Invasive Fetal Therapy

Ex Utero Intrapartum Treatment Procedure

Ex utero intrapartum treatment (EXIT) procedure is a multistaged cesarean delivery in which the fetus is partially delivered to preserve uteroplacental circulation until a functional fetal airway is established. To permit optimal uteroplacental perfusion and hence ample time to perform a potentially complex fetal airway establishment procedure, EXIT is done under maximal uterine relaxation, typically provided by deep inhalational general anesthesia. Therefore, the maternal risks of this procedure are mainly related to hemorrhage. Because of the complex interactions that are necessary among anesthesiology, obstetrics, and pediatrics personnel, EXIT procedures require significant advance preparation with roles preassigned to the many providers involved. Drills and rehearsals for EXIT as well as experience enhance the safety and efficacy of the procedure. ^, Page 2

The indications for EXIT have increased, but most share an anticipated difficulty in establishing the neonatal airway ( Table 34.3 ). Disorders with a potential to cause congenital airway obstruction, including laryngeal atresia (congenital high airway obstruction syndrome), large head and neck tumors, and other upper airway problems that might cause difficult intubation (e.g., micrognathia), are the main indications for an EXIT procedure. This decision is largely based on the findings of advanced imaging techniques (e.g., magnetic resonance imaging [MRI]); predictive indices regarding the tracheoesophageal complex have been suggested but are not yet validated. Another indication for EXIT is the need for fetal cardiopulmonary support during surgery, such as in the EXIT-to-ECMO (extracorporeal membrane oxygenation) procedure for specific cardiac defects, for certain types of conjoined twins, or in surgery for congenital pulmonary airway malformation (CPAM). EXIT has also been proposed for selected cases of congenital diaphragmatic hernia (CDH), although the early experience did not support that indication. The literature suggests that the use of EXIT-to-ECMO for CDH does not confer an increase in survival or decrease in morbidity compared with starting ECMO after delivery.

As in other forms of obstetric anesthesia, maternal aspiration prophylaxis and left uterine displacement to prevent aortocaval compression are important. In contrast to routine obstetric anesthesia or anesthesia in most fetal therapy cases, anesthesia for EXIT employs inhalation agents. The maternal anesthetic protocol typically involves adequate preoxygenation and rapid-sequence induction with propofol, rocuronium bromide, and remifentanil, followed by intubation and maintenance of anesthesia by propofol and remifentanil and 0.2% to 0.5% minimum alveolar concentration of sevoflurane in oxygen. Sevoflurane is preferred to isoflurane because of its faster onset of action and faster elimination to regain uterine tone after cord clamping. To support adequate uteroplacental perfusion, maternal arterial pressure must be well maintained with ephedrine or phenylephrine, which are used for their minimal effect on uterine blood flow. For the fetus, umbilical arterial and venous catheters ensure adequate vascular access for perinatal resuscitation. After the airway is established, the fetus is exteriorized from the uterus, the halogenated gas is decreased, and pitocin 20 IU in 500 mL of normal saline is given as an intravenous bolus. Pitocin is then infused as 10 IU in 1000-mL drip and titrated to uterine response. An injection of 10 IU pitocin in the myometrium may be given as well, and methergine (0.25 mg) and prostaglandin F _2α (250 μg) should be readily available. An alternative approach to general anesthesia has been described in small case series ^, using combined spinal-epidural anesthesia, intravenous nitroglycerin for uterine relaxation, and remifentanil for fetal anesthesia, without any sign of maternal sedation or respiratory depression.

