Fetal Surgery for Congenital Pulmonary Airway Malformation 

Updated: Nov 05, 2019
Author: Eric Bradley Jelin, MD; Chief Editor: Hanmin Lee, MD 

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, antenatal 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 antenatal ultrasonography (US; see the images below) has increased the recognition of CPAMs and has helped characterize their natural history.[5, 8, 9, 15]  Antenatal 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.[16] Subsequently, growth of these lesions plateaus. In many cases, the lesions actually regress,[17, 18] and some disappear completely.[19, 20] 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]).[21, 22] A CVR of greater than 1.6 suggests hydrops development and warrants close antenatal surveillance.[1, 21]

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 (UCSF), 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.[23]

Simple cyst aspiration usually precedes thoracoamniotic shunt placement to ensure the efficacy of CPAM fluid removal.[24] 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 antenatal 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.[25] 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.

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 must 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 must be considered on a case-by-case basis.

EXIT procedure

The EXIT procedure requires maternal laparotomy and hysterotomy.[26] If maternal health is significantly endangered by these interventions, EXIT should not be performed.

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%).[23] 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.[27] 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.[17, 28]

 

Periprocedural Care

Patient Education and Consent

Extensive counseling for families with fetuses with lesions amenable to fetal resection is mandatory. The risks and benefits of fetal intervention to both mother and fetus must be discussed frankly.

Preprocedural Planning

The assembly of a multidisciplinary team that includes an expert sonologist, an anesthesiologist, and a fetal surgeon is critical for intervention success in catheter-based therapies, fetal resections, and ex-utero intrapartum treatment (EXIT) procedures.

With ultrasonography (US), finding an appropriate window that does not traverse the placenta is a key first step in catheter-based therapies. Thoracoamniotic shunts must be placed with exquisite precision to ensure that the double-pigtail shunt has one limb in the dominant cyst and one limb in the amniotic cavity.

Patient Preparation

Anesthesia

Maternal anesthesia for catheter-based therapies consists of conscious sedation augmented by subcutaneous local anesthesia. Oral tocolysis with indomethacin or nifedipine should be used.

Maternal anesthesia for fetal resection consists of deep general anesthesia and uterine relaxation. Fetal anesthesia is achieved with an intramuscular shot of “the fetal cocktail,” which includes opiates and paralytics.

Deep general anesthesia with isoflurane for uterine relaxation is used for EXIT procedures. A delicate balance between uterine tone and maternal blood pressure must be maintained. Maternal/fetal oxygenation must also be optimized.[28]

Monitoring & Follow-up

Catheter-based therapies

After catheter-based therapies, serial sonograms are taken to ensure continued shunt patency, appropriate shunt position, and fetal well-being. Vaginal delivery is possible but must be pursued only after a complete obstetric evaluation. It is critical that the obstetrics and pediatrics teams be aware of the shunt so that it can be clamped, attached to suction, or removed immediately after birth.

Steroid administration

Surveillance US should be performed to document the response to therapy. If hydrops persists, successive rounds of steroids can be considered.

 

Technique

Approach Considerations

Therapy for fetal congenital pulmonary airway malformation (CPAM) depends on the size of the lesion, its physiologic consequences, and its cystic features.[1]  The presence of fetal abnormalities in addition to CPAM has traditionally been a contraindication for intervention, but this may be changing, now that therapy has become less invasive.[4]

Until comparatively recently, the only options for treatment of microcystic lesions resulting in hydrops were (1) fetal resection if hydrops developed prior to 32 weeks’ gestation and (2) ex-utero intrapartum treatment (EXIT)–to–neonatal resection if hydrops developed after 32 weeks.[5]  This paradigm changed after the serendipitous discovery that short courses of maternal steroids seemed to be much more effective at reversing hydrops than surgery.[4, 29, 30]

Macrocystic lesions that cause hydrops can be treated with catheter-based drainage techniques of the dominant cyst. Simple aspiration of the cyst is usually a temporizing measure but can slow down disease progression and help determine if a thoracoamniotic shunting will be effective.[21]  In lesions without a significant solid component, placement of a thoracoamniotic shunt can effectively decrease the CPAM volume ratio (CVR) and reverse hydrops (see the image below).[5]

Algorithm for the treatment of fetal congenital pu Algorithm for the treatment of fetal congenital pulmonary airway malformation (CPAM).

Fetal Resection

An extended Pfannenstiel incision is made across the maternal abdomen. The uterus is exposed, and a hysterotomy is made with the aid of intraoperative ultrasonography (US) to delineate fetal and placental position.

Two large absorbable monofilament sutures are placed parallel to the putative hysterotomy. The uterus is then incised, and a cutting stapler that utilizes Lactomer absorbable staples (US Surgical Corporation, Norwalk, CT) is inserted into the uterine cavity and fired. This forms a hemostatic hysterotomy and fixes the amniotic membranes to the myometrium. A fetal cocktail of analgesics and paralytics is then administered intramuscularly.

The fetal thorax is exposed through the hysterotomy, and a thoracotomy is made in the fifth intercostal space. Once the fetal chest is opened, the lesion is usually obvious and will actually deliver itself into the operative field because of increased intrathoracic pressure.

The lesion is then dissected away from normal lung and isolated on its vascular and airway pedicles. These pedicles are ligated and the lesion is removed (see the image below).

Congenital pulmonary airway malformation resection Congenital pulmonary airway malformation resection.

The fetal thorax is closed, and the fetus is replaced into the uterus along with warm antibiotic containing lactated Ringer solution. The hysterotomy and the Pfannenstiel incision are then closed in the standard fashion.

Tocolysis with intravenous magnesium is initiated as soon as maternal anesthesia is withdrawn.[8]

EXIT Procedure

If an EXIT procedure is being done on a nonemergency basis, an amniocentesis can be performed to determine lung maturity, and steroids can be administered, as necessary.

The fetus is accessed via maternal laparotomy and hysterotomy. Specially designed hemostatic staplers are used to avoid uterine bleeding. The head, neck and thorax of the fetus are then delivered, and the fetus is intubated (see the image below). The umbilical cord is kept warm and moist, and the uterine cavity is continuously irrigated with warm saline. The CPAM is then resected by a pediatric surgeon through a thoracotomy.

Ex-utero intrapartum treatment (EXIT) procedure. Ex-utero intrapartum treatment (EXIT) procedure.

Once the chest is closed, the umbilical cord is clamped and cut, and the neonate is resuscitated by the neonatologist.[1, 28]

Complications

Catheter-based therapies

Maternal and fetal trauma due to trocar and shunt placement are rare but have been reported[31] ; these include both vascular and structural injuries. In addition, shunts can migrate into a nontherapeutic location, neccesitating another intervention; this tends to happen more often with the smaller and flimsier Harrison shunt than with the Rocket shunt. Shunt insertion can also cause premature rupture of membranes, preterm labor, and chorioamnionitis.

Fetal resection

Possible complications during and after fetal CPAM resection are significant for both the mother and fetus. Maternal complications include bleeding, infection and wound issues. Uterine rupture is a risk after the hysterotomy and necessitates cesarean delivery for the fetus with CPAM and for any subsequent pregnancies. For the fetus, the physiologic stress of the operation is significant, and perioperative fetal demise is not infrequent. Subsequent chest wall deformity is also possible.

EXIT procedure

Blood loss and wound infections are the most common maternal complications with the EXIT procedure.[28]  Long-term maternal fertility does not appear to be affected.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Betamethasone (Celestone, Soluspan)

As with betamethasone administration for lung immaturity, two 12-mg doses are given 24 hours apart. Maternal intramuscular administration is standard.