Fetal interventional procedures and surgeries: a practical approach

History of fetal surgery

The first successful fetal interventional procedure performed was an intrauterine transfusion of red blood cells for erythroblastosis fetalis. This was done in 1963 by Sir William Liley who completed the procedure via the intra-peritoneal route [2]. In 1982 a landmark meeting occurred involving almost all of the clinicians who, at that time were actively involved in fetal treatment and surgery. They met in what was the first organized conference in the field of fetal surgery, and agreed to share information, establish a registry and provide guidelines for this promising, and rapidly growing, discipline. Dr. Michael Harrison stated at the meeting that “All case material, regardless of outcome, should be reported to a fetal-treatment registry, so that the benefits and liabilities of fetal therapy can be established as soon as possible”, and this statement remains as true today as it was almost 35 years ago [3].

The rapid advances in imaging techniques and prenatal diagnosis over the last three decades have allowed for the progressive development of prenatal interventions and surgeries and today they have become an integral part of the management of high risk pregnancies. In addition, the rapidly growing capability of digital optics and miniaturized instrumentation has now allowed fetoscopic procedures to become a reality.

We did not just arrive here, several years of painstaking work taking research from bench utilizing non-human primates, creating pathologies similar to that seen in humans and attempting various therapeutic approaches including safe and effective medications have been invaluable. During these efforts as well, criteria were generated to determine biological plausibility and rationale for selected procedures [4]. Crucial to this evolution has been a generally agreed principle of reporting of all outcomes including those where surgical expectations were met and those less so.

Ethical considerations in fetal surgery

A keen understanding of the ethics surrounding fetal surgery is necessary to help guide decisions regarding if to intervene, when to intervene, and how to intervene. The decision to intervene must pass three criteria: (1) invasive therapy should have high probability of being life-saving or of preventing serious and irreversible disease, injury, or disability for a fetus and the child to be; (2) invasive therapy poses low mortality risk and low or manageable risk of serious disease, injury, or disability to the fetus and the child to be; (3) the maternal mortality and morbidity risk is very low or manageable. The autonomy of the pregnant woman must be central to any decisions regarding intervention as she is assuming risk to self with a potential of no benefit to self [5].

Control of fetal pain

One of the concerns in fetal surgery relates to the potential for fetal pain from interventions. Although we do not have a lot of evidence in this regard, analgesia should be administered during fetal interventional procedures that are expected to evoke fetal pain, especially after 18–20 weeks of gestation as nociceptive sensory pathways and electroencephalographic (EEG) activity are present midgestation [6]. Usually a combination of atropine, fentanyl and vecuronium are administered using a 22-gauge needle under ultrasound or endoscopic guidance through intramuscular or intravenous routes. The doses are adjusted to estimated fetal weight (20 μg/kg, 15 μg/kg and 0.2 mg/kg, respectively) and are repeated every 45 min. The purpose of this combination is to suppress any bradycardic response to stress, to decrease fetal movement, and to effectively control any potential pain during and after the procedure as fentanyl has a half-life >12 h in the fetal/premature infant populations. Despite the addition of atropine, the most worrisome complication is cardiac depression secondary to profound bradycardia [6], [7]. The cardiac function of the fetus is monitored by fetal ultrasound by a fetal cardiologist during the procedure to assess if cardiac function requires augmentation.

Closed fetal interventions

The term closed fetal surgery, or intervention, refers to any procedure performed through a needle or trocar inserted through the uterine wall under ultrasonographic guidance. This obviates the need for creating hysterotomy (which has significant obstetric implications). These procedures can be performed either percutaneously or in some cases after exposing the uterus via a laparotomy. The latter approach (one championed by the team at Texas Children’s Hospital for minimally invasive fetal interventional procedures) allows for successful completion of procedure in cases of complete anterior placenta, protects the membranes by allowing anchoring of the membranes in complex fetal surgical procedures, and promotes enhanced visualization by enabling a low pressure CO₂in-utero environment [8], [9]. In addition, we feel that an exposed uterus leads to easier fetal manipulation to change and maintain fetal positioning in difficult cases. In most fetal interventions and surgeries access to the amniotic cavity is obtained via disposable flexible plastic ports, or in some cases non-disposable rigid metal cannulas. Fetoscopes and instruments can be inserted though these ports or cannulas. The steps for fetoscopic procedures are noted in Table 1.

