Delayed Cord Clamping With Oxygen In Extremely Low Gestation Infants

Overview

This study is being conducted to determine whether provision of a higher level of supplemental oxygen with CPAP/PPV during delayed cord clamping improves peripheral oxygen saturation in infants born at 23+0 to 27+6 gestational age compared to a lower level of supplemental oxygen.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 31, 2023

Detailed Description

Prenatal consent will be obtained on infant's with estimated gestational age of 23+0 to 27+6. Shortly before delivery, infant's will be randomly assigned to receive either Low oxygen concentration (FiO2 .30) OR High oxygen concentration (FiO2 1.0) during 60 seconds of delayed cord clamping.

Randomization and intervention will remain blinded to the clinical care team during the entire study period. The research team member will open a randomization card when notified of a subject's impending birth, review the protocol with the obstetric provider performing the procedure, set-up the sterile special bed, and note the time it takes from delivery until the clamping and cutting of the umbilical cord in both groups.

The research team member will set the oxygen blender as indicated by the randomization card and cover the blender to blind the FiO2 setting. The research team member will not be involved in the clinical care of the infant. The oxygen blender will be concealed from the clinical care team to ensure resuscitation maneuvers will not be biased.

Data will be submitted to the statistician, who will remain blinded to the intervention for the duration of the study.

If an infant is randomized to the DCC and Low Oxygen concentration (DCC LO group), the following procedure will ensue:

At delivery, the infant will be placed on a special bed that allows the infant to be close to the mother, adequate to keep the umbilical cord intact. These beds are equipped with an oxygen blender, humidifier, t-piece resuscitator with mask, necessary to provide CPAP/PPV. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 or positive pressure ventilation (starting PIP of 20 cm H20) and a FiO2 .30 oxygen. The infant's face will be dried and a non-sterile mask will be placed on the infant's face to deliver pressure to help open their lungs. The infant will remain on this support up until the umbilical cord is clamped. Once the cord is clamped, resuscitation will continue according to unit protocol.

If an infant is randomized to the DCC and High Oxygen concentration (DCC HI group), the following procedure will ensue:

At delivery, the infant will be placed on a special bed that allows the infant to be close to the mother, adequate to keep the umbilical cord intact. These beds are equipped with an oxygen blender, humidifier, t-piece resuscitator with mask, necessary to provide CPAP/PPV. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 or positive pressure ventilation (starting PIP of 20 cm H20) and a FiO2 1.0 oxygen. The infant's face will be dried and a non-sterile mask will be placed on the infant's face to deliver pressure to help open their lungs. The infant will remain on this support up until the umbilical cord is clamped. Once the cord is clamped, resuscitation will continue according to unit protocol.

Patency of the airway will be assessed by a Colorimetric CO2 detector. Lack of color change will indicate that the airway is not patent (obstructed), the pressure is not sufficient to expand the lungs, there was excessive air leak, or there was no or inadequate pulmonary blood flow. If there is no color change, the neonatal provider will reposition and reattempt to open the airway with CPAP or PPV. PIP pressures can be increased if there is no change in color by the CO2 detector.

The Near-Infrared Spectroscopy (NIRS) will be applied once the infant is considered stable by the medical team. The NIRS sensor will be placed on the infant's forehead. Cerebral StO2, SpO2, blood pressure (once in the NICU) and Heart rate will be recorded every two seconds and linked with other variables. These variables will continue to be recorded for the first 24 hours of life.

Interventions

  • Procedure: Delayed Cord Clamping with Low Oxygen concentration
    • During delayed umbilical cord clamping of 60 seconds, breathing assistance with CPAP/PPV and low oxygen concentration (FiO2 0.30) will be provided.
  • Procedure: Delayed Cord Clamping with High Oxygen concentration
    • During delayed umbilical cord clamping of 60 seconds, breathing assistance with CPAP/PPV and high oxygen concentration (FiO2 1.0) will be provided.

Arms, Groups and Cohorts

  • Active Comparator: DCC and Low Oxygen Concentration
    • During 60 seconds of delayed cord clamping and oxygen blender set at FiO2 .30, breathing assistance with CPAP of 5 cmH20 or positive pressure ventilation (starting PIP of 20 cmH20) is provided. The infant will remain on this support up until the umbilical cord is clamped. Once the cord is clamped, resuscitation will continue according to unit protocol.
  • Experimental: DCC and High Oxygen Concentration
    • During 60 seconds of delayed cord clamping and oxygen blender set at FiO2 1.0, breathing assistance with CPAP of 5 cmH20 or positive pressure ventilation (starting PIP of 20 cmH20) is provided. The infant will remain on this support up until the umbilical cord is clamped. Once the cord is clamped, resuscitation will continue according to unit protocol.

