Alejandro Garcia, MD and William Middlesworth, MD

Prenatal Consultation and Fetal Interventions

Numerous structural congential malformations can be detected prenatally, including the following: anencephaly, encephalocele, spina bifida, hydrocephalus, transposition of the great arteries, hypoplastic left heart syndrome, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele, and gastroschisis. Prenatal diagnosis of gastrointestinal atresia and obstruction is suggested by the presence of polyhydramnios and dilated bowel loops, which develop proximal to the obstructed site. The overall prenatal detection rate for gastrointestinal obstruction is 34%; it is 52% for duodenal, 40% for small intestine, 29% for large intestine, 25% for esophageal, and 7% for anal atresia.

Congenital diaphragmatic hernia (CDH): A few centers are reporting early trials using techniques that permit expansion of the affected lung prenatally. Most trials involve internal or external obstruction of the trachea, which allows expansion of the lungs in utero. Trials have been limited by concerns regarding maternal safety, premature labor, and miscarriage. The results of recent randomized control trials using tracheal occlusion show survival benefits for fetuses with severe CDH compared with those receiving standard postnatal management, but with higher rates of premature rupture of membranes and preterm delivery. Multicenter trials of temporary tracheal occlusion are planned.

Myelomeningocele: Prenatal repair for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks.

Twin-twin transfusion syndrome: In monochorionic twins with evidence of unequal distribution of blood flow between fetuses, fetoscopic laser surgery can be performed to disconnect some of the communicating blood vessels in utero. This procedure stops the flow of blood from the donor to the recipient and halts the progression of twin-twin transfusion. Occasionally, one twin is lacking a functioning cardiac system, and reversed arterial perfusion occurs, with blood flow traveling from the normal twin to the abnormal twin leading to cardiac failure in the normal twin; this is known as the twin reversed arterial perfusion (TRAP) sequence. Fetal laser surgery can be used to interrupt blood supply to the nonviable twin.

Congenital cystic adenomatoid malformation (CCAM): Infants with prenatally diagnosed CCAM with hydrops are at very high risk for fetal or neonatal demise. This has led to the performance of either fetal surgical resection of the massively enlarged pulmonary lobe (fetal lobectomy) for cystic or solid lesions or thoracoamniotic shunting for lesions with a dominant cyst. It was discovered that administration of betamethasone, performed preoperatively to induce fetal lung maturity, also caused regression of these lesions. The role for fetal intervention in fetuses with CCAM and hydrops refractory to medical treatment is currently unknown.

Sacrococcygeal teratoma: Fetuses with evidence of hydrops have been treated with trials of radiofrequency ablation of feeding vessels or fetal resection of the teratoma. The benefit of these treatment modalities is unknown. ¹²³⁴⁵

Congenital Diaphragmatic Hernia (CDH)

The posterolateral portion of the diaphragm is the last to form, when the pleuroperitoneal canal closes. If it has remained open by the time the extruded midgut returns to the peritoneal cavity between the ninth and tenth weeks of gestation, the viscera will pass into the chest, and a CDH will result.

Although affected infants will occasionally be asymptomatic, they usually present with moderate to severe respiratory distress. There are diminished breath sounds on the side of the hernia and usually a shift of the heart and trachea to the opposite side. The abdomen is characteristically scaphoid. Increasingly, CDH is being diagnosed in utero by antenatal ultrasound.

Many studies have looked at lung-to-head ratio (LHR, the ratio of contralateral lung diameter to head circumference measured during 24-28 weeks’ gestation), liver position, and mediastinal shift as tools to predict mortality. Although reports have been conflicting, LHR is increasingly used to predict mortality in infants with left-sided CDH. Recent studies of infants with left-sided CDH have shown that an LHR value of less than 0.85 carries a very poor prognosis and is predictive of mortality 95% of the time. An LHR greater than 1.4, however, is virtually always associated with survival. ⁶⁷

The most useful tool is a chest x-ray, which will usually demonstrate air-filled intestinal loops in the chest (once the baby has had time to swallow air); the diaphragmatic contour on the affected side is obliterated, and the mediastinum is often shifted to the opposite side ( Fig. 19-1). In babies with the less common right-sided CDH, the findings may be more confusing, with opacification of the right lower chest from the herniated liver; in these cases, ultrasonography will provide clarification.