Mychaliska and colleagues were the first to describe a series of eight successful procedures and coined the acronym EXIT to describe the fetal procedure. However, the largest single-center experience, with 43 EXIT procedures, was reported by Children’s Hospital of Philadelphia (CHOP) (see Table 34.3 ). ^, The most common indications were fetal neck masses and reversal of tracheal clipping (a procedure no longer performed). A single case of EXIT-to-ECMO was done for an infant with a left CDH and tetralogy of Fallot at 36 weeks’ gestation. Less common indications were congenital high airway obstruction syndrome, unilateral pulmonary agenesis, and a large lung lesion that was anticipated to cause ventilation problems at birth (the tumor was resected while the fetus was on placental bypass). EXIT also allows elective rather than emergency tracheostomy if intubation fails for other anatomic reasons. The estimated blood loss was 938 ± 532 mL, with an average time on uteroplacental circulation of 33.8 ± 16.9 minutes (range, 8 to 69 minutes). There were no recorded episodes of significant maternal hemodynamic instability in this series. Maternal complications consisted of placental abruption during EXIT ( n = 1), intraoperative blood transfusion ( n = 2), and chorioamnionitis believed to have arisen from earlier interventions ( n = 2). Despite the preparation that goes into the timing for the EXIT procedure, a report from Baylor University Medical Center found approximately 36% rates of emergency delivery, and 13.3% of their subjects underwent maternal blood transfusion. ^, EXIT procedures have also been successfully performed in twin pregnancies at 35 and 36 weeks’ gestation, in both cases owing to a large neck mass in one of the twins.

Placental histopathologic examination may identify the risk of fetal and neonatal coagulopathy in fetuses undergoing EXIT. In these fetuses, placentas have a higher frequency of fetal thrombotic vasculopathy, a risk factor for thromboembolic disease and cerebral palsy. In this setting, this pathology most likely reflects venous stasis in cases of a thoracic mass, heart failure with a teratoma, or consumptive coagulopathy in arteriovenous (AV) malformation. Routine placental examination may therefore provide prognostic information for thromboembolic and hemorrhagic sequelae, providing a useful adjunct to laboratory indices and cranial ultrasonography.

Fetoscopy

Fetoscopic procedures are minimally invasive interventions that can be considered as a cross between ultrasound-guided and formal surgical procedures. The surgeons involved may be maternal-fetal medicine specialists or pediatric surgeons, largely depending on local expertise. Fetoscopy must be organized so that the surgical team can see the ultrasound monitor and the fetoscopic image simultaneously. Cannulas, instruments, and endoscopes continue to evolve. Specifically designed fetoscopes typically have deported eyepieces to reduce weight and facilitate precise movements. Almost all are flexible fiber endoscopes, and as the number of pixels has increased, image quality has improved markedly. Working length must be sufficient to reach all regions of the intrauterine space, and a longer, integrated endoscope has been introduced ( Fig. 34.2 ). Current scope diameters are between 1.0 and 2.0 mm with a 0-degree direction of view and an opening angle of 70 to 80 degrees.

Amniotic access is facilitated by thin-walled, semiflexible, disposable or larger-diameter, rigid, reusable metal cannulas so that instrument changes are possible. Alternatively, the fetoscopic sheath is introduced directly with the use of a sharp obturator to stab the uterus under ultrasound guidance. Once inside the amniotic cavity, the obturator is replaced by the fetoscope. Technical handbooks and a review article provide details of the use of these instruments and a discussion of distention media. ^{, ,} Instrument insertion is usually done under local anesthesia, which is injected along the anticipated track of the cannula down to the myometrium.

Anesthetic Considerations

Administering anesthesia can be challenging in a pregnant patient because of complexities involved, balancing maternal concerns as well as the potential negative side effects to the fetus with the need for adequate pain sensory management.

Diagnosis of Twin-Twin Transfusion Syndrome

The diagnosis of TTTS is based on stringent sonographic criteria of amniotic fluid levels and bladder size discordance. There is oligohydramnios in the donor twin, with a deepest vertical pocket of 2 cm or less. In contrast, the recipient twin presents with polyhydramnios and a deepest vertical pocket cutoff of 8 cm or greater. Although growth restriction is often present in the donor twin, it is not essential for the diagnosis of TTTS. In severe cases, sonographic signs of congestive cardiac failure resulting from fluid overload in the recipient include a negative or reversed a wave in the ductus venosus, pulsatile flow in the umbilical vein, and tricuspid regurgitation; signs of hypovolemia or increased vascular resistance in the donor with absent or reversed flow in the umbilical artery may be seen.

