Delayed Cord Clamping for Congenital Diaphragmatic Hernia

Study Overview
=================
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.

Official Title
-----------------
Delayed Cord Clamping for Intubation and Gentle Ventilation in Infants With Congenital Diaphragmatic Hernia

Conditions
-----------------
Congenital Diaphragmatic Hernia

Intervention / Treatment
-----------------
* Procedure: DING


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Antenatal diagnosis of CDH, with care in the Center for Fetal Treatment Gestational age ≥ 36 weeks at birth Exclusion Criteria: Multiple gestation Major anomalies or aneuploidy Enrolled in fetal endoluminal tracheal occlusion (FETO) trial Palliative care planned or considered Maternal diagnosis placenta previa, accreta, or abruption Maternal diagnosis pre-eclampsia requiring Magnesium sulfate therapy at time of delivery Obstetrics (OB) or Neonatal provider concerns for the clinical care of the mother or infant, or study team not available

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 1 Day

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Unblinded single-arm pilot interventional trial. All enrolled infants will receive the DING intervention (Delayed cord clamping for INtubation and Gentle ventilation)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DING intervention<br>Delayed Cord Clamping | Procedure: DING<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping | Infants who are intubated and have ventilation initiated prior to umbilical cord clamping | 3 minutes of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Arterial Potential of Hydrogen (pH) in Arterial Blood | Arterial pH on first blood gas | Approximately 1 hour of life | 
| Mean Partial Pressure of O2 in Arterial Blood (PaO2) | Arterial PaO2 on first blood gas | Approximately 1 hour of life | 
| Oxygenation Index (OI) | Oxygenation index [OI] with first obtained blood gas | First obtained blood gas | 
| Proportion of Infants Who Require Vasopressors | Proportion of infants who require vasopressors in first 48 hours of life | First 48 hours of life | 
| Presence of Severe Pulmonary Hypertension | Presence of severe pulmonary hypertension on first echocardiogram | Approximately 24 hours of life | 
| Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment | Proportion of infants who require ECMO treatment in first 7 days of life | 7 days of life | 
| Mortality in First 7 Days of Life | Proportion of infants with mortality in the first 7 days of life | First 7 days of life |