Cardiovascular Phenotypes in CDH

What is CDH?

Congenital diaphragmatic hernia (CDH) is a rare developmental anomaly characterized by a defect in the diaphragm that allows abdominal organs to herniate into the thoracic cavity. This intrusion occurs during critical periods of fetal growth, resulting in the compression of the heart and lungs. CDH is not merely a problem of one side; the prevailing two-hit theory suggests that a primary insult leads to developmental arrest in both lungs, while a second insult involves the secondary compression of the ipsilateral lung by herniated viscera. This results in bilateral pulmonary hypoplasia, characterized by fewer bronchial divisions and reduced pulmonary arterial branching. Consequently, the condition represents a complex cardiorespiratory emergency rather than a simple surgical defect. 

In addition to these external and hemodynamic influences, there is evidence suggesting that primary developmental or metabolic errors may play a role. The "two-hit" theory of CDH pathogenesis implies that the initial insult affecting diaphragmatic development may also involve mesenchymal migration anomalies that independently arrest the growth of cardiac structures. Furthermore, experimental models have demonstrated abnormal cardiomyocyte structures and the downregulation of genes essential for mitochondrial and fatty acid biogenesis in CDH hearts, suggesting that the myocardium itself may be inherently compromised from an early stage. While the right ventricle predominantly supports the systemic circulation in fetal life, the left ventricle enters the postnatal period underdeveloped and ill-equipped for the acute transition to extra-uterine life. Upon the removal of the low-resistance placenta at birth, the left ventricle faces an immediate increase in systemic afterload while often remaining underfilled due to persistent pulmonary hypertension. Although this underdevelopment is associated with increased risks of mortality and the need for extracorporeal support, clinical data indicate that if an infant is successfully stabilized, the hypoplastic left ventricle is often "recruitable" and its dimensions may normalize over the first weeks of postnatal life.

A subset of infants with CDH presents with isolated aortic arch anomalies, most commonly coarctation of the aorta or a hypoplastic aortic arch. These anomalies occur in approximately seven percent of cases and are significantly associated with larger diaphragmatic defects and increased mortality. Clinically, these findings often represent the severity of the thoracic anatomic derangement and mediastinal shift rather than unique, physiologically independent aortic pathology, as evidenced by the fact that only seventeen percent of these patients eventually require aortic intervention. In many instances, the hypoplastic appearance of the arch may normalize following the surgical reduction of herniated organs and the resolution of pulmonary hypertension.

"As a general guideline, the following parameters can be utilized to stratify high from low risk infants with CDH, LHR <1, O/E LHR <25%, PPLV <15%, TLV <20ml, O/E TLV <30% and %LH >21% and LiTR (liver/thoracic volume ratio) greater than 14." (reference)

In TOTAL Trial:

• Moderate: "Quotient of observed-to-expected lung-to-head ratios of 25.0 to 34.9%, irrespective of liver position, or 35.0 to 44.9% with intrathoracic liver herniation" (reference)

• Severe: "The inclusion criteria were a maternal age of 18 years or more, singleton pregnancy, gestational age at randomization of less than 29 weeks 6 days, congenital diaphragmatic hernia on the left side with no other major structural or chromosomal defects, and severe pulmonary hypoplasia, defined as a quotient of the observed-to-expected lung-to-head ratios of less than 25.0%, irrespective of liver position". (reference)

Right-Sided CDH (RCDH) - Right-sided defects are more difficult to diagnose because the liver and lung have similar echogenicity on ultrasound.

• Mild: Indicated by an o/e LHR greater than 55%.

• Moderate: Indicated by an o/e LHR of 45 to 55%; survival is approximately forty percent in this range.

• Severe: Defined by an o/e LHR of 45 (some say 50%) or less. Cases with an o/e LHR below forty-five percent are associated with ninety percent mortality.

