Effects of Delayed Cord Clamp and/or Indomethacin on Preterm Infant Brain Injury

• Sponsor: Hong Huang (Other)
• Overall Status: Completed
• CT.gov ID: NCT02221219
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 256
• Location: 1
• Arms: 4
• Actual Duration (Months): 84.9
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are brain lesions that commonly occur in preterm infants and are well-recognized major contributors to long-term brain injury and related disabilities later in life. Despite its prevalence, long term consequences, and enormous medical and social costs, mechanisms of IVH and optimal strategies to prevent or treat its occurrence are poorly defined, especially for extremely premature infants. Only one medical therapy, prophylactic indomethacin during the first 3 days of life, has been shown to prevent or decrease the severity of IVH in preterm infants, but its use is limited by toxic side effects and debatable effects on long-term outcomes. Several small studies and case reports suggest that delayed umbilical cord-clamping (DCC) may also decrease the incidence of IVH in premature infants, but thus far these trials have indomethacin treatment mixed within their cord clamping protocols. The investigators are conducting a randomized, blinded investigation of 4 treatment groups: 1) Control (no intervention); 2) DCC alone; 3) Prophylactic indomethacin alone; 4) Combination of DCC/indomethacin, with respect to survival, IVH or PVL incidence and severity, neurodevelopmental outcomes, and relevant mechanistic effects. With the steady rise in extreme prematurity births and clear links of IVH to long-term disabilities there is a need to improve care for these patients. This multi- disciplinary project addresses an important medical problem for an understudied patient population, where the current practice has clear limitations.

Condition or Disease	Intervention/Treatment	Phase
Intraventricular Hemorrhage; Periventricular Leukomalacia; Brain Injury; Renal Injury	Drug: Indomethacin; Procedure: delay in umbilical cord clamp at birth; Drug: placebo infusion; Procedure: immediate cord clamp at birth	Phase 1/Phase 2

Detailed Description

The investigators will compare efficacy and safety of prophylactic indomethacin, DCC, and their combination, in affecting the incidence and severity of IVH/PVL in infants <30wks gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL' among the 4 groups), and longer term neurocognitive function. Other secondary endpoints and investigations include mechanistic effects of prophylactic indomethacin, DCC, and their combination (blood volume/circulatory status, inflammatory stress, progenitor cells) as well as defining relationships between clinical outcomes and mechanistic measurements among treatment groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Oct 27, 2019
• Actual Study Completion Date: Aug 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: immediate cord clamp & placebo IV solution This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.	Drug: placebo infusion; saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff); Procedure: immediate cord clamp at birth; no delay in umbilical cord clamp; <10sec (recorded in delivery note)
Experimental: delay cord clamp & placebo IV solution A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.	Procedure: delay in umbilical cord clamp at birth; provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note); Drug: placebo infusion; saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)
Active Comparator: immediate cord clamp & indomethacin IV Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).	Drug: Indomethacin; indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants; Other Names: indocin ; Procedure: immediate cord clamp at birth; no delay in umbilical cord clamp; <10sec (recorded in delivery note)
Experimental: indomethacin iv & delayed cord clamp A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.	Drug: Indomethacin; indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants; Other Names: indocin ; Procedure: delay in umbilical cord clamp at birth; provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)

Outcome Measures

Primary Outcome Measures

1. Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL [within first 60 days of life]

   determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age

Secondary Outcome Measures

1. Number of Participants With Acute Kidney Injury [first 60 days of life]

   measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).

Other Outcome Measures

1. Hematological Status [first 60 days of life]

   hematocrit, ferritin, hemoglobin at various times during NICU stay

2. Inflammatory Stress [first 60 days of life]

   measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay

3. Circulating Progenitor Cell Subpopulations [first 60 days of life]

   measures of several progenitor cell subtypes in blood during the NICU stay

4. Neurocognitive Assessments at Post-NICU Followup [up to 24 months of corrected gestational age]

   standardized neurocognitive assessments done at NICU graduate clinic.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Weeks to 30 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• pregnant women admitted >24weeks and <30weeks gestational age,

• in-hospital birth (allowing for cord clamp randomization)

Exclusion Criteria:

• preterm infant <24weeks or >30weeks at birth

• maternal risks identified by obstetrician

• fetal risks identified by obstetrician

• any congenital abnormality of newborn infant

• placental abruption/placental previa

• delivery less than 2hrs from consenting to study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kentucky Childrens Hospital Neonatal Intensive Care Unit	Lexington	Kentucky	United States	40506

Sponsors and Collaborators

• Hong Huang
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Director: Vicki Whitehead, RN, UK Section of Neonatology
• Principal Investigator: John Bauer, PhD, UK Department of Pediatrics
• Study Director: Hong Huang, MD-PhD, University of Kentucky Section of Neonatology

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - May 15, 2019

More Information

Publications

None provided.

