Congenital Diaphragmatic Hernia
Conditions
Brief summary
Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with a high risk of mortality and need for life-saving interventions such as extracorporeal membrane oxygenation (ECMO), nitric oxide, and vasopressor support. Although infants with CDH experience significant morbidity and mortality starting immediately after birth, high quality evidence informing delivery room resuscitation in this population is lacking. Infants with CDH are at risk for pulmonary hypoplasia and pulmonary hypertension and often experience hypoxemia and acidosis during neonatal transition. The standard approach to DR resuscitation is immediate umbilical cord clamping (UCC) followed by intubation and mechanical ventilation. Animal models suggest that achieving lung aeration prior to UCC results in improved pulmonary blood flow and cardiac function compared with immediate UCC before lung aeration is established. Trials of preterm infants demonstrated that initiating respiratory support prior to UCC is safe and feasible. Because infants with CDH are at high risk for pulmonary hypertension and systemic hypotension, they may benefit from the hemodynamic effects of lung aeration before UCC, namely increased pulmonary blood flow, decreased pulmonary vascular resistance, and improved cardiac output. To date, this approach has not been studied in infants with CDH.
Detailed description
Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with a high risk of mortality (29%) and need for life-saving interventions such as ECMO (33%), nitric oxide (62%), and vasopressor support (73%).1 Although infants with CDH experience significant morbidity and mortality starting immediately after birth, high quality evidence informing delivery room resuscitation in this population is lacking. Infants with CDH are at risk for pulmonary hypoplasia and pulmonary hypertension and often experience hypoxemia and acidosis during neonatal transition. The standard approach to delivery room (DR) resuscitation is immediate UCC followed by intubation and mechanical ventilation. The goals of this strategy are to immediately recruit and aerate the lung for gas exchange and oxygenation, while simultaneously avoiding gaseous distention of the thoracic gastrointestinal contents. Animal models suggest that achieving lung aeration prior to UCC results in improved pulmonary blood flow and cardiac function compared with immediate UCC before lung aeration is established. Trials of preterm infants demonstrated that initiating respiratory support prior to UCC is safe and feasible. Because infants with CDH are at high risk for pulmonary hypertension and systemic hypotension, they may benefit from the hemodynamic effects of lung aeration before UCC, namely increased pulmonary blood flow, decreased pulmonary vascular resistance, and improved cardiac output. The investigators hypothesize that a sequence of intubation, gentle ventilation, and then umbilical cord clamping will result in improved cardiovascular transition after birth in infants with CDH. To date, this approach has not been studied in infants with CDH. The DING trial will assess the feasibility and safety of this intervention in infants with CDH.
Interventions
PROCEDUREDING
Immediately after birth, the infant will be placed on a Lifestart trolley with an intact umbilical cord, intubated, and ventilated with the Children's Hospital of Philadelphia (CHOP) gentle ventilation protocol.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Unblinded single-arm pilot interventional trial. All enrolled infants will receive the DING intervention (Delayed cord clamping for INtubation and Gentle ventilation)
Eligibility
Sex/Gender
ALL
Age
1 Days to 1 Days
Healthy volunteers
No
Inclusion criteria
1. Antenatal diagnosis of CDH, with care in the Center for Fetal Treatment 2. Gestational age ≥ 36 weeks at birth
Exclusion criteria
1. Multiple gestation 2. Major anomalies or aneuploidy 3. Enrolled in fetal endoluminal tracheal occlusion (FETO) trial 4. Palliative care planned or considered 5. Maternal diagnosis placenta previa, accreta, or abruption 6. Maternal diagnosis pre-eclampsia requiring Magnesium sulfate therapy at time of delivery 7. Obstetrics (OB) or Neonatal provider concerns for the clinical care of the mother or infant, or study team not available
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping | 3 minutes of life | Infants who are intubated and have ventilation initiated prior to umbilical cord clamping |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Partial Pressure of O2 in Arterial Blood (PaO2) | Approximately 1 hour of life | Arterial PaO2 on first blood gas |
| Oxygenation Index (OI) | First obtained blood gas | Oxygenation index \[OI\] with first obtained blood gas |
| Proportion of Infants Who Require Vasopressors | First 48 hours of life | Proportion of infants who require vasopressors in first 48 hours of life |
| Mean Arterial Potential of Hydrogen (pH) in Arterial Blood | Approximately 1 hour of life | Arterial pH on first blood gas |
| Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment | 7 days of life | Proportion of infants who require ECMO treatment in first 7 days of life |
| Mortality in First 7 Days of Life | First 7 days of life | Proportion of infants with mortality in the first 7 days of life |
| Presence of Severe Pulmonary Hypertension | Approximately 24 hours of life | Presence of severe pulmonary hypertension on first echocardiogram |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DING Intervention Delayed Cord Clamping
DING: Immediately after birth, the infant will be placed on a Lifestart trolley with an intact umbilical cord, intubated, and ventilated with the Children's Hospital of Philadelphia (CHOP) gentle ventilation protocol. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | No longer eligible at time of delivery | 1 |
Baseline characteristics
| Characteristic | DING Intervention |
|---|---|
| Age, Customized Gestational Age | 38.7 weeks STANDARD_DEVIATION 0.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping
Infants who are intubated and have ventilation initiated prior to umbilical cord clamping
Time frame: 3 minutes of life
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DING Intervention | Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping | 17 Participants |
Secondary
Mean Arterial Potential of Hydrogen (pH) in Arterial Blood
Arterial pH on first blood gas
Time frame: Approximately 1 hour of life
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DING Intervention | Mean Arterial Potential of Hydrogen (pH) in Arterial Blood | 7.02 pH | Standard Deviation 0.15 |
Secondary
Mean Partial Pressure of O2 in Arterial Blood (PaO2)
Arterial PaO2 on first blood gas
Time frame: Approximately 1 hour of life
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DING Intervention | Mean Partial Pressure of O2 in Arterial Blood (PaO2) | 47 PaO2 |
Secondary
Mortality in First 7 Days of Life
Proportion of infants with mortality in the first 7 days of life
Time frame: First 7 days of life
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DING Intervention | Mortality in First 7 Days of Life | 0 Participants |
Secondary
Oxygenation Index (OI)
Oxygenation index \[OI\] with first obtained blood gas
Time frame: First obtained blood gas
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DING Intervention | Oxygenation Index (OI) | 17.5 oxygenation index |
Secondary
Presence of Severe Pulmonary Hypertension
Presence of severe pulmonary hypertension on first echocardiogram
Time frame: Approximately 24 hours of life
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. 1 trial participant was supported with ECMO when the echocardiogram was obtained and therefore was not assessed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DING Intervention | Presence of Severe Pulmonary Hypertension | 12 Participants |
Secondary
Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment
Proportion of infants who require ECMO treatment in first 7 days of life
Time frame: 7 days of life
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DING Intervention | Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment | 7 Participants |
Secondary
Proportion of Infants Who Require Vasopressors
Proportion of infants who require vasopressors in first 48 hours of life
Time frame: First 48 hours of life
Population: 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DING Intervention | Proportion of Infants Who Require Vasopressors | 13 Participants |