"For infants with right-sided CDH, data is more limited but to date O/E LHR < 45% is associated with > 90% mortality, with mortality decreasing to 40% with O/E LHR 45−55% and 30% with O/E LHR >55%. Based on these outcome data, infants with right-sided CDH and O/E LHR <45%, are also candidates for FETO under compassionate use and should be referred to a center capable of performing this procedure." (reference)

Fetal Endoscopic Tracheal Occlusion (FETO) 

While the primary rationale is to accelerate airway and pulmonary vessel development, fetal echocardiography has shown that FETO is also associated with improved left ventricular growth and a more robust response to maternal hyperoxia compared to newborns managed expectantly. Despite the survival benefit observed in the most severe defects, the use of FETO is associated with significant obstetric risks, including a four-fold increase in the incidence of preterm premature rupture of membranes (PPROM) and a markedly high rate of preterm delivery. In contrast to the results for severe cases, a randomized trial for moderate CDH (o/e LHR between twenty-five and forty-five percent) did not show a statistically significant improvement in survival or oxygen requirement at six months of age, suggesting that the risks of prematurity may outweigh the benefits in these less severe phenotypes. Because the procedure must be performed in highly specialized centres with extensive fetoscopic experience, the clinical management of these families requires shared decision-making to account for the maternal risks, the potential for neonatal morbidity due to prematurity, and the logistical burdens of displacement from home. Long-term outcome data indicate that while FETO can rescue the high-risk fetus from early demise, survivors exhibit similar cardiopulmonary and gastrointestinal morbidities between age four and six compared to their non-FETO-treated peers.

Survival and ECMO

Certain anatomical and physiological subgroups face much higher risks, as infants presenting with isolated aortic arch anomalies have an in-hospital mortality rate of fifty-eight percent compared to twenty-four percent in those without such anomalies. Furthermore, mortality remains concentrated in the first week of life, often occurring as a result of severe pulmonary hypertension, cardiac dysfunction, or profound hypoxic respiratory failure. 

Antenatal prognostic calculator here

ECMO

Extracorporeal membrane oxygenation (ECMO) serves as a vital rescue strategy for neonates with congenital diaphragmatic hernia who experience severe cardiorespiratory failure that remains refractory to optimized conventional management. As the most frequent indication for neonatal respiratory extracorporeal support, ECMO provides a necessary bridge by sustaining gas exchange and systemic circulation, allowing time for the pathologically high pulmonary vascular resistance to decrease and for ventricular function to stabilize. While both veno-arterial and veno-venous modes are utilized, veno-arterial support is frequently the preferred approach in cases complicated by significant biventricular or primary left ventricular dysfunction. Despite its essential role in managing life-threatening instability, survival for infants with congenital diaphragmatic hernia requiring this level of intervention remains approximately fifty percent, and those who survive often face increased risks of long-term neurodevelopmental and pulmonary morbidities. Registry data indicates that ECMO is utilized in roughly twenty to thirty-nine percent of neonatal CDH cases. While ECMO is an essential strategy for managing severe cardiorespiratory failure, survival for infants requiring this level of support is significantly lower than the general CDH population, with only about fifty percent of those placed on the circuit ultimately surviving to discharge. Survival on ECMO is also closely tied to the duration of the run; outcomes drop significantly to fifteen percent for cases exceeding five weeks of support and reach near zero for those requiring more than forty days of continuous extracorporeal life support. Additionally, the risk of mortality is higher for infants who require surgical repair while on the ECMO circuit compared to those who can be successfully decannulated prior to surgery. As survival rates have increased, the focus of clinical management has shifted from survivorship alone to the identification and mitigation of long-term morbidities that affect many graduates.

