Physiological Changes With High-Flow Nasal Cannula Compared to Nasal CPAP in Extremely Low Birth Weight Infants
Phase: NA
Conditions: Respiratory Distress Syndrome in Premature Infant
Sponsor: Sharp HealthCare

HFNC / IRB #1807906 
 
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Protocol 
 
 
HFNC 
Physiological Changes with High-Flow Nasal Cannula compared to Nasal 
CPAP in Extremely Low Birth Weight Infants.   
 
 
 
Sharp IRB number: 
 
1807906 
Protocol date & version:  
Version 1.1 
 
  
 
 
11Feb2019    
 
 
Principal Investigator:  
 
 
Anup Katheria, MD 
Sharp Mary Birch Hospital for Women and Newborns 
3003 Health Center Drive 
San Diego, CA  92123  
Anup.Katheria@sharp.com 
(P) 858 939-4170 
 
 
 
Sponsor: 
 
 
 
None 

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Objective 
 
 
To measure changes in physiologic parameters in extremely low birthweight 
(ELBW) infants on high-flow nasal cannula compared to nasal continuous positive 
airway pressure (nCPAP).  
 
Background and Significance 
 
 
Non-invasive ventilation with nCPAP is commonly used in ELBW neonates for 
post extubation respiratory support and improves the rate of extubation success. (1) 
Pressure is transmitted from the nCPAP device to distend the upper airways and lungs 
to promote gas exchange. (2) Nasal masks or short nasal prongs that fit snugly in the 
nose to provide nCPAP can cause damage to the delicate skin of the bridge of the nose 
or nasal septum. Although skin damage from nCPAP is usually mild it can lead to 
serious skin break down and functional and cosmetic side effects. High Flow Nasal 
Cannula (HFNC) are widely used in Neonatal Intensive Care Units (NICU’s) worldwide. 
HFNC have a simpler, softer interface leading to less nasal trauma and easier patient 
positioning facilitating mother infant bonding. (3) HFNC leads to significantly less nasal 
trauma than nCPAP in the first 7 days post extubation especially in ELBW infants. (4)  
Other benefits of HFNC include reduced infant pain scores and survey’s showing it is 
preferred by both nurses and parents. (5) Recent meta-analysis of HFNC in neonates 
have concluded “non-inferiority” (6) or “similar rates of efficacy” (7) compared to other 
methods of non-invasive respiratory support.  
 
There are currently inadequate data on the effects of HFNC in ELBW, or infants 
<29 weeks gestational age. A recent Cochrane Review (7) included only four small trials 
studying HFNC as a post-extubation modality including ELBW infants (1, 3, 8, 9). While 
nCPAP has been shown to be effective as post extubation support in infants with 
respiratory distress syndrome, it is unclear whether ELBW infants can be successfully 
transitioned to HFNC once they are stable on nCPAP, due to the small number of 
ELBW babies in previous studies. Further trials of HFNC in this population, which is the 
population at highest risk of chronic lung disease and neurodevelopmental impairment, 

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are required. Furthermore, the starting flow rates currently used for HFNC may vary 
based on the severity of lung disease, gestational age, and a variety of other factors 
including clinician preference. (10). A physiological study evaluating lung mechanics 
and hemodynamics comparing nCPAP to HFNC on 8 liters per minute may be a 
practical first step to understanding HFNC comparability to nCPAP.   
 
Research Design and Methods 
 
 
 
 
Prospective crossover study (nCPAP to HFNC and back to nCPAP) of 80 stable 
premature infants born at <29 weeks requiring nCPAP therapy at Sharp Mary Birch 
Hospital for Women & Newborns (SMBHWN) NICU. The primary endpoint to be used for 
efficacy evaluation is the percentage of atelectasis as measured by EIT. The non-
inferiority margin is set at 3% (0.03). In order to have at least 80 percent power with a 
one sided alpha of 0.05 at least 40 subjects in each arm would be required. If non-
inferiority is established by rejecting that the outcome event rate is worse by 1% or more 
in the HFNC group, then superiority will be tested at the 3% level.  For all superiority 
testing, the intention to treat analysis will be utilized with a per protocol analysis as a 
sensitivity analysis.  There are no published references using EIT. The study period is up 
to 8 hours. The enrollment period is estimated at 2-4 years or until the requisite sample 
size is achieved, whichever is earlier. The pace of enrollment will be influenced by the 
number of neonates born in the desired gestational age who are utilizing the type of 
respiratory support under study. 
 
