Congenital diaphragmatic hernia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Congenital diaphragmatic hernia (CDH) is a term applied to a variety of congenital birth defects that involve abnormal development of the diaphragm. The term is used most commonly in reference to Bochdalek hernia, however it can also apply to Morgagni’s hernia, diaphragm eventration and central tendon defects of the diaphragm. A common theme in all scenarios is malformation of the diaphragm; this allows the abdominal contents to protrude into the chest thereby impeding proper lung formation. Newborns with CDH often have severe respiratory distress which can be life-threatening unless treated appropriately.

CDH was first discovered in 1575, and later received its name in 1848 by Bochdalek, which would end up becoming an alternative name for CDH. Surgical treatment began in 1902 but this was beyond 24 hours after birth. Neonates began to receive surgery within 24 hours of life in 1946. Mortality rates were high due to reduced diagnosis. Multiple studies continue to be conducted in hopes of further understanding the disease, identifying it early and treating it promptly.

There are multiple subtypes of Congenital Diaphragmatic Hernia. These include Bochdalek hernia, Morgagni’s hernia and Diaphragm Eventration. Of these, the most common subtype is a  Bochdalek hernia in which there is an anatomical defect in the postero-lateral corner of the diaphragm. Morgagni’s hernia, which is responsible for approximately 2% of cases, are due to herniation through the foramina of Morgagni.

Congenital diaphragmatic hernia occurs when the development of the diaphragm during the 12th week of gestation is inadequate leading to a discontinuity. Such a defect leads to herniation into the thoracic cavity and resultant  lung hypoplasia. Affected children often experience decreased lung volume, reduced blood circulation through the lungs and resultant respiratory complications.

he underlying causes for congenital diaphragmatic hernia are still to be determined, but there have been studies to show a high rate of incidence in occurrence with certain exposures. These include genetic factors and teratogenic exposures such as allopurinol, lithium and mycophenolate mofetil. Genetic Factors can further be sub-divided into aneuploidies, chromosomal anomalies and syndromes. Aneuploidies include Trisomy 13, Trisomy 18, Trisomy 21, and Turner syndrome. Chromosomal anomalies include Pallister-Killian syndrome, Wolf-Hirschhorn syndrome and various other gene deletion syndromes. Associated syndromes include Donnai-Barrow syndrome, LTBP4-related cutis laxa, Cardiac-urogenital syndrome and Tonne-Kalscheuer syndrome.

Congenital diaphragmatic hernia is a condition that often presents in infants, but there are differential diagnosis’ to be considered. Some of these include congenital cystic adenomatoid malformation, bronchopulmonary sequestration, bronchogenic cyst, cystic teratoma, neurogenic tumors, and pulmonary agenesis. Hiatal hernia is often seen in adults rather than neonates but should still be differentiated from congenital hernias. Various imaging modalities may be utilized to further differentiate the potential diagnosis’.

Approximately 4 in every 10,000 live births are affected with  congenital diaphragmatic hernia, with most cases being on the left side and amongst male newborns. due to the development of severe respiratory failure, the mortality rate remains high regardless of the treatment related advancements. In the last two decades, antenatal diagnosis has increased resulting in prompt and more effective treatment.

Unlike other hernias that develop to a progressive weakening in the abdominal wall, CDH occurs due to anatomical defects leading to postero-lateral wall weakness. The use of medications and environmental exposures such as allopurinol, lithium and mycophenolate mofetil as well as phenmetrazine, thalidomide, quinine, cadmium and lead can all contribute to the development of CDH. Genetic factors such as trisomy 13, trisomy 18, trisomy 21 and turner syndrome have all been associated with an increased incidence of CDH. A family history such as a parent or sibling affected may contribute to increased risk of CDH development.

CDH screening is not done commonly and is often found incidentally. Affected patients can range from being symptomatic to asymptomatic. Second trimester screening can determine cases through the use of ultrasonography and MRI, methods that have been able to detect 60% of right-sided defects and more than 80% of those with left-sided CDH. Patients with polyhydramnios and an extended familial history of CDH dating back three generations should undergo further testing for diagnosis confirmation. Methods to evaluate for CDH include chorionic villus sampling, amniocentesisas well as chromosomal microarray analysis with the help of SNPs.