Terminology: Extracorporeal life support (ECLS) is an umbrella term that refers to any form of temporary extracorporeal technology used to support failing cardiac and/or pulmonary function, whereas extracorporeal membrane oxygenation (ECMO) is a specific modality within ECLS that provides gas exchange with or without circulatory support through a membrane oxygenator. In practice, ECMO represents the most commonly used and standardized form of ECLS, delivered as venovenous ECMO for isolated respiratory failure or venoarterial ECMO for combined cardiac and respiratory failure. Thus, all ECMO is ECLS, but not all ECLS is ECMO; the distinction is useful because ECLS reflects a broader strategic concept of extracorporeal support, while ECMO refers to a defined technique with specific circuits, flow targets, and physiological implications. Extracorporeal life support (ECLS) encompasses a spectrum of extracorporeal technologies designed to provide temporary support for failing cardiac and/or pulmonary function. This includes extracorporeal membrane oxygenation (ECMO), ventricular assist devices (VADs) used for short- or intermediate-term circulatory support, conventional cardiopulmonary bypass used during cardiac surgery, and partial-support systems such as extracorporeal carbon dioxide removal (ECCO₂R). Together, these modalities differ in cannulation strategy, degree of cardiac versus respiratory support, flow targets, and duration of use, but all share the common principle of diverting blood outside the body to replace or augment native cardiopulmonary function during critical illness or perioperative care. See neonatal ECMO section here.

ELSO Criteria for ECMO here

Oxygenation Index (OI)

The Oxygenation Index (OI) is a critical numerical value used by clinicians to assess the severity of hypoxic respiratory failure and to guide escalating life-support interventions in neonates with congenital diaphragmatic hernia (CDH). Calculation of the Oxygenation Index The OI is calculated using the following formula, which integrates the amount of ventilator support provided with the infant's actual arterial oxygenation: OI= (Mean Airway Pressure (MAP)×Fraction of Inspired Oxygen (FiO2​))/Partial Pressure of Arterial Oxygen (PaO2). The FiO2 ​ is expressed as a percentage (e.g., 100), while the PaO2 ​ is measured in mmHg. The OI is a standard metric for initiating Extracorporeal Membrane Oxygenation (ECMO). A common institutional threshold for ECMO in CDH is an OI greater than 40 for at least 3 hours despite the optimization of conventional or high-frequency ventilation. Registry data shows that the average OI immediately prior to ECMO cannulation in CDH patients is approximately 52.6 ± 31.9.

Post-Natal Evaluation

Cardiac function is now recognized as a key pathophysiological determinant of clinical outcomes and disease progression in infants with congenital diaphragmatic hernia. Specifically, impaired ventricular performance measured within the first 48 hours of life is strongly associated with a significantly higher risk of mortality and the requirement for extracorporeal membrane oxygenation (ECMO). Large registry analyses indicate that infants presenting with isolated left ventricular (LV) dysfunction on their initial echocardiogram have a lower survival rate of approximately fifty-seven percent compared to eighty percent in those with normal cardiac function. Biventricular dysfunction represents the most severe hemodynamic profile, associated with survival rates as low as fifty-one percent and ECMO utilization rates that can exceed ninety percent. Beyond survival, cardiac behavior profoundly impacts morbidity; survivors with LV or biventricular dysfunction typically require a longer duration of mechanical ventilation and experience extended neonatal hospital stays. Morphometric parameters are also highly prognostic, as an increased right-to-left ventricular diameter ratio greater than 1.1 or reduced fetal mitral valve diameters are predictive of the need for advanced rescue support or death. Additionally, the presence of isolated aortic arch anomalies is significantly associated with larger diaphragmatic defects and a three-fold increase in the odds of in-hospital mortality. Ultimately, while early pulmonary hypertension is common, its persistence beyond the first weeks of life serves as a critical marker for poor long-term cardiorespiratory outcomes and late mortality.

These infants therefore exhibit a reduced pulmonary-to-systemic blood flow ratio (Qp:Qs), with poor pulmonary perfusion and lungs that often appear relatively oligemic or “dark” on chest radiography. The magnitude of shunting depends on both shunt size and the instantaneous pressure gradient across the shunt communications. As the PDA becomes restrictive or closes, the pre- and post-ductal saturation difference may diminish or disappear, resulting in uniform systemic oxygenation (and PaO2). However, in the setting of suprasystemic PVR, ductal restriction or closure can precipitate abrupt hemodynamic deterioration by eliminating a critical RV decompression pathway. The resulting acute increase in RV afterload impairs RV output, reduces pulmonary blood flow and left atrial/left ventricular preload, and leads to low systemic cardiac output. Clinically, this may manifest as rising central venous pressure with hepatomegaly (which may be difficult to appreciate in infants with CDH), worsening tissue perfusion, and progressive lactic acidosis.

