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Long Term Follow up of Children Enrolled in the REDvent Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03709199
Recruitment Status : Recruiting
First Posted : October 17, 2018
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Los Angeles

Brief Summary:

This is a prospective observational follow-up study of children enrolled in a single center randomized controlled trial (REDvent).

Nearly 50% of adult Acute Respiratory Distress Syndrome (ARDS) survivors are left with significant abnormalities in pulmonary, physical, neurocognitive function and Health Related Quality of Life (HRQL) which may persist for years.Data in pediatric ARDS (PARDS) survivors is limited. More importantly, there are no data identifying potentially modifiable factors during ICU care which are associated with long term impairments, which may include medication choices, or complications from mechanical ventilator (MV) management in the ICU including ventilator induced lung injury (VILI) or ventilator induced diaphragm dysfunction (VIDD).

The Real-time effort driven ventilator (REDvent) trial is testing a ventialtor management algorithm which may prevent VIDD and VILI. VIDD and VILI have strong biologic plausibility to affect the post-ICU health of children with likely sustained effects on lung repair and muscle strength. Moreover, common medication choices (i.e. neuromuscular blockade, corticosteroids) or other complications in the ICU (i.e. delirium) are likely to have independent effects on the long term health of these children. This proposed study will obtain serial follow-up of subjects enrolled in REDvent (intervention and control patients). The central hypothesis is that preventing VIDD, VILI and shortening time on MV will have a measureable impact on longer term function by mitigating abnormalities in pulmonary function (PFTs), neurocognitive function and emotional health, functional status and HRQL after hospital discharge for children with PARDS.

For all domains, the investigators will determine the frequency, severity and trajectory of recovery of abnormalities amongst PARDS survivors after ICU discharge, identify risk factors for their development, and determine if they are prevented by REDvent. They will leverage the detailed and study specific respiratory physiology data being obtained in REDvent, and use a variety of multi-variable models for comprehensive analysis. Completion of this study will enable the investigators to identify ICU related therapies associated with poor long term outcome, and determine whether they can be mitigated by REDvent.


Condition or disease Intervention/treatment
Respiratory Distress Syndrome, Adult Ventilator-Induced Lung Injury Neurocognitive Dysfunction Quality of Life Respiration Disorders Diagnostic Test: Ventilation Inhomogeneity Diagnostic Test: Diaphragm Ultrasound Diagnostic Test: Respiratory Inductance Plethysmography Diagnostic Test: Spirometry Diagnostic Test: Functional Residual Capacity Diagnostic Test: MIP/MEP Diagnostic Test: 6 minute walk test Diagnostic Test: Neurocognitive Testing Diagnostic Test: Emotional Health Assessment Diagnostic Test: Health Related Quality of Life Diagnostic Test: Functional Status Diagnostic Test: Respiratory Status Questionnaire

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Study Type : Observational
Estimated Enrollment : 240 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Intensive Care Unit Therapies and Mechanical Ventilation Strategy on Long Term Outcome in Pediatric ARDS A Follow-up of the Real-time Effort Driven VENTilator Management Study (REDvent)
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : June 1, 2023



