Pediatric Pulmonary Hypoplasia Treatment & Management

Updated: Nov 11, 2022
  • Author: Terry W Chin, MD, PhD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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Treatment

Medical Care

In fetuses with pulmonary hypoplasia, interventions can be done prenatally and treatment goals should be established for postnatal care. Prenatal interventions are performed with the goal of delaying preterm labor and allowing for lungs to mature.

Preterm rupture of membranes without signs of fetal distress or intrauterine infection is treated conservatively with or without tocolytics, antibiotics, and steroids in various combinations. Antenatal corticosteroids enhance fetal lung maturation in pregnancies less than 34 weeks of gestation. If gestational age is uncertain, lung maturity can be determined by aspiration of amniotic fluid from the vaginal vault. The lamellar body counts are a direct measurement of surfactant production by type II pneumocytes. If this initial screen shows neither clearly mature nor immature fetal lung, then the lecithin/sphingomyelin (L/S) ratio can be determined from amniotic fluid. The risk of respiratory distress is very low when the L/S ratio is greater than 2.0.

Amnioinfusions and amniopatch techniques have shown promising results in the treatments of preterm labor. Amnioinfusion consists of instilling isotonic fluid into the amniotic cavity. Amniopatch consists of intraamniotic injection of platelets and cryoprecipitate with the goal of sealing amniotic fluid leak. Small cases series have reported that both techniques reduce perinatal complications and prolong pregnancy particularly in severe oligohydramnios. [55, 56]

After delivery, the infant needs respiratory support, which can range from supplying supplemental oxygen to mechanical ventilation, including high-frequency ventilation and extracorporeal membrane oxygenation (ECMO). Ventilatory strategies that have veered toward the use of gentle volume recruitment, permissive hypercapnia, especially in cases of congenital diaphragmatic hernia (CDH), have led to increased survival and improved outcomes. [57] Fetal MRI based lung volume assessment may be useful in predicting the severity of pulmonary hypoplasia and may also predict the need for ECMO. Weidner and colleagues demonstrated lower FLV:FBV ratios in infants who required ECMO. [58] While the timing of CDH repair for infant on ECMO remains controversial, there are studies that show that surgical repair of CDH while on ECMO, can be done safely and is associated with good survival and there may be increased mortality associated with delayed repair. [59, 60] Pulmonary hypertension contributes to significant mortality in patient with CDH and this particular subset of patients may have additional benefit from early ECMO support.

There is conflicting data regarding the efficacy of iNO to manage pulmonary HTN secondary to CDH. Randomized controlled trials of inhaled nitric oxide (iNO) treatment for infants with CDH have shown marginal, if any, efficacy. Poor left ventricular function and/or left ventricular hypoplasia may account for some of the poor response to iNO. Infants with severe respiratory failure secondary to pulmonary hypoplasia and documented persistent pulmonary hypertension of the newborn may benefit from iNO, but the data are limited. [61]  Aggressive ventilation in these infants causes overexpansion of lungs with compresses intra-alveolar capillaries which further aggravates pulmonary hypertension. If this is the case, hemodynamics should be optimized prior to initiating nitric oxide. More recently there are smaller population studies that show that nitric oxide may be beneficial as adjunct therapy in combination with Sildenafil and dopamine infusions to improve survival, but larger studies are needed. [62]

Low lung compliance associated with CDH is thought to be secondary to surfactant deficiency, although there is very limited and conflicting data regarding this theory. One study shows that infants with CDH had lower rates of synthesis of surfactant protein B (SP-B) and less SP-B in tracheal aspirates compared with age-matched controls without lung disease. [63] While surfactant is not contraindicated, it does not seem to provide additional survival benefit in infants with CDH.

Of note, overexpansion of hypoplastic lungs compresses intra-alveolar capillaries and aggravates pulmonary hypertension. Partial liquid ventilation has also been used; however, data are lacking to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome. [64]

Dialysis for support of renal function is provided in some cases, but it should be started only after careful consideration. Patients with severe chronic renal impairment with pulmonary hypoplasia have a poor prognosis; the ultimate outcome is difficult to improve, even with optimal renal and respiratory support.

Some studies suggest that strict infection control may improve the outcome of neonates with CDH without the need for ECMO. [65]

Medical management of cystic adenomatoid malformations (CCAM) and prognosis is dependent on the size of the lesion. Microcysts < 5cm will regress on their own while, macrocysts are progressive, can cause mass effect and results in hydrops fetalis. The presence of hydrops fetalis in CCAM is indicative of poor fetal outcome and will typically require prenatal interventions in order to prevent pulmonary hypoplasia. [66]  Spontaneous improvement and possible resolution may occur over months to years in many of these lesions. [67] Their management must be individualized, with very large lesions resulting in lung hypoplasia or fetal hydrops required possible fetal surgery. [68] In most cases of fetal lung lesions, continued observation with possible postnatal therapy occurs if respiratory distress or failure to thrive develops. [69]

Multiple studies have proven the importance of the retinoic acid signaling pathway in lung development as mentioned above. In keeping with this, the role of retinoic acid supplementation and antioxidants in pulmonary hypoplasia has been extensively studied. There is some promising human data that demonstrated decrease in incidence of bronchopulmonary dysplasia in extremely low birth infants who received vitamin A supplementation. [70] There are also several animal models that show an increase in VEGF expression and increased lung alveolarization in response to vitamin A supplementation. Despite encouraging in vitro work, supplementation with vitamin A failed to reverse oligohydramnios-induced pulmonary hypoplasia in fetal rats.

