Delayed Cord Clamping for Congenital Diaphragmatic Hernia (DING)

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Procedure: DING

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DING intervention; Delayed Cord Clamping	Procedure: 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.

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Elizabeth Foglia, MD, Childrens Hospital of Philadelphia

Publications and helpful links

General Publications

• Grover TR, Murthy K, Brozanski B, Gien J, Rintoul N, Keene S, Najaf T, Chicoine L, Porta N, Zaniletti I, Pallotto EK; Children's Hospitals Neonatal Consortium. Short-term outcomes and medical and surgical interventions in infants with congenital diaphragmatic hernia. Am J Perinatol. 2015 Sep;32(11):1038-44. doi: 10.1055/s-0035-1548729. Epub 2015 Mar 31.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2017
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 9, 2018

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: 17-014125; K23HD084727 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No