• Responsible Party: Hong Huang, Research Protocol Manager/Clinical/UKHC, University of Kentucky
• ClinicalTrials.gov Identifier: NCT02221219
• Other Study ID Numbers: HD070792; R01HD070792
• First Posted: Aug 20, 2014
• Last Update Posted: Nov 23, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Hong Huang, Research Protocol Manager/Clinical/UKHC, University of Kentucky: infant; brain injury; renal; indomethacin
• Additional relevant MeSH terms: Brain Injuries; Leukomalacia, Periventricular; Hemorrhage; Wounds and Injuries; Indomethacin

Study Results

Participant Flow

Arm/Group Title	Immediate Cord Clamp & Placebo IV Solution	Delay Cord Clamp & Placebo IV Solution	Immediate Cord Clamp & Indomethacin IV	Indomethacin iv & Delayed Cord Clamp
Arm/Group Description	This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)	Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
Period Title: Overall Study
STARTED	36	87	41	92
COMPLETED	36	87	41	92
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Immediate Cord Clamp & Placebo IV Solution	Delay Cord Clamp & Placebo IV Solution	Immediate Cord Clamp & Indomethacin IV	Indomethacin iv & Delayed Cord Clamp	Total
Arm/Group Description	This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)	Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)	Total of all reporting groups
Overall Participants	36	87	41	92	256
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	26.2 (1.8)	26.6 (2.0)	26.6 (1.8)	26.4 (1.8)	26.5 (1.9)
Sex/Gender, Customized (Count of Participants)
Male	19 52.8%	47 54%	19 46.3%	47 51.1%	132 51.6%
Female	17 47.2%	39 44.8%	21 51.2%	45 48.9%	122 47.7%
Unknown	0 0%	1 1.1%	1 2.4%	0 0%	2 0.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%	2 2.3%	1 2.4%	2 2.2%	7 2.7%
Not Hispanic or Latino	32 88.9%	84 96.6%	39 95.1%	90 97.8%	245 95.7%
Unknown or Not Reported	2 5.6%	1 1.1%	1 2.4%	0 0%	4 1.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	6 16.7%	10 11.5%	3 7.3%	12 13%	31 12.1%
White	27 75%	74 85.1%	36 87.8%	76 82.6%	213 83.2%
More than one race	1 2.8%	2 2.3%	1 2.4%	3 3.3%	7 2.7%
Unknown or Not Reported	2 5.6%	1 1.1%	1 2.4%	1 1.1%	5 2%
Region of Enrollment (participants) [Number]
United States	36 100%	87 100%	41 100%	92 100%	256 100%
Birth Weight (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	797.2 (267.4)	935.1 (295.0)	902.4 (369.8)	916.8 (254.8)	903.9 (291.2)

Outcome Measures

1. Primary Outcome

Title	Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
Description	determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
Time Frame	within first 60 days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immediate Cord Clamp & Placebo IV Solution	Delay Cord Clamp & Placebo IV Solution	Immediate Cord Clamp & Indomethacin IV	Indomethacin iv & Delayed Cord Clamp
Arm/Group Description	This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)	Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
Measure Participants	36	87	41	92
Number [percent of participants]	22.2 61.7%	14.9 17.1%	17.1 41.7%	10.9 11.8%

