Fetal Surgery for Congenital Pulmonary Airway Malformation

Updated: Sep 13, 2017
  • Author: Eric Bradley Jelin, MD; Chief Editor: Hanmin Lee, MD  more...
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Overview

Background

Congenital pulmonary airway malformations (CPAMs) are lung lesions that result from disordered development of the lower respiratory tract. These malformations have a wide spectrum of severity and vary substantially in size and composition. [1]

CPAMs are characterized by airway cysts of varying size that are connected to the tracheobronchial tree. [2]  Although an elaborate postnatal staging system exists, prenatal diagnosis focuses on the size of the lesion—that is, whether the cysts are smaller than 5 mm (microcystic) or larger than 5 mm (macrocystic). [3, 4]

These lesions are almost always unilateral and can be associated with other lung lesions such as bronchopulmonary sequestrations and congenital lobar emphysema. [5, 6, 7]  The vascular supply and drainage from CPAMs is almost always to the pulmonary circulation; however, bronchopulmonary sequestrations may be connected to the systemic circulation.

CPAMs are the most common congenital lung lesion. [8, 9]  Registry data suggest that CPAM affects 1 in 8000-35,000 live births. [2]  This may be an underestimate of the true incidence of the disease, given the existence of nonregistered in-utero mortality, such as the “hidden mortality” that was seen with congenital diaphragmatic hernia. [10]

The cause of CPAM is unknown, but several hypotheses have been advanced. One prevailing theory is that CPAM is caused by airway obstruction. The different presentation and types of lesions are accounted for by the timing and location of obstruction. [2, 11]  It has also been proposed that an imbalance between cell proliferation and apoptosis during airway branching morphogenesis may lead to CPAM. [12, 13]  Dysregulation the genes HOXB5  [14]  and glial cell-derived neurotrophic factor [13]  have also been implicated in CPAM pathogenesis.

The expanded use of prenatal ultrasonography (see the images below) has increased the recognition of CPAMs and has helped characterize their natural history. [5, 8, 9]  Prenatal therapy for CPAM is considered if the affected fetus begins to show signs of hydrops fetalis. [1]  Although the natural history of CPAMs varies, several trends have been described.

Sonographic images of fetal congenital pulmonary a Sonographic images of fetal congenital pulmonary airway malformation. (A) Microcystic congenital pulmonary airway malformation, with ultrasound showing a solid echogenic mass. (B) Macrocystic congenital pulmonary airway malformation, with one or more cysts >5 mm.

Microcystic lesions typically have a rapid growth phase between 20 and 26 weeks’ gestation that usually peaks at about 25 weeks. [15] Subsequently, growth of these lesions plateaus. In many cases, the lesions actually regress, [16, 17] and some disappear completely. [18, 19] Macrocystic lesions may grow rapidly throughout gestation and do not have the characteristic pattern of growth through the late second trimester with subsequent plateau or decrease in size.

Large CPAM lesions that are either microcystic or macrocystic can compress other thoracic structures such as the esophagus, mediastinum, and inferior vena cava (see image below). This compression can result in impaired venous return, polyhydramnios, and hydrops fetalis. The small percentage of CPAMs with this behavior that lead to hydrops are associated with a high mortality, and fetal intervention may be considered in these patients. [1]

Diagram of cystic lung mass compressing the lung a Diagram of cystic lung mass compressing the lung and displacing the mediastinum. Illustration by Colin Fahrion, University of California-San Francisco.

Determining which fetuses will develop hydrops is critical to formulating appropriate surveillance and therapeutic strategies. Investigators have used a ratio that compares the calculated volume of the lesion to the fetal head circumference (CPAM volume ratio [CVR]). [20] A CVR of greater than 1.6 suggests hydrops development and warrants close prenatal surveillance. [1, 20]

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Indications

Steroid therapy

The use of steroid therapy is clearly indicated for microcystic CPAMs that have resulted in hydrops. [4] There is minimal maternal morbidity associated with this intervention, and efficacy is superior to fetal resection.

Uncertainty remains about nonhydropic fetuses with large microcystic CPAMs. A randomized trial led by the University of California, San Francisco, attempted to address the use of steroids in this context, but recruitment was hampered because of the increasing use of maternal steroids for nonhydropic microcystic CPAMs. In most centers, steroids are administered for microcystic CPAMs with a CVR greater than 1.0. 

Catheter-based therapies

Macrocystic lesions are best treated with catheter-based therapies. [1]  Drainage of macrocystic CPAMs decreases the size and compressive effects of CPAMs; it is indicated in lesions that cause hydrops. [21]

Simple cyst aspiration usually precedes thoracoamniotic shunt placement to ensure the efficacy of CPAM fluid removal. [22] Gestational age should be greater than 20 weeks and less than 32 weeks. The risk of chest-wall deformity is extremely high if catheter-based interventions are pursued before 20 weeks. After 32 weeks, delivery and neonatal resection are indicated rather than prenatal therapy.

Shunt choice also changes with gestational age.  Before 24-25 weeks, Harrison shunts (Cook Medical, Bloomington, IN) are preferred because of their smaller size. After 25 weeks, Rocket shunts (Rocket Medical, Hingham, MA) are preferred because of the decreased likelihood of migration and ease of insertion.

Fetal resection

Fetal resection of CPAMs is much less common than steroid therapy, owing to the efficacy of maternal steroid administrations. The general consensus is that large microcystic lesions that threaten fetal well-being are best treated with steroid therapy. [23] Macrocystic lesions are best treated with catheter-based therapies. [1] If steroids are ineffective, open fetal resection can be used as salvage therapy.

EXIT procedure

In rare cases, hydrops and fetal compromise can occur in or persist into the third trimester. In these cases, the CVR is typically greater than 1.6-2.0, and significant respiratory distress is anticipated at birth. The ex-utero intrapartum treatment (EXIT) procedure utilizes the placenta for gas exchange so that the fetal lungs can be bypassed while airway access is gained and lung lesions can be resected.

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Contraindications

Catheter-based therapies

Contraindications for macrocystic drainage include a predominately solid CPAM, abnormal fetal karyotype, severe fetal cardiac abnormalities or lack of a window for uterine access. Other associated congenital abnormalities may also represent contraindications but need to be considered on a case-by-case basis.

Fetal resection

Contraindications for fetal resection include significant maternal operative risk, abnormal fetal karyotype, and fetal cardiac abnormalities. Other associated congenital abnormalities may also represent contraindications but need to be considered on a case-by-case basis.

EXIT procedure

The EXIT procedure requires maternal laparotomy and hysterotomy. If maternal health is significantly endangered by these interventions, EXIT should not be performed.

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Outcomes

Overall survival data for thoracoamniotic shunts for macrocystic CPAM can be derived from the aggregation of several small reports of its use. In a study by Wilson, 26 of the 41 patients treated survived (63%). [21] A large single-center report by Peranteau et al described thoracoamniotic shunt placement in 38 patients with macrocystic lung lesions that were either causing hydrops or believed to be at high risk for causing lung hypoplasia. [24] Hydrops was present in 69% of the population. Overall survival in this group was 73%.

Several investigators have demonstrated a survival rate of approximately 50% for hydropic fetuses with microcystic CPAM after surgery. [1] Hydropic fetuses treated with steroids, however, have survival rates near 85%. [4] The superiority of steroid therapy combined with its complete abrogation of serious maternal risk has made it the standard of care for hydrops caused by microcystic CPAM before 32 weeks’ gestation. If hydrops persists or emerges past 32 weeks, EXIT and neonatal resection remain options. [16, 25]

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