CDH can present as small or large defects, both of which can be detected antenatally and present with varying symptoms depending on the size. Many neonates are initially stable for 24-48 hours, after which they experience acute respiratory distress. Some concerning complications include tracheobronchomalacia, pneumothorax, pulmonary hypertension, pulmonary infections and respiratory failure. Children often experience reduced exercise tolerance, stunted growth due to aversion to oral feeding, gastroesophageal reflux and anatomical chest deformities. Prognosis varies and is dependent on multiple factors. These include defect size, degree of pulmonary hypoplasia, development of pulmonary hypertension and other factors like birth weight and gestational age at birth. Due to ongoing advances in neonatal care, survival rate is now greater than 60%-80%.

CDH symptoms are often affected by the degree of pulmonary hyperplasia. Common symptoms include severe breathing difficulty, Tachypnea, Tachycardia, and Cyanosis. Morgagni’s Hernia may present with chest infections and gastrointestinal symptoms.

Generally, affected neonates present with respiratory distress, but this may be dependent on the size of the defect to some extent. Tachypnea and tachycardia are common findings. The skin often appears cyanotic. Physical exam findings are of a wide variety and present with findings affecting all systems except ENT and hematological. Children born with CDH should be evaluated for structural birth defects such as cardiovascular, CNS, genitourinary, craniofacial, and ocular defects.

Due to the fact that it is an anatomical defect, CDH is primarily diagnosed using screening modalities. Lab values may be deranged in correlation with underlying genetic defects. Due to the respiratory complications, arterial blood gases may also be abnormal, indicating an underlying respiratory acidosis.

Common findings on chest x-ray include cyst like structures representing loops of bowel filling the left hemithorax, mediastinal shift to the right, and varying degrees of gas in the abdomen.

CT findings include diaphragm discontinuity and herniation of large and small bowel as well as intrabdominal solid organs. In cases of Morgagni’s Hernia, the liver, mesenteric fat and the bowel can be seen herniating through.

Fetal MRI is a useful diagnostic tool that is commonly used in the second and third trimester. It’s ability to measure total lung volume and assess herniated liver mass has particularly proven to be helpful. Lungs appear hyperintense whereas the heart, liver, and mediastinum appear hypointense.

Ultrasonography findings in cases of CDH include polyhydramnios, an absent or intrathoracic stomach bubble,  mediastinal shift towards the normal side and herniationinto the chest. Ultrasound findings can also help detect the observed-to-expected lung-to-head ratio, which can assist in predicting survival rate.

Colour doppler can help identify abnormal positioning of the  umbilical and portal veins that can indicate liver herniation. Findings can help differentiate between left and right sided CDH.

Diagnostic studied that can be utilized include high resolution ultrasound, chorionic villus sampling, amniocentesis, microarray analysis, and karyotyping. Although these studies are not necessarily diagnostic for CDH, they help identify underlying genetic defects which have a high correlation rate with diaphragmatic hernia’s.

Medical therapy can be subdivided according to antenatal and postnatal management. Antenatal management focuses on close monitoring. Fetal therapy may be an option for eligible patients with resultant fetal tracheal occlusion performed at 26-30 weeks to allow increased surfactant formation. Postnatal management primarily focuses on preventing birth before 37 weeks of gestation, as these neonates have been shown to have worse outcomes comparatively. Other postnatal options include the use of ECMO, the use of a nasogastric tube and intubation where required as well as maintaining adequate ventilation and oxygenation. Medications that may be helpful in reducing pulmonary hypertension include inhaled nitric oxide, sildenafil, bosentan, PGE1, and PGI2.

Minimally invasive surgery has become the preferred method of treatment, which can be done thoracoscopically. Such techniques also lead to reduced postoperative pain and potential complications that may be seen with more invasive surgeries.

The goal of Primary prevention is to prevent the occurrence of an illness or a disease before it occurs. Since CDH may be due to genetic abnormalities that develop due to defects early in gestation, they are difficult to detect and prevent until they have developed. In cases where risk factors lead to CDH, avoidance of causative drugs may prove helpful. For drugs that may lead to increased risk of CDH, it is important to provide alternative medications to affected individuals.

Secondary prevention occurs once the disease has developed and aims to prevent progression and development of further complications. CDH related complications include tracheobronchomalacia, pneumothorax, pulmonary hypertension, pulmonary infections and respiratory failure. Early screening may assist in complication prevention. Genetic counselling should be offered to all affected families as well as the importance of regular follow up.