Clinical Trial Outcome Measures

Primary Measures

  • Peripheral arterial oxygen saturation at 5 minutes of life
    • Time Frame: at 5 minutes of life
    • Peripheral arterial oxygen saturation at 5 minutes of life in infants 23-27 weeks receiving assisted breathing with CPAP/PPV and either an FiO2 of .30 or 1.0 during delayed cord clamping

Secondary Measures

  • All Grade IVH
    • Time Frame: Through study completion at hospital discharge, up to 6 months corrected gestational age (CGA)
    • Any Intraventricular Hemorrhage (grades 1-4)
  • Frequency of Grade III and IV intraventricular hemorrhage
    • Time Frame: Through study completion at hospital discharge, up to 6 months corrected gestational age (CGA)
    • Intraventricular hemorrhages (grades 3-4) (bleeding in the brain parenchyma and/or ventricular dilation
  • Resuscitation interventions
    • Time Frame: In the first 10 minutes of life
    • Resuscitation interventions including positive pressure ventilation, continuous positive airway pressure, intubation, chest compressions, medications
  • Assignment of correct FiO2
    • Time Frame: During delayed cord clamping up to 60 seconds
    • Infant receiving FiO2 as assigned by randomization
  • Time to demonstrate cycling of end tidal CO2 (seconds)
    • Time Frame: During delayed cord clamping up to 60 seconds
    • Time to demonstrate cycling of end tidal CO2 (seconds)
  • Procedure Failure
    • Time Frame: During delayed cord clamping up to 60 seconds
    • (i.e. Inability to get infant on special bed (trolley), cord avulsion)
  • Time to Cord Clamping
    • Time Frame: During delayed cord clamping up to 60 seconds
    • Time to cord clamping
  • Changes in heart rate (BPM) in the first 10 minutes of life
    • Time Frame: In the first 10 minutes of life
    • Changes in heart rate (BPM) in the first 10 minutes of life
  • Changes in SpO2 (%) in the first 10 minutes of life
    • Time Frame: In the first 10 minutes of life
    • Changes in SpO2 (%) in the first 10 minutes of life
  • Changes in cerebral oxygen saturation, StO2 (%)
    • Time Frame: In the first 10 minutes of life
    • Changes in cerebral oxygen saturation, StO2 (%)
  • Changes in Inspired fractional oxygen (FiO2)
    • Time Frame: In the first 10 minutes of life
    • Changes in Inspired fractional oxygen (FiO2)
  • Changes in Mean airway pressure, MAP (cm H20)
    • Time Frame: In the first 10 minutes of life
    • Changes in Mean airway pressure, MAP (cm H20)
  • Duration of Positive Pressure Ventilation
    • Time Frame: The first 10 minutes of life in the delivery room
    • Duration of positive pressure ventilation
  • Duration of Hypoxia
    • Time Frame: The first 10 minutes of life in the delivery room
    • Duration of Hypoxia (defined as oxygen saturation <25th percentile of target ranges defined by Dawson et al.) in the first 10 minutes after birth
  • Duration of Hyperoxia
    • Time Frame: The first 10 minutes of life in the delivery room
    • Duration of Hyperoxia (defined as oxygen saturation > 95%) in the first 10 minutes after birth
  • Blood pressures in the first 24 hours of life
    • Time Frame: In the first 24 hours of life
    • Blood pressures every hour in the first 24 hours of life
  • Cerebral tissue oxygenation in the first 24 hours of life
    • Time Frame: In the first 24 hours of life
    • Cerebral tissue oxygenation every hour in the first 24 hours of life
  • Average oxygen saturation in the first 5 minutes after birth
    • Time Frame: at 5 minutes of life
    • Oxygen saturation in the first 5 minutes after birth
  • Average Heart rate in the first 5 minutes after birth
    • Time Frame: at 5 minutes of life
    • Heart rate in the first 5 minutes after birth
  • Intubation in the Delivery room or Neonatal Intensive Care Unit (NICU)
    • Time Frame: Birth through study completion at discharge, up to 6 months of corrected gestational age
    • Intubation in the Delivery room or Neonatal Intensive Care Unit (NICU)
  • Chest compressions or epinephrine
    • Time Frame: Delivery room intervention
    • Chest compressions or epinephrine
  • Volume Bolus given in delivery room
