Extreme Prematurity, Hyperoxia, Hypoxia Neonatal, IVH- Intraventricular Hemorrhage, Respiratory Insufficiency
Conditions
Keywords
Delayed Cord Clamping, IVH- Intraventricular Hemorrhage, Hyperoxia in Neonates, Hypoxia Neonatal, Continuous Positive Airway Pressure (CPAP)
Brief summary
This study is being conducted to compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life (MOL) given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC for 90 seconds (LO Group).
Detailed description
Prenatal consent will be obtained on infant's with estimated gestational age up to 28+6 weeks. 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 90 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 stabilization 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. At delivery, the infant will be placed on a platform that allows the infant to be close to the mother and the umbilical cord to remain intact for DCC. These beds are equipped with an oxygen blender, humidifier, t-piece resuscitator with mask, necessary to provide CPAP/PPV. At some centers the bed will be equipped with a radian warmer (Ceramotherm, Wyer GmbH, Germany) to maintain thermoregulation on the infant during delayed cord clamping. If an infant is randomized to the DCC and Low Oxygen concentration (DCC LO group), the following procedure will ensue: During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 0.3 will be provided. If an infant is randomized to the DCC and High Oxygen concentration (DCC HI group), the following procedure will ensue: During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 1.0 will be provided. Patency of the airway in both groups 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, if no improvement they will initiate PPV (starting PIP of 20 cm H20) by 60 seconds of life. Cord clamping will occur at 90 seconds or greater and the infant will be transferred to a standard neonatal warmer and resuscitated per NRP guidelines. Additionally, when available heart rate data will be collected using a non-invasive dry-electrode monitor, (NeoBeat, Laerdal Medical, Stavanger, Norway) and applied over the infant's chest or abdomen to provide continuous display of heart rate during 90 seconds of DCC. Pulse oximetry, ECG sensors and Near-Infrared Spectroscopy (NIRS) sensors will be applied after cord clamping. 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. Blood sample will be collected at two different time points: Cord blood sample (T1: Cord blood collected after the cord is cut) and at 2 hours of life or NICU admission (T2). This is extra few drops of blood that is drawn from the baby for medical purposes (cord blood from cord gases and admission blood work up). Samples will be tested for oxidized and reduced glutathione which are the most reliable and comprehensive biomarkers of oxidative stress.
Interventions
PROCEDUREDelayed Cord Clamping with Low Oxygen concentration
During delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and low oxygen concentration (FiO2 0.30) will be provided.
PROCEDUREDelayed Cord Clamping with High Oxygen concentration
During delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and high oxygen concentration (FiO2 1.0) will be provided.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sharp Mary Birch Hospital for Women & Newborns
Sharp HealthCare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Once consent is obtained and the research staff is notified of a subject's impending birth, our research team member will open a randomization card and set the oxygen blender on the special bed to either an FiO2 of .30 or 1.0 and cover the blender. The research team member will not be involved in the clinical care for the infant and will blind the clinical care team from the randomized assignment.
Eligibility
Sex/Gender
ALL
Age
22 Weeks to 28 Weeks
Healthy volunteers
No
Inclusion criteria
* up to 28+6 weeks Gestational age * Single and Multiple pregnancy * All modes of delivery (vaginally or caesarean section)
Exclusion criteria
* Parents decline consent * Congenital anomalies of the newborn * Bleeding Accreta * Monochorionic multiples with evidence of TTTS * Fetal or maternal risk (i.e. compromise) * Preterm Premature Rupture of Membranes prior to 20 weeks gestation * Parents request no resuscitation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of administration of oxygen during delayed cord clamping and it's impact on the incidence of preterm infants (up to 28 +6 weeks) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life | by 5 minutes of life | To assess the feasibility and compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 MOL given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC for 90 seconds (LO Group). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Grade IVH | 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 | 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 | In the first 10 minutes of life | Resuscitation interventions including intubation, chest compressions, medications |
| Changes in heart rate (BPM) in the first 10 minutes of life | In the first 10 minutes of life | Changes in heart rate (BPM) in the first 10 minutes of life |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Hyperoxia | 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 |
| Changes in Mean airway pressure, MAP (cm H20) | In the first 10 minutes of life | Changes in Mean airway pressure, MAP (cm H20) |
| Duration of Positive Pressure Ventilation | The first 10 minutes of life in the delivery room | Duration of positive pressure ventilation |
| Blood pressures in the first 24 hours of life | 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 | In the first 24 hours of life | Cerebral tissue oxygenation in the first 24 hours of life |