CDH is primarily treated with extensive surgical intervention which can be very expensive. Annual costs increase with the addition of ECMO. The average cost is USD $137,000 per patient and the estimated cost of CDH per year in the United States alone is more than USD $230 million.

Many advances have been made to detect or treat CDH earlier than before. These include fetal endoscopic tracheal occlusion, ventilation, in depth studies using chromosome microarray analysis and continued genetic counselling.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

CDH was first discovered in 1575, and later received its name in 1848 by Bochdalek, which would end up becoming an alternative name for CDH. Surgical treatment began in 1902 but this was beyond 24 hours after birth. Neonates began to receive surgery within 24 hours of life in 1946. Mortality rates were high due to reduced diagnosis. Multiple studies continue to be conducted in hopes of further understanding the disease, identifying it early and treating it promptly.

The earliest case of congenital diaphragmatic hernia dates back to 1575 but the term was not coined until 1848, when a scientist by the name of Bochdalek described it as a posterolateral wall defect. After its diagnosis, surgical treatment began in 1902, but the first neonate to undergo surgical reparations within 24 hours of birth wouldn’t be until 1946. Due to limited information and technique, survival rates were approximately 50%.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

There are multiple subtypes of Congenital Diaphragmatic Hernia. These include Bochdalek hernia, Morgagni’s hernia, and Diaphragm Eventration. Of these, the most common subtype is a Bochdalek hernia in which there is an anatomical defect in the postero-lateral corner of the diaphragm. Morgagni’s hernia, which is responsible for approximately 2% of cases, are due to herniation through the foramina of Morgagni.

Bochdalek hernia, also known as a postero-lateral diaphragmatic hernia, is the most common manifestation of CDH, accounting for more than 95% of cases.^[1][2] In this instance, the diaphragm abnormality is characterized by a hole in the postero-lateral corner of the diaphragm which allows passage of the abdominal viscera into the chest cavity. The majority of Bochdalek hernias (80-85%) occur on the left side of the diaphragm, a large proportion of the remaining cases occur on the right side, and a small fraction are bilateral i.e., left and right sided defects. ^[3][4]

This rare anterior defect of the diaphragm is variably referred to as Morgagni’s, retrosternal, or parasternal hernia. Accounting for approximately 2% of all CDH cases, it is characterised by herniation through the foramina of Morgagni which are located immediately adjacent to the xyphoid process of the sternum.^[5]

The diagnosis of congenital diaphragmatic eventration is used when there is abnormal displacement (i.e. elevation) of part or all of an otherwise intact diaphragm into the chest cavity. This rare type of CDH occurs because the diaphragm is thinner in the region of eventration, allowing the abdominal viscera to protrude upwards. This thinning is thought to occur because of incomplete muscularisation of the diaphragm, and can be found unilaterally or bilaterally.^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Congenital diaphragmatic hernia occurs when the development of the diaphragm during the 12th week of gestation is inadequate leading to a discontinuity. Such a defect leads to herniation into the thoracic cavity and resultant lung hypoplasia. Affected children often experience decreased lung volume, reduced blood circulation through the lungs and resultant respiratory complications.

To best understand the underlying cause of CDH, there are some anatomical aspects that should be explained. The main components of the diaphragms development are completed by the 12th week of gestation, and primarily include the septum transversum and pleuroperitoneal membranes. In the event of any disturbance to this process, there may be some discontinuity leading to weakness of the wall and the potential for a hernia to develop. Once herniation occurs into the thoracic cavity, normal pulmonary development is often compromised resulting in lung hypoplasia and a marked decrease in the airways of terminal bronchioles and alveoli.^[1] Pulmonary hypertension is a restriction of blood flow through the lungs thought to be caused by defects in the lung.

