Trial Proves Feasibility of Initiating Resuscitation Before Umbilical Cord Clamping In Infants with CDH

Physiological adaptation after birth is a critical transition for infants with congenital diaphragmatic hernia (CDH), who often experience hypoxemia with acidosis in the immediate postnatal period. The traditional approach in the delivery room is cord clamping followed by intubation. However, a physiologically based approach to umbilical cord clamping (UCC) for infants with CDH may smooth the postnatal transition and prevent acidosis and hypoxemia.

In utero, the fetus has fluid-filled lungs, and gas exchange occurs at the placenta. Immediately after birth, the infant must aerate the lungs, which triggers a physiological transition of reduced pulmonary vascular resistance, increased pulmonary blood flow and gas exchange in the lung. Infants with CDH struggle to independently achieve lung aeration due to pulmonary hypoplasia and space-occupying effects of herniated abdominal organs. They are also at risk for decreased pulmonary blood flow due to pulmonary hypertension.

Novel approaches to infant resuscitation

There are currently no guidelines for resuscitation of infants with CDH due to limited data. The standard approach is immediate UCC followed by intubation and ventilation. An alternative strategy is to establish lung aeration prior to UCC, which has been called “physiologically based cord clamping.” Physiologically based cord clamping may stabilize gas exchange during neonatal transition among infants with CDH by supporting aeration of the hypoplastic lung and increasing pulmonary blood flow through the thickened pulmonary vasculature before UCC.

At CHOP, our Garbose Family Special Delivery Unit provides a special opportunity to systematically assess novel approaches to resuscitate babies with anomalies. We recently undertook a single-arm, single-site study to determine if intubation and ventilation prior to UCC is safe and feasible among infants with CDH. The objectives of our pilot trial were to:

• Establish the safety and feasibility of intubation and ventilation prior to UCC for infants with CDH and gestational age ≥36 weeks
• Compare short-term outcomes between infants treated with intubation and ventilation prior to UCC and matched historical controls treated with immediate cord clamping before intubation and ventilation

Quick trial takeaways

• Infants with congenital diaphragmatic hernia often experience physiological compromise immediately after birth.
• The traditional approach in the delivery room is immediate cord clamping followed by intubation and ventilation.
• Establishing lung aeration through intubation and ventilation prior to umbilical cord clamping may support neonatal transition in these infants.
• Intubation and ventilation prior to umbilical cord clamping is safe and feasible among infants with congenital diaphragmatic hernia and may result in short-term physiological benefit.
• The impact of this approach on clinical outcomes requires investigation in a randomized trial.

Study design

Performing intubation and establishing ventilation prior to UCC in the delivery room entails coordination of multiple team members and equipment. For our study, an attending neonatologist, respiratory therapist and neonatal nurse were present for each delivery. Immediately after delivery, the obstetrical provider placed the infant on a mobile trolley. The neonatologist intubated the infant, and ventilation was commenced using settings per hospital protocol (initial pressures 20–25/5 cm H2O, fractional inspired oxygen 0.5). UCC was performed after consistent qualitative colorimetric CO2 detection, with guidelines for maternal uterotonic administration after UCC. The primary feasibility endpoint was successful intubation prior to UCC within three minutes of birth. The threshold of allowing three minutes for intubation prior to UCC was considered to represent a reasonable balance between providing sufficient time for the neonatologist to intubate the infant without introducing an excessive delay in intubation and onset of ventilation if intubation before UCC was not possible.

Findings

Of 20 enrolled infants, all were placed on the trolley, and 17 (85%) infants were intubated before UCC. The first hemoglobin and mean blood pressure at one hour of life were significantly higher in trial participants than controls. We compared short-term outcomes between trial participants and matched controls treated with immediate cord clamping before intubation and ventilation. There were no significant differences between groups for subsequent blood pressure values, vasoactive medications, inhaled nitric oxide or extracorporeal membrane oxygenation. These studies contribute to a growing body of literature demonstrating the feasibility and safety of initiating resuscitation prior to UCC. The impact of this approach on clinically relevant outcomes deserves investigation in a randomized trial, which is currently occurring in the Netherlands.

Maternal experience

We also conducted a separate study of the maternal experience of resuscitation before cord clamping. This mixed-methods ancillary study of our pilot feasibility trial included:

• A multiple-choice questionnaire administered to mothers within one month after delivery
• An open-ended interview

Most mothers reported positive experiences with neonatal intubation and ventilation prior to UCC and did not report serious negative emotional after-effects. Key takeaways included:

• The importance of preparation for viewing intubation
• The need for reassurance during intubation
• The value of staff and family support

By Elizabeth Foglia, MD, MA, MSCE, Attending Neonatologist