Laser photocoagulation of the communicating placental anastomoses in twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) complicates 9%–15% of monochorionic diamniotic twin pregnancies and typically presents between 16 and 26 weeks of gestation. It is associated with high fetal mortality in theses pregnancies [10], [11]. The pathophysiology of the syndrome is explained by the presence of unbalanced vascular connections between twins. Basically, the placental vascular anastomoses can be categorized into four types: arteriovenous (AV), venoarterial (VA), arterio-arterial (AA) and veno-venous (VV). AV and VA connections are unidirectional while AA and VV anastomoses allow blood to flow in both directions (bidirectional). It is believed that unidirectional flow in AV anastomoses accounts for circulatory imbalance in TTTS while bidirectional flow in AA connections protects against development of such an imbalance.

Cardiovascular imbalance in TTTS eventually leads to significant circulatory maladaptive responses. Excessive blood volume in the recipient twin increases cardiac preload causing right ventricular hypertrophy, and consequently hypertension and cardiomyopathy. On the other hand, the donor twin usually maintains a normal cardiac function in the majority of cases.

The diagnosis of TTTS depends on the finding of polyhydramnios/oligohydramnios sequence in a monochorionic, diamniotic pregnancy. In TTTS, oligohydramnios is defined as a deepest vertical pocket (DVP) of 2 cm or less in the donor sac, while polyhydramnios is defined as DVP of 8 cm or more in the recipient sac. In Europe, polyhydramnios is further subdivided based on gestational age at diagnosis, and requires a DVP of 8 cm or more in the recipient sac if the pregnancy is <20 weeks of gestation, but 10 cm or more after 20 weeks of gestation [12]. The staging system for TTTS was proposed by Quintero et al. [13] in 1999 (Table 2).

Options for treatment include expectant management, laser ablation, repeated amnioreduction, septostomy of the inter-twin dividing membrane, selective reduction, and termination of the entire pregnancy. With the exception of selective fetal reduction, treatment options have been evaluated by randomized controlled trials [14], [15]. The Eurofetus trial compared laser ablation to amnioreduction in TTTS patients (stage 1–4) and demonstrated a higher likelihood of survival of at least one twin to 28 days (P=0.009) as well as to 6 months (P=0.002) of age in the group treated with laser. In addition, the same group showed a lower risk of periventricular leukomalacia (P=0.02), and evaluation of the infants at 6 months of age showed less evidence of neurological complications (P=0.003) [16].

Typically, laser is offered between 17 and 26 weeks of gestation. Recently, preliminary data has suggested that laser before 17 weeks and after 26 weeks shows similar beneficial outcomes, however, this practice is not universally accepted [17]. Indications for laser therapy include patients with stage 2 to stage 4 TTTS, and special cases of stage 1 TTTS including rapidly progressive polyhydramnios, preterm contractions, significant maternal discomfort, and/or progressive shortening of the cervix [18]. Besides the indications listed above, stage 1 TTTS is expectantly managed as outcomes are similar if expectantly managed or treated by laser ablation [12].

A recent retrospective study conducted by the North American Fetal Therapy Network included a large cohort of stage 1 TTTS and compared fetal intervention vs. expectant management. This study showed that few number of cases with stage 1 TTTS remained stable or improved with expectant management and the majority of cases progressed to higher stages within 1 or 2 weeks or had fetal demise. The authors concluded that early fetal intervention in the form of amnioreduction or laser therapy is associated with significantly better outcomes and chances of dual fetal survival [19]. Given the limitations of this study, stage 1 TTTS should be managed according to the usual recommendations until the ongoing multicenter randomized trial (ClinicalTrials.gov NCT01220011) answers that question.

Initially, laser was performed using a non-selective technique in which all the vessels crossing the dividing membrane were ablated (membranous equator) [20]. More recently it has become obvious that a more selective technique [selective laser coagulation of placental vessels (SLCPV)] is more effective and has better outcomes [21]. In the latter technique, the vascular anastomoses between the twins are carefully identified (outlining a vascular equator) and coagulated with minimal regard to the membranous equator. In order to physically separate the vascular territories on the placental surface, a technique called “Solomonization” was proposed by Chalouhi et al. [22] and this has been shown to significantly decrease the risk of twin anemia polycythemia sequence and recurrent TTTS [22], [23], [24].