The differential diagnosis for TTTS includes monoamniotic twins, isolated discordant growth, isolated polyhydramnios or oligohydramnios, and severe intertwin hemoglobin differences at the time of birth. TTTS can occur in monoamniotic pregnancies and is characterized by polyhydramnios of the common amniotic cavity with discordant bladder sizes. However, monoamniotic twins can move freely, and usually their umbilical cords are entangled, whereas in diamniotic twins with TTTS, the donor is usually stuck against the uterine wall. The distinction between TTTS and discordant growth is critical because most pregnancies with discordant growth have an acceptable outcome without intervention. Also, the isolated presence of polyhydramnios or oligohydramnios in one sac and normal amniotic fluid in the other precludes the diagnosis of TTTS and should provoke the search for discordant congenital anomalies (e.g., bilateral renal agenesis as the cause for anhydramnios in one twin).

Prediction of Monochorionic Pregnancies at Risk for Twin-Twin Transfusion Syndrome

Several unsuccessful attempts have been made to predict monochorionic twin pregnancies that will develop TTTS. Discordant first-trimester nuchal translucency is associated with an increased risk for subsequent development of TTTS because it may reflect impaired ventricular function in the hypervolemic recipient twin. A discordance in nuchal translucency of greater than 20% is present in about 25% of monochorionic twin pregnancies and can detect 52% of cases complicated by TTTS, but the positive predictive value is only 36%. Other predictive factors that have been considered include discordant crown-rump length in the first trimester, discordant abdominal circumference in the second trimester, umbilical cord insertion site discordance, and amniotic fluid discordance). ^,

Finally, it may be impossible to accurately predict TTTS owing to dynamic changes in the vascular anastomotic patterns and flows associated with a rapidly growing placenta. Most fetal care centers recommend that all monochorionic twin pregnancies be monitored by ultrasound evaluation every 2 weeks. At these examinations, relative amniotic fluid volumes, bladder filling, growth, and visualization of a free-floating intertwin membrane should be evaluated, perhaps with Doppler studies as well. Patients should also be informed of the symptoms of TTTS and advised to seek immediate medical advice if they notice rapidly increasing abdominal girth or premature contractions.

Staging of Twin-Twin Transfusion Syndrome

The Quintero staging system is still the most universally accepted method for staging TTTS ( Table 34.5 ).

• In stage I, the donor displays oligohydramnios, and the recipient displays polyhydramnios, with normal Doppler findings. The bladder is visible in the donor.

• In stage II, the bladder is not visible in the donor, but both twins have normal Doppler measurements.

• In stage III, there are abnormal Doppler measurements in one or both twins including absent or reversed end-diastolic flow in the umbilical artery (usually in the donor) or a reversed a wave in the ductus venosus or venous pulsations in the umbilical vein (typically in the recipient).

• In stage IV, hydrops is present (usually in the recipient).

• In stage V, IUFD of one or both twins is found.

Progression of TTTS is not sequential through the Quintero’s stages, as cases can progress directly from stage I to stage V, and TTTS can manifest with stage III findings from the beginning. In stage III and beyond, there is obvious and measurable hemodynamic impact, as documented in the review by Van Mieghem and associates. ^, Several attempts have been made to incorporate a fetal cardiac function score in the staging of TTTS. These include the Children’s Hospital of Philadelphia (CHOP) cardiovascular score, Cincinnati score, and cardiovascular profile score. A significant number of fetuses classified as having abnormal cardiac function would have been classified at a lower severity if the Quintero system alone had been used. However, the clinical utility of adding a formal cardiovascular scoring system to the staging of TTTS remains unproven. ^{, ,} Given the burden of abnormal cardiac function on both the donor and the recipient, it seems likely that fetal echocardiography will form an important adjunct in the evaluation of TTTS cases.

Treatment of Twin-Twin Transfusion Syndrome

Untreated TTTS can be associated with mortality rates of 80% to 90%. Other contributors to mortality and morbidity include polyhydramnios, which may lead to spontaneous abortion or extreme preterm delivery, and IUFD may result from cardiac failure in the recipient or poor perfusion in the donor. In view of the poor outcome of untreated midtrimester TTTS, there is general consensus that treatment should be offered. Even with the latest treatment modalities, the risks of adverse outcome are significant, and after treatment the pregnancy must be monitored carefully and remains at high risk until delivery. Therefore, the option of a pregnancy termination should be part of every patient’s counseling.