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Surgical Care

A multidisciplinary team with expertise in fetal surgery should be involved, when feasible, in all cases of severe pulmonary hypoplasia. A major indication for fetal surgery is the presence of hydrops and a gestation of less than 32 weeks. In general cases that require surgical intervention are large cystic lung malformations and congenital diaphragmatic hernias.

Cystic lung malformations

Thoracocentesis or thoracoamniotic shunts can allow for drainage of fluid from the congenital CAM, but the fluid usually rapidly re-accumulates. Thoracoamniotic shunts may be offered in pregnancies complicated by hydrops secondary to the presence of a large or multiple communicating macrocysts or severe pleural effusions. Shunt placement has been reported to decrease congenital CAM mass volumes by an average of 50%, and as much as 80% in some cases. [56]

In cases of significant mass effect due to congenital CAMs (or other solid lung mases) recommendations for delivery can range from an ex utero intrapartum treatment (EXIT) procedure with tumor resection while still on placental bypass, to elective cesarean delivery and immediate pediatric surgical evaluation and resection, to delivery with on-site pediatric surgical services. In cases in which masses plateau earlier in their growth phase, and presents a nonsignificant risk of pulmonary hypoplasia or hemodynamic compromise, surgery can be planned as an outpatient at age 4-6 week. [66]  Therefore, the management of the congenital cystic lung abnormalities needs to consider the spontaneous improvement and possible resolution that occurs over months to years in many of these lesions. [67] Up to 15% of prenatally diagnosed congenital CAMs regress and may sonographically "disappear" by becoming isoechoic within the surrounding normal lung tissue. However, these lesions can still be identified on postnatal CT scan with contrast.

The risks of subsequent malignant degeneration of congenital CAMs are poorly understood. After removal by lobectomy, the remaining normal ipsilateral lung demonstrates compensatory lung growth, and in general these children have no residual respiratory problems. [66]

Thoracocentesis or thoracoamniotic shunts can allow for drainage of fluid from the congenital CAM, but the fluid usually rapidly reaccumulates. Thoracoamniotic shunts may be offered in pregnancies complicated by hydrops secondary to the presence of a large or multiple communicating macrocysts or severe pleural effusions. Shunt placement has been reported to decrease congenital CAM mass volumes by an average of 50%, and as much as 80% in some cases. [66]

Intrauterine vesicoamniotic shunts and endoscopic ablation of posterior urethral valves are other techniques that are currently used in fetuses with urinary tract obstruction and pulmonary hypoplasia. With careful case selection, pulmonary hypoplasia is prevented, and postnatal renal and respiratory function is improved. [71]

Congenital diaphragmatic hernia

In experimental animals, percutaneous fetal endoluminal tracheal occlusion (FETO) induces lung growth and morphologic maturation. FETO with a clip may lead to accelerated lung growth and prevent pulmonary hypoplasia. FETO is currently being studied at some centers across Europe, as a way to improve survival in cases of pulmonary hypoplasia associated with severe CDH. [72] There are variations in the technique but most centers prefer the non-invasive technique, where a balloon, inserted into the tracheal lumen at 22-28 weeks' gestation. [73] Balloon occlusion creates a transpulmonic pressures, prevent fluid egress of fluid from the fetal lung which stimulate lung growth. It has been suggested that later insertion of the balloon beyond 29 weeks does not results in significant lung growth. [74]   A recent study from Texas has reported improved postnatal outcomes in infants with severe CDH. [75] This procedure was found to be minimally invasive, may reverse pulmonary hypoplasia changes, and may improve survival rate in these highly selected cases. In addition, the airways can be restored before birth.

The optimal time of surgery for CDH repair varies from center to center. Surgical repair typically involves primary or patch closure of the diaphragm through an open abdominal approach. Successes have been reported with an endoscopic approach; however, it is associated with an increased incidence of hernia recurrence. [76] The decision is made based on the severity of the lesion, hemodynamics of the patient and the center's preferences. Intraoperative considerations include the length of operative time, as thoracoscopic repair is associated with substantially longer operative times, leading to concerns for intraoperative instability, carbon dioxide retention, and pulmonary vasospasm for patients with moderate-to-severe pulmonary hypertension. [77]  There are some studies that suggest that early intervention in patients on ECMO, reduced the total duration of ECMO, reduced surgical complications and increased survival. However, this data may be skewed toward patients who may have been too sick to be weaned off ECMO prior to surgery and further studies are needed. [78]  

 

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Consultations

These patients should be followed by a pediatric pulmonologist after birth so that appropriate diagnostic tests can be performed and routinely followed. If early surgery is not performed during infancy, close follow-up of these patients is needed. As indicated above, some cystic lung abnormalities can spontaneously resolve over months to years. Newborns who have been referred for a cystic lesion observed by fetal ultrasonography may have complete resolution on postnatal chest CT. Also, the occurrence of pneumonia or repeated respiratory infections may suggest surgical intervention is needed in a patient who has been conservatively managed.

Consult a pediatric surgeon for CDH, CAM, or any other lesion that requires surgery. Also, consult a pediatric surgeon in cases that involve pulmonary hypertension or respiratory failure that requires ECMO.

Consult a nephrologist and a urologist if a renal obstructive, cystic, or agenetic lesion is the cause of the pulmonary hypoplasia.

Consult a cardiologist and cardiothoracic surgeon if the patient has a causative or coexisting cardiac lesion, such as anomalous pulmonary venous connection.

Consult a neurologist in cases of congenital neuromuscular diseases.

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