A complete anterior placenta represents a real challenge in laser procedures. Several techniques have been used to optimize outcome in these cases including the performance of a laparotomy and exteriorizing the uterus before placing the ports [25], the use of intra-cannula laser deployment [26] and the use of 30 degree fetoscope [27]. In difficult cases with no available access, laparoscopic-assisted laser procedure can be resorted to where laparoscopy is utilized to facilitate fetoscopic entry through the posterior aspect of the uterus. Technical details of the procedure have been previously published [28].

Tips and tricks:

1. Avoid entering the uterus near the donor as this will likely create a septostomy.

2. Utilize a curved scope for anterior placentas.

3. A 70-degree scope can be used to help identify potential anastomoses that were not identified.

4. To enhance the speed of the procedure and limit the time lag between ablation of different vascular anastomoses, we mark the vascular equator using the laser with a dotted line and then “Solomonize” the equator including the vascular anastomoses from one edge of the placenta to the other.

5. For anterior placentas with no accessible window, a laparoscopic-assisted tilt of the uterus can provide access to the posterior half of the uterus.

Fetoscopic Endoluminal Tracheal Occlusion (FETO)

Congenital diaphragmatic hernia (CDH) is a rare condition that occurs in 1–5/10,000 live births [29]. Most cases occur on the left side. The incidence of right sided and bilateral cases is about 13% and 2%, respectively [30]. CDH can be an isolated finding or associated with other abnormalities. A significant number of CDH fetuses (from 26% to 58%) may have associated abnormalities, e.g. cardiac, gastrointestinal, renal or neurological) which may or may not be part of genetic syndromes [31]. Usually only isolated cases of CDH are considered candidates for fetal intervention.

The prenatal diagnosis of CDH is usually established by ultrasound which shows the abdominal organs (stomach, intestine and/or liver) in the chest cavity and a shift of the cardiac axis from these herniated abdominal organs. Polyhydramnios may be present in these cases from esophageal compression. Several prenatal ultrasound parameters are used to classify the condition based on severity. The lung head ratio (LHR) is one of the most widely used indicators of the severity of CDH [30] but more recently, observed-to-expected (o/e) LHR and o/e total lung volume (TLV) are being used [32].

FETO is currently the only available fetal interventional procedure for CDH and is being studied in two randomized controlled trials – one in severe CDH and one in moderate CDH (see TOTAL Trial – http://www.totaltrial.eu/). The aim of this procedure is to prevent escape of pulmonary fluid from the lungs by temporarily occluding the fetal trachea. This is believed to increase airway pressure, stimulate pulmonary proliferation and alveolar airspace and promote pulmonary vascular development [33]. After a period of 4–6 weeks (depending on fetal lung response), the balloon is removed and the pregnancy allowed to continue normally until delivery at term (if possible). This procedure can only be offered in facilities with 24/7 capability of emergency balloon removal and EXIT surgery since delivery of a fetus with an occluded trachea is an emergency that requires immediate removal. Neonatal deaths have occurred when patients carrying a fetus with a FETO balloon in-situ have delivered prematurely and the balloon could not be removed. The steps for preparing a patient for FETO are summarized in Table 3.

Prior to starting the procedure for balloon placement, the fetus is positioned with the face up ideally in the upper half of the uterus. The fetus is next anesthetized with the combination listed in “Control of fetal pain”. With the complete fetal profile in a sagittal plane, the fetal trachea is accessed and balloon is placed. This technique works for posterior placentation or anterior placentation with an adequate lateral window. Balloon retrieval proceeds in similar fashion to balloon placement.

Based on data from a prenatal CDH registry, survival in cases of severe left sided CDH can be improved following the FETO procedure from 24.1% to about 49.1%, and from 0% to 35.3% in severe cases of right-sided CDH (P<0.001) [36], [37]. A recent study reported a 70% 12-month survival and a 30% ECMO usage after FETO in patients with severe left sided CDH, however, the sample size was small (10 patients)[38]. It must be stressed however that FETO is still considered an experimental procedure and should only be performed under a research protocol in an adequately established and equipped fetal center.

