challenging moral and ethical conflicts that must be considered and balanced in each circumstance.

Chervenak and McCullough14 and others have helped to provide an ethical framework within which

fetal surgery should exist. The keys to this framework are that (a) the fetal operation has significant

chance of being lifesaving or of preventing serious or irreversible disease in the fetus; (b) the procedure

involves low mortality and morbidity risk to the fetus; and (c) the operation has very low mortality and

morbidity risk to the pregnant woman, including risks to future pregnancies. In light of these

considerations, a number of contraindications to fetal intervention exist, including chromosomal

abnormalities, the presence of other major anomalies, and significant maternal comorbidities.

There are significant maternal and fetal risks associated with fetal surgery that must be weighed for

each patient. For the fetus, there is risk of preterm delivery, fetal death, or survival with poor outcome.

Most indications for fetal surgery, however, are ones in which the fetus would die without it, and

therefore the risk-to-benefit ratio is very favorable. For those interventions aimed at improving the

outcome of fetuses with nonlethal conditions, the risk–benefit ratio is much more difficult to assess.

The risks and benefits to the mother depend on the invasiveness of the fetal surgical operation. In any

intervention, benefits to the mother include the psychological reward from doing everything possible to

improve the condition of the unborn baby. In selected cases, there is physiologic benefit in preventing

the possibility of “mirror syndrome,” a preeclampsia like condition in which the mother’s condition

“mirrors” that of a sick or dying fetus.15 In the presence of this syndrome, fetal surgery is

contraindicated and urgent fetal delivery is important to ensure maternal health. For the mother, fetal

surgery adds the discomfort of one or two operations that would not have been required otherwise. For

mothers who have hysterotomy other than low transverse, and for all mothers having open fetal

surgery, there are theoretical risks to subsequent pregnancies and future fertility. When maternal

fertility following fetal surgery was studied, however, it was found that 32 of 35 mothers were able to

achieve successful subsequent pregnancies and 31 live births resulted.11 Furthermore, if a classic

cesarean section is performed during open fetal surgery, subsequent deliveries must be performed by

cesarean section. Specific complications resulting from a classic cesarean section in subsequent

pregnancies include uterine dehiscence and uterine rupture.16 Postoperatively, nonhydrostatic

pulmonary edema may occur in the mother. This problem was more prevalent in the early experience of

open fetal surgery, but it still persists. In a trial reported by Harrison et al.17 3 of 11 mothers developed

pulmonary edema and required oxygen after fetal surgery. In each of these patients the symptoms were

mild and resolved within 48 hours. The cause of this phenomenon remains unclear, but is likely related

to uterine manipulation and the release of prostaglandins or thromboplastins that alter maternal lung

vascular permeability.18 As with all obstetric surgery, blood loss may be significant and mothers

undergoing fetal surgery occasionally require blood transfusion.19 Chorioamniotic membrane separation

and preterm labor remain the Achilles’ heel of fetal interventions.20,21 Surgical approaches that involve

a smaller hysterotomy and more minimally invasive techniques appear to lower these risks.22

Specifically, fetoscopic and percutaneous approaches lessen the maternal and fetal risks.23 These

techniques allow vaginal delivery after fetal surgery and appear to decrease the incidence of preterm

delivery.24 Thus far, no maternal deaths have occurred at the major fetal surgery centers in the United

States and Europe.

SURGICAL TECHNIQUES: OPEN, FETOSCOPIC, AND

PERCUTANEOUS APPROACHES

Numerous technical aspects of fetal surgical procedures have evolved over 30 years of experimental and

clinical work and have been reviewed in detail elsewhere.25–28 The comprehensive care of the fetal

surgery patient is labor intensive and requires multidisciplinary cooperation between all team members.