It involves three major defects:

• A failure of the diaphragm to completely close during development
• Herniation of the abdominal contents into the chest
• Pulmonary hypoplasia or decreased lung volume is directly related to the abdominal organs presence in the chest cavity which causes the lungs to be severely undersized, especially on the side of the hernia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

The underlying causes for congenital diaphragmatic hernia are still to be determined, but there have been studies to show a high rate of incidence in occurrence with certain exposures. These include genetic factors and teratogenic exposures such as allopurinol, lithium and mycophenolate mofetil. Genetic factors can further be sub-divided into aneuploidies, chromosomal anomalies and syndromes. Aneuploidies include Trisomy 13, Trisomy 18, Trisomy 21, and Turner syndrome. Chromosomal anomalies include Pallister-Killian syndrome, Wolf-Hirschhorn syndrome and various other gene deletion syndromes. Associated syndromes include Donnai-Barrow syndrome, LTBP4-related cutis laxa, Cardiac-urogenital syndrome and Tonne-Kalscheuer syndrome.

Although the aetiology for CDH remains largely unclear, it has been presumed that many factors may contribute to the condition. These include:^[1]

• Genetic factors
• Teratogenic exposures

To date, there have been many genetic factors associated with the development of CDH. These range from gene deletions and mutations to aneuploidies. There have also been some syndromes associated with CDH. Disturbances in the retinoid-signalling pathway may also contribute to disease development but are still being studied.

• Aneuploidies
• Chromosomal Anomalies
• Syndromes

Although there are a multitude of associated conditions, the following have been shown to have high rates of occurrence in children concomitantly affected with CDH:

Aneuploidies Associated with CDH Development ^[1]

Aneuploidies	Clinical Features
Trisomy 13 [2]	Intellectual disability Rocker-bottom feet Microcephaly Cleft lip and palate Holoprosencephaly Polydactyly Cutis aplasia Congenital heart disease Polycystic kidney disease Omphalocele
Trisomy 18 [3]	Intellectual disability Rocker-bottom feet Prominent occiput Clenched fists with overlapping fingers Low-set ears Congenital heart disease Omphalocele
Trisomy 21 [4]	Intellectual disability Flat facial features Prominent epicanthal folds Single palmar crease Gap between first and second toes Gastrointestinal anomalies (duodenal atresia and hirschsprung disease) Congenital heart disease Brushfield spots
Turner syndrome [5]	Short stature Ovarian dysgenesis Shield chest Bicuspid aortic valve Coarctation of the aorta Webbed neck or cystic hygroma Horseshoe kidney

Chromosome Anomalies Associated with CDH Development (Table adapted from ^[6])

Chromosomal Anomaly	Clinical Features
Pallister-Killian syndrome (tetrasomy 12p)	Prenatal Findings: short limbs, CNS anomalies, hydrops fetalis Postnatal findings: sparse hair, broad forehead, low set ears, broad hands, seizures, congenital heart defects Normal growth
Wolf-Hirschhorn syndrome (deletion 4p16.3)	Seizures Stunted growth
Deletion 1q41-q42	Limb anomalies Seizures
Deletion 15q26.2	Cryptorchidism Congenital heart defects Stunted growth
Deletion 17q12	Genitourinary defects Maturity-onset diabetes of the young Intellectual disability

Syndromes Associated with CDH Development (Table adapted from ^[6])

Syndrome	Mode of Inheritance	Clinical Features
Donnai-Barrow syndrome	AR	Enlarged anterior fontanelle Sensorineural hearing loss Proteinuria
LTBP4-related cutis laxa	AR	Loose skin Emphysema GI & bladder diverticula
Cardiac-urogenital syndrome	AD	Congenital heart defects Genitourinary defects
Tonne-Kalscheuer syndrome	X-linked	Intellectual disability Genitourinary defects

• Allopurinol
• Lithium
• Mycophenolate mofetil
• Phenmetrazine
• Thalidomide
• Quinine

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Congenital diaphragmatic hernia is a condition that often presents in infants, but there are differential diagnosis’ to be considered. Some of these include congenital cystic adenomatoid malformation, bronchopulmonary sequestration, bronchogenic cyst, cystic teratoma, neurogenic tumors, and pulmonary agenesis. Hiatal hernia is often seen in adults rather than neonates, but should still be differentiated from congenital hernias. Various imaging modalities may be utilized to further differentiate the potential diagnosis’.