Intervention Details:
  • Diagnostic Test: Ventilation Inhomogeneity
    Ventilation inhomogeneity will be measured using the Lung Clearance Index (LCI), derived from multiple breath Nitrogen washout during tidal breathing, measured by a mouthpiece or mask covering nose and mouth.
    Other Name: Lung Clearance Index
  • Diagnostic Test: Diaphragm Ultrasound
    Diaphragm thickness and contractile activity measured during tidal breathing.
  • Diagnostic Test: Respiratory Inductance Plethysmography
    Measure of thoraco-abdominal asynchrony during tidal breathing
    Other Name: Phase Angle
  • Diagnostic Test: Spirometry
    Measurement of Forced Expiratory Volume (FEV1), Forced Vital Capacity and other lung volumes using standard pulmonary function techniques
    Other Name: Pulmonary Function Tests
  • Diagnostic Test: Functional Residual Capacity
    Measurement using body box plethysmography of functional residual capacity and other lung volumes using standard pulmonary function techniques
    Other Name: Pulmonary Function Tests
  • Diagnostic Test: MIP/MEP
    Measurement of maximal inspiratory and expiratory pressures during airway occlusion
  • Diagnostic Test: 6 minute walk test
    Measurement of cardio-respiratory function and capabilities during treadmill walking for 6 minutes.
  • Diagnostic Test: Neurocognitive Testing
    Detailed in person neuro-cognitive testing using standardized inventories using either the Battelle Developmental Inventory, second edition (Battelle-2) (age birth to 5 years 11 months) and the Wechsler Intelligence Scale for Children, fifth edition (WISC-5, for age 6 years to 19 years).
  • Diagnostic Test: Emotional Health Assessment
    In person and written assessments of children and parents using the Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years and the UCLA PTSD Reaction Index (UCLA RI) for children ≥ 8 years.
  • Diagnostic Test: Health Related Quality of Life
    Standardized instruments to assess (in person, over the phone, or via mail) health related quality of life in children. Parent and child questionnaires.
    Other Name: PEDS-QL
  • Diagnostic Test: Functional Status
    Survey of overall functional status, administrated by asking a series of questions to patient and families.
    Other Name: Functional Status Scale
  • Diagnostic Test: Respiratory Status Questionnaire
    Survey of respiratory health, administrated by asking a series of questions to patient and families.


Primary Outcome Measures :
  1. Ventilation In-homogeneity using lung clearance index with nitrogen washout [ Time Frame: 6 months after ICU discharge ]
    Measured by lung clearance index during multiple breath nitrogen washout testing reported as percent predicted based on age and height as well as a raw number typically ranging from 5-15.

  2. Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests [ Time Frame: 3 months after ICU discharge ]
    Standardized IQ-like score derived from Batelle-2 or WISC-5 cognitive tests based on age. Children < 6 years will receive the Batelle-2 and children >=6 will receive the WISC-5. Overall score will be use for analysis with a higher value indicating better cognitive function. The range of "average" cognitive function lies between 90-109. Both tests are scored on the same scale

  3. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: 3 months after ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  4. Functional Status as measured by the pediatric functional status scale [ Time Frame: 3 months after ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline to 3 months will be considered as a decline in functional status.


Secondary Outcome Measures :
  1. Functional Residual Capacity (Lung volume at end-expiration). [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Measured by body box plethysmography and nitrogen washout techniques, normalized by age, height and gender. Values below or above normative values will be considered abnormal.

  2. Functional Residual Capacity (Lung volume at end-expiration). [ Time Frame: 6 months after ICU discharge ]
    Measured by body box plethysmography and nitrogen washout techniques, normalized by age, height and gender. Values below or above normative values will be considered abnormal.

  3. Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Respiratory Inductance Plethysmography belts are used during tidal breathing to measure thoraco-abdominal asyncrhony. Higher values will be considered abnormal with a range from 0-180.

  4. Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics) [ Time Frame: 6 Months after ICU Discharge ]
    Respiratory Inductance Plethysmography belts are used during tidal breathing to measure thoraco-abdominal asyncrhony. Higher values will be considered abnormal with a range from 0-180.

  5. Diaphragm Thickness on exhalation [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Diaphragm ultrasound measurement of thickness at end exhalation measured in zone of apposition of right hemi-diaphragm

  6. Diaphragm Thickness on exhalation [ Time Frame: 6 months after ICU discharge ]
    Diaphragm ultrasound measurement of thickness at end exhalation measured in zone of apposition of right hemi-diaphragm

  7. Diaphragm Thickness on inspiration [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Diaphragm ultrasound measurement of thickness at end inspiration measured in zone of apposition of right hemi-diaphragm

  8. Diaphragm Thickness on inspiration [ Time Frame: 6 months after ICU discharge ]
    Diaphragm ultrasound measurement of thickness at end inspiration measured in zone of apposition of right hemi-diaphragm

  9. Diaphragm Thickening fraction (measure of contractile activity) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Diaphragm ultrasound measurement calculated as (thickness at end inspiration-thickness at end expiration)/(thickness at end expiration) measured in zone of apposition of right hemi-diaphragm.

  10. Diaphragm Thickening fraction (measure of contractile activity) [ Time Frame: 6 months after ICU discharge ]
    Diaphragm ultrasound measurement calculated as (thickness at end inspiration-thickness at end expiration)/(thickness at end expiration) measured in zone of apposition of right hemi-diaphragm.

