Hypoplastic Lung Disease

Etiology

The etiology of hypoplastic lung disease is multifactorial, encompassing a complex interplay of genetic, environmental, maternal, and nutritional factors. Primary pulmonary hypoplasia, a condition not associated with secondary causes, remains poorly understood. Contributing factors include reduced intrathoracic space during gestation, anomalies in the airways or pulmonary vasculature, oligohydramnios, and certain neuromuscular conditions.[4] Familial cases, first described in 1974, have been linked to syndromes involving facial abnormalities, joint deformities, and skeletal anomalies such as hip dysplasia and clubfoot.[5]

Secondary pulmonary hypoplasia arises from extrinsic factors leading to fetal lung compression or reduced amniotic fluid volume. Commonly implicated are intrathoracic or intraabdominal space-occupying lesions, such as congenital diaphragmatic hernia and congenital pulmonary airway malformations, which disrupt normal lung development, leading to cystic and/or adenomatous pulmonary areas.[6] Chest wall deformities, including skeletal dysplasia, an inherited disorder of cartilage and/or bone that interferes with fetal lung development before 16 weeks of gestation, affect their growth.[7] In contrast, oligohydramnios caused by renal anomalies (eg, renal agenesis, Potter syndrome), urinary outflow tract obstruction, or prolonged premature rupture of membranes (PPROM) after 16 weeks gestation compromises lung maturation.[8] PPROM before 25 weeks with severe oligohydramnios significantly increases the risk of fatal pulmonary hypoplasia.[9]

At the molecular level, experimental studies highlight the role of altered transcription factors such as thyroid transcription factor 1, FOG-2, SOX7, Wilms tumor protein 1, FREM1, and GATA-4, alongside growth factors including vascular endothelial growth factor, insulin-like growth factors 1 and 2, and epidermal growth factor, in lung underdevelopment.[10] Understanding these mechanisms is crucial for advancing diagnostic and therapeutic strategies for hypoplastic lung disease.

Epidemiology

The true incidence of hypoplastic lung disease is difficult to ascertain due to variations in diagnostic criteria and the potential for mild cases to remain undiagnosed until later in life. Estimates place the incidence at approximately 1.4 per 1000 births and 0.9 to 1.1 per 1000 live births.[11][12] However, these figures likely underestimate the actual prevalence, as infants with milder forms often survive the neonatal period and are diagnosed with respiratory issues in childhood or adulthood.

Specific risk populations show significantly higher incidence rates. For example, results from a prospective study by Winn et al in the United States found an incidence of 12.9% in pregnancies complicated by midtrimester rupture of membranes between 15 and 28 weeks of gestation. The study also highlighted the high mortality associated with pulmonary hypoplasia in this group, with a death rate of 95.2% in affected neonates compared to 48.2% in those without hypoplasia.[13]

Mortality statistics vary globally but underscore the severe prognosis associated with the disease. A retrospective analysis in Spain provided results showing a 47% mortality rate within the first 60 days of life, with most deaths (75%) occurring on the first day of life.[14] These findings emphasize the critical need for early identification, intervention, and coordinated care for at-risk populations.

Pathophysiology

The development of the lungs begins early in embryogenesis, with the laryngotracheal groove forming from the primitive pharynx during the fourth week of intrauterine life. This groove elongates into the splanchnopleuric mesoderm, giving rise to the respiratory diverticulum. At its distal end, the diverticulum bifurcates to form 2 lung buds, the precursors of the right and left lungs. These buds undergo a complex branching morphogenesis and elongation process, culminating in the formation of the conducting airways by the sixteenth week of gestation.

The subsequent canalicular (16–26 weeks) and terminal sac (26 weeks to birth) stages mark the development of acini and the maturation of the gaseous exchange system, with lung growth continuing into childhood. Mechanical forces, such as spontaneous airway contractions and fetal breathing movements, play a critical role in this process, particularly during the pseudoglandular stage (5–17 weeks). These forces facilitate fluid movement in and out of the lung, ensuring proper structural and functional maturation.[3] 

Oligohydramnios decreases the distensibility of the lungs by reducing the fluid around the potential airspaces. Severe hypoplasia is associated with reduced alveolar size and number with a proportional decrease in the pulmonary vasculature.[15] Factors such as early gestational age at rupture of membranes, a latency period of more than 6 days, and amniotic fluid index less than 1 to 2 cm (single deepest cord-free pocket of amniotic fluid) are independent risk factors for pulmonary hypoplasia in neonates with premature rupture of membranes. Pulmonary hypoplasia is an important nonrenal feature of Potter syndrome. In Potter syndrome, oligohydramnios is due to renal agenesis or outflow tract abnormality with a decrease in fetal urine excretion into the amniotic space. The oligohydramnios leads to prolonged fetal lung compression with subsequent hypoplasia.[16] 