| Average oxygen saturation in the first 5 minutes after birth | by 5 minutes of life | Oxygen saturation in the first 5 minutes after birth |
| Average Heart rate in the first 5 minutes after birth | by 5 minutes of life | Heart rate in the first 5 minutes after birth |
| Intubation in the Delivery room or Neonatal Intensive Care Unit (NICU) | 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) |
| Lowest and Highest Hemoglobin and/or Hematocrit | First 24 hours of life | Hemoglobin and/or Hematocrit levels (before transfusion) |
| Mean arterial blood pressure | First 24 hours of life | Mean arterial blood pressure (collected hourly) |
| Surfactant administration | Immediately after intervention through study completion at hospital discharge, up to 6 months of corrected gestational age | Surfactant administration |
| Number of RBC Transfusions since birth | First 10 days after birth | Number of RBC Transfusions since birth |
| Patent Ductus Arteriosus requiring pharmacological or surgical treatment | Through study completion at discharge, up to 6 months of corrected gestational age | Patent Ductus Arteriosus requiring pharmacological or surgical treatment |
| Spontaneous Intestinal Perforation (SIP) requiring surgery or peritoneal drain | 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) | Through study completion at discharge, up to 6 months of corrected gestational age | Necrotizing Enterocolitis (Modified Bell's stage 2-3) |
| Bronchopulmonary Dysplasia (mode of respiratory support administered at 36 weeks postmenstrual age; as defined and categorized in; Jensen, Dysart, Gantz, et al: Defining Bronchopulmonary Dysplasia) http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6775872/ | Hospital course until 36 weeks PMA | Bronchopulmonary Dysplasia (mode of respiratory support administered at 36 weeks postmenstrual age; as defined and categorized in; Jensen, Dysart, Gantz, et al: Defining Bronchopulmonary Dysplasia) http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6775872/ |
| Severe ROP (stage 3 or treated with laser or bevacizumab) | After the intervention through study completion at hospital discharge, up to 6 months of corrected gestational age | Severe ROP (stage 3 or treated with laser or bevacizumab) |
| Combined outcome of severe IVH and/or death | Through study completion at death or discharge, up to 6 months of corrected gestational age | Combined outcome of severe IVH and/or death |
| Death | Through study completion at death or discharge, up to 6 months of corrected gestational age | Death |
| SVC Flow | 6 hours of life | Superior Vena Cava flow by echocardiography |
| RVO | 6 hours of life | Right Ventricular output by echocardiography |
| Left Ventricular Output | 6 hours of life | Left Ventricular output by echocardiography |
| Cognitive Composite Score | 24 months corrected age | Composite Score (cognitive 45-155; higher scores are better) as assessed by the Bayley Scales of Infant and Toddler Development Fourth Edition |
| Language Composite Score | 24 months corrected age | Composite Score (language 45-155; higher scores are better) as assessed by the Bayley Scales of Infant and Toddler Development Fourth Edition |
| Motor Composite Score | 24 months corrected age | Composite Score (motor 45-155; higher scores are better) as assessed by the Bayley Scales of Infant and Toddler Development Fourth Edition |
| Cerebral Palsy | 24 months corrected age | As assessed by Gross Motor Function Classification System (GMFCS) Levels 1-5 |
| Neurodevelopmental Outcome at 2 Years of Age | 22-26 months corrected age | Overall and Domain Scores- Ages and Stages, 3rd ed. Questionnaire |
| Pulsatility Index | 6 hours of life | Pulsatility index calculated from Doppler of the Middle Cerebral Artery |
| Resistive Index | 6 hours of life | Resistive index calculated from Doppler of the Middle Cerebral Artery |
| Changes in cerebral oxygenation saturation, StO2 (%) | In the first 10 minutes of life | Changes in cerebral oxygenation saturation, StO2 (%) |
| Changes in SpO2 (%) in the first 10 minutes of life | In the first 10 minutes of life | Changes in SpO2 (%) in the first 10 minutes of life |
| Inhaled Nitric Oxide | Immediately after intervention through study completion at hospital discharge, up to 6 months of corrected gestational age | Use of Inhaled Nitric Oxide for Respiratory failure or Pulmonary Hypertension |
| Glutathione (GSH/GSSG ratio) | from birth up to NICU admission or in the first 2 hours of life | Assessment of oxidative biomarkers from birth up to 2 hours of life |
| Thermoregulation | from 5 minutes of life up to NICU admission in the first 2 hours of life | Assessment of thermoregulation (axillary temperatures measured in degrees Celsius) during delayed cord clamping on extremely low gestational infants |
| Rate of Early Onset Sepsis | From birth up to 72 hours of life | assessment of early onset sepsis with a positive blood or CSF culture at \</= 72 HOL |
| Duration of mechanical ventilation and/or CPAP | Birth through study completion at discharge, up to 6 months of corrected gestational age | Number of days on mechanical ventilation and/or CPAP |
| Rate of Late Onset Sepsis | From > 72 hours of life through study completion at death or discharge, up to 6 months of corrected gestational age | assessment of late onset sepsis with a positive blood or CSF culture at \> 72 HOL |
| Medication for Low Blood Pressure | First 24 hours of life | Medication for Low Blood Pressure (e.g. hydrocortisone or pressors) |
| CRIB-II (Clinical Risk Index for Babies) | First 12 hours of life | CRIB-II (Clinical Risk Index for Babies) |
| Changes in Inspired fractional oxygen (FiO2) | In the first 10 minutes of life | Changes in Inspired fractional oxygen (FiO2) |
| Duration of Hypoxia | 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 |
Countries
United States
Outcome results
None listed