Differential Diagnosis for CDH^[1][2]

Condition	Cause	Presenting Symptoms	Workup to differentiate condition from CDH
Congenital Cystic Adenomatoid Malformation[3]	Abnormal cell proliferation and apoptosis; a developmental abnormality	Symptoms present upon compression of surrounding structures in the mediastinum upon growth of cyst	Ultrasound
Bronchopulmonary Sequestration[4]	Lung tissue unconnected to the tracheobronchial tree	Often asymptomatic; larger defects may present with respiratory distress, high output cardiac failure or pleural hemorrhage	Imaging (digital angiography, CT, MRA)
Bronchogenic Cyst[5]	Abnormal budding of the ventral foregut	These often remain asymptomatic and undiagnosed, but may be detected in the setting of an underlying infection	CT
Cystic Teratoma[6]	Rare tumors composed of cells derived from the endoderm, ectoderm, and or mesoderm	Often asymptomatic; an increase in size may result in increased abdominal girth, and gastrointestinal and urinary symptoms due to compression	Ultrasound, Pathology specimen examination
Neurogenic Tumors	A lesion of neural crest origin most commonly found in the posterior mediastinum	Symptoms of compression of surrounding structures; cough, shortness of breath, hoarseness	CT, MRI[7]
Hiatal Hernia (Paraesophageal)[8]	Herniation of a portion of the stomach through the phrenoesophageal membrane	Heart burn, Regurgitation, Dysphagia; most commonly present in adults	Manometry, Endoscopy
Pulmonary agenesis[9]	Failure of lung bud development resulting in complete or partial absence of lung tissue; associated with congenital defects	Respiratory distress in newborns	Chest X-ray

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Approximately 4 in every 10,000 live births are affected with congenital diaphragmatic hernia, with most cases being on the left side and amongst male newborns. Due to the development of severe respiratory failure, the mortality rate remains high regardless of the treatment related advancements. In the last two decades, antenatal diagnosis has increased resulting in prompt and more effective treatment.

Of every 10,000 live births, 3-4 are affected with congenital diaphragmatic hernia. Cases are slightly more prominent in males and on the left side.^[1] Although there have been many advances in the treatment of congenital diaphragmatic hernia, the mortality and morbidity rate amongst affected children is still relatively high due to the development of severe respiratory failure.^[2] The most commonly affected demographic is reported to be Caucasians, followed by Asians and African Americans. Studies show that affected neonates had an average gestational age of 35.9 weeks and a low birth weight.^[3] In the last two decades, antenatal diagnosis has increased resulting in prompt and more effective treatment.^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

Unlike other hernias that develop to a progressive weakening in the abdominal wall, CDH occurs due to anatomical defects leading to postero-lateral wall weakness. The use of medications and environmental exposures such as allopurinol, lithium and mycophenolate mofetil as well as phenmetrazine, thalidomide, quinine, cadmium and lead can all contribute to the development of CDH. Genetic factors such as trisomy 13, trisomy 18, trisomy 21 and turner syndrome have all been associated with an increased incidence of CDH. A family history such as a parent or sibling affected may contribute to increased risk of CDH development.

Risk factors for CDH include certain drugs and genetic factors.^[1] Having a parent or sibling with the condition slightly increases your risk.

Causative drugs and Environmental exposures:^[2]

• Allopurinol
• Lithium
• Mycophenolate mofetil
• Phenmetrazine
• Thalidomide
• Quinine
• Cadmium
• Lead

Genetic Factors:

• Trisomy 13
• Trisomy 18
• Trisomy 21
• Turner syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

CDH screening is not done commonly and is often found incidentally. Affected patients can range from being symptomatic to asymptomatic. Second trimester screening can determine cases through the use of ultrasonography and MRI, methods that have been able to detect 60% of right-sided defects and more than 80% of those with left-sided CDH. Patients with polyhydramnios and an extended familial history of CDH dating back three generations should undergo further testing for diagnosis confirmation. Methods to evaluate for CDH include chorionic villus sampling, amniocentesis as well as chromosomal microarray analysis with the help of SNPs.

Antenatal screening in the second trimester can determine cases through the use of ultrasonography and MRI. According to the Canadian Pediatric Surgery Network, these methods were able to determine 60% of right-sided defects and more than 80% of those with left-sided CDH.^[1] On ultrasonography, a stomach bubble may be noted along with intestinal peristalsis.^[2] Ultrasound can also show herniation of the viscera. Patients with polyhydramnios and an extended familial history of CDH dating back three generations should undergo further testing for diagnosis confirmation.