Mechanical compression and impaired fetal breathing movements are significant contributors to abnormal lung development and hypoplastic lung disease. Compression may stem from intrathoracic or extrathoracic lesions, such as congenital diaphragmatic hernia, diaphragm eventration, ascites, pleural effusion, or cystic malformations of the lung. These conditions restrict the expansion of the fetal lungs, impeding their normal growth and maturation.

A regular fetal breathing pattern is essential for adequate lung development. Conditions such as brainstem anomalies (eg, iniencephaly) and neuromuscular disorders (eg, spinal muscular atrophy or congenital myotonic dystrophy) result in ineffective fetal breathing movements, leading to a reduction in lung volume. Restrictive chest wall defects, such as those seen in congenital thoracic dystrophy or short rib polydactyly syndrome, further compromise the breathing mechanics, exacerbating the impairment in lung maturation and development. These disruptions highlight the interplay between mechanical and physiological factors critical for fetal lung health.

The hypoplastic lung may arise as part of broader abnormalities, such as Scimitar syndrome, associated with an abnormally formed right lung and anomalous pulmonary venous drainage. Primary pulmonary hypoplasia remains a relatively understudied condition, with its development intricately linked to various signaling pathways essential for normal lung formation. These pathways include fibroblast growth factor, retinoic acid, sonic hedgehog, wingless-related integration site, transforming growth factor β, bone morphogenetic protein, and the hippo pathway. Mutations or disruptions in these pathways can result in lung underdevelopment.[17]

Primary pulmonary hypoplasia may also stem from abnormalities in fetal breathing activity, thoracic cavity morphology, or amniotic fluid volume. These disruptions may delay lung development or cause functional lung compression without overt structural defects.[18] The multifactorial nature of these influences underscores the complexity of primary pulmonary hypoplasia and the need for further research to elucidate its mechanisms and contributing factors.

Histopathology

Several pathological criteria are present for diagnosing pulmonary hypoplasia, but there is no particular gold standard. The most commonly used measure is the lung weight to body weight ratio (LW:BW). The typical ratio is 0.012 for more than 28 weeks of gestation and 0.015 for younger fetuses. The pitfall of this criterion is that it is affected by pulmonary congestion or pulmonary edema.[19] 

The second method for detecting hypoplasia is the radial alveolar count (RAC), which Emery and Mithal initially proposed. The RAC is the number of alveoli crossing a line drawn from a respiratory bronchiole center to the nearest and definitive connective tissue septum. Askenazi and Perlman modified the counting of the alveolar septae instead of the alveoli. They suggested that RAC less than 75% of the mean or LW:BW  less than or equal to 0.012 be used for diagnosing pulmonary hypoplasia.[20] Results from a recent study demonstrated that a diagnosis was established in more cases when the LW:BW ratio and RAC were considered for analysis, with concordance observed in 73.33% of cases.[21]

History and Physical

History

Pulmonary hypoplasia presents a spectrum of clinical manifestations depending on the extent of lung underdevelopment and associated anomalies. Prenatal care often provides critical clues, such as decreased fetal movement, PPROM, or oligohydramnios. Severe cases are frequently lethal, while sublethal forms manifest in early infancy with mild to severe respiratory insufficiency. Severe cases may present with complications such as pulmonary hypertension with persistent fetal circulation, bronchopulmonary dysplasia, or alveolar hemorrhage. In contrast, mild cases may remain undiagnosed until adulthood, presenting as incidental findings on imaging, recurrent respiratory infections, or isolated exercise desaturation.[4] A detailed history may reveal prenatal diagnoses of associated anomalies like congenital diaphragmatic hernia, renal hypoplasia, or obstructive uropathies. Postnatally, respiratory distress, poor feeding, or signs of chronic lung disease are common.