The investigator will ensure that all physicians assisting in the trial are informed at monthly 
meetings, the respiratory therapists and nurses at the bedside will be educated at weekly 
meetings (change of shift and sign out rounds).   
 
Inclusion Criteria:  
• 
23 to 28+6 weeks at birth  
• 
Corrected gestational age less than or equal to 30 weeks 
 

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• 
   Over 72 hours of life 
• 
Stable on Nasal CPAP of 5-7cm H20  
• 
Hemodynamically stable 
• 
Tolerating routine handling 
• 
Nares size appropriate for Fisher & Paykel Optiflow Jr 2 HFNC size 
 
XS or small 
• 
Successfully extubated for 12 hours after administration of surfactant  
• 
Caffeine Citrate at a maintenance dose of 5 to 10 mg /kg 
• 
Transcutaneous monitoring in place 
• 
        Stable blood gas (pH ≥ 7.25 and PaCO2 < 60 mmHg torr) 
 
Exclusion Criteria:  
• 
Prior pneumothorax or evidence of pulmonary interstitial emphysema. 
• 
Prior or current pulmonary hemorrhage 
• 
Congenital malformations of the upper airway 
•      Congenital Diaphragmatic hernia or untreated bowel obstruction 
• 
Poor respiratory drive unresponsive to CPAP therapy. 
• 
Requirement of a nCPAP of >8 cmH20 or FiO2 > 0.3 to maintain 
 
oxygen saturations between 90-95 percent. 
• 
Receiving positive pressure breaths or SIPAP on prongs 
• 
Conflicting clinical trial 
• 
Clinically unstable per physician discretion  
 
 
 
Screening & the Informed Consent Process 
 
 
 
 
 
Subjects will be identified by reviewing the medical records of neonates in the NICU 
at SMBHWN, which will require a partial HIPAA waiver and informed consent waiver 
limited to screening purposes. The parents or guardians of the potential subjects will be 
approached for consent if: The subject qualifies for the trial after a review of the study 
inclusion and exclusion criteria, and the subject’s physician also agrees to allow 
participation in the trial. Consent will be obtained by the primary investigator or a delegated 

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sub-investigator or research associate prior to any research procedures. The mother, or 
legally authorized representative must sign the informed consent document. Mother (or 
surrogate mother) must sign a HIPAA authorization providing access to her medical 
records for collection of maternal data. Either mother or father or legal guardian can sign a 
HIPAA authorization providing access to the child’s medical records for data collection 
purposes. The subject’s legally authorized representatives will be given ample time to read 
the informed consent, ask questions of the research team, and discuss the study with their 
family and/or the subject’s physician. The informed consent process will be documented in 
the electronic medical record and copies of the signed and dated consent will be given to 
the subject’s representatives, placed in the subject’s physical chart, and stored in a locked 
cabinet in the offices of the Neonatal Research Institute.  
 
 
Description of Intervention 
 
 
Study Period 1 
 
 
 After informed consent is obtained, eligible infants who are stable on nCPAP 
therapy of 5-7 cm H20 achieved with a ventilator, an underwater “bubble” system, or a 
variable-flow device will be enrolled. (Figure 1) All of these methods of providing the 
therapy are done with FDA approved devices in current use in the NICU. NCPAP 
treatment can be delivered through short nasal prongs or a nasal mask with sizing per 
manufacturer’s instructions. A data acquisition cart will be placed at the subject’s bedside 
to collect hemodynamic and respiratory parameters measured including: Heart rate (HR), 
blood pressure (BP), respiratory rate (RR), fraction of inspired oxygen (FiO2), 
transcutaneous carbon dioxide (TcCO2), and peripheral oxygen saturation (SpO2) via 
bedside monitoring devices. A neonatal chest belt, sized to the infant’s chest 
circumference (nipple level) using warmed ultrasound gel applied to the belt beforehand, 
will collect regional lung volume measurements using electrical impedance tomography 
(EIT). EIT is currently not used for patient care management at SMBHWN. EIT’s use for 
patient care management is purely experimental. EIT, when used solely for physiologic 
data collection, its use is not subject to 21 CFR 50, 21 CFR 56, or 21 CFR 812. Subject 
video recording will capture apnea events and the interventions used to resolve them such 