• Chorionic villus sampling and Amniocentesis: these methods can help detect genetic anomalies such as trisomies and turner syndrome
• Chromosomal microarray analysis: Single Nucleotide Polymorphisms (SNPs) can detect microdeletions and microduplications
• Karyotyping: a process by which chromosomes are identified and sorted^[3]

Screening based on Trimesters^[4]

Trimester	Optimal time to screen	Screening Methods
First	11-13 weeks	Maternal blood serum used to measure hCG and plasma protein A (PAPP-A); abnormal protein levels may indicate the presence of a a chromosomal disorder that must be assessed further Ultrasound assesses for the presence of increased fluid
Second	15-20 weeks	Maternal serum screen (referred to as triple screen or quad screen) measurement of alpha-fetoprotein (AFP), hCG, estriol and inhibin-A Fetal Echocardiogram assess for cardiac defects that may indicate underlying chromosomal abnormalities Ultrasound

In addition to the commonly utilized methods mentioned above, evaluation can be done via:

• Standard cytogenetic testing
• Serial single-gene testing
• Multigene panel
• Comprehensive genomic testing
• Exome sequencing

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arooj Naz, M.B.B.S

CDH can present as small or large defects, both of which can be detected antenatally and present with varying symptoms depending on the size. Many neonates are initially stable for 24-48 hours, after which they experience acute respiratory distress. Some concerning complications include tracheobronchomalacia, pneumothorax, pulmonary hypertension, pulmonary infections and respiratory failure. Children often experience reduced exercise tolerance, stunted growth due to aversion to oral feeding, gastroesophageal reflux and anatomical chest deformities. Prognosis varies and is dependent on multiple factors. These include defect size, degree of pulmonary hypoplasia, development of pulmonary hypertension and other factors like birth weight and gestational age at birth. Due to ongoing advances in neonatal care, survival rate is now greater than 60%-80%.

CDH can be affected by a multitude of genetic syndromes and environmental factors. Approximately 2/3 cases of CDH can be detected antenatally and its presentation in the postnatal period largely depends upon the size of the defect. Smaller hernias often have a delayed presentation and are accompanied by mild respiratory symptoms and feeding difficulties. Comparatively, large defects present upon birth with decreased breath sounds, displaced heart sounds as well as abdominal changes such as a scaphoid abdomen.^[1]

In many neonates, there is an initial period of 24-48 hours of stability after which acute respiratory distress develops. Pulmonary hypoplasia is a common complication amongst almost all affected children.^[2] Major complications include:

• Tracheobronchomalacia
• Pneumothorax
• Pulmonary Hypertension
• Pulmonary infection; especially viral pneumonia and aspiration pneumonia
• Respiratory failure
• Increased incidence of congenital heart disease^[3]
• Reduced exercise tolerance
• Stunted growth due to aversion to oral feeding
• Gastroesophageal reflux^[4]
• Chest asymmetry, pectus excavatum and scoliosis following surgical repair of the chest wall
• Sensorineural hearing loss^[5]
• Uncommon complications: bowel obstruction, pectus excavatum, varying degrees of scoliosis, cryptorchidism, vesicoureteral reflux, and kidney stones^[6]

A diaphragmatic hernia is a very serious disorder. The outcome of surgery depends on how well the baby’s lungs have developed. Usually, the outlook is very good for infants who have enough lung tissue. Affected infants often require mechanical ventilation and oxygenation, followed by the use of diuretics after surgical correction. The use of oxygen and diuretics can be discontinued, often within the first two years of life.^[2] For children presenting with intermittent wheezing, bronchodilators are required. Some children require continued nutritional supplements. With advances in neonatal and surgical care, survival is now greater than 60%-80%. Ventilation strategies have also contributed to this increased survival rate. Although survival rates have increased, affected patients continue to have an increased risk of long term complications due to which continuous follow up in required.^[7]

Some important factors contributing to the prognosis include:^[8][9][10]

• Defect size
• Degree of pulmonary hypoplasia
• Development of pulmonary hypertension; this is often unresponsive to medical therapy
• Isolated or complex defect; complex defects are associated with higher mortality rates
• Presence of CVS malformations
• Birth weight
• Gestational age at birth
• Need for oxygenation

Proposed indicative methods include prenatal estimates of lung-to-head ratio, observed/expected-total fetal lung volume, as well as liver herniation percentage. Liver herniation is associated with a poor prognosis.