: 18004390
citation: Chandrasekaran M, Chaban B, Montaldo P, Thayyil S. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a meta-analysis. J Perinatol. 2017 Jun;37(6):684-689. doi: 10.1038/jp.2017.14. Epub 2017 Mar 2.
PMID: 28252661
citation: Ancora G, Maranella E, Grandi S, Sbravati F, Coccolini E, Savini S, Faldella G. Early predictors of short term neurodevelopmental outcome in asphyxiated cooled infants. A combined brain amplitude integrated electroencephalography and near infrared spectroscopy study. Brain Dev. 2013 Jan;35(1):26-31. doi: 10.1016/j.braindev.2011.09.008. Epub 2011 Nov 13.
PMID: 22082686
citation: Jain SV, Pagano L, Gillam-Krakauer M, Slaughter JC, Pruthi S, Engelhardt B. Cerebral regional oxygen saturation trends in infants with hypoxic-ischemic encephalopathy. Early Hum Dev. 2017 Oct;113:55-61. doi: 10.1016/j.earlhumdev.2017.07.008. Epub 2017 Aug 1.
PMID: 28772198
citation: Lemmers PM, Zwanenburg RJ, Benders MJ, de Vries LS, Groenendaal F, van Bel F, Toet MC. Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value? Pediatr Res. 2013 Aug;74(2):180-5. doi: 10.1038/pr.2013.84. Epub 2013 May 31.
PMID: 23728382
citation: Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R, Stewart J, Volpe J, Bourgeois B, du Plessis AJ. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics. 2006 Apr;117(4):1270-80. doi: 10.1542/peds.2005-1178.
PMID: 16585324
citation: Hellstrom-Westas L, Rosen I, Svenningsen NW. Cerebral function monitoring during the first week of life in extremely small low birthweight (ESLBW) infants. Neuropediatrics. 1991 Feb;22(1):27-32. doi: 10.1055/s-2008-1071411.
PMID: 2038424
citation: Wikstrom S, Pupp IH, Rosen I, Norman E, Fellman V, Ley D, Hellstrom-Westas L. Early single-channel aEEG/EEG predicts outcome in very preterm infants. Acta Paediatr. 2012 Jul;101(7):719-26. doi: 10.1111/j.1651-2227.2012.02677.x. Epub 2012 Apr 24.
PMID: 22530996
citation: Soubasi V, Mitsakis K, Sarafidis K, Griva M, Nakas CT, Drossou V. Early abnormal amplitude-integrated electroencephalography (aEEG) is associated with adverse short-term outcome in premature infants. Eur J Paediatr Neurol. 2012 Nov;16(6):625-30. doi: 10.1016/j.ejpn.2012.02.008. Epub 2012 Mar 15.
PMID: 22425390
citation: Klebermass K, Olischar M, Waldhoer T, Fuiko R, Pollak A, Weninger M. Amplitude-integrated EEG pattern predicts further outcome in preterm infants. Pediatr Res. 2011 Jul;70(1):102-8. doi: 10.1203/PDR.0b013e31821ba200.
PMID: 21436758
citation: Variane GFT, Magalhaes M, Gasperine R, Alves HCBR, Scoppetta TLPD, Figueredo RJG, Rodrigues FPM, Netto A, Mimica MJ, Gallacci CB. Early amplitude-integrated electroencephalography for monitoring neonates at high risk for brain injury. J Pediatr (Rio J). 2017 Sep-Oct;93(5):460-466. doi: 10.1016/j.jped.2016.12.003. Epub 2017 Feb 23.
PMID: 28238681
citation: Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, Claris O, Dempsey E, Franz AR, Fumagalli M, Gluud C, Grevstad B, Hagmann C, Lemmers P, van Oeveren W, Pichler G, Plomgaard AM, Riera J, Sanchez L, Winkel P, Wolf M, Greisen G. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015 Jan 5;350:g7635. doi: 10.1136/bmj.g7635.