Tips and tricks:

1. Preload the curved scope with the balloon.

2. Position the fetus head up with the profile in sagittal view.

3. Administer fentanyl, atropine and vecuronium once the fetus is in ideal position to avoid further movements.

4. Identify both vocal cords and carina to aid in balloon positioning.

5. Use the same technique for retrieving the balloon as was used for placement.

Other fetoscopic procedures

Fetal lower urinary tract obstruction (LUTO)

LUTO is a group of conditions involving obstruction of the fetal urinary bladder neck. It is a rare condition that occurs in approximately 2.2/10,000 live births [50]. LUTO is most commonly caused by posterior urethral valves (PUV) that occurs almost exclusively in males. Other less common causes include: anterior urethral valves, urethral atresia, urethral stenosis, and obstructive ureterocele which can occur in both males and females [51].

LUTO is commonly diagnosed at time of fetal anatomic survey (18–20 week) by a combination of an of enlarged fetal urinary bladder (megacystis), a “key-hole” sign due to a dilated proximal urethra, bilateral hydronephrosis, bilateral hydroureter, and oligohydramnios. The kidneys may or may not show dysplastic changes (renal cortical cysts and hyperechogenicity) [52].

Complete LUTO is usually associated with high perinatal mortality from pulmonary hypoplasia and renal failure. Several fetal interventional procedures have been described for antenatal treatment of LUTO including vesico-amniotic shunt, fetal cystoscopy and repeated vesicocentesis. However, careful evaluation of cases is needed to ensure appropriate selection of candidates for antenatal intervention which include those with isolated LUTO and demonstrable preservation of renal function.

Such evaluation should follow a standardized multidisciplinary approach which includes detailed obstetrical ultrasound, fetal echocardiography, genetic consultation, genetic amniocentesis or cordocentesis, and consultation with specialists in pediatric nephrology and urology. Fetal renal function is evaluated by ultrasound morphology of the kidneys to detect cases with evidence of dysplasia (hyperechogenicity, the presence of renal cortical cysts, and the absence of cortico-medullary differentiation) and repeated vesicocentesis (potentially repeated up to three times) for examination of fetal urinary biochemistry after 18 weeks [53] (Table 4). Only those with isolated LUTO and favorable fetal renal parameters are generally offered fetal intervention [56].

Vesico-amniotic shunting (VAS) is the most commonly performed intrauterine therapy for cases with LUTO in the United States. The procedure entails an amnioinfusion followed by insertion of a double pig-tail catheter (Harrison or Rocket) under ultrasound guidance [57]. The distal end of catheter is deployed inside the fetal bladder while the proximal end is deployed in the amniotic sac.

A recent systematic review and meta-analysis that evaluated effectiveness of VAS in LUTO cases demonstrated a perinatal survival advantage in treated fetuses, however, the 1–2 year survival and long term renal function are still uncertain [58].

Fetal cystoscopy with mechanical or laser fulguration of the PUV for treatment of LUTO has been reported by Ruano et al. [59]. Despite the promising potential of the procedure, the current limitations of the equipment and the risk of fetal fistula formation make the procedure investigational and something that should be done on a research protocol under IRB or fetal therapy board oversight [60].

Practical considerations (Tips/tricks):

1. Ultrasound modality is invaluable not only in defining the extent of disease but also in ancillary testing such as genetic amniocentesis, cordocentesis and placement of vesico-amniotic shunts.

2. Magnetic resonance imaging is of value in better delineation of the ureters, urachus, bladder, particularly in cases of oligohydramnios.

3. The value of serial fetal urinary biochemistry in determining suitability for fetal intervention is still debatable. Nonetheless, in our practice we continue to offer fetal intervention utilizing results of fetal urinary chemistry and ultrasonographic appearance of the fetal kidneys in determining the suitability for intervention.

4. Adequate amnioinfusion is needed to allow for successful deployment of the amniotic end of the shunt.

5. The Rocket shunt is associated with increased likelihood to remain in place compared to the Harrison shunt [61].

6. Vesico-amniotic shunt should be placed in the lower part of the fetal bladder to allow for adequate drainage.

7. Avoid puncturing the fetal abdominal wall and bladder directly as this can lead to deployment of the proximal end of the shunt into the uterine wall. Instead, the trocar should be directed into the amniotic fluid pocket first and then redirected into the fetal bladder.

8. Fetoscopy can be inserted through the shunt cannula to ensure correct placement in difficult cases.

Thoraco-amniotic shunt for fetal pleural effusion and fluid filled space occupying chest lesions

Primary fetal pleural effusion is mostly caused by abnormalities of lymphatic development and drainage. Secondary pleural effusions occur as a result of chromosomal or structural fetal abnormalities [62]. The most commonly encountered fetal lung masses are congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestration and mixed lesions [63].