Endotracheal intubation with mechanical ventilation, supplemental oxygen, and orogastric decompression are used immediately in the presence of respiratory distress. Positive pressure ventilation through a face mask is not recommended because gas will enter the gastrointestinal tract and further compress the lungs. Exogenous surfactant, high-frequency ventilation, and inhaled nitric oxide are occasionally used but have no proven benefit. Barotrauma to the lungs caused by aggressive ventilation should be avoided. The level of PCO₂ may be allowed to rise to 50 to 60 mmHg (permissive hypercapnia) as long as the arterial pH remains greater than 7.25. The arterial PaO₂ should be kept between 50 and 80 mmHg but not above 100 mm Hg. ⁸⁹¹⁰

ECMO, the use of a modified heart–lung machine to provide cardiorespiratory support independent of the lungs, may be used before or after corrective surgery if the baby does not respond to the ventilatory therapy described previously. Supporting an infant on ECMO and delaying surgery allow time for pulmonary hypertension to improve while avoiding lung damage caused by barotrauma and excessive oxygen concentrations from the ventilator. The availability of ECMO may be associated with an increased chance of survival among infants with CDH. ¹¹

CDH was once thought to be a surgical emergency, but now repair is deferred intentionally to allow for normal physiologic changes to occur in the postnatal circulation. Current recommendations are for resuscitation followed by a period of stabilization until the neonate’s clinical condition improves. If the baby requires ECMO preoperatively, surgical repair is usually delayed until the ECMO settings have been lowered and the patient is considered ready to come off ECMO, but before decannulation. ¹²¹³

Several institutions are now reporting survival rates of 80% to 90% (compared with historical survival rates of 50% to 60%) for infants with left-sided CDH and approximately 55% for right-sided CDH. Most of the improvement is believed to be attributable to referral to high-volume tertiary care centers for management of these babies, as well as minimization of iatrogenic pulmonary injury through the avoidance of high ventilatory settings. However, many single institution–based reports are confounded by case selection bias, which fails to consider those CDH patients who do not reach referral centers. This is referred to as the “hidden mortality” of CDH. ^14151617

ECMO

ECMO support can provide heart–lung bypass (venoarterial support) or simply lung bypass (venovenous support). For infants with signs of hemodynamic instability such as in sepsis, heart failure, or CDH, venoarterial support is most commonly used. A cannula is placed into the right atrium via the right internal jugular vein for venous return, and a second cannula is placed into the aortic arch by way of the right common carotid artery for arterial delivery. In cases of isolated respiratory failure such as in meconium aspiration, venovenous support can be used. A double-lumen cannula is placed into the right internal jugular vein, and the tip of the cannula lies in the right atrium. Blood is removed from the right atrium, gas exchange occurs in the ECMO circuit ( Fig. 19-2), and the blood is returned to the right atrium.

The selection of neonates as potential ECMO candidates remains controversial and varies according to the institution. Relative contraindications that must be considered are the presence of an irreversible cardiopulmonary disorder, coexisting anomalies incompatible with life (e.g., trisomy 13 or 18), uncorrectable bleeding diathesis, and existing intracranial hemorrhage (above grade II). Infants who are younger than 35 weeks’ gestation are at a high risk of developing intracranial hemorrhage with systemic heparinization.

Vascular Anomalies

Vascular anomalies represent a spectrum of conditions that result from focal aberrations of blood vessel development. According to the International Society for the Study of Vascular Anomalies (ISSVA), vascular anomalies are classified as hemangiomas (proliferating endothelial tumors) and congenital vascular malformations ( Table 19-1). Hemangiomas are proliferative lesions that typically undergo periods of rapid growth and involution after birth. Hemangiomas can be distinguished from congenital vascular malformations by immunoreactivity for the glucose-1 transporter (GLUT-1). Congenital vascular malformations have been defined as lesions that are present at birth that do not further proliferate postnatally, although more recent data suggest that remodeling and growth can occur in some settings. Congenital vascular malformations can be subclassified further according to hemodynamic characteristics. Fast-flow lesions include arteriovenous fistulas and malformations, and slow-flow lesions include venous, lymphatic, and mixed malformations. ¹⁸¹⁹²⁰

Formerly known as cystic hygromas, lymphatic malformations are congenital vascular anomalies that can develop in areas of lymphatic drainage and are occasionally diagnosed in utero. Lymphatic malformations are hypothesized to develop from primitive lymphatic sacs that arise from mesenchyme or embryologic endothelial networks. Contraction of thickened muscular linings may increase intramural pressure and cause cystic dilation. Children can present with macrocystic or microcystic disease or a mixture of the two. Lymphatic malformations most commonly occur in the cervicofacial and cervicothoracic regions, although they can arise in virtually any location. They can cause complications such as obstruction of airway or vital organs, recurrent infection, bleeding, destruction of involved bones, and disfigurement.

