# Handbook of Genetic Counseling/Congenital Diaphragmatic Hernia

Congenital Diaphragmatic Hernia

## Definition

* The presence of a hole in the diaphragm (the muscle that separates the thoracic and abdominal cavities) allows abdominal organs and intestines to enter the thoracic cavity.
* The most common type (36%) is on the left side of the diaphragm towards the back of the body (Bochdalek hernia). A hernia on the left side is more likely to allow organs to protrude. On the right side, the liver blocks the hole and therefore there is less chance of severe organ herniation.
* A less common hernia is located near the front of the body near the breastbone (Morgagni hernia).

## Incidence

* 1/3000- 1/5000 live births
* 1/2200 including stillbirths, spontaneous miscarriages, and neonatal deaths before reaching treatment facility

## Cause

* Multifactorial

## Maternal exposures

THE CAUSE OF CDH IS NOT YET KNOWN.
Studies have been done on the following:
* Thalidomide
* Bendectin
* Quinine
* Anti-epileptic drugs.

## Embryological cause

* At 9-10 weeks the peritoneal canals close creating the diaphragm and the separation between the thoracic and abdominal cavities is complete. If the closure does not occur properly, when the midgut returns to the abdomen, the abdominal viscera herniated through the opening. This causes compression on the developing lung, resulting in a decreased number of bronchial branches and mild to severe lung hypoplasia. There can also be compression on the heart causing cardiac deformities.

## Associated anomalies/conditions

* 10-20% of CDH have chromosome anomalies
* Trisomy 21, 13, 18 most common
* Tetrasomy 12p has been noted)
* Other anomalies occur in 25-57% of all cases of CDH (suspected 95% in stillborns with CDH)
* Congenital heart defects (16-23%)
* Hydronephrosis or renal agenesis
* Intestinal atresia
* Neurological defects (spina bifida, anencephaly, hydrocephalus)
* Bronchial anomalies (18-40%)
* Also seen to be associated with genetic conditions
* Fryns syndrome (RARE - 25 cases reported. Autosomal recessive condition that is usually fatal. Includes cleft palate, hypoplastic nails, cystic kidneys, genital malformations, CNS malformations, and dysmorphic features)
* Beckwith-Weidemann (usually sporadic. Macroglossia, large kidneys, macrosomia, other abnormalities)
* Pierre-Robin syndromes
* Outcome of pregnancies with CHD
* The extent of pulmonary hypoplasia at birth is the single most important factor to predict morbidity and mortality.
* Isolated CHD = 60-78% mortality rate
* Death usually caused by complications of prematurity and pulmonary hypoplasia
* Variation in outcome is dependent upon the timing, volume, and duration of the herniation
* No CHD on US at 20-38 weeks but present at birth = 100% survival
* Thought to be caused by a small herniation or "sliding" herniation.
* Prenatal Diagnosis
* Polyhydramnios caused by the obstruction in the herniated stomach.
* Polyhydramnios is an indication for poor prognosis (only 11% of 94 cases survived compared to 55% survival when no polyhydramnios was present)

## Ultrasound markers

* Abdominal viscera at the level of the scapula or heart
* Liver herniation into chest area
* Herniation or misplacement the gallbladder
* Ultrasound measurements
* Lung to thorax ratio (L:T ratio) : a study found fetuses with CHD had a L:T ratio 2 SD below that in normal controls.
* Right-lung: head circumference ratio (LHR) in those with left-sided CHD: predictive of outcome
* LHR <0.6 = no survival with postnatal treatment
* LHR <1.0 = survival 11%
* LHR >0.6 and <1.35 = survival 61%
* LHR >1.35 = 100% survival
* Pregnancy Management (Depends on gestational age and degree of herniation)

## All gestational ages

* Level II ultrasound to identify any other anomalies
* Serial ultrasounds to watch progression of pregnancy
* Fetal karyotyping offered
* Fetal echocardiogram
* Large volume herniation (LHR<1.35, L:T ratio<0.5, dilated misplaced fetal stomach, and polyhydramnios):
* Counseling for very poor outcome and possible termination
* Option of delivery at term with conventional management
* Option of surgical repair or tracheal clip procedure in utero (<26 weeks)
* Smaller volume herniation (LHR>1.35, L:T ratio>0.5):
* Serial ultrasounds
* Discuss options of prenatal repair (inclusion criteria specific)
* Delivery at high-risk center with postnatal repair
* Recurrence risks
* Sporadic in most cases
* Recurrence risk for siblings ~2% (Fetology)
* Females more commonly affected 3:2
* AD familial cases have been reported (higher chance of bilateral hernias)
* Fetal Treatment