In the operating room, the leader of the fetal surgery team is either a pediatric surgeon or maternal–

fetal medicine specialist with specific training in fetal surgical techniques. The leader should be chosen

depending on the procedure and specific expertise.29 Responsibility for the patient’s anesthesia is shared

between an obstetric anesthesiologist for the mother and a pediatric anesthesiologist for the fetus. Both

anesthesiologists should have special expertise in maternal–fetal anesthesia and work together as a

team. A high-resolution ultrasound machine with color and enhanced Doppler is essential and used

throughout the procedure to assess fetal and placental position; monitor fetal heart rate, cardiac

function, and volume status; and assess amniotic fluid levels.30 A pulse oximetry probe is placed on the

fetal hand to assess fetal oxygen saturation and continuous heart rate. A peripheral intravenous catheter

2881

is often placed in the fetus for fluid, blood, and medication delivery. A surgical nursing team trained in

the specific aspects of fetal surgical procedures and instrumentation is mandatory.

Open fetal surgery is performed with general and epidural anesthesia. Epidural delivery of a

fentanyl/bupivacaine mixture provides optimal postoperative analgesia and minimizes uterine

irritability. Intraoperatively, inhaled isoflurane titrated to an end-tidal concentration of 2% or higher is

used to achieve uterine relaxation, which is critical to successful outcomes. Because of the risk of

postoperative pulmonary edema, the mothers are fluid restricted during these procedures and receive as

little as 500 mL of crystalloid. The patient is positioned supine with a roll under the right side to avoid

compression of the inferior vena cava by the gravid uterus. The uterus is exposed through a low

transverse abdominal incision. If the placenta is positioned posteriorly, subcutaneous flaps and a midline

incision from the umbilicus to the pubis permit adequate uterine exposure. In cases of an anterior

placenta, the fascia and rectus muscles are divided transversely so that the uterus can be tilted forward

for a posterior hysterotomy. A large abdominal ring retractor is useful for abdominal wall retraction.

After uterine relaxation is confirmed by palpation, the orientation of the fetus and placenta is confirmed

by ultrasound. For open fetal surgery during pregnancy, a classical cesarean section incision is made.

For the EXIT procedure, it is preferable to perform a low transverse hysterotomy. Two opposing

traction sutures are placed with ultrasound guidance to provide hemostasis and to secure the fetal

membranes to the uterine wall. The myometrium is then incised, and a hemostatic uterine stapler is

used to open the uterine wall in both directions. A rubber catheter connected to a rapid infuser is

inserted into the amniotic space to replace egress of amniotic fluid with warmed Ringer lactate. Infusion

of warmed fluids is critical to maintain fetal temperature and amniotic volume and to minimize the risk

of uterine contractions and umbilical cord compression (Fig. 100-4).

One of the unique requirements of fetal surgery is that the surgeon must operate on the fetus and

then return the fetus to the amniotic environment in such a way as to minimize disturbance to the

continuing pregnancy. The uterine closure must have adequate strength to prevent rupture, must have

membrane reapproximation to prevent amniotic fluid leakage, and must limit risks for preterm labor or

future infertility. Currently, the uterus is closed in two layers using an outer layer of full-thickness 0

polydioxanone (PDS) retention sutures and an inner running layer of 2-0 PDS to close the myometrium

and membranes. Before the closure is complete, the rapid infuser is used to restore amniotic volume and

administer antibiotics. An omental pedicle is secured over the hysterotomy to seal any small leaks from

the full-thickness sutures.

2882

Figure 100-4. Fetal surgery of a hydropic 24-week fetus with a large left lung mass. A: Intraoperative ultrasound to locate the

placenta and fetus. B: Uterine stay sutures are elevated to facilitate the use of the uterine stapler. C: The mass has been removed

and the remaining normal left lung is evident. A bolus of crystalloid is given into the umbilical vein, and the chest is being closed.

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

The mother receives a 50-mg indomethacin suppository 4 hours before surgery, and remains on

indomethacin for 48 hours postoperatively. Daily echocardiography is essential; if there is evidence of

patent duct arteriosus (PDA) restriction, then the indomethacin is stopped. During the operation

terbutaline or nitroglycerin infusion can be used to help control uterine irritability and enhance

relaxation. During closure of the hysterotomy, the mother is given a 6-g bolus dose of magnesium

sulfate followed by a continuous infusion of 2 to 4 g/h. Postoperatively the mother is observed in an

intensive care unit (ICU) setting for close monitoring for pulmonary edema, fluid management, and

uterine irritability. The magnesium sulfate is continued for 48 to 72 hours with close monitoring of

magnesium levels and signs of toxicity. On the second to third postoperative day, usually the

magnesium and indomethacin can be weaned, and the patient is converted to subcutaneous terbutaline

or oral nifedipine. The patient is maintained on bed rest until the time of delivery. Postoperatively,

daily ultrasound examinations help to assess the ductus arteriosus, amniotic fluid index (estimate of

fetal urine output or of amniotic fluid leak), and fetal movement (marker of fetal well-being).