Large fetal pleural effusions or lung lesions can cause compression of the chest structures and significant mediastinal shift with consequent risk of pulmonary hypoplasia and/or development of hydrops [64]. The presence of concomitant pulmonary hypoplasia significantly increases neonatal morbidity and mortality, and fetuses with hydrops are at greatly increased risk of intrauterine demise [65].

Certain groups of fetuses with significant primary pleural effusion, and those with lung masses associated with evidence of cardiac dysfunction or hydrops are considered candidates for fetal intervention.

Our protocol for the management of fetuses with pleural effusion includes a detailed ultrasound evaluation to exclude associated structural abnormalities, a genetic consultation, an amniocentesis for genetic studies, and fetal echocardiography to evaluate the structure and function of the fetal heart. Evaluation of a TORCH panel for infections, the maternal blood type and antibody status, and the Kleihauer-Betke test are also recommended [62]. The presence of associated lethal chromosomal or significant structural abnormalities are considered contraindications for fetal intervention.

Fetuses that have a pleural effusion thought to be causing cardiac dysfunction leading to the development of hydrops or polyhydramnios leading to preterm labor/shortened cervix are considered candidates for fetal intervention. Other authors have considered additional criteria such as isolated effusion occupying more the 50% of chest space, mediastinal shift and rapid increase in the effusion size as indications for fetal intervention [66].

Our protocol includes performing thoracocentesis to evaluate whether there is re-accumulation of the effusion and to test whether there is re-expansion of the lungs. Sampling of the pleural fluid also allows analysis of the effusion for lymphocytes. Fetuses with a rapidly re-accumulating pleural effusion usually benefit from shunt placement. The procedure entails placement of a double pig-tail catheter(s) (Harrison or Rocket) under real-time ultrasound guidance.

Another fetal congenital abnormality that may benefit from thoracoamniotic shunting is CCAM type 1 which has a macrocystic component. CCAM volume ratio (CVR) is usually used to assess the prognosis and evaluate the risk of developing hydrops in cases with a fetal lung mass. CVR is calculated according to the following formula: (length×height×width×0.52)/head circumference. A CVR>1.6 is associated with a high risk of developing hydrops (about 80%). These cases should be followed by ultrasound two to three times weekly. Our protocol suggests weekly follow up for cases with CVR<1.2 and twice weekly for CVR 1.2–1.6.

For CCAM cases with fetal hydrops, fetal pulmonary drainage has been associated with improved survival [67]. Fetal intervention may be unnecessary in the subset of hydropic fetuses with a lung mass in the absence of fetal cardiac dysfunction [68].

In a very small subset of preterm patients with fetus that has a lung mass that is causing hydrops on the basis of cardiac dysfunction open fetal resection of the mass may be required. In addition, cases of fetal broncho-pulmonary sequestration can be successfully managed by percutaneous interstitial laser ablation of the feeding blood vessel [69].

Practical considerations (Tips/tricks):

1. Thoracic shunts have been proven to be safe and effective in pleural effusion, decompression of cysts in CCAMs.

2. Harrison and Rocket catheters are two widely used devices.

3. It is prudent to attempt permanent resolution of fetal hydrothorax with initial thoracentesis and reserve shunt placement for recurrent episodes while avoiding complications associated with shunt placement [70].

4. It has been our practice to restrict shunt placement to fetuses with evidence of cardiac decompensation as derived based on fetal echocardiogram.

Selective feticide in complicated monochorionic, diamniotic twin gestation

Monochorionic twin pregnancies can be complicated by TTTS, selective intrauterine growth restriction (sIUGR), twin reversed arterial perfusion (TRAP) sequence or twin anemia polycythemia sequence (TAPS). In some cases, selective termination of one fetus may be an option to protect the healthy co-twin. Intra-fetal injection as a method of selective termination is not suitable in cases of monochorionic twins due to the presence of vascular connections leading to risks to the other fetus [71].

Several techniques have been used for selective termination which include use of monopolar diathermy, laser, radiofrequency ablation (RFA) or, more recently microwave [72] energy, through ultrasound guided needles ranging from 14 to 18 gauge [71]. The needle is usually inserted into the fetal abdomen adjacent to the umbilical cord insertion. The procedure can also be performed using ultrasound guided bipolar forceps (2.4–3 mm) to occlude the umbilical cord (bipolar cord coagulation) [73]. Bipolar cord coagulation is possibly best suited for cases that require selective termination at a more advanced gestational age because of the inefficiency of RFA, laser and microwave energy to coagulate large blood vessels with fast flowing blood.