Physical Examination

The physical findings reflect the severity and distribution of hypoplasia. Three types of clinical features are associated with pulmonary hypoplasia and include:

• Thoracic deformities
  • Unilateral hypoplasia
    • The thoracic cage is asymmetric on the affected side, with restricted chest wall expansion and diminished breath sounds. Mediastinal shift and herniation of contralateral organs into the hypoplastic hemithorax may also be present.
  • Bilateral hypoplasia
    • This consists of a bell-shaped thoracic cage with shallow breathing patterns, tachypnea, and respiratory distress.[22]
• Obstructive airway and vasculature findings
  • Severe forms may present with signs of pulmonary hypertension, such as a loud second heart sound or right heart strain.[23] 
• Renal hypoplasia and obstructive uropathies
  • Renal agenesis
    • The complete absence of functional renal tissue reduces amniotic fluid volume, causing severe pulmonary hypoplasia.[24]
  • Obstructive uropathies
    • Conditions like posterior urethral valves or ureteropelvic junction obstruction hinder urinary output, reducing the amniotic fluid necessary for lung development.[24]
  • Potter syndrome
    • This syndrome is characterized by renal agenesis or severe dysplasia.
    • Nonrenal features include facial abnormalities (hypertelorism, flat nose, large floppy ears), spade-like hands, and flexion contractures associated with hypoplastic lungs due to oligohydramnios.[23]
    • Other associated anomalies may include gastrointestinal, genitourinary, or skeletal system defects, further complicating the clinical presentation.

Other congenital anomalies may exist, such as congenital diaphragmatic hernias. These patients tend to have a scaphoid abdomen, severe respiratory distress at birth, and associated congenital defects such as neural tube defects or congenital heart disease.

Evaluation

Laboratory Tests

• Arterial blood gas
  • This lab is used to assess respiratory insufficiency and hypoxemia, particularly in neonates with suspected pulmonary hypoplasia. Severe cases often show respiratory acidosis and hypoxia.
• Renal function tests
  • Evaluating serum creatinine, blood urea nitrogen, and electrolytes is critical in cases associated with oligohydramnios, renal anomalies, or obstructive uropathies.
• Genetic testing
  • Microarray analysis from amniotic fluid cells obtained via amniocentesis can identify chromosomal abnormalities, such as trisomy 13 or triploidy, often linked to early-onset oligohydramnios and associated pulmonary hypoplasia.[25]

Radiographic and Imaging Studies

• Chest x-ray
  • This imaging demonstrates an opaque hemithorax, ipsilateral mediastinal shift, and rib crowding in unilateral hypoplasia.
  • Contralateral lung hyperinflation may be seen.
  • Air leaks such as pneumothorax or pneumomediastinum can also be evident in severe cases.
• Prenatal ultrasound
  • This is a primary tool for detecting oligohydramnios, thoracic deformities, and chest asymmetry.
  • Oligohydramnios is usually diagnosed by ultrasound examination with objective measurement of the amniotic fluid index.[26] Doppler imaging is not routinely recommended.[27]
  • Biometric indices, such as lung area, thoracic circumference (TC), and thoracic circumference to abdominal circumference (TC:AC) ratio, have been used during 2-dimensional (2D) sonography to assess the fetal risk for pulmonary hypoplasia. 
  • Volumetric assessment by 3D ultrasonography has shown some promise. However, unreliable positive and negative predictive values preclude its routine use for diagnosis.[28] 
• Computed tomography
  • This imaging confirms the diagnosis and differentiates pulmonary hypoplasia from conditions like Swyer-James syndrome or atelectasis.[29]
  • Findings include absent or rudimentary bronchus, reduced pulmonary vasculature, and collapsed lung segments on the same side.
• Magnetic Resonance Imaging
  • This is useful for volumetric assessment of fetal lungs during pregnancy, but as with 3D ultrasound, unreliable positive and negative predictive value precludes its routine use for diagnosis.[28] 
• Ventilation-perfusion scanning
  • This demonstrates absent ventilation and perfusion in affected areas with mismatched perfusion defects.
• Echocardiography
  • This evaluates for congenital cardiac anomalies and assesses pulmonary hypertension, which commonly complicates severe cases.
  • Two-dimensional echocardiography can rule out congenital cardiac anomalies.[30] 
• Electrocardiography 
  • Differentiates dextrocardia from dextroversion in right lung hypoplasia, showing right axis deviation, positive QRS complex in an aortic valve replacement, and inversion of all waves in lead-I.[31]

Pulmonary Function Testing 

• This is conducted in late childhood or adulthood for sublethal cases.
• This testing reveals restrictive or obstructive lung defects with reduced diffusion capacity.[32]
• Impulse oscillometry is a low-effort alternative for evaluating lung function in children aged as young as 3.[33]

Pathological and Histological Evaluation

• Pathological criteria
  • Criteria include a lung weight less than 60% of predicted, RAC less than 4.1%, or LW:BW less than 0.015 (infants  younger than 28 weeks) or less than 0.012 (infants older than 28 weeks)
  • Alternative metrics include alveolar count per unit volume, reduced airway branching, or lung deoxyribonucleic acid content less than 100 mg/kg body weight.
• Microscopic findings
  • This includes a reduced number of lung cells, fewer bronchial branches, immature epithelial cells, thickened pulmonary vessels, and low surfactant concentrations.

