Trial Outcomes & Findings for Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome (NCT NCT01941745)

NCT ID: NCT01941745

Last Updated: 2019-09-10

Results Overview

Number of events of survived participants without one or more of the CPIP components defined below: 1. Medical/ER visits (CPIP-DV): At least one non-routine medical visit for respiratory causes. 2. Respiratory re-hospitalizations (CPIP-RH): One or more re-hospitalizations for respiratory causes. 3. Respiratory Symptoms (CPIP-SS): Evidence of respiratory symptoms (e.g. coughing and wheezing) or use of respiratory medications by parental diaries or pulmonary questionnaires. 4. Respiratory Medications (CPIP-RM): Administration of respiratory medications (including oxygen). CPIP is defined as the presence of one or more parent-reported outcomes at 12 months CGA, validated by Respiratory diaries (presence of wheezing, coughing, and/or respiratory medication use ≥2 days per week for 3 consecutive weeks), and Pulmonary questionnaires (decrease in respiratory illness requiring medications, unscheduled medical visits and/or ER or hospital admissions).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

12 Months Corrected Gestational Age (*no imputation for missing data)

Results posted on

2019-09-10

Participant Flow

Recruitment spanned October 2013 - August 2017 at ICUs at Tufts Medical Center (Boston, MA), Brigham and Women's Hospital (Boston, MA), and BayState Medical Center (Springfield, MA). Three hospital sites in Poland were later added for the second high-dose/high dose placebo cohort of 44 neonates.

No washout/run-in events to report.

Participant milestones

Participant milestones
Measure	Placebo (Associated w/ Low Dose Cohort) Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Overall Study STARTED	22	22	21	23
Overall Study COMPLETED	22	22	21	23
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates With Respiratory Distress Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=22 Participants Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants	High Dose (rhCC10) n=23 Participants Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants	Total n=88 Participants Total of all reporting groups
Age, Customized	26.1 weeks STANDARD_DEVIATION 1.3 • n=5 Participants	26.5 weeks STANDARD_DEVIATION 1.1 • n=7 Participants	27.0 weeks STANDARD_DEVIATION 1.3 • n=5 Participants	26.6 weeks STANDARD_DEVIATION 1.2 • n=4 Participants	26.6 weeks STANDARD_DEVIATION 1.2 • n=21 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants	40 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	48 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	22 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	15 Participants n=7 Participants	16 Participants n=5 Participants	18 Participants n=4 Participants	66 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	54 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	34 Participants n=21 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	10 participants n=5 Participants	11 participants n=4 Participants	65 participants n=21 Participants
Region of Enrollment Poland	0 participants n=5 Participants	0 participants n=7 Participants	11 participants n=5 Participants	12 participants n=4 Participants	22 participants n=21 Participants
Mean birth weight	877.4 grams STANDARD_DEVIATION 170.9 • n=5 Participants	859.3 grams STANDARD_DEVIATION 140.9 • n=7 Participants	885.5 grams STANDARD_DEVIATION 173.9 • n=5 Participants	867.2 grams STANDARD_DEVIATION 187.2 • n=4 Participants	874.5 grams STANDARD_DEVIATION 168.2 • n=21 Participants
Median 5 min APGAR score	8 Scores on a scale n=5 Participants	7 Scores on a scale n=7 Participants	7 Scores on a scale n=5 Participants	7 Scores on a scale n=4 Participants	7 Scores on a scale n=21 Participants

PRIMARY outcome

Timeframe: 12 Months Corrected Gestational Age (*no imputation for missing data)

Population: Subjects were recruited from Tufts Medical Center, Brigham and Women's Hospital, Baystate Medical Center, Ginekologiczno-Położniczy Szpital Kliniczny Uniwersytetu Medycznego (UM), Instytut Centrum Zdrowia Matki Polski and Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie (USA, Poland).

Outcome measures

Outcome measures
Measure	Placebo (Associated w/ Low Dose Cohort) n=41 Number of events Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=25 Number of events Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=33 Number of events Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=29 Number of events Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) Survived with no CPIP-DV (Medical/ER visits)	8 Number of events	2 Number of events	6 Number of events	6 Number of events
Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) Survived with no CPIP-RH	20 Number of events	12 Number of events	11 Number of events	10 Number of events
Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) Survived with no CPIP-SS (Respiratory Symptoms)	2 Number of events	3 Number of events	6 Number of events	5 Number of events
Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) Survived with no CPIP-RM (Respiratory Medications	10 Number of events	7 Number of events	6 Number of events	5 Number of events
Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 12 Months Corrected Gestational Age (CGA) Survived with no CPIP events (-DV, -RH, -SS, -RM)	1 Number of events	1 Number of events	3 Number of events	3 Number of events

SECONDARY outcome

Timeframe: 6 months Corrected Gestational Age

Population: Subjects were recruited from Tufts Medical Center, Brigham and Women's Hospital, Baystate Medical Center, Ginekologiczno-Położniczy Szpital Kliniczny UM, Instytut Centrum Zdrowia Matki Polski and Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie (USA, Poland).