Practical considerations (Tips/tricks):

1. It is crucial to determine chorionicity whenever selective feticide is being considered.

2. In TRAP sequence, there is some evidence that early intervention (from 12 weeks onward) using intrafetal laser is associated with better outcomes compared to expectant management [74].

3. In a monochorionic monoamniotic twin gestation complicated by TRAP sequence or significant fetal anomalies, cord transection in addition to cord occlusion is needed.

4. It is worth a mention that successful sequential approach of intracardiac postassium chloride (KCL) following Laser photocoagulation of placental anastomoses have been described with survival of the healthy fetus [75].

Fetal cardiac intervention

Severe fetal aortic stenosis is a congenital cardiac defect that usually presents in the second trimester of pregnancy and is manifested by enlargement of the left ventricle and progressive left ventricular dysfunction. This condition frequently evolves into hypoplastic left heart syndrome (HLHS). As a result of poor perinatal outcomes associated with HLHS, severe aortic stenosis has become the main indication for fetal cardiac intervention using aortic balloon valvuloplasty. The main purpose of the procedure is to prevent progressive left ventricular dysfunction and to prevent postnatal single ventricle physiology. With successful intervention, biventricular physiology is achieved in about 43% of live born neonates [76].

After administering fetal anesthesia, the procedure is performed by directing a 17–19-gauge needle into the fetal heart under continuous ultrasound guidance. The needle is aligned with the left ventricular outflow tract, the trocar is removed, and a guide wire with a preloaded measured balloon is then advanced through the valve. Once the position of the wire is confirmed to be across the valve, the balloon is inflated and the valve is dilated. The balloon is then deflated and the entire system is removed with the needle. Pericardial effusion is an expected complication with cardiac interventions, and bradycardia may result. When that happens the pericardial effusion needs to be aspirated and fetal resuscitation medications should always be available for immediate use in these procedures.

Other procedures include the creation of an atrial septostomy using a stent placed across a restrictive/occluded foramen ovale in HLHS [77] and pulmonary valvuloplasty for cases with severe pulmonary stenosis and intact septum [78].

Practical considerations (Tips/tricks):

1. Indications for fetal cardiac intervention (FCI) include, critical aortic stenosis with the aim of attaining a biventricular repair postnatally, pulmonic stenosis with an intact septum, restrictive foramen ovale.

2. Timing is of the essence in FCI efforts to prevent HLHS if fetuses diagnosed with critical aortic stenosis are to have a realistic chance at postnatal biventricular circulation.

3. Presently, FCI presents significant morbidity and mortality risks to the fetus, uncertain longer-term risks and benefits to the developing child while not obviating the adverse neurodevelopmental outcomes seen at least in HLHS cases not otherwise treated [79].

Open fetal surgery

Dr. Michael Harrison and his team at UCSF performed the first open fetal surgery when they created a vesicostomy in a fetus with urinary obstruction in 1981. As the field has progressed, the presence of a well-orchestrated multidisciplinary team has been paramount to continued success in open fetal surgery. Open fetal surgery involves performing surgery on a fetus via a hysterotomy with closure of the uterine incision after conclusion of surgery. These surgeries should be performed in concordance with Harrison’s principles for fetal surgery (Table 5) [3]. The steps for open fetal surgery are summarized in Table 6.

Open spina bifida

Neural tube defects (NTD) result from failure of closure of the neural tube during embryogenesis and include anencephaly, encephalocele and myelomeningocele (MMC). The incidence of NTDs was in the range of 1%–2% before folic acid supplementation.

MMC is associated with adverse motor and mental effects including major disabilities, paralysis, disturbances in bowel and bladder control, and learning disabilities [80]. The neurological consequences of MMC are explained by the “two-hit hypothesis”. The first hit results from failure of closure of the spinal canal and the second hit is believed to be a consequence of exposure of the neural tissue to direct trauma and toxic agents in the amniotic fluid [80]. As a result of the anomaly more than half of these fetuses will have ventriculomegaly before 24 weeks of gestation, and most will have ventriculomegaly by term [81]. Many of these children will suffer additional neurological morbidity on an ongoing basis because of shunt procedures and the repeated surgeries that may be required to replace malfunctioning or infected ventriculo-peritoneal shunts. This hypothesis was the rational for the trial of prenatal repair of MMC at mid-gestation.