Fetoscopic surgery has been used most recently to permit a number of fetal surgical interventions,

such as tracheal occlusion, laser ablation of communicating vessels in TTTS, and fetoscopic ablation of

posterior urethral valves for fetuses with obstructive uropathy. Initially, these procedures were

performed by exposing the uterus through a maternal laparotomy. More recently, surgeons have placed

trocars percutaneously into the uterus through the intact maternal abdominal wall. Specially designed

fetoscopic instruments have been developed that have allowed for single-port procedures.31

Visualization during fetoscopy requires continuous irrigation through the fetoscope. This permits

maintenance of uterine fluid volume, avoids risk of air embolus with gas distention of the uterus,

ensures a continuously washed operative field, improves visibility by exchanging the cloudy amniotic

fluid with lactated Ringer solution, and keeps the fetus warm.

RATIONALE AND OUTCOME OF FETAL SURGERY FOR SPECIFIC

CONGENITAL ANOMALIES

Lung Malformations

CCAM and bronchopulmonary sequestration are the most common congenital lung malformations, and

the most common fetal thoracic lesions that may benefit from fetal intervention.32 The incidence of

these lesions has been estimated at 1 in 25,000 to 35,000 pregnancies;33 however, current referral

patterns to fetal therapy centers suggest they may occur more frequently. Grossly, a CCAM is a discrete,

space-occupying intrapulmonary mass that contains variable-sized cysts. These lesions do not function in

normal gas exchange; however, airspaces within these masses communicate with the tracheobronchial

tree. Histologically, CCAM is distinguished from other lesions and normal lung by (a) polypoid

projections of the mucosa, (b) an increase in smooth muscle and elastic tissue within cyst walls, (c) an

absence of cartilage (except that found in “entrapped” normal bronchi), (d) the presence of mucussecreting cells, and (e) the absence of inflammation. In contrast, bronchopulmonary sequestrations

(BPSs) (intralobar or extralobar) are masses of nonfunctioning lung tissue that are supplied by an

anomalous systemic artery and do not have connection to the native tracheobronchial tree. The

pathogenesis of both lesions is unknown, but they are thought to arise during the fifth to sixth week in

embryonic development, and may result from abnormalities in growth signals between the branching

airway epithelium and pulmonary mesenchyme.34,35 Congenital lung lesions are commonly diagnosed

by prenatal ultrasound as an echogenic solid, or cystic and solid thoracic mass. Not infrequently, these

lesions may be seen to have a systemic blood supply on Doppler ultrasound. Although CCAM and BPS

have been distinguished prenatally in the past by the presence or absence of a systemic vessel, it is now

recognized that these lung lesions represent a continuum of pulmonary maldevelopment and there are

lesions that have clinicopathologic features of both.36,37 Fetal MRI may enhance diagnostic accuracy in

examining these lesions and distinguishing them from other thoracic abnormalities, such as congenital

lobar emphysema, bronchial atresia, bronchogenic cyst, and congenital diaphragmatic hernia

(CDH).38,39

2883

The natural history and clinical spectrum of these anomalies are variable, but they appear to depend

mostly on the size of the mass and the secondary physiologic derangement. The growth of CCAMs

usually plateaus between 25 and 28 weeks, at which time the fetus appears to grow around the lesion.

The vast majority of small to moderate-sized CCAMs remain asymptomatic during fetal life.