Number of events of survived participants, graded as not having 1, 2, 3, or 4 of the CPIP components defined below: Medical/ER visits (CPIP-DV): ≥1 non-routine medical visit(s) for respiratory causes. Respiratory re-hospitalizations (CPIP-RH): ≥1 re-hospitalization(s) for respiratory causes Respiratory Symptoms (CPIP-SS): Parent-reported evidence of respiratory symptoms (e.g. coughing and wheezing) or use of respiratory medications Respiratory Medications (CPIP-RM): Administration of respiratory medications (including oxygen) A participant graded without 4 CPIP components is considered in better health than a participant graded without 1 CPIP component. CPIP components were parent-validated via respiratory diaries (wheezing, coughing, and/or respiratory medication use ≥2 days/wk for 3 consecutive wks), and pulmonary questionnaires (decrease in respiratory illness requiring medications, unscheduled medical visits and/or ER or hospital admissions).

Outcome measures

Outcome measures
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=22 Participants Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=23 Participants Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA) Survived without 1 CPIP component	4 Number of Events	3 Number of Events	7 Number of Events	4 Number of Events
Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA) Survived without 2 CPIP components	10 Number of Events	6 Number of Events	8 Number of Events	7 Number of Events
Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA) Survived without 3 CPIP components	15 Number of Events	11 Number of Events	10 Number of Events	10 Number of Events
Long Term Efficacy - Survival Without Evidence of Chronic Pulmonary Insufficiency of Prematurity (CPIP) at 6 Months Corrected Gestational Age (CGA) Survived without 4 CPIP components	21 Number of Events	16 Number of Events	17 Number of Events	14 Number of Events

SECONDARY outcome

Timeframe: Adverse events are monitored through 36 wks post-menstrual age (PMA)

The safety of the study drug was assessed by accounting the number of participants with Adverse Events (AEs) in the treatment and placebo groups.

Outcome measures

Outcome measures
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=22 Participants Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=23 Participants Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Safety and Efficacy - Number of Participants With Adverse Events	22 Participants	22 Participants	21 Participants	23 Participants

SECONDARY outcome

Timeframe: 36 weeks post-menstrual age

Short term efficacy evaluations involve number of neonates with oxygen requirement at 36 weeks post menstrual age.

Outcome measures

Outcome measures
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=44 Participants Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 Participants Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=44 Participants Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Short Term Efficacy - Number of Neonates With Oxygen Requirement at 36 Weeks Post Menstrual Age	8 Participants	10 Participants	8 Participants	4 Participants

Adverse Events

Placebo (Associated w/ Low Dose Cohort)

Serious events: 16 serious events

Other events: 22 other events

Deaths: 0 deaths

Low Dose (rhCC10)

Serious events: 17 serious events

Other events: 22 other events

Deaths: 2 deaths

Placebo (Associated w/ High Dose Cohort)

Serious events: 17 serious events

Other events: 21 other events

Deaths: 2 deaths

High Dose (rhCC10)

Serious events: 19 serious events

Other events: 23 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Jonathan M. Davis, MD

Tufts Medical Center | Division of Newborn Medicine

Phone: (617) 636-5322

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 participants at risk Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=22 participants at risk Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 participants at risk Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=23 participants at risk Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Eye disorders ROP Stage 3	22.7% 5/22 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	14.3% 3/21 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Nervous system disorders IVH grade 3-4	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Nervous system disorders PVL	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	14.3% 3/21 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Congenital, familial and genetic disorders PDA	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.0% 3/23 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	14.3% 3/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	21.7% 5/23 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders NEC Stage II-III	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders Intestinal Perforation	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Respiratory Acidosis	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pulmonary Hemorrhage	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pulmonary Interstitial Emphysema	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Apnea	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	22.7% 5/22 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pneumothorax	9.1% 2/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations Respiratory Infections	22.7% 5/22 • Number of events 12 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	42.9% 9/21 • Number of events 19 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	39.1% 9/23 • Number of events 17 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.