Novel Diagnostic Approach

• Advanced fetal magnetic resonance imaging techniques
  • These provide stratified lung volume measurements based on fetal weight, detecting anomalies that may be missed on routine ultrasound.[34]

This multimodal approach, incorporating laboratory, radiographic, and histological findings, enables a comprehensive evaluation of pulmonary hypoplasia, guiding diagnosis and management. Despite advancements, no universally accepted diagnostic criterion exists, and clinical context remains critical for interpreting these findings.[1][8]

Treatment / Management

The treatment of hypoplastic lung disease is multifaceted, beginning in antenatal and extending into the postnatal and adult stages of care. The management approach is tailored to the severity of the condition, associated anomalies, and specific complications.

Antenatal Management

• Corticosteroids
  • These are administered to promote fetal lung maturation in pregnancies beyond 24 weeks of gestation, especially in cases of PPROM.[35]
  • A lecithin-to-sphingomyelin ratio greater than 2 in amniotic fluid suggests a reduced risk of neonatal distress.[36]
  • Antibiotics, tocolytics, and corticosteroids are frequently administered in cases of PPROM to prevent infection and prolong pregnancy.[37]
• Hydration therapy
  • A meta-analysis that included 1121 pregnant women provided results showing that hydration to the mother may improve amniotic fluid volume in cases of οligοhydramnios and was safe.[38] 
  • However, the combination of hydration and sildenafil was discontinued due to safety concerns (higher than expected rates of lung disease and death of newborns) in the STRIDER trial.[39]
• Amnioinfusion
  • Results from a study conducted by Locatelli et al in 49 patients with premature rupture of membranes at less than 26 weeks of gestation demonstrated that serial amnioinfusions reduce perinatal complications and prolong pregnancy.[40]
  • Results from the amnioinfusion in preterm premature rupture of membranes (AMIPROM) pilot study conducted on 56 patients found no statistically significant differences in fetal or maternal outcomes. More extensive studies are needed to ascertain its benefits.[41]
• Amnio patch
  • This involves intraamniotic injections of platelets and cryoprecipitate to manage PPROM.[42]
• Fetal interventions
  • In cases of congenital diaphragmatic hernia, fetal endoscopic tracheal occlusion can reduce pulmonary arterial hypertension and enhance lung development.
  • The tracheal occlusion reduces the number of type 2 pneumocytes and reduces surfactant proteins. The tracheal balloon is deflated shortly before delivery to help restore the surfactant expression.[43]  
(A1)

Postnatal and Neonatal Management

• Respiratory support
  • This support includes supplemental oxygen, mechanical ventilation, high-frequency oscillatory ventilation, and, in severe cases, extracorporeal membrane oxygenation (ECMO).
• Pulmonary hypertension
  • This condition is treated with inhaled nitric oxide (iNO), sildenafil, or prostacyclin analogs. Limited data suggest potential benefits of iNO, but further studies are required.
• Surfactant therapy
  • This is used to improve lung compliance in neonates with respiratory distress.
• Timing of surgery
  • In congenital diaphragmatic hernias, surgical repair is typically delayed 48 to 72 hours after birth to achieve cardiopulmonary stability.[44] For neonates on ECMO, delayed surgical repair reduces operative morbidity and improves survival.[45] 
• Experimental therapies
  • Antenatal administration of extracellular vesicles from amniotic fluid stem cells has shown promise in animal models of pulmonary hypoplasia secondary to congenital diaphragmatic hernias.[46] 
(B2)

Long-Term Management

• Chronic lung disease
  • This is managed conservatively with bronchodilators for airway symptoms, antibiotics for infections, chest physiotherapy, and prophylactic vaccinations.
• Localized bronchiectasis
  • This may require surgical resection if associated with recurrent infections.
• Rehabilitation
  • Pulmonary rehabilitation and nutritional support are essential for improving quality of life and functional outcomes.