On echocardiography, the pre-capillary profile shows right ventricular dysfunction and dilation, a mainly right-to-left (most often bidirectional) shunt at the patent foramen ovale, and a right-to-left or bidirectional shunt across the ductus arteriosus, while left ventricular function remains relatively preserved. In contrast, the post-capillary phenotype is driven by primary left ventricular dysfunction and elevated pulmonary venous pressure, presenting with systemic hypotension, hypercarbia, and metabolic acidosis. 

The reduction in systemic cardiac output leads to hypotension and global hypoperfusion, manifesting clinically as prolonged capillary refill, oliguria or anuria, worsening metabolic acidosis with lactate accumulation, altered level of consciousness, tachycardia with weak pulses, and a narrow pulse pressure, depending on the severity of LV failure and the capacity of the ductus arteriosus to sustain systemic flow via the right ventricle. At the atrial level, shunting typically becomes predominantly or exclusively left-to-right as left atrial pressure rises, often with a high-velocity interatrial gradient. In this setting, pre-ductal oxygenation increasingly reflects pulmonary venous saturation, and hypoxemia is driven mainly by ventilation–perfusion mismatch related to progressive pulmonary edema and abnormal pulmonary architecture with areas of derecruitment or poor recruitment. When LV dysfunction becomes severe enough to markedly limit antegrade systemic flow, the ductus arteriosus may contribute retrograde perfusion of the ascending aorta and coronary arteries. This introduces desaturated blood into the pre-ductal circulation and further lowers pre-ductal PaO₂ and saturation. Targeted echocardiography is critical in this context, as identification of retrograde flow in the ascending aorta supplied by the ductus is a marker of profoundly impaired native LV output. In this LV predominant phenotype, the PDA becomes bidirectional or predominantly right-to-left, not only due to a relatively elevated PVR/SVR ratio but also because the right ventricle is effectively acting as the systemic pump. In this phenotype, ductal patency becomes essential for systemic perfusion; ductal restriction or closure precipitates abrupt cardiovascular collapse with severe hypotension, marked hypoperfusion, worsening acidosis, and a characteristic “gray” appearance. Clinically, these infants often develop worsening pulmonary edema (white-out on radiography) and may be at risk for pulmonary hemorrhage, particularly if exposed to pulmonary vasodilator therapies that increase pulmonary blood flow into a noncompliant LV. Ventilatory requirements typically escalate, accompanied by signs of low-output shock. 

Importantly, this phenotype is dynamic and fluctuates in response to transitional physiology, cardiopulmonary interactions, and therapeutic interventions. Ventilation strategies, oxygen exposure, pharmacologic agents, sedation, pain, manipulation, surgery, infection, and prematurity all influence the evolving hemodynamic state. Echocardiographic findings for the post-capillary profile include a hypoplastic or compressed left ventricle with impaired systolic and diastolic function, typically resulting in a left-to-right atrial shunt despite the presence of a right-to-left ductal shunt. 

Biventricular Dysfunction - Severe Phenotype

Some infants progress to biventricular dysfunction, likely reflecting adverse ventricular interdependence, impaired coronary perfusion pressure (determined by systemic blood pressure and ventricular end-diastolic pressures), and severe cardiopulmonary uncoupling. This biventricular phenotype is characterized by profound hemodynamic instability with severe hypoperfusion, and represents the most critical end of the CDH cardiovascular spectrum. It combines elements of both pre- and post-capillary hypertension with significant impairment of both ventricles. Clinically, these infants demonstrate profound cardiorespiratory instability and are at the highest risk for requiring extracorporeal membrane oxygenation. Echocardiography for the biventricular phenotype reveals diminished global longitudinal strain in both the right and left ventricles, alongside complex shunting patterns and significant septal distortion. 