PMID: 25569128
citation: Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics. 2008 Jan;121(1):142-7. doi: 10.1542/peds.2007-0925.
PMID: 18166568
citation: Underwood MA, Milstein JM, Sherman MP. Near-infrared spectroscopy as a screening tool for patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2007;91(2):134-9. doi: 10.1159/000097131. Epub 2006 Nov 20.
PMID: 17344664
citation: Olischar M, Shany E, Aygun C, Azzopardi D, Hunt RW, Toet MC, Hamosh A, de Vries LS, Hellstrom-Westas L, Theda C. Amplitude-integrated electroencephalography in newborns with inborn errors of metabolism. Neonatology. 2012;102(3):203-11. doi: 10.1159/000339567. Epub 2012 Jul 12.
PMID: 22797054
citation: Helderman JB, Welch CD, Leng X, O'Shea TM. Sepsis-associated electroencephalographic changes in extremely low gestational age neonates. Early Hum Dev. 2010 Aug;86(8):509-13. doi: 10.1016/j.earlhumdev.2010.06.006. Epub 2010 Aug 12.
PMID: 20708356
citation: ter Horst HJ, Mud M, Roofthooft MT, Bos AF. Amplitude integrated electroencephalographic activity in infants with congenital heart disease before surgery. Early Hum Dev. 2010 Dec;86(12):759-64. doi: 10.1016/j.earlhumdev.2010.08.028.
PMID: 20970264
citation: Latal B, Wohlrab G, Brotschi B, Beck I, Knirsch W, Bernet V. Postoperative Amplitude-Integrated Electroencephalography Predicts Four-Year Neurodevelopmental Outcome in Children with Complex Congenital Heart Disease. J Pediatr. 2016 Nov;178:55-60.e1. doi: 10.1016/j.jpeds.2016.06.050. Epub 2016 Jul 22.
PMID: 27453368
citation: Dodge-Khatami J, Gottschalk U, Eulenburg C, Wendt U, Schnegg C, Rebel M, Reichenspurner H, Dodge-Khatami A. Prognostic value of perioperative near-infrared spectroscopy during neonatal and infant congenital heart surgery for adverse in-hospital clinical events. World J Pediatr Congenit Heart Surg. 2012 Apr 1;3(2):221-8. doi: 10.1177/2150135111426298.
PMID: 23804778
citation: Colasacco C, Worthen M, Peterson B, Lamberti J, Spear R. Near-infrared spectroscopy monitoring to predict postoperative renal insufficiency following repair of congenital heart disease. World J Pediatr Congenit Heart Surg. 2011 Oct 1;2(4):536-40. doi: 10.1177/2150135111411932.
PMID: 23804464
citation: Hoffman GM, Ghanayem NS, Scott JP, Tweddell JS, Mitchell ME, Mussatto KA. Postoperative Cerebral and Somatic Near-Infrared Spectroscopy Saturations and Outcome in Hypoplastic Left Heart Syndrome. Ann Thorac Surg. 2017 May;103(5):1527-1535. doi: 10.1016/j.athoracsur.2016.09.100. Epub 2016 Dec 21.
PMID: 28012642
citation: Clair MP, Rambaud J, Flahault A, Guedj R, Guilbert J, Guellec I, Durandy A, Demoulin M, Jean S, Mitanchez D, Chalard F, Sileo C, Carbajal R, Renolleau S, Leger PL. Prognostic value of cerebral tissue oxygen saturation during neonatal extracorporeal membrane oxygenation. PLoS One. 2017 Mar 9;12(3):e0172991. doi: 10.1371/journal.pone.0172991. eCollection 2017.
PMID: 28278259
citation: Sood BG, McLaughlin K, Cortez J. Near-infrared spectroscopy: applications in neonates. Semin Fetal Neonatal Med. 2015 Jun;20(3):164-72. doi: 10.1016/j.siny.2015.03.008. Epub 2015 Apr 29.
