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Chapter 100

Fetal Intervention

George B. Mychaliska and Darrell L. Cass

Key Points

1 Four fetal conditions clearly benefit from fetal intervention: congenital cystic adenomatoid

malformation (CCAM), fetal sacrococcygeal teratoma (SCT), a fetus with airway obstruction from a

giant neck mass or laryngeal atresia, and twin-to-twin transfusion syndrome (TTTS).

2 Any fetal therapy requires (a) accurate diagnosis of the condition and any associated anomalies that

may have an impact on outcome, (b) reliable prediction of which individual fetuses will die or suffer

serious long-term morbidity without fetal intervention, and (c) that the procedure improves the

outcome of the fetus with little to no maternal risk.

3 Preterm labor is the single biggest concern during the operation and in the postoperative period.

4 For a fetus with a lung mass, the only indication for fetal interv-ention is the presence of hydrops.

5 For a fetus with sacrococcygeal teratoma, increased aortic velocity, increased combined cardiac

output, increased cardiac-to-thoracic ratio, a dilated inferior vena cava, or reversed end-diastolic

umbilical blood flow are sensitive early predictors of impending hydrops and fetal demise; before 28

weeks’ gestation, open fetal surgery and resection is the treatment of choice.

6 Fetal intervention may play a role in the management of a small cohort of fetuses with the most

severe form of congenital diaphragmatic hernia (CDH).

7 An ex utero intrapartum treatment (EXIT) procedure is the treatment of choice for fetuses with a

giant neck mass or congenital high airway obstruction syndrome (CHAOS).

Fetal surgery has emerged as an independent subspecialty at the intersection of pediatric surgery and

maternal–fetal medicine. It is a field that has arisen from clinical necessity. Pediatric surgeons,

maternal–fetal medicine specialists, and neonatologists became frustrated with the management of a

number of congenital structural anomalies in which the baby died or suffered severe lifelong disability

despite all efforts at postnatal treatment. With the advent of prenatal ultrasound in the 1970s, many

conditions were diagnosed before birth. Fetuses were followed, and the prenatal natural history was

elucidated. It became clear that a component of organ failure was acquired because of ongoing

alterations in fetal development caused by the anomaly. Thus, it made sense that fetal interventions

may be of benefit to correct the pathophysiology and restore normal fetal development in the hope of

improving survival and decreasing morbidity.

1 The first successful fetal intervention was reported by Sir A. W. Liley, who successfully transfused a

hydropic fetus for Rh disease.1 Although a few attempts were made at exchange transfusion by an open

technique in the 1960s, modern fetal surgery was envisioned and developed by Dr. Michael Harrison at

the University of California, San Francisco (UCSF) in the late 1970s.2 It was at UCSF that the concept of

a fetal treatment program was developed, permitting a true multidisciplinary approach to fetal

diagnosis and treatment. The first open fetal operation was performed in 1982, at which bilateral

ureterostomies were performed in a 21-week-gestation fetus with obstructive uropathy.3 In the

intervening years, tremendous progress has been made in the development of fetal surgery techniques,

including advances in maternal–fetal anesthesia, tocolysis (prevention of preterm labor), and the

development of less invasive surgical techniques. During this same period, there have been significant

advances in neonatal surgical critical care that has improved the outcome of fetuses with congenital

anomalies. Thus, fetal surgery indications must be continually reassessed in the context of emerging

prenatal and postnatal therapies. At the present time, there are only three fetal conditions that show

clear benefit from fetal surgery during pregnancy: congenital cystic adenomatoid malformation

(CCAM), fetal SCT, and twin-to-twin transfusion syndrome (TTTS). Open fetal surgery at the end of

pregnancy, the ex utero intrapartum treatment (EXIT) procedure, has proven effective for the treatment

of giant neck masses and laryngeal atresia. The EXIT procedure has been expanded to treat conditions

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that result in impending respiratory failure at birth using the EXIT–ECMO (extracorporeal membrane

oxygenation) strategy, but the efficacy of this technique is still unproven. Fetal interventions, including

open, fetoscopic, and percutaneous, have been used to treat a number of other fetal disorders, such as

congenital diaphragmatic hernia (CDH), myelomeningocele (MMC), urologic obstruction, chylothorax,

and, most recently, congenital heart malformations. Many of these procedures are promising, but

questions remain regarding the natural history of these disorders, selection criteria, and efficacy.