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as positive pressure ventilation, repositioning, or stimulation. Data will be collected for  
approximately 15 minutes or less on nCPAP. Data collection via EIT will occur when the 
subject is in a quiet, sleeping state, and can be accomplished in a convenient time period 
when care givers or parents are not interacting with the subject. 
 
 
 
Study Period 2 
 
 
Once data has been collected  on nCPAP, the infant’s respiratory support will be 
crossed over to a HFNC Optiflow Jr 2 (Fisher & Paykel Healthcare, Auckland, New 
Zealand) at a flow rate of 8 LPM. (Figure 2) The size of the nasal cannula will be 
determined according to the manufacturer’s instructions in order to maintain a leak at the 
nares. After 30 minutes of cross over to a HFNC Optiflow Jr, identical data collection will  
be obtained for 15 minutes or less on HFNC as occurred in Study Period 1.  
 
 
 
Study Period 3 
 
 
 After 6 hours on HFNC of 8 LPM, identical data collection will be collected for 
approximately 15 minutes or less prior to cross back to nCPAP. 
 
           Study Period 4 
 The infant will then be crossed back to the nCPAP device and at the settings previously 
utilized in Study Period 1. The infant will remain on the nCPAP device and settings. After 
30 minutes of crossover to nCPAP, and infant is in a quiet, sleeping state, identical data 
collection will be obtained for approximately 15 minutes or less. The total duration of the 
study and data collection will be 8 hours or less. The infant’s body positon will be similar 
for each EIT measurement during the study periods. EIT will not be used for any medical 
decision making during or after the study period of 8 hours. Information for clinical decision 
making and any patient interventions will be guided by information from the NICU bedside 
monitors and dictated by the assessment of the clinical team.  
 
 
 
 

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Figure 1 Nasal Continuous Positive Airway Pressure with Inca prongs 
 
 
 
Figure 2: High Flow Nasal Cannula Optiflow Jr 2 
 
 

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Patient Discontinuation and withdrawal 
 
 
The participant’s parents are free to withdraw the participant from the trial 
at any time, and this will not have any consequences for the participant’s further 
treatment. Parents will be notified if the subject fails HFNC. The attending 
physician can withdraw the participant from the trial at any time.  
HFNC failure criteria: 
 
Subjects should be returned to nCPAP if at HFNC of 8 LPM: 
o there is any hemodynamic instability (bradycardia and hypotension 
(i.e. mean arterial pressure less than gestational age) 
o there is respiratory deterioration i.e. significant sustained increase in 
oxygen requirement (more than a 0.2 increase in FiO2) or increase in 
PaCO2 >15 mm Hg and above ordered parameters. 
o there is an apneic event requiring positive pressure ventilation. 
o Device associated pressure injury stage I/II  
 
Compliance with the Protocol 
 
The clinical investigation will be conducted in compliance with this protocol. 
Modifications to the protocol will not be implemented before the relevant ethics 
committee approvals are obtained.  Any serious or safety related deviation will be 
recorded, summarized and monitored. All research study personnel will be adequately 
trained on the research protocol, trial related duties and functions, and equipment utilized 
by the research staff. All medical decisions will be made by subject’s physician and clinical 
care team not by the research team. 
Enrollment in any concurrent research trials that may involve patients who are 
eligible for this HFNC study must be approved by the PI for co-enrollment after review 
of the protocols. 
 