TnECHO Evaluation

Management strategies

Specific pharmacological approaches

Prostangladin

Prostaglandin E1 is specifically indicated to maintain ductal patency in cases of suprasystemic pulmonary hypertension or severe left ventricular output compromise. By keeping the ductus arteriosus open, Prostaglandin E1 allows the ductus to function as a pressure relief valve for the failing right ventricle and provides an alternate route for systemic blood flow. Indeed, prostaglandin E1 (PGE1) helps manage cardiac output in patients with CDH through several distinct but interrelated physiological mechanisms, primarily by ensuring the patency of the ductus arteriosus. In the context of severe pulmonary hypertension (PH), PGE1 maintains the ductus as a pressure relief or "blow-off" valve, which reduces the effective afterload on a failing or pressure-loaded right ventricle (RV). By allowing blood to shunt from the pulmonary artery to the descending aorta, PGE1 alleviates maladaptive RV dilatation and hypertrophy, thereby improving RV performance and decreasing myocardial oxygen demand. PGE1 is particularly vital for supporting systemic blood flow in patients exhibiting significant left ventricular (LV) dysfunction - especially when the ductus becomes restrictive. In these infants, the LV may be unable to provide adequate systemic output due to developmental hypoplasia or the acute increase in afterload at birth. By keeping the ductus arteriosus open, PGE1 facilitates a right-to-left ductal shunt that allows the RV to augment systemic circulation, ensuring that vital organs receive blood flow even when the LV output is compromised. While this may result in lower post-ductal oxygen saturations, the overall effect is an increase in systemic oxygen delivery through improved total cardiac output. Furthermore, PGE1 assists cardiac output by optimizing LV filling through the reduction of adverse ventricular interdependence. In severe CDH, a dilated and hypertensive RV often causes the interventricular septum to bow into the LV cavity, which restricts LV diastolic filling and volume. By unloading the RV through the opening of a restrictive ductus, PGE1 helps restore a more normal septal configuration (by pressure equalization), thereby improving LV diastolic performance and increasing the preload available for systemic ejection. Beyond its mechanical role at the ductus, PGE1 acts as a direct pulmonary vasodilator. It increases intracellular cyclic adenosine monophosphate (cAMP) in pulmonary artery smooth muscle cells, which leads to decreased pulmonary vascular resistance (PVR). This reduction in PVR can improve the perfusion gradient for the right coronary artery, potentially reversing myocardial ischemia and further supporting biventricular contractility. Clinical evidence has demonstrated that PGE1 initiation in high-risk CDH patients is associated with significant decreases in B-type natriuretic peptide (BNP) levels, indicating a reduction in myocardial wall stress. It has also been shown to improve LV Tei indices and reduce the need for high fractional inspired oxygen by stabilizing circulatory function. However, clinicians must monitor the ductal shunt closely; once PVR falls below systemic resistance, PGE1 should be discontinued to prevent a hemodynamically significant left-to-right shunt, which could lead to pulmonary overcirculation or a "systemic steal" effect.

Later outcomes

Neurodevelopmental delay is a frequent outcome, affecting approximately twenty-five percent of survivors in recent cohorts, though some systematic reviews suggest a more modest rate of sixteen percent. High-risk infants who require prosthetic patch repair or prolonged respiratory support exhibit more complex, multifaceted deficits in both motor and language domains. Chronic pulmonary hypertension also persists in a significant subset of the population, being present in ninety-four percent of infants during the first week of life and remaining in twenty-eight percent by the sixth week. These patients often require prolonged hospital stays and may be discharged on home oxygen or specialized vasodilator therapies. Beyond neurodevelopmental and vascular issues, CDH survivors face various multisystem challenges that impact their quality of life. Chronic lung disease is highly prevalent, affecting between thirty-three and fifty-two percent of patients, with the need for ECMO support increasing the risk of this complication nine-fold. Severe gastroesophageal reflux is another common morbidity, persisting in over sixty percent of infants beyond one year of age and often leading to oral aversion or the need for gastrostomy tube feeding. The long-term trajectory for many of these children involves ongoing medical care, with reports indicating that some survivors continue to require supplemental oxygen, mechanical ventilation, or enteral nutrition through age twelve. Managing the outcomes of CDH has thus evolved into navigatiing a long-term journey where the immediate surgical success is only the first step in a complex pathway of multidisciplinary care.