FETAL IMAGING AND PRENATAL DIAGNOSIS

2 Fetal imaging is a critical component of the decision-making process in fetal surgery. Criteria that

must be met to consider fetal surgery include (a) accurate diagnosis of the condition and any associated

anomalies that may have an impact on outcome, (b) reliable prediction of which individual fetuses will

die or suffer serious long-term morbidity without fetal intervention, and (c) demonstration of improved

fetal outcome with minimal maternal risk.

Most congenital defects can now be detected before birth with the use of high-resolution ultrasound,

color Doppler, and fetal magnetic resonance imaging (MRI). Frequently diagnosed anomalies include

diaphragmatic hernia (Fig. 100-1), congenital lung lesions (Fig. 100-2), obstructive uropathy, neural

tube defects, neck masses (Fig. 100-3), congenital heart defects, and SCT. Other surgical disorders

include abdominal wall defects (gastroschisis and omphalocele), intestinal atresias, and cystic and solid

abdominal masses. Although ultrasound is the predominant prenatal screening and diagnostic modality,

fetal MRI has proven particularly helpful in the further evaluation of central nervous system, chest, and

neck anomalies.4–6 Fetal echocardiography is essential in the evaluation of congenital heart disease and

is also useful in evaluating abnormal cardiac function associated with other birth defects.7–9

Prenatal detection and serial ultrasonographic evaluation of these disorders have enhanced our

understanding of their natural history, and have significantly improved perinatal management. Pediatric

surgeons familiar with the management of congenital malformations before and after birth, along with

obstetricians, neonatologists, geneticists, and other specialists, participate in family counseling and

together contribute to optimal maternal–fetal management. Such multidisciplinary teams may

recommend that the timing, mode (cesarean vs. vaginal delivery), or location of delivery be altered.

Furthermore, in rare circumstances prenatal diagnosis permits in utero treatment of the developing

fetus to prevent, reverse, or minimize fetal organ injury or death. In one study, prenatal consultation

led to a change in pregnancy management in 67% of 221 pregnancies, of which 11 patients (5% of

total) benefited from fetal intervention.10

Although most congenital anomalies are best managed with the use of appropriate medical and

surgical therapy after delivery at term, rare fetal anomalies may benefit from surgery before birth. The

innovations required for fetal surgery include the development of new surgical, anesthetic, and tocolytic

techniques, as well as the resolution of such ethical issues as maternal safety and future maternal

reproductive potential.11–13

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Figure 100-1. Coronal section of fetal magnetic resonance image (MRI) of a 30-week fetus with left congenital diaphragmatic

hernia (CDH). The stomach (small arrow) and intestines are herniated into the left chest. The left lung is severely hypoplastic (large

arrow).

Figure 100-2. Coronal section of a fetal magnetic resonance image (MRI) of a 24-week fetus with a large left lung mass

(bronchopulmonary sequestration). The left diaphragm is flattened and there is moderate dextroposition of the heart. A large

vessel is seen coming from the low thoracic aorta (arrow). The congenital cystic adenomatoid malformation volume ratio (CVR)

was 1.96; however, hydrops did not develop and the baby “grew around” the mass.

Figure 100-3. Coronal section of a fetal magnetic resonance image (MRI) of a 31-week fetus with a large left neck lymphatic

malformation. The mass extends to the apex of the left chest (arrow). There is moderate left-to-right tracheal deviation. This fetus

was delivered with an ex utero intrapartum treatment (EXIT) procedure.

MATERNAL–FETAL RISKS

Fetal surgery is unlike all other surgical specialties in that it involves two patients; the surgeon must

operate on a healthy maternal patient to fix a disease in the affected fetus. This paradigm presents

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