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Potential Risks  
 
 
There should be no more risks for babies in this study than are possible for any ELBW 
baby needing intensive care. HFNC and nCPAP are commonly used in our NICU.  A 
recent review of all of the studies using HFNC found no significant differences in safety 
outcomes between HFNC and other methods of respiratory support such as nCPAP.  As 
with all procedures, when the respiratory modality is changed or when the non-adhesive 
belt is placed around the baby, there is a possibility the infant will have a change in vital 
signs such as a brief oxygen desaturation. We will make every attempt to minimize this. 
The EIT that is placed around the chest of the baby could result in skin irritation. Skin 
assessments will occur and device-associated pressure injuries will be addressed per 
current SMBHWN NICU unit policy and guidelines of care. If any breakdown or 
barotrauma from devices would occur they would be treated as clinically indicated by 
the appropriate team (wound RN etc.) 
All of the devices that are being used in this study (nCPAP and High Flow Nasal 
Cannula) are currently being used in the SMBHWN NICU as part of routine care, and 
are being used in accordance with their FDA-approved/cleared labeling.  
 
 
Expected Adverse Events 
 
 
The population  being studied is at increased risk of all complications associated 
with prematurity and the following adverse events are expected for neonates < 29 weeks 
gestational age and will be included in data collection: 
1. Intraventricular Hemorrhage 
2. Periventricular Leukomalacia 
3. Sepsis 
4. Chronic Lung Disease 
5. Necrotizing Enterocolitis 
6. Spontaneous Intestinal Perforation 
7. Patent Ductus Arteriosus requiring treatment 

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Potential Benefits 
 
 
 
 
There are no direct benefits to participation in this trial. If the investigators are able 
to show a physiologic similarity between HFNC and nCPAP, a transition from nCPAP to 
HFNC may be shown to be possible for this population.   
 
Expense to Subjects 
 
 
 
There is no added expense for the subject to be in the study. 
 
Compensation to Subjects 
 
 
 
There is no compensation for the subject in the study.  
 
Waiver of Informed Consent and Waiver of HIPAA Authorization for Pre-Screening 
 
Waivers of informed consent and of HIPAA Authorization are requested for pre-
screening medical records. The use or disclosure will not adversely affect the rights and 
welfare of the subjects.  This research protocol cannot be conducted without partial 
waiver because investigators would be unable to identify eligible subjects. This will 
involve no more than minimal risk to the privacy of subjects. Only research 
investigators/assistants will access PHI for eligibility and screening purposes.  
 
PHI that will be accessed for screening will be identifiable on research-related forms by 
a study number.  We will take the following precautions to maintain the confidentiality of 
identifiable subject information.  We will also keep subject’s identity separate from their 
data on a Master log and coded. PHI will not be used or disclosed to any other person 
or entity, except as required by law. 
1. Paper-based records will be kept in a secure location and accessible only to 
persons involved in the study 
2. Computer-based files will be available only to persons involved in the study 
through the use of access privileges and passwords. 

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3. Prior to accessing any PHI, personnel will be required to sign statements 
agreeing to protect the security and confidentiality of identifiable health 
information 
4. Whenever feasible, identifiers will be removed from study-related information 
5. PHI will not be disclosed or re-used for other purposes 
6. Collect only the minimum necessary subject identifiers. 
7. Remove/destroy subject identifiers as soon as they are no longer needed. See 
the following website for record retention requirements. 
8. Limit physical access to any area or computer that contains subject identifiers. 
9. Limit electronic access to any computer that contains subject identifiers. 
10. Avoid storing subject identifiable data on portable devices (such as laptop 
computers, digital cameras, portable hard drives including flash drives, USB 
memory sticks, iPods or similar storage devices) as these devices are particularly 
susceptible to loss or theft. If there is a necessity to use portable devices for 
initial collection of subject identifiers, the data files must be encrypted, and 
subject identifiers transferred to a secure system as soon as possible. 
11. Remove necessary subject identifiers from data files, and encrypt data files if 
stored electronically. Identifiers will be stored in a physically separate and secure 
location from the data files, and associated with the data files through a key code 
that is also stored in a separate and secure location. 
12. Use only secure modes of transmission of data; subject identifiers submitted over 
a public network will be encrypted. 
13. Review the Information Security & Privacy website for additional 
recommendations on how to best secure confidential data. 
14. If there is an inadvertent breach of confidentiality of the research data which 
causes harm or places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm), the Lead Researcher will 
report this to the IRB through the electronic Unanticipated Problems reporting 
process within 5 working days of the researcher becoming aware of the event. 