Important links

• TOTAL trial calculator

• Perinatology CDH calculators

• Due date calculator (perinatology)

• TOTAL Trial Results - Severe CDH, Moderate CDH

References:

1. Le Duc K, Mur S, Sharma D, Aubry E, Recher M, Rakza T, et al. Prostaglandin E1 in infants with congenital diaphragmatic hernia (CDH) and life-threatening pulmonary hypertension. Journal of Pediatric Surgery. 2020;55(9):1872-1878.

2. Hassan M, Patel D, LaRusso K, Koclas L, Smith-Morin OT, Shapiro AJ, et al. Risk stratification helps identify congenital diaphragmatic hernia (CDH) infants in need of formal neurodevelopmental assessment: Observations from a structured, interdisciplinary long-term follow-up clinic. Journal of Pediatric Surgery. 2022;57(5):846-850.

3. Moore SS, Keller RL, Altit G. Congenital Diaphragmatic Hernia: Pulmonary Hypertension and Pulmonary Vascular Disease. Clinics in Perinatology. 2024;51(1):151-170.

4. Altit G, Lapointe A, Kipfmueller F, Patel N. Cardiac function in congenital diaphragmatic hernia. Seminars in Pediatric Surgery. 2024;33(4):151438.

5. Altit G, Gien J, DeLeon N, Keijzer R. HRF in Congenital Diaphragmatic Hernia. In: Hypoxic Respiratory Failure in the Newborn. CRC Press; 2021. p. 216-223.

6. Puligandla P, Skarsgard E, Baird R, Guadagno E, Dimmer A, Ganescu O, et al. Diagnosis and management of congenital diaphragmatic hernia: a 2023 update from the Canadian Congenital Diaphragmatic Hernia Collaborative. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2024;109(3):F239-F252.

7. Altit G, Bhombal S, Van Meurs K, Tacy TA. Diminished Cardiac Performance and Left Ventricular Dimensions in Neonates with Congenital Diaphragmatic Hernia. Pediatric Cardiology. 2018;39(5):993-1000.

8. Altit G. Congenital Diaphragmatic Hernia, A Hemodynamics perspective and 2023 update of the CDH collaborative. Sydney Neonatal Lecture; 2024.

9. Altit G, Bhombal S, Van Meurs K, Tacy TA. Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia. The Journal of Pediatrics. 2017;191:28-34.e1.

10. Altit G, Lee HC, Hintz S, Tacy TA, Feinstein JA, Bhombal S. Practices surrounding pulmonary hypertension and bronchopulmonary dysplasia amongst neonatologists caring for premature infants. Journal of Perinatology. 2018;38(4):361-367.

11. Altit G, Dancea A, Renaud C, Perreault T, Lands LC, Sant'Anna G. Pathophysiology, screening and diagnosis of pulmonary hypertension in infants with bronchopulmonary dysplasia - A review of the literature. Paediatric Respiratory Reviews. 2017;23:16-26.

12. Altit G, Bhombal S, Hopper RK, Tacy TA, Feinstein J. Death or resolution: the “natural history” of pulmonary hypertension in bronchopulmonary dysplasia. Journal of Perinatology. 2019;39(3):415-425.

13. Altit G, Bhombal S, Feinstein J, Hopper RK, Tacy TA. Diminished right ventricular function at diagnosis of pulmonary hypertension is associated with mortality in bronchopulmonary dysplasia. Pulmonary Circulation. 2019;9(3):2045894019878598.

