Delayed Cord Clamping for Congenital Diaphragmatic Hernia

Not Applicable

Completed

Conditions: Congenital Diaphragmatic Hernia

Interventions: Procedure: DING

Registration Number: NCT03314233

Lead Sponsor: Children's Hospital of Philadelphia

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DING intervention	DING	Delayed Cord Clamping

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Presence of Severe Pulmonary Hypertension	Approximately 24 hours of life	Presence of severe pulmonary hypertension on first echocardiogram
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
Mean Partial Pressure of O2 in Arterial Blood (PaO2)	Approximately 1 hour of life	Arterial PaO2 on first blood gas
Mean Arterial Potential of Hydrogen (pH) in Arterial Blood	Approximately 1 hour of life	Arterial pH 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
Mortality in First 7 Days of Life	First 7 days of life	Proportion of infants with mortality in the first 7 days of life