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15. Assurance that the privacy of the subject will be maintained by avoiding 
discussions about the patient within earshot of other patients or non-paripants. 
 
Outcome Measures 
 
Primary Outcome 
• % Unventilated Lung: The primary endpoint to be used for HFNC efficacy 
evaluation as compared to nCPAP is the percentage of unventilated lung as 
measured by EIT. The non-inferiority margin is set at 3% (0.03). If non-inferiority 
is established by rejecting that the outcome event rate is worse by 1% or more in 
the HFNC group, then superiority will be tested at the 3% level.  For all 
superiority testing, the intention to treat analysis will be utilized with a per 
protocol analysis as a sensitivity analysis.  Atelectasis will be calculated using the 
percentage of the lung fields that are not engaged in tidal volume (VT) during the 
recording with the in-built silent space algorithm. This provides a quantitative 
value for relative atelectasis and also describes the regional distribution of 
atelectasis within the chest. 
 
 
Secondary Outcomes 
 
• Geometric Center of Ventilation(CoV) HFNC compared to nCPAP: CoV is a 
numeric value that describes the geographic point within the thorax that 
represents the statistical center of VT and is calculated from the EIT VT data and 
the mathematically determined point of perfect VT homogeneity within the chest 
based on the patients age and chest shape. It is calculated on a right/left and 
dependent/non-dependent plane, and described as the percentage point 
between the extremes of that plane. As the chest is not circular and the lung 
contents not uniform in shape within the chest, the CoV is referenced to the 
expected CoV for uniform ventilation within the chest shape. The magnitude of 
the CoV difference from this ideal provides a simple numeric index for the degree 
and direction of ventilation inhomogeneity. For example, in the human lung the 

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ideal non-dependent to dependent CoV is 63%. Thus a value of 55% would 
indicate greater ventilation in the non-dependent lung. 
 
• Functional Tomography Images: % of total VT within 8 lung regions, 
relative change in uncalibrated aeration (end-expiratory lung volume) and 
tidal volume. The pattern of VT and atelectasis distribution of HFNC compared 
to nCPAP periods and will also be displayed using a functional tomogram. The % 
of total VT within 8 lung regions (4 right lung and 4 left lung) of equal anatomical 
size. The relative change in uncalibrated aeration (end-expiratory) and tidal 
volume will be determined from the trough and peak-to-peak height of the time-
volume EIT within the 8 regions of interest. 
 
 
All of the following will be compared between HFNC and nCPAP periods (Time 
period 1, 2, 3, 4): 
• Oxygenation, expressed as the SpO2/FiO2 ratio  
• Incidence of Oxygen Desaturation (defined as a SpO2 <90%).  
• Incidence of Apnea (20 seconds)  
• Incidence of Bradycardic ( HR <100) 
•  Events Requiring Interventions (type and number of interventions) 
• The  Relationship Between Oxygenation and VT Homogeneity (ratio of 
the SpO2/FiO2 to % atelectasis) 
 
Data Collection & Data Analysis 
 
 
Maternal and Infant demographics will be collected from the mother’s and/or 
infant’s electronic medical record. Maternal information is critical to assess how maternal 
morbidities such as infection, growth restriction could confound the treatment effect. The 
data regarding clinical interventions during the study period will be collected on an 
electronic case report form from the electronic medical record. All physiologic data during 
the study period will be recorded using a real-time data acquisition system which includes 