14. Dal Col AK, Bhombal S, Tacy TA, Hintz SR, Feinstein J, Altit G. Comprehensive Echocardiographic Assessment of Ventricular Function and Pulmonary Pressure in the Neonatal Omphalocele Population. American Journal of Perinatology. 2021;38(4):341-347.

15. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews. 2017;1(1):CD000399.

16. Guner Y, Jancelewicz T, Di Nardo M, Yu P, Brindle M, Vogel AM, et al. Management of Congenital Diaphragmatic Hernia Treated With Extracorporeal Life Support: Interim Guidelines Consensus Statement From the Extracorporeal Life Support Organization. ASAIO Journal. 2021;67(2):113-120.

17. Bhombal S, Patel N. Diagnosis & management of pulmonary hypertension in congenital diaphragmatic hernia. Seminars in Fetal and Neonatal Medicine. 2022;27(4):101383.

18. Patel N, Massolo AC, Kraemer US, Kipfmueller F. The heart in congenital diaphragmatic hernia: Knowns, unknowns, and future priorities. Frontiers in Pediatrics. 2022;10:890422.

19. Hari Gopal S, Patel N, Fernandes CJ. Use of Prostaglandin E1 in the Management of Congenital Diaphragmatic Hernia—A Review. Frontiers in Pediatrics. 2022;10:911588.

20. Lapointe A, Kipfmueller F, Patel N, Altit G. Pharmacology in Congenital Diaphragmatic Hernia: A Focus on Cardiovascular Management. NeoReviews. 2025;26(10):e660-e678.

21. Johng S, Fraga MV, Patel N, Kipfmueller F, Bhattacharya A, et al. Unique Cardiopulmonary Interactions in Congenital Diaphragmatic Hernia: Physiology and Therapeutic Implications. NeoReviews. 2023;24(11):e720-e732.

22. Gupta VS, Popp EC, Ebanks AH, Greenleaf CE, Annavajjhala V, et al. Isolated aortic arch anomalies are associated with defect severity and outcome in patients with congenital diaphragmatic hernia. Pediatric Surgery International. 2023;39(1):69.

23. Jani J, Nicolaides KH, Keller RL, Benachi A, Peralta CF, Favre R, Moreno O, Tibboel D, Lipitz S, Eggink A, Vaast P, Allegaert K, Harrison M, Deprest J; Antenatal-CDH-Registry Group. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007 Jul;30(1):67-71. doi: 10.1002/uog.4052. PMID: 17587219.

24. Russo FM, Eastwood MP, Keijzer R, Deprest J. Prenatal diagnosis and risk stratification of congenital diaphragmatic hernia: controversies and current evidence. Prenat Diagn. 2024.​

25. Ruano R, Yoshisaki CT, da Silva MM, et al. Prenatal diagnosis of congenital diaphragmatic hernia: prognostic factors and perinatal outcomes. Clinics (Sao Paulo). 2018.​

26. Gorincour G, et al. Mediastinal shift angle in fetal MRI is associated with survival in congenital diaphragmatic hernia. Front Pediatr. 2022.​

27. Jani J, et al. Role of fetal MRI in the diagnosis and prognostication of congenital diaphragmatic hernia. Prenat Diagn. 2022.​

28. Tsai J, et al. Imaging assessment of prognostic parameters in congenital diaphragmatic hernia. J Clin Med. 2022.​

29. Snoek KG, Reiss IKM, Greenough A, Capolupo I, Schaible T, Allegaert K, et al. Diagnosis and management of congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed. 2024.​

30. Russo FM, et al. Prenatal and postnatal markers of severity in congenital diaphragmatic hernia. Prenat Diagn.​

31. Ruano R, Benachi A, et al. Advances in prenatal diagnosis of congenital diaphragmatic hernia. Semin Fetal Neonatal Med.​

32. Cordier AG, Russo FM, Deprest J, et al. Stomach position as a predictor of survival in left‑sided congenital diaphragmatic hernia. Ultrasound Obstet Gynecol.​