Surgical Innovations

• Lung volume reduction surgery
  • This may be considered for localized hypoplasia with compensatory hyperinflation.
• Congenital defect repair
  • Repair of congenital diaphragmatic hernias and other structural abnormalities is critical to improve thoracic dynamics and lung function.

Future Directions

• Gene and stem cell therapy
  • This is emerging as a potential treatment to regenerate lung tissue.
• Advanced imaging
  • Novel techniques like fetal magnetic resonance imaging were developed to guide management and provide earlier and more accurate diagnoses.

This comprehensive, multidisciplinary approach underscores the importance of early diagnosis, personalized care, and collaboration across specialties to improve outcomes for patients with hypoplastic lung disease.

Differential Diagnosis

Hypoplastic lung disease can present with clinical and imaging findings that overlap with other conditions. Differentiating these disorders is essential for accurate diagnosis and management. The differential diagnosis includes:

• Congenital Conditions
  • Congenital diaphragmatic hernia is a congenital condition.
    • This is characterized by herniation of abdominal contents into the thoracic cavity, leading to secondary pulmonary hypoplasia.
    • Imaging reveals bowel loops or liver in the thorax.
  • Pulmonary agenesis
    • This is a complete absence of lung tissue, vasculature, and bronchial structures, usually unilateral.
    • This is distinguished from hypoplasia by the complete absence of lung structures on imaging.
  • Bronchopulmonary sequestration
    • This condition includes aberrant, nonfunctional lung tissue lacking normal connections to the bronchial tree and receiving blood supply from systemic arteries.
    • This can be identified on imaging with computed tomography angiography.
  • Scimitar syndrome
    • This syndrome includes hypoplasia of the right lung with anomalous pulmonary venous return, typically presenting with an abnormal curvilinear shadow on imaging.
• Airway Disorders
  • Congenital lobar emphysema
    • Hyperinflation of a lung lobe causes compression of adjacent lobes.
    • Imaging shows hyperlucency and mediastinal shift, unlike the smaller lung volume seen in hypoplasia.
  • Tracheobronchomalacia
    •  This is an airway collapse leading to respiratory distress.
    • Diagnosis requires bronchoscopy or dynamic imaging.
• Vascular Disorders
  • Pulmonary arteriovenous malformations 
    • These abnormal vascular connections cause shunting and hypoxemia.
    • Computed angiography confirms the diagnosis.
  • Swyer-James syndrome
    • Postinfectious unilateral hyperlucent lung with reduced vascularity and volume.
    • This is differentiated from hypoplasia by history and imaging.
• Chest Wall and Spinal Abnormalities
  • Thoracic insufficiency syndrome
    • These are caused by rib or spine deformities (eg, scoliosis) leading to restrictive lung disease.
  • Jeune syndrome (asphyxiating thoracic dystrophy)
    • Short ribs and a small thoracic cavity restrict lung growth.
• Infectious and Postinfectious Conditions
  • Postinfectious bronchiectasis
    • This includes chronic airway damage following severe infections.
    • Imaging shows dilated bronchi and scarring, unlike the rudimentary bronchial structures in hypoplasia.
  • Tuberculosis
    • This may cause localized lung volume loss mimicking hypoplasia.
• Other Acquired Disorders
  • Pulmonary atelectasis
    • This is a collapse of lung tissue due to obstruction or compression.
    • The condition resolves with treatment, unlike permanent hypoplasia.
  • Chronic lung disease of prematurity (bronchopulmonary dysplasia)
    • This occurs in neonates with prolonged mechanical ventilation or oxygen therapy, presenting with chronic respiratory symptoms.

Prognosis

The prognosis of hypoplastic lung disease varies widely and is influenced by the severity of pulmonary underdevelopment, associated anomalies, and complications such as pulmonary hypertension. Primary pulmonary hypoplasia is extremely rare and often lethal, with perinatal mortality as high as 70%, depending on the extent of hypoplasia and associated fetal anomalies.[1][47] Secondary pulmonary hypoplasia, which is far more common, demonstrates various phenotypes driven by the underlying cause.

Severe and Lethal Forms

Bilateral pulmonary hypoplasia, particularly in the context of complications like persistent pulmonary hypertension of the newborn, carries a grim prognosis, with neonatal mortality rates exceeding 95% in severe cases. Similarly, conditions like congenital diaphragmatic hernia have high mortality rates, up to 50% in the perinatal period, particularly in right-sided congenital diaphragmatic hernia. The significant deterrents to survival in congenital diaphragmatic hernia include pulmonary hypoplasia and severe pulmonary hypertension.