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video as well as physiologic data for all monitored infants. Data is collected, processed, 
and analyzed using Acqknowledge software. Heart rate via Electrocardiogram (ECG), BP, 
FiO2, TcCO2, and SpO2, are sampled at 200 samples per second (Hz), and the files will be 
linked to the video to allow for review of temporal relationships. EIT data will be acquired at 
48 frames per second using the cross-sectional neonatal chest belt sized to the infant’s 
chest circumference. This belt consisted of 32 integrated AgCl electrodes woven into a 
non-adherent material which enclosed 0.5 cm of foam padding and flexible printed 
circuitry to allow unobstructed chest wall movement. Conductance with the skin is 
achieved using warmed ultrasound gel applied to the belt beforehand. The belt is placed 
on the infant prior to recording and secured around the chest at nipple level and below 
the armpit using a Velcro tab. Parameters will be continuously recorded over15 minutes 
or less of quiet breathing in the  supine positon and repeated during each study period 
to account for the potential of movement artifact and variable ventilation patterns. The 
EIT files will be analyzed post hoc in IBEX-neo using anatomic finite element models of the 
human infant chest.  Acqknowledge and EIT data will be analyzed to determine stable 
artifact free periods of tidal ventilation (using video confirmation). From these a total of six 
30 s segments will be chosen from each study period to be used for data analysis. The 
infants will also be maintained in similar positions in both arms. This will be confirmed with 
continuous video recording. For all measurements, the absolute change in a 
physiological parameter is of lesser importance in this study than the relative change 
from a baseline state. Consequently all parameters will be described as the change 
from the baseline value as well as the absolute value.  
As a single center trial we will review the safety outcomes and report all SAEs to the IRB. 
Adverse outcomes will be reviewed in real time and submitted in progress reports. A 
DSMB is not needed for lower risk single center studies like this. 
 
Data Security 
 
 
Each subject will be assigned a study subject ID number. This ID number will also 
be used on other CRFs and data collection tables or spreadsheets.  No other patient 
identifiers will be used. Only investigators and research personnel who are involved with 

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the study will access EMRs or physiologic data files.  Access to direct identifiers will be 
limited to research staff who meet all relevant training requirements and are assigned to 
or support this project, and who must have access to these identifiers. This will be stored 
on the Sharp NRI network drive on firewall-protected secure servers. Video and 
physiologic recordings will be viewed and maintained at Sharp HealthCare on a password 
protected system. Only investigators who are involved with the study will have access.    
All investigators, statisticians, and staff will have completed the Human Subjects 
Protection training.  Data, such as the final results of the study or de-identified data 
collected as part of the study, may be shared with co-investigators or Fisher & Paykel 
Healthcare so that they may better understand breathing patterns of premature babies on 
HFNC and nCPAP. Fisher & Paykel Healthcare will not use the data for marketing 
purposes. Following completion of the study, documentation will be stored in secure long 
term storage per hospital policy.  
 
Publication plan 
 
 
 
The study will be registered in ClinicalTrials.Gov prior to the enrollment of 
the first subject. Attempts will be sought to publish all results, positive, neutral, as 
well as negative, in a peer-reviewed international journal. 
 
Appendix One: Data Collected  
 
 
References 
 
1. 
Collins CL, Holberton JR, Barfield C, Davis PG. A randomized controlled trial to compare heated 
humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in 
premature infants. The Journal of pediatrics. 2013;162(5):949-54.e1. 
2. 
Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S. Heated, humidified high-flow nasal 
cannula versus nasal CPAP for respiratory support in neonates. Pediatrics. 2013;131(5):e1482-90. 
3. 
Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, et al. High-flow 
nasal cannulae in very preterm infants after extubation. The New England journal of medicine. 
2013;369(15):1425-33. 
4. 
Collins CL, Barfield C, Horne RS, Davis PG. A comparison of nasal trauma in preterm infants 
extubated to either heated humidified high-flow nasal cannulae or nasal continuous positive airway 
pressure. European journal of pediatrics. 2014;173(2):181-6. 

