Children's Hospital Colorado

Improved Survival for Infants with Severe Congenital Diaphragmatic Hernia

Maternal and Fetal Medicine | June 22, 2022

For families

  • A congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that occurs when a baby's diaphragm does not form correctly before birth.
  • Children’s Colorado has some of the highest CDH survival rates in the country.
  • Colorado Fetal Care Center experts studied survival rates of babies with a severe form of CDH, comparing different management approaches.
  • Babies with severe CDH surgically repaired soon after birth and while on extracorporeal membrane oxygenation (ECMO) support were found to have improved survival.

For health professionals

  • Survival rates for infants with mild to moderate CDH have greatly improved in the past decade. For infants with severe CDH, management is still challenging.
  • A Colorado Fetal Care Center study found the potential for greater survival for these babies when they:
    • Were managed at a high-volume CDH center with a protocolized care approach
    • Received aggressive early intervention with ECMO and early repair on ECMO
  • In contrast to European data, use of ECMO early repair along with coagulation strategies resulted in 29% higher survival.

Stats

  • 1 in 2,500 babies is born with a congenital diaphragmatic hernia (CDH)
  • 50% survival rates previously reported for babies with severe CDH
  • 69% survival rate for babies in study with severe CDH treated at Colorado Fetal Care Center 

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 greater than 50% (although O:E LHR was not used). Another identified the most severe infants an institution; all 16 of those infants required ECMO and survival was 63%.

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

CHCO_Improved survival infants graphics-1.jpg

Methods: patient data for repair on ECMO, survival

Study authors reviewed the patient database for CDH with an O:E LHR < 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 1 and 5 minutes
  • ECMO utilization, time of initiation and duration
  • Days to initial repair and repair type
  • Survival
  • Length of stay

CHCO_Improved survival infants graphics-2.jpg

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) < 15% electively placed on ECMO in delivery room
  • Patients with O:E LHR < 25% and PPLV > 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 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 

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

Demographics 

  • 37 weeks median gestational age
  • 2559g ± 396g mean birthweight
  • 4 male, 9 female
  • 85% delivered by Cesarean Section
  • 4 median Apgar score at 1 minute
  • 7 medial Apgar score at 5 minutes
  • 76% (10) survived ECMO
  • 69% (9) survived to discharge
  • 135 days median length of stay 

ECMO utilization 

  • All infants managed on ECMO
  • 10 in delivery room
  • 2 in first 12 hours
  • 1 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
  • 3-day median time to repair

Surgical technique 

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

Complications 

  • 1 of 2 patients with bleeding complications died
  • 1 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
    • 3 had mild chronic lung disease
    • 4 had moderate chronic lung disease
    • 2 had severe chronic lung disease, underwent tracheostomy
    • 5 had mild PH
    • 2 had moderate PH
    • 2 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
  • 4 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: 

  • 3 placed on ECMO in delivery room 
  • 1 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 <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 with 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
 

CHCO_Improved survival infants graphics-3.jpgStudy authors conclude that survival for infants with severe CDH can be optimized with aggressive intervention in a high-volume center using protocolized approach to care. They caution against the widespread implementation of FETO in ECMO centers until more comparative studies can be done.