## Done at the following major centers

* Columbia University Medical Center/Children's Hospital of NY - 1-877-THE-BABY
* UCSF Fetal Treatment Center 1-800-RX-FETUS
* CHOP Center for Fetal Diagnosis and Treatment 1-800-IN-UTERO
* Florida Institute for Fetal Diagnosis and Therapy - limited no. of patients
* Complete repair of CHD (no longer done) - studies done reported no significant increase in survival rate in cases that did not involve herniation of the left liver lobe (44% survival w/ surgery, 41% w/out surgery).
* Tracheal occlusion surgery - theory behind surgery is that throughout gestation, the fetal lung produces fluid that leaves the body through the trachea. When this occurs in CHD, it causes a lung hypoplasia. However, when the trachea is blocked, the fluid becomes trapped causing a lung hyperplasia which forces the viscera back into the abdominal cavity.
* This procedure requires a postnatal surgical procedure to remove the clip and may require postnatal repair of the diaphragm.
* Studies have shown 90% mortality rate and have resulted in 50% of surviving fetuses to have vocal-cord paralysis requiring permanent tracheotomies.
* Current recommendations are to do the surgery only in those with isolated CDH, an LHR<1.0 and a herniated liver.(Fetology) However, inclusion criteria at CHOP for tracheal clip is LHR<1.4 and liver herniation.

## Newborn treatment

* Immediate intubation
* Neuromuscular blockade
* Positive pressure ventilation
* Nasogastric tube to avoid dilation of the bowel
* Treatment with either high frequency oscillatory ventilation (HiFi) or traditional ventilation

## Postnatal repair

* WAIT UNTIL INFANT HAS STABILIZED
* If necessary, place the infant on extracorporeal membrane oxygenation (ECMO)
* 65% require it.
* Increased risk for neurological difficulties later on.
* The defect is repaired primarily or by a patch
* Surgery uses muscle biopsy or foreign substance to close the diaphragm
* (If a foreign substance is used, it will not grow with the child and may require additional surgeries. When the muscles are sewn together, the diaphragm is not as flexible as normal. Can lead to respiratory dysfunction.)
* Sometimes a silo is required if there is not enough room for the bowel in the stomach cavity.
* Chest tube is inserted
* Average intubation period of 20 days (Maratore et al. 2001)
* Average length of stay in hospital of 60 days

## Long-term outcome

* Possibility of bronchopulmonary dysplasia from long-term ventilation
* Increased risk for
* Neurological problems regardless of exposure to ECMO
* Developmental delay (20-30%)
* Sensorineural hearing loss
* Failure to thrive resulting from feeding difficulties
* Gastroesophageal reflux (50-60%)
* Musculoskeletal deformities (10-21%)
* A study of 48 infants with postnatal repair (Chu et al. 2000) showed a 73% survival rate with leading causes of death being severe respiratory failure, pulmonary hypertension, pneumothorax, and anomalies.
CHERUBS - The Association of Congenital Diaphragmatic Hernia Research, Advocacy and Support Over 2100 families affected by CDH supporting and encouraging each other Message Boards, Research Library, Free Membership, Newsletters, Awareness Activities
    http://www.cdhsupport.org
    Breath of Hope, Inc., Congenital Diaphragmatic Hernia, Supporting all, together searching for a cure.
    PO Box 6627
    Charlottesville, VA 22906
    http://www.breathofhopeinc.com
    Adam.com website has details and pictures of a variety of conditions, the surgical procedures to repair them, and the follow-up from surgery. Very easy to understand.
    http://www.adam.com
    Each fetal surgery location has its own website
    http://fetalsurgery.chop.edu
    http://fetalsurgery.ucsf.edu
    http://www.fetalmd.com/research
    http://www.prenatalpediatrics.org - The Center for Prenatal Pediatrics at Columbia University

## References

* Bianchi et al. Fetology: Diagnosis & Management of the Fetal Patient (2000).
* Chu et al. Treatment and outcome of congenital diaphragmatic hernia. L Formos Med Assoc. Nov 2000: 99 (11) p 844-7.
* Muratore et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Pediatr Surg. Jan 2001: 36(1) p133-40.
* Nose et al. Airway anomalies in patients with congenital diaphragmatic hernia. J Pediatr Surg. Nov 2000: 35 (11) p1562-5.
* Snijders RJM & Nicolaides KH. Ultrasound Markers for Fetal Chromosomal Defects.

## Notes

The information in this outline was last updated in 2001.