  11. Ventilation In-homogeneity using lung clearance index with nitrogen washout [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Measured by lung clearance index during multiple breath nitrogen washout testing reported as percent predicted based on age and height as well as a raw number typically ranging from 5-15.

  12. Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Spirometry based measures of pulmonary function of forced expiratory volume, normalized based on age, height, and gender and reported as percent predicted.

  13. Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 6 months after ICU discharge ]
    Spirometry based measures of pulmonary function of forced expiratory volume, normalized based on age, height, and gender and reported as percent predicted.

  14. Forced Vital Capacity (FVC) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Spirometry based measures of pulmonary function of forced vital capacity, normalized based on age, height, and gender and reported as percent predicted.

  15. Forced Vital Capacity (FVC) [ Time Frame: 6 months after ICU discharge ]
    Spirometry based measures of pulmonary function of forced vital capacity, normalized based on age, height, and gender and reported as percent predicted.

  16. Forced expiratory flow at 25-75% (FEF 25-75) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Spirometry based measures of pulmonary function of forced expiratory flow at 25-75% of breath, normalized based on age, height, and gender and reported as percent predicted.

  17. Forced expiratory flow at 25-75% (FEF 25-75) [ Time Frame: 6 months post ICU discharge ]
    Spirometry based measures of pulmonary function of forced expiratory flow at 25-75% of breath, normalized based on age, height, and gender and reported as percent predicted.

  18. VT - tidal volume from spirometry during tidal breathing [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Lung volume measurements obtained during tidal breathing, normalized in ml/kg ideal body weight.

  19. VT - tidal volume from spirometry during tidal breathing [ Time Frame: 6 months after ICU discharge ]
    Lung volume measurements obtained during tidal breathing, normalized in ml/kg ideal body weight.

  20. Total Lung Capacity- TLC measured during spirometry [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Lung volume measurements obtained during pulmonary function tests with spirometry and body box plethysmography to calculate total lung capacity, normalized by age, height and gender.

  21. Total Lung Capacity- TLC measured during spirometry [ Time Frame: 6 months after ICU discharge ]
    Lung volume measurements obtained during pulmonary function tests with spirometry and body box plethysmography to calculate total lung capacity, normalized by age, height and gender.

  22. Forced vital capacity- measured during spirometry [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Lung volume measurements obtained during pulmonary function tests with spirometry to calculate forced vital capacity, normalized by age, height and gender.

  23. Forced vital capacity- measured during spirometry [ Time Frame: 6 months after ICU discharge ]
    Lung volume measurements obtained during pulmonary function tests with spirometry to calculate forced vital capacity, normalized by age, height and gender.

  24. Respiratory Muscle Strength Maximum inspiratory pressure (MIP) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Maximal inspiratory pressure measurements during airway occlusion in cm H20

  25. Respiratory Muscle Strength Maximum inspiratory pressure (MIP) [ Time Frame: 6 months after ICU discharge ]
    Maximal inspiratory pressure measurements during airway occlusion in cm H20

  26. Respiratory Muscle Strength Maximum expiratory pressure (MEP) [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Maximal expiratory pressure measurements during airway occlusion in cm H20

  27. Respiratory Muscle Strength Maximum expiratory pressure (MEP) [ Time Frame: 6 months after ICU discharge ]
    Maximal expiratory pressure measurements during airway occlusion in cm H20

  28. Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests [ Time Frame: 12 months after ICU discharge ]
    Standardized IQ-like score derived from Batelle-2 or WISC-5 cognitive tests. Overall score will be use for analysis with a higher value indicating better cognitive function. The range of "average" cognitive function lies between 90-109.

  29. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  30. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: 1 month after ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  31. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: 2 months after ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  32. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: 6 months after ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  33. Health Related Quality of Life as measured by PedsQL generic core scale [ Time Frame: 12 months after ICU discharge ]
    PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  34. Functional Status as measured by the pediatric functional status scale [ Time Frame: ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.

  35. Functional Status as measured by the pediatric functional status scale [ Time Frame: 1 month after ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.