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5. 
Roberts CT, Owen LS, Manley BJ, Froisland DH, Donath SM, Dalziel KM, et al. Nasal High-Flow 
Therapy for Primary Respiratory Support in Preterm Infants. The New England journal of medicine. 
2016;375(12):1142-51. 
6. 
Kotecha SJ, Adappa R, Gupta N, Watkins WJ, Kotecha S, Chakraborty M. Safety and Efficacy of 
High-Flow Nasal Cannula Therapy in Preterm Infants: A Meta-analysis. Pediatrics. 2015;136(3):542-53. 
7. 
Wilkinson D, Andersen C, O'Donnell CP, De Paoli AG, Manley BJ. High flow nasal cannula for 
respiratory support in preterm infants. The Cochrane database of systematic reviews. 2016;2:Cd006405. 
8. 
Campbell DM, Shah PS, Shah V, Kelly EN. Nasal continuous positive airway pressure from high 
flow cannula versus Infant Flow for Preterm infants. Journal of perinatology : official journal of the 
California Perinatal Association. 2006;26(9):546-9. 
9. 
Miller SM, Dowd SA. High-flow nasal cannula and extubation success in the premature infant: a 
comparison of two modalities. Journal of perinatology : official journal of the California Perinatal 
Association. 2010;30(12):805-8. 
10. 
Yoder BA, Manley B, Collins C, Ives K, Kugelman A, Lavizzari A, et al. Consensus approach to 
nasal high-flow therapy in neonates. Journal of perinatology : official journal of the California Perinatal 
Association. 2017;37(7):809-13. 
 
 
 
Appendix 1 
DATA COLLECTED FROM INFANTS AND MOTHERS 
 
Clinical Data collected from all enrolled mothers: 
1. Age 
2. Race/Ethnicity 
3. Antenatal Steroids (yes/no) (include partial course) 
4. Antenatal Magnesium (yes/no) 
5. Diabetes (gestational, Type 1 or 2) (yes/no) 
6. Chorioamnionitis (yes/no) 
7. Hypertension/Pre-eclampsia (yes/no) 
8. Rupture of Membranes (hours) 
9. Mode of Delivery 
 
Clinical Data collected from all enrolled infants: 
10. Gestational Age 
11. Multiple gestation (yes/no)    
12. Gender 
13. Birthweight (grams) 
14. APGARS at 1 and 5 minutes 
15. Race/Ethnicity 
 
Measured Endpoints and Recorded Outcomes 
 
Primary Outcome  
16. % unventilated lung  

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Secondary Outcomes 
17. Geometric centre of ventilation(CoV) 
18. % of total VT within 8 lung regions 
19. End Expiratory Lung Volume  
20. Oxygenation (SpO2/FiO2 ratio) 
21. Incidence of oxygen desaturation (SpO2 <90%) 
22. Apneic and bradycardic events requiring interventions (type and number of 
interventions) 
23. The relationship between oxygenation and VT homogeneity (ratio of the SpO2/FiO2 
to % atelectasis) 
24. Hemodynamic & Respiratory Parameters during the study period (HR, BP, RR, 
FiO2, TcCO2, SPO2) 
 
Resuscitation Interventions  
25. Maximum inspired oxygen (FiO2) (percentage) 
26. DR Interventions: PPV, CPAP, intubation, chest compressions, medications (Y/N) 
27. Intubation (yes/no) (indicate Delivery Room or NICU) 
28. Surfactant (yes/no) (Delivery Room or NICU) 
 
Clinical Outcomes 
29. SGA (<10%) 
30. Venous and/or arterial cord gas  (pH+BE) 
31. Worst BE on blood gas within 1 hour of life 
32. Use of cardiac inotropes (dopamine, dobutamine, epinephrine) (yes/no) 
33. Presence of any intraventricular hemorrhage  (yes/no)   
34. Presence of severe intraventricular hemorrhage (Grade 3 or 4) (yes/no) 
35. Presence of PVL, echodense lesions or ventriculomegaly on any US prior to 
discharge (yes/no) 
36. Early onset sepsis (positive blood or CSF culture at < 72 HOL) (yes/no) 
37. Late onset sepsis (> 72 HOL)  (yes/no) 
38. Chronic lung disease (receiving supplemental O2 at 36 weeks (yes/no) 
39. Duration of intubated and mechanical ventilation (days) 
40. Necrotizing Enterocolitis Bell (Stage ≥ 2) (yes/no) 
41. Spontaneous Intestinal Perforation 
42. Retinopathy stage 3 or greater (yes/no) 
43. Patent Ductus Arteriosus requiring treatment (medical and/or ligation) (yes/no) 
44. Length of hospitalization (total days) 
45. Death (only)