Approximately 15% of CCAMs will shrink significantly before birth.40 In contrast, large lesions

represent 5% to 10% of CCAMs and may produce significant mass effect, which can lead to pulmonary

hypoplasia, impaired fetal swallowing and polyhydramnios, and impaired venous return and heart

failure. Congestive heart failure in the fetus, known as nonimmune fetal hydrops, is defined by the

presence of skin or scalp edema, or by fluid accumulation in one or more serous cavities (ascites or

pericardial or pleural effusions). The risk of hydrops appears to depend on the size and rate of growth

of the mass, and results from compression of the superior vena cava and impaired venous return.41 It

has been demonstrated that hydrops is a harbinger of fetal demise, and is associated with near 100%

mortality.42 Rarely, hydrops is due to a tension hydrothorax from extralobar sequestration.42 As a

prognostic factor, the CCAM volume ratio (CVR) has been developed to correlate the relative size of

these lesions with fetal and postnatal outcome.43 In one series in which 58 fetuses with a lung mass

were followed prospectively, 75% of fetuses (12 of 16) with a CVR greater than 1.6 developed hydrops,

whereas only 17% (7 of 42) with a CVR of 1.6 or less had this complication. However, the CVR was not

predictive of hydrops if a CCAM had a dominant cyst, which may enlarge at an unpredictable rate.

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

Most commonly, hydrops occurs in the period of rapid growth of these lesions between 19 and 26

weeks’ gestation.32,42,43 Fetuses with a lung mass should be followed closely. It is recommended that

those with a CVR less than 1.6 receive weekly ultrasound up to about 28 weeks’ gestation, whereas

those with a CVR greater than 1.6 should be examined as frequently as two to three times per week. If

signs of hydrops appear, the treatment options include percutaneous placement of a thoracoamniotic

shunt for lesions with a dominant cyst, and open fetal thoracotomy and mass resection for more solid

lesions. Use of the laser or radiofrequency ablation to debulk a large CCAM cannot be recommended

now because of technical limitations and inability to control energy distribution and postprocedure

swelling.44,45

Fetal surgery for fetal lung masses requires open hysterotomy (Fig. 100-4). Intraoperative

echocardiography is critical to assess fetal intravascular volume and right ventricle filling. These fetuses

have tamponade physiology and generally benefit from a fluid bolus before thoracotomy. A relatively

large thoracotomy is required to permit adequate exposure, and the mass is delivered slowly to prevent

rapid decreased cardiac venous return. At resection, the presence of a systemic vessel must be

considered.

The first successful open fetal surgery for CCAM was reported in 1990 by Harrison et al. at UCSF.46

Since then, there have been reports of 22 open fetal resections of lung masses, with 50% survival.32

Delays in referral and intervention, the presence of maternal “mirror” syndrome, preterm labor,

chorioamnionitis, and technical difficulties associated with the procedure have limited outcomes in half

of the cases. Recent evidence suggests that administration of maternal steroids may reverse the

pathophysiology of hydrops, but this strategy requires further validation.47,48

Sacrococcygeal Teratoma

Sacrococcygeal teratoma (SCT) is the most common neonatal tumor, with an incidence of 1 in 35,000

live births.49,50 Thought to arise from totipotent somatic cells originating in the caudal cell mass, this

tumor contains multiple neoplastic tissues that lack organ specificity, are foreign to the sacrococcygeal

region, and are derived from all three germ layers. The postnatal mortality of SCT is low, despite that

about 10% of neonatal lesions are malignant. However, the prenatal mortality from SCT is greater than

50%. The causes of death in fetal SCT are multifactorial, but primarily involve dystocia with tumor

rupture and bleeding at the time of delivery, or high-output cardiac failure and hydrops from high blood

flow within the mass.51 The evolution of high-output cardiac failure before the development of

placentomegaly and hydrops in a fetus with SCT is the sole indication for fetal surgical intervention.

Furthermore, SCT may lead to maternal mirror syndrome (Ballantine syndrome).52 In this condition, the

mother experiences progressive preeclampsia like symptoms, including vomiting, hypertension,

peripheral edema, proteinuria, and pulmonary edema, caused by the release of placental vasoactive

factors or endothelial cell toxins from the edematous placenta. This syndrome is reversed only by

delivering the child and the placenta, but not by removing the SCT prenatally.

5 The diagnosis of SCT can be made by fetal ultrasound as early as 14 weeks’ gestation.53 The

2884