  36. Functional Status as measured by the pediatric functional status scale [ Time Frame: 2 months after ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.

  37. Functional Status as measured by the pediatric functional status scale [ Time Frame: 6 months after ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.

  38. Functional Status as measured by the pediatric functional status scale [ Time Frame: 12 months after ICU discharge ]
    Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline will be considered as a decline in functional status.

  39. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: ICU discharge ]
    Series of questions to detail respiratory based morbidity

  40. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: 1 month after ICU discharge ]
    Series of questions to detail respiratory based morbidity

  41. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: 2 months after ICU discharge ]
    Series of questions to detail respiratory based morbidity

  42. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: 3 months after ICU discharge ]
    Series of questions to detail respiratory based morbidity

  43. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: 6 months after ICU discharge ]
    Series of questions to detail respiratory based morbidity

  44. Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization. [ Time Frame: 12 months after ICU discharge ]
    Series of questions to detail respiratory based morbidity

  45. Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress [ Time Frame: 3 months after ICU discharge ]
    The Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years will be used to assess for emotional and behavioral abnormalities as a survey tool. The UCLA PTSD Reaction Index (UCLA RI) will be used for children ≥ 8 years. The UCLA RI is a semi-structured interview assessing for exposure to traumatic events and PTS in children.

  46. Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress [ Time Frame: 12 months after ICU discharge ]
    The Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years will be used to assess for emotional and behavioral abnormalities as a survey tool. The UCLA PTSD Reaction Index (UCLA RI) will be used for children ≥ 8 years. The UCLA RI is a semi-structured interview assessing for exposure to traumatic events and PTS in children.


Other Outcome Measures:
  1. 6 minute walk test [ Time Frame: Prior to Hospital Discharge and no more than 1 month after ICU discharge ]
    Measure of cardio-respiratory function after treadmill walking

  2. 6 minute walk test [ Time Frame: 6 months after ICU discharge ]
    Measure of cardio-respiratory function after treadmill walking



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Month to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This is a long term follow-up of children already enrolled in the RED-vent study.
Criteria

Inclusion Criteria:

  1. Children > 1 month (at least 44 weeks Corrected Gestational Age) and ≤ 18 years of age AND
  2. Supported on mechanical ventilation for pulmonary parenchymal disease (i.e., pneumonia, bronchiolitis, Pediatric Acute Respiratory Distress Syndrome (PARDS)) with Oxygen Saturation Index (OSI) ≥ 5 or Oxygenation Index (OI) ≥4 115 AND
  3. Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution) AND
  4. Enrolled in the REDvent Study

Exclusion Criteria (1-5 are REDvent exclusion):

  1. Contraindications to use of an esophageal catheter (i.e. severe mucosal bleeding, nasal encephalocele, transphenoidal surgery) OR
  2. Contraindications to use of RIP bands (i.e. omphalocele, chest immobilizer or cast) OR
  3. Conditions precluding diaphragm ultrasound measurement (i.e. abdominal wall defects, pregnancy) OR
  4. Conditions precluding conventional methods of weaning (i.e., status asthmaticus, severe lower airway obstruction, critical airway, intracranial hypertension, Extra Corporeal Life Support (ECLS), intubation for UAO, tracheostomy, DNR, severe chronic respiratory failure, spinal cord injury above lumbar region, cyanotic heart disease (unrepaired or palliated)) OR
  5. Primary Attending physician refuses (will be cleared with primary attending before approaching the patient) OR
  6. Death in the ICU OR
  7. New DNR orders during acute illness in ICU OR
  8. Primary Language not English or Spanish OR
  9. Children in foster care or a ward of the state.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03709199


Contacts
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Contact: Robinder G Khemani, MD 323-361-2376 rkhemani@chla.usc.edu

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Robinder G Khemani, MD       rkhemani@chla.usc.edu   
Sponsors and Collaborators
Children's Hospital Los Angeles
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Responsible Party: Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT03709199    
Other Study ID Numbers: CHLA-18-00354
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD with other researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Lung Injury
Acute Lung Injury
Ventilator-Induced Lung Injury
Respiration Disorders
Cognitive Dysfunction
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Wounds and Injuries
Cognition Disorders
Neurocognitive Disorders
Mental Disorders