Other adverse events
Measure	Placebo (Associated w/ Low Dose Cohort) n=22 participants at risk Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Low Dose (rhCC10) n=22 participants at risk Dosage: 1.5 mg/kg study drug rhCC10 in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 22 participants	Placebo (Associated w/ High Dose Cohort) n=21 participants at risk Dosage: Single dose of half normal saline at 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 21 participants	High Dose (rhCC10) n=23 participants at risk Dosage: 5 mg/kg of rhCC10 given in 2 ml/kg Administration: once intratracheally within the first 24 hours of life, and once within 4 hours of the first dose of exogenous surfactant (CurosurfTM) Enrollment: 23 participants
Respiratory, thoracic and mediastinal disorders Apnea	100.0% 22/22 • Number of events 29 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	77.3% 17/22 • Number of events 22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	47.6% 10/21 • Number of events 13 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	47.8% 11/23 • Number of events 12 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Blood and lymphatic system disorders Anemia	45.5% 10/22 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	36.4% 8/22 • Number of events 9 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	76.2% 16/21 • Number of events 39 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	78.3% 18/23 • Number of events 50 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations Pneumonia	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	38.1% 8/21 • Number of events 14 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Eye disorders ROP Stages I-IV	31.8% 7/22 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	28.6% 6/21 • Number of events 7 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	34.8% 8/23 • Number of events 12 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Nervous system disorders IVH Grades I-IV	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	31.8% 7/22 • Number of events 7 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	42.9% 9/21 • Number of events 9 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	47.8% 11/23 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Nervous system disorders PVL Grades I-IV	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders NEC Grades I-IV	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders Intestinal Perforation	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Congenital, familial and genetic disorders PDA +ASD	31.8% 7/22 • Number of events 7 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	40.9% 9/22 • Number of events 10 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	61.9% 13/21 • Number of events 14 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	60.9% 14/23 • Number of events 18 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	14.3% 3/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	21.7% 5/23 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations UTI	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	14.3% 3/21 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Metabolism and nutrition disorders Hyponatremia	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Metabolism and nutrition disorders Metabolic Acidosis	36.4% 8/22 • Number of events 8 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	28.6% 6/21 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	39.1% 9/23 • Number of events 12 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Blood and lymphatic system disorders Neutropenia	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	21.7% 5/23 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pneumothorax	9.1% 2/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pulmonary Hemorrhage	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders PIE	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Infections and infestations Bronchitis/ bronchiolitis/ tracheitis/laryngitis	31.8% 7/22 • Number of events 7 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	18.2% 4/22 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	26.1% 6/23 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Respiratory distress	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.0% 3/23 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Respiratory, thoracic and mediastinal disorders Respiratory Acidosis	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Metabolism and nutrition disorders Hyperglycemia	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	47.6% 10/21 • Number of events 10 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	34.8% 8/23 • Number of events 8 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Vascular disorders Hypertension	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	8.7% 2/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Vascular disorders Hypotension	9.1% 2/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	23.8% 5/21 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	39.1% 9/23 • Number of events 10 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders Hernia (inguinal)	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.0% 3/23 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Hepatobiliary disorders Hyperbilirubinemia	68.2% 15/22 • Number of events 16 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	50.0% 11/22 • Number of events 11 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	52.4% 11/21 • Number of events 16 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	65.2% 15/23 • Number of events 20 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Gastrointestinal disorders GERD	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	21.7% 5/23 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Blood and lymphatic system disorders Thrombocytopenia	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	27.3% 6/22 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	23.8% 5/21 • Number of events 5 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	21.7% 5/23 • Number of events 6 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	13.6% 3/22 • Number of events 3 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/21 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Investigations Desaturation after study medication administration	18.2% 4/22 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.8% 1/21 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/23 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Blood and lymphatic system disorders Coagulation disorders or circulatory insufficiency	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	0.00% 0/22 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	19.0% 4/21 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	17.4% 4/23 • Number of events 4 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.
Metabolism and nutrition disorders Hypoglycemia	9.1% 2/22 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.5% 1/22 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	9.5% 2/21 • Number of events 2 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.	4.3% 1/23 • Number of events 1 • A given participant was monitored for Adverse Events (AE) and Serious Adverse Events (SAE) for an average of 34 months. Note: Some infants experienced the same AE on multiple occasions. AEs and SAEs were reported according to std. definitions, except AEs specific to this population and possibly relevant to the drug were automatically categorized as SAEs, regardless of severity, so each event would generate a report and be reviewed by study staff and the Data Safety and Monitoring Board (DSMB). AEs selected for automatic SAE reporting included; sepsis, pneumonia, air leaks (pneumothorax, pulmonary interstitial edema, pneumomediastinum), and pulmonary hemorrhage.