Moderate and Mild Forms

Infants with moderate hypoplasia may survive but often face chronic respiratory morbidities, including recurrent infections, bronchopulmonary dysplasia, and exercise intolerance. Unilateral pulmonary hypoplasia generally allows for healthy growth and development without associated lesions. Mild forms may remain undiagnosed until adulthood when symptoms such as recurrent respiratory infections or exercise desaturation prompt evaluation.[48]

Prognostic Indicators and Long-Term Challenges

• Pulmonary hypertension
  • This is a critical determinant of survival in both primary and secondary forms.
• Associated anomalies
  • Neurological, gastrointestinal, and musculoskeletal comorbidities worsen prognosis.
• Congenital diaphragmatic hernia
  • Prognosis is particularly poor in right-sided cases, with outcomes influenced by associated complications.
• Timing of diagnosis and intervention
  • Early identification and neonatal intensive care can improve survival rates in moderate cases.

Survivors of hypoplastic lung disease often experience chronic lung conditions such as reduced pulmonary capacity, heightened susceptibility to infections, and impaired exercise tolerance. Multidisciplinary care is essential for optimizing long-term outcomes and managing complications. While advances in neonatal care have improved survival rates for some forms of hypoplastic lung disease, severe cases remain a significant challenge, with morbidity persisting in survivors.

Complications

The complications of hypoplastic lung disease are diverse and influenced by the extent of lung underdevelopment, associated anomalies, and comorbid conditions. They can manifest in the neonatal period, infancy, or later in life and affect the pulmonary, cardiovascular, gastrointestinal, and other systems.

• Respiratory Complications
  • Respiratory insufficiency
    • Neonates with severe hypoplasia often experience respiratory failure due to insufficient alveolar surface area for gas exchange.
  • Pulmonary hypertension
    • Persistent pulmonary hypertension of the newborn is common, especially in bilateral hypoplasia or conditions like congenital diaphragmatic hernia—hypertension results from reduced vascular bed size and increased pulmonary vascular resistance.
  • Chronic lung disease
    • Survivors often develop bronchopulmonary dysplasia, characterized by reduced lung compliance, recurrent respiratory infections, and exercise intolerance.
  • Alveolar hemorrhage
    • Severe cases may involve pulmonary hemorrhage due to compromised vascular integrity.
  • Recurrent respiratory infections
    • Impaired mucociliary clearance and reduced pulmonary reserve increase infection susceptibility, exacerbating morbidity.
• Cardiovascular Complications
  • Cor pulmonale
    • Chronic hypoxia and pulmonary hypertension can lead to right heart strain and eventual right ventricular failure.
  • Congenital heart defects
    • Often coexisting with hypoplasia, these defects can exacerbate hemodynamic instability.
• Neonatal Complications
  • Persistent fetal circulation
    • In severe cases, failure to transition from fetal to neonatal circulation results in profound hypoxia.
  • Perinatal mortality
    • High rates of perinatal mortality are associated with bilateral hypoplasia, severe pulmonary hypertension, and associated anomalies.
• Associated Systemic Complications
  • Neurological impairment
    • Chronic hypoxemia during critical periods of brain development can lead to neurodevelopmental delays.
  • Gastrointestinal and nutritional issues
    • Conditions like congenital diaphragmatic hernia may result in gastroesophageal reflux, feeding difficulties, or failure to thrive.
  • Musculoskeletal anomalies
    • Coexisting skeletal deformities, such as thoracic cage abnormalities, may exacerbate respiratory insufficiency.
  • Renal anomalies
    • Renal agenesis or obstructive uropathies can contribute to secondary hypoplasia and systemic complications like fluid imbalances.
• Long-Term Complications in Survivors
  • Reduced pulmonary reserve
    • Survivors may have limited lung capacity, affecting physical activity and increasing the risk of pulmonary decompensation.
  • Psychosocial challenges
    • Chronic illness and frequent hospitalizations can affect quality of life, requiring multidisciplinary support.

Multidisciplinary Management to Mitigate Complications

Comprehensive care involving neonatologists, pulmonologists, cardiologists, and other specialists is critical. Early diagnosis, aggressive management of pulmonary hypertension, and optimization of nutritional and respiratory support are essential for improving outcomes and reducing the long-term burden of complications.