    • Time Frame: Delivery room intervention
    • Volume bolus given in delivery room
  • NICU admission Temperature
    • Time Frame: Upon NICU admission up to 24 hours after birth
    • NICU admission temperature
  • Lowest and Highest Hemoglobin and/or Hematocrit
    • Time Frame: First 24 hours of life
    • Hemoglobin and/or Hematocrit levels (before transfusion)
  • Mean arterial blood pressure
    • Time Frame: First 24 hours of life
    • Mean arterial blood pressure (collected hourly)
  • Pneumothorax requiring intervention
    • Time Frame: First 24 hours of life
    • Pneumothorax requiring intervention
  • Medication for Low Blood Pressure
    • Time Frame: First 24 hours of life
    • Medication for Low Blood Pressure (e.g. hydrocortisone or pressors)
  • SNAPPE-II (Score for Neonatal Acute Physiology-Perinatal Extension)
    • Time Frame: First 12 hours of life
    • SNAPPE-II (Score for Neonatal Acute Physiology-Perinatal Extension)
  • Duration of mechanical ventilation and/or CPAP
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Number of days on mechanical ventilation and/or CPAP
  • Surfactant administration
    • Time Frame: First 10 days after birth
    • Surfactant administration
  • Highest Bilirubin
    • Time Frame: First 10 days after birth
    • Highest Bilirubin
  • Days on Phototherapy
    • Time Frame: First 10 days after birth
    • Days on Phototherapy
  • Number of RBC Transfusions since birth
    • Time Frame: First 10 days after birth
    • Number of RBC Transfusions since birth
  • Patent Ductus Arteriosus requiring pharmacological or surgical treatment
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Patent Ductus Arteriosus requiring pharmacological or surgical treatment
  • Early onset septicemia (</=72 hours from birth) (positive blood culture and at least 5 days of antibiotic therapy
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Early onset septicemia (</=72 hours from birth) (positive blood culture and at least 5 days of antibiotic therapy
  • Late onset septicemia (>72 hours from birth) (positive blood culture and at least 5 days of antibiotic therapy
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Late onset septicemia (>72 hours from birth) (positive blood culture and at least 5 days of antibiotic therapy
  • Spontaneous Intestinal Perforation (SIP) requiring surgery or peritoneal drain
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Spontaneous Intestinal Perforation (SIP) requiring surgery or peritoneal drain
  • Necrotizing Enterocolitis (Modified Bell’s stage 2-3)
    • Time Frame: Through study completion at discharge, up to 6 months of corrected gestational age
    • Necrotizing Enterocolitis (Modified Bell’s stage 2-3)
  • Bronchopulmonary Dysplasia (receiving continuous supplemental oxygen at 36 weeks corrected gestational age
    • Time Frame: Hospital course until 36 weeks PMA
    • Bronchopulmonary Dysplasia (receiving continuous supplemental oxygen at 36 weeks corrected gestational age
  • Severe ROP (stage 3 or treated with laser or bevacizumab) prior to 36 weeks PMA
    • Time Frame: Hospital course until 36 weeks PMA
    • Severe ROP (stage 3 or treated with laser or bevacizumab) prior to 36 weeks PMA

Participating in This Clinical Trial

Inclusion Criteria

  • 23+0 to 27+6 weeks Gestational age
  • Single and Multiple pregnancy

Exclusion Criteria

  • Parents decline consent
  • Congenital anomalies of the newborn
  • Placental abruption, accreta, percreta
  • Monochorionic multiple pregnancy (i.e. Di/Mo or Mo/Mo twins)
  • Prolonged premature rupture of membranes (>2 weeks) prior to 23 weeks gestation

Gender Eligibility: All

Minimum Age: 23 Weeks

Maximum Age: 27 Weeks

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sharp HealthCare
  • Collaborator
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Anup Katheria, M.D., Director of Neonatal Research Institute – Sharp HealthCare
  • Overall Official(s)
    • Anup Katheria, MD, Principal Investigator, Sharp HealthCare
  • Overall Contact(s)
    • Anup Katheria, MD, 858-939-4170, anup.katheria@sharp.com

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