Improved Survival for Infants with Severe Congenital Diaphragmatic Hernia

Background: surgical approaches

Congenital diaphragmatic hernia (CDH) is a life-threatening defect that causes pulmonary hypoplasia and pulmonary hypertension resulting from abdominal visceral herniation in the chest. While CDH survival rates have improved to 70% to 80% in recent years (with some centers reporting even higher survival), survival for infants with severe CDH remains around 15% to 25%. 

In this report, severe CDH was defined by study authors as an observed-to-expected lung-to-head ratio (O:E LHR) of less than 25%, which is associated with the highest mortality rates. 

Management strategies to improve outcomes for severe CDH have included fetal intervention with fetal endoscopic tracheal occlusion (FETO). European reports of FETO survival rates demonstrate improvement from 15% to as high as 40%. However in these reports, extracorporeal membrane oxygenation (ECMO) was not routinely offered to all patients. In addition the success of FETO was tempered by high preterm delivery rates. 

In previous reports of similar cohorts in the U.S., ECMO utilization was greater than 95% and survival rates were greater than 50% (O:E LHR was not used). Another report identified the most severe infants at an institution; all 16 of those infants required ECMO and that survival was 63%.

These reports indicate that survival rates of 15 to 24% underestimate true survival in high-volume CDH centers that routinely utilize ECMO for stabilization and management of infants with high-risk CDH.

Methods: patient data for repair on ECMO, survival

Study authors reviewed the patient database for CDH with an O:E LHR less than 25% between 2013 and 2021. (In 2013, the Colorado Fetal Care Center standardized prenatal evaluation to perform fetal MRI, fetal echocardiogram and ultrasound on all patients.)

Collected demographic information included: 

• Gestational age
• Birthweight
• APGAR scores at one and five minutes
• ECMO utilization, time of initiation and duration
• Days to initial repair and repair type
• Survival
• Length of stay

Colorado Fetal Care Center infant management protocol 

• Veno-arterial ECMO (VA-ECMO) used exclusively for infants with CDH
• Patients with percent predicted lung volume (PPLV) less than 15% electively placed on ECMO in delivery room
• Patients with O:E LHR less than 25% and PPLV greater than 15% stabilized in delivery room and placed on ECMO if certain criteria met

Repair on ECMO 

• Infants placed on ECMO were repaired within 48 hours of cannulation
• Infants hemodynamically unstable or with persistent coagulopathy post-cannulation repaired on ECMO after issues resolved

Perioperative algorithm 

• Heparin anticoagulation prior to surgery
• Aminocaproic acid (Amicar) in perioperative period
• Bivalirudin post procedure

Infants who survived to discharge 

• Respiratory variables collected
• Medication administration a surrogate for severity of pulmonary hypertension (PH)

Results: improved survival to discharge rate

Of the 140 infants managed at the Colorado Fetal Care Center during the study period, 19 had O:E LHR less than 25%. After exclusions for right-sided defects and presence of large ventricular septal defects, 13 infants met the study parameters.

Prenatal parameters 

• Mean gestational age at diagnosis: 23 and 2/7 weeks ± 3 6/7 weeks 
• Median PPLV: 14% 
• Median lung-to-head ratio (LHR): 0.7 
• Median O:E LHR: 20% 
• Median total lung volume (TLV): 19 ml 

Demographics 

• Median gestational age: 37 weeks 
• Mean birthweight: 2559g ± 396g 
• Four males, Nine females
• 85% delivered by cesarean section
• Median Apgar score of four at one minute
• Median Apgar score of seven at five minutes
• 76% (10) survived ECMO
• 69% (nine) survived to discharge
• Median length of stay:135 days  

ECMO utilization 

• All infants managed on ECMO
• 10 in delivery room
• Two in first 12 hours
• One placed late, 54th day of life (pulmonary hypertension crisis)
• 14-day median ECMO cannulation
• All patients requiring ECMO within first 12 hours were repaired on ECMO
• Three-day median time to repair

Surgical technique 

• 11 repaired with transversus abdominus flap
• Two repaired with Gore-Tex patch

Complications 

• One of two patients with bleeding complications died
• One patient had thrombotic complications and died

Respiratory outcomes 

• 39-day median mechanical ventilation
• 23-day median non-invasive ventilation
• All surviving infants discharged home on oxygen of which:
  • Three had mild chronic lung disease
  • Four had moderate chronic lung disease
  • Two had severe chronic lung disease, underwent tracheostomy
  • Five had mild PH
  • Two had moderate PH
  • Two had severe PH

Gastrointestinal outcomes

• All surviving infants discharged home with gastrostomy tube (GT)
• All had gastroesophageal reflux diagnosis
• All underwent Nissen fundoplication at time of GT placement
• Four weaned off reflux medications before discharge 

Clinical characteristics of survival 

There were no differences between survivors and non-survivors in: 

• PPLV
• O:E LHR
• LHR
• TLV

Survivors and non-survivors had similar: 

• Birthweight
• APGARs

Of the four infants who did not survive: 

• Three placed on ECMO in delivery room 
• One placed on ECMO on 54th day of life secondary to a PH crisis

Discussion: improving outcomes for high-risk CDH infants 

Study authors believe this is the first published report from a high-volume U.S. CDH center to evaluate survival for O:E LHR less than 25%.

Prior reports demonstrated varying incidence of bleeding complications between 15% and 36% with on-ECMO repair and mortality as high as 70% when bleeding complications occur. The higher rates of survival in this study’s cohort may be attributed to the lower rates of bleeding complications with repair on ECMO.

This study suggests management at a high-volume CDH center, with a protocolized approach to care, aggressive early intervention and early repair on ECMO has the potential to improve outcomes for this high-risk subset of CDH infants. These findings raise concern about recommendations for widespread implementation of FETO for this group of patients.

While the sample size was small and the patients were not randomized, the 69% survival rate despite CDH severity suggests aggressive intervention at a high-volume ECMO and CDH center could exceed the 15% to 24% prior published survival rate in for this population.

Conclusion: Aggressive intervention at high-volume centers with protocols improves severe CDH survival
 

Study authors conclude that survival for infants with severe CDH can be optimized with aggressive intervention in a high-volume center using a protocolized approach to care. They caution against the widespread implementation of FETO in ECMO centers until more comparative studies can be done.