2. Secondary Outcome

Title	Number of Participants With Acute Kidney Injury
Description	measures of serum creatinine and urine output during Neonatal Intensive Care Unit (NICU) stay. General measures of renal injury (which is a common risk of indomethacin treatment in this patient population).
Time Frame	first 60 days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immediate Cord Clamp & Placebo IV Solution	Delay Cord Clamp & Placebo IV Solution	Immediate Cord Clamp & Indomethacin IV	Indomethacin iv & Delayed Cord Clamp
Arm/Group Description	This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)	Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)	A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
Measure Participants	36	87	41	92
No acute kidney injury	20 55.6%	48 55.2%	23 56.1%	48 52.2%
Grade 1 Acute Kidney Injury	8 22.2%	27 31%	15 36.6%	29 31.5%
Grade 2 Acute Kidney Injury	6 16.7%	8 9.2%	3 7.3%	14 15.2%
Grade 3 Acute Kidney Injury	2 5.6%	4 4.6%	0 0%	1 1.1%
Grade 4 Acute Kidney Injury	0 0%	0 0%	0 0%	0 0%

3. Other Pre-specified Outcome

Title	Hematological Status
Description	hematocrit, ferritin, hemoglobin at various times during NICU stay
Time Frame	first 60 days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Inflammatory Stress
Description	measurement of inflammatory biomarkers (CRP, Interleukin-6, soluble ICAM) at various times during NICU stay
Time Frame	first 60 days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Circulating Progenitor Cell Subpopulations
Description	measures of several progenitor cell subtypes in blood during the NICU stay
Time Frame	first 60 days of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Neurocognitive Assessments at Post-NICU Followup
Description	standardized neurocognitive assessments done at NICU graduate clinic.
Time Frame	up to 24 months of corrected gestational age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	First 60 days of life.
Arm/Group Title	Immediate Cord Clamp & Placebo IV Solution		Delay Cord Clamp & Placebo IV Solution		Immediate Cord Clamp & Indomethacin IV		Indomethacin iv & Delayed Cord Clamp
Arm/Group Description	This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life. placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff) immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)		A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth. delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note) placebo infusion: saline infusion to match input of indomethacin treatment group (and serve as drug-dosing 'blinding' for bedside staff)		Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns). Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants immediate cord clamp at birth: no delay in umbilical cord clamp; <10sec (recorded in delivery note)		A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses. Indomethacin: indomethacin at standard dose for prevention of intraventricular hemorrhage in preterm infants delay in umbilical cord clamp at birth: provision of a ~45 second delay of umbilical cord clamping at birth in preterm infants (recorded in delivery note)
All Cause Mortality
	Immediate Cord Clamp & Placebo IV Solution		Delay Cord Clamp & Placebo IV Solution		Immediate Cord Clamp & Indomethacin IV		Indomethacin iv & Delayed Cord Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)		10/87 (11.5%)		2/41 (4.9%)		6/92 (6.5%)
Serious Adverse Events
	Immediate Cord Clamp & Placebo IV Solution		Delay Cord Clamp & Placebo IV Solution		Immediate Cord Clamp & Indomethacin IV		Indomethacin iv & Delayed Cord Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/36 (13.9%)		7/87 (8%)		3/41 (7.3%)		10/92 (10.9%)
Blood and lymphatic system disorders
Septic Shock	0/36 (0%)	0	1/87 (1.1%)	1	0/41 (0%)	0	0/92 (0%)	0
Gastrointestinal disorders
Necrotizing Enterocolitis	1/36 (2.8%)	1	0/87 (0%)	0	0/41 (0%)	0	0/92 (0%)	0
Bowel Perforation	0/36 (0%)	0	1/87 (1.1%)	1	1/41 (2.4%)	1	3/92 (3.3%)	3
General disorders
Multiorgan Failure	0/36 (0%)	0	1/87 (1.1%)	1	0/41 (0%)	0	0/92 (0%)	0
Infections and infestations
CMV	0/36 (0%)	0	1/87 (1.1%)	1	0/41 (0%)	0	0/92 (0%)	0
Pregnancy, puerperium and perinatal conditions
Extreme Prematurity	4/36 (11.1%)	4	5/87 (5.7%)	5	1/41 (2.4%)	1	5/92 (5.4%)	5
Respiratory, thoracic and mediastinal disorders
Free Air in Abdomen	1/36 (2.8%)	2	0/87 (0%)	0	0/41 (0%)	0	1/92 (1.1%)	1
Pneumothorax	0/36 (0%)	0	0/87 (0%)	0	1/41 (2.4%)	1	1/92 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Immediate Cord Clamp & Placebo IV Solution		Delay Cord Clamp & Placebo IV Solution		Immediate Cord Clamp & Indomethacin IV		Indomethacin iv & Delayed Cord Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/87 (0%)		0/41 (0%)		0/92 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.