PMID: 25934116
citation: Johnson BA, Hoffman GM, Tweddell JS, Cava JR, Basir M, Mitchell ME, Scanlon MC, Mussatto KA, Ghanayem NS. Near-infrared spectroscopy in neonates before palliation of hypoplastic left heart syndrome. Ann Thorac Surg. 2009 Feb;87(2):571-7; discussion 577-9. doi: 10.1016/j.athoracsur.2008.10.043.
PMID: 19161781
citation: Hanson SJ, Berens RJ, Havens PL, Kim MK, Hoffman GM. Effect of volume resuscitation on regional perfusion in dehydrated pediatric patients as measured by two-site near-infrared spectroscopy. Pediatr Emerg Care. 2009 Mar;25(3):150-3. doi: 10.1097/PEC.0b013e31819a7f60.
PMID: 19262423
citation: Pichler G, Holler N, Baik-Schneditz N, Schwaberger B, Mileder L, Stadler J, Avian A, Pansy J, Urlesberger B. Avoiding Arterial Hypotension in Preterm Neonates (AHIP)-A Single Center Randomised Controlled Study Investigating Simultaneous Near Infrared Spectroscopy Measurements of Cerebral and Peripheral Regional Tissue Oxygenation and Dedicated Interventions. Front Pediatr. 2018 Feb 1;6:15. doi: 10.3389/fped.2018.00015. eCollection 2018.
PMID: 29450194
citation: Variane GFT, Chock VY, Netto A, Pietrobom RFR, Van Meurs KP. Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology. Front Pediatr. 2020 Jan 21;7:560. doi: 10.3389/fped.2019.00560. eCollection 2019.
PMID: 32039117
citation: Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8(3):e58834. doi: 10.1371/journal.pone.0058834. Epub 2013 Mar 19.
PMID: 23527034
citation: Frenkel N, Friger M, Meledin I, Berger I, Marks K, Bassan H, Shany E. Neonatal seizure recognition--comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings. Clin Neurophysiol. 2011 Jun;122(6):1091-7. doi: 10.1016/j.clinph.2010.09.028. Epub 2011 Jan 7.
PMID: 21216190
citation: Rakshasbhuvankar A, Paul S, Nagarajan L, Ghosh S, Rao S. Amplitude-integrated EEG for detection of neonatal seizures: a systematic review. Seizure. 2015 Dec;33:90-8. doi: 10.1016/j.seizure.2015.09.014. Epub 2015 Sep 26.
PMID: 26456517
citation: Udeh C, Udeh B, Rahman N, Canfield C, Campbell J, Hata JS. Telemedicine/Virtual ICU: Where Are We and Where Are We Going? Methodist Debakey Cardiovasc J. 2018 Apr-Jun;14(2):126-133. doi: 10.14797/mdcj-14-2-126.
PMID: 29977469
citation: Kahn JM, Le TQ, Barnato AE, Hravnak M, Kuza CC, Pike F, Angus DC. ICU Telemedicine and Critical Care Mortality: A National Effectiveness Study. Med Care. 2016 Mar;54(3):319-25. doi: 10.1097/MLR.0000000000000485.
PMID: 26765148
citation: Maldonado JM, Marques AB, Cruz A. Telemedicine: challenges to dissemination in Brazil. Cad Saude Publica. 2016 Nov 3;32Suppl 2(Suppl 2):e00155615. doi: 10.1590/0102-311X00155615. English, Portuguese.
PMID: 27828681
responsible party type: Principal Investigator
investigator affiliation: Protecting Brains Saving Futures
investigator full name: Dr Gabriel Variane
investigator title: Physician
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Cross Infection
mesh term: Central Nervous System Infections
mesh term: Brain Injuries
mesh term: Seizures
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain
mesh term: Perinatal Death
mesh term: Heart Defects, Congenital
mesh term: Metabolism, Inborn Errors
mesh term: Hemorrhage