Treatment of hemangiomas is selective, with intervention reserved for lesions that threaten vital functions, such as vision or respiration, or cause deformity or pain ( Box 19-1). Current first-line medical therapy for common hemangiomas of infancy has shifted in recent years from corticosteroids to beta blockers. The molecular mechanisms of response are still not fully defined, but both agents appear to induce or accelerate involution.

Treatment of congenital vascular malformations is highly dependent on the type of lesion and its location. Some lymphatic malformations, such as unilocular macrocystic malformations of the neck, may be amenable to surgical excision; other macrocystic lesions can often be treated successfully by sclerotherapy with doxycycline or other agents. Arteriovenous and venous malformations are generally treated using interventional radiologic techniques, such as transarterial embolization or sclerotherapy. Others, such as Klippel–Trénaunay–Weber syndrome, are in general treated conservatively and supportively. Current trials examining the role of oral therapy for diffuse, extensive, refractory, and recurrent lymphatic or mixed lesions with agents such as sirolimus [ http://clinicaltrials.gov/ct2/show/NCT00975819] and sildenafil are currently under way. ²¹²²

The ex utero intrapartum treatment (EXIT) procedure is available at selected centers for fetuses with evidence of airway compression in utero. A standard cesarean section is performed, and the baby is partially delivered but remains attached by its umbilical cord to the placenta. While the infant is maintained on placental circulation, an airway can be established, the mass resected, or extracorporeal life support can be initiated. Studies have shown that the EXIT procedure can be performed with minimal maternal morbidity and effective rescue of threatened infants. ²³

Congenital Lung Abnormalities

Increasingly, lung malformations are being discovered in utero by ultrasonography. These anomalies may be asymptomatic and discovered incidentally on an imaging study for another condition. They may produce symptoms related to respiratory compromise in neonates. Later in life, symptoms may be attributed to compression (e.g., chest pain, wheezing, dyspnea) or infection (e.g., chest pain, fever, cough, dyspnea). Occasionally, cross-sectional imaging is necessary because these lung malformations might be missed with traditional radiographs.

The treatment is almost always surgical excision, although the timing of surgery remains controversial. Increasingly, thoracoscopic resection is safe and feasible in infancy. CPAMs may resolve after a course of prenatal steroids with bethamethasone given during the second trimester. Some evidence suggests that CPAMs may develop into pleuropulmonary blastoma if left untreated. Asymptomatic congenital lobar emphysema may be observed, and many cases will regress over time. ²⁵

Esophageal Atresia and Tracheoesophageal Fistula

The precise etiology is unknown, but it is believed that the septation process that normally separates the foregut into the trachea and esophagus by the seventh week of gestation is incomplete. The more rapidly dividing trachea separates the upper and lower portions of the esophagus into discontinuous segments.

Esophageal atresia and tracheoesophageal fistula usually occur in combination but may occur in isolation.

VACTERL is an acronym for a combination of congenital abnormalities that frequently occur together; the presence of one or more should prompt a search for the others. These anomalies may involve the following structures:

Infants with esophageal atresia drool excessively because they cannot swallow their oral secretions. If feeding is attempted, the baby may develop respiratory distress as a result of aspiration from the blind-ending upper esophageal pouch. The clinician should attempt to pass a nasogastric tube, which will encounter resistance. A chest radiograph will demonstrate the tip of the tube coiled in the upper chest, confirming the diagnosis of esophageal atresia. Air visualized in the gastrointestinal tract indicates the presence of a fistula distal to the trachea, whereas a gasless abdomen implies an isolated esophageal atresia. Infants with an isolated tracheoesophageal fistula may exhibit symptoms later in life related to soiling of the lungs and respiratory distress.

The prevention of aspiration is most crucial. A nasogastric or orogastric sump tube is placed into the blind upper esophageal segment and connected to suction while the baby is maintained in a head-up position to minimize gastroesophageal reflux into the distal fistula. Intravenous fluids and broad-spectrum antibiotics are administered, and the baby is investigated for additional VACTERL abnormalities (see answer to Question 23). Positive pressure ventilation is not recommended because it can cause abdominal distention through the fistula.

If the baby is stable and the gap between esophageal segments is short, operative division of the fistula and a primary esophageal anastomosis is performed. When the infant is extremely premature or sick or has a long esophageal gap (as frequently occurs in isolated esophageal atresia without a fistula), the repair is done in stages. Division of any fistula and placement of a feeding gastrostomy are the initial procedures. Numerous classification systems have been developed to predict the outcome of infants with tracheoesophageal fistulas, such as the Waterson and Spitz criteria. Generally, infants weighing less than 1.5 kg and those with cardiac abnormalities carry a poor prognosis. Infants with one risk factor generally have good outcomes; those with both factors have a poor prognosis. ²⁶