The majority of centers performing fetal surgery for MMC do so in an open fashion. The key tenants for this procedure can be found in Table 6. Additionally, antibiotic-enriched warmed saline is infused throughout the case into amniotic cavity to prevent placental abruption, a no-touch technique for freeing the neural placode is utilized, and complete coverage of the defect should proceed in a water-tight fashion. In cases where skin coverage is difficult, vertical relaxing incisions can be made laterally to aid in skin coverage in the midline.

The Management of Myelomeningocele Study (MOMS) trial was the first prospective multicenter randomized controlled trial evaluating fetal surgery for MMC. The main findings of this trial were a decrease in the rate of postnatal shunt from 82% to 40% in the prenatal surgery group [relative risk (RR) 0.48, 97.7% confidence interval (CI) 0.36–0.64, P<0.001], improvement in the composite score for mental and motor function at 30 month of age (P-value 0.007) and improvement in several secondary outcomes, including hindbrain herniation and ambulation [82]. However, the trial demonstrated significantly higher rates of complications such as preterm birth and uterine dehiscence [82].

Tips and tricks:

1. Follow generalized approach in Table 6.

2. Keep mother and fetus warm during procedure.

3. Perform frequent monitoring of fetal cardiac function during case.

4. Perform vertical relaxing skin incisions lateral to defect to aid in midline skin coverage in needed cases (e.g. myeloschisis).

5. Initiate magnesium sulfate bolus and infusion prior to completion of the case.

CCAM

Congenital cystic adenomatoid malformation (CCAM), is a congenital malformation of the lung that occurs in approximately one every 30,000 pregnancies [83]. CCAM is classified into Stocker type I (macrocystic) which contains one or more cysts (3–10 cm), type III (microcystic) with an echogenic homogenous mass and no visible cysts, and type II (mixed) [84].

Large lesions can cause mediastinal shift and caval compression with subsequent development of hydrops. Prenatal steroid administration in these cases has been reported to cause resolution of hydrops in about 78% of cases [85]. The exact mechanism of steroid action is still unclear, however, it has been postulated that it may help involution of the lesion. The efficacy of prenatal steroids in these lesions is currently being evaluated in a randomized controlled trial.

There is a subset of steroid nonresponsive fetuses with microcystic lesions who develop hydrops associated with evidence of cardiac dysfunction who may benefit from fetal surgery although this indication is rare since the addition of steroids to the treatment paradigm [86]. Fetal surgery is usually offered up until approximately 32 weeks, and after that gestational age, delivery by ex-utero intrapartum treatment (EXIT) to resection may be required. Again, key generalized tenants of open fetal surgery from Table 6 can be applied to open fetal surgery for CCAMs.

Fetuses with macrocystic lesions or those with dominant cysts may benefit from shunting and decompression (thoraco-amniotic shunt) if cardiac-driven hydrops is present.

Tips and tricks:

1. Perform amnioreduction if symptomatic polyhydramnios occurs.

2. Follow generalized approach in Table 6 should open fetal surgery be indicated.

3. Position the fetus for exteriorization of the arm and the posterior chest on the affected side.

4. Keep mother and fetus warm during the procedure.

5. Monitor fetal cardiac function closely during the procedure and especially once the mass is exteriorized and removed.

6. For EXIT to resection, have two operating rooms set up (one for EXIT and a second if resection can occur after clamping of the umbilical cord).

7. Gain IV access and intubate the neonate, but do not ventilate.

8. Perform posterolateral thoracotomy on affected side and ventilate.

9. If tolerating ventilation, disconnect from placental circulation and proceed to second operating room for resection. If not tolerating ventilation, stop ventilating and perform resection on placental circulation.

Sacrococcygeal teratoma (SCT)

SCT is the most common fetal tumor and occurs in approximately one in every 27,000 pregnancies. Both large and vascular tumors can be complicated by high cardiac output failure and fetal demise due to the presence of arterio-venous fistulas [87]. However, up to 50% of antenatally diagnosed SCT proceed uneventfully [88].

Careful monitoring of the growth rate, tumor size and fetal cardiac function allows for early recognition of cases at high risk for cardiac failure and fetal demise [89]. These represent the subset of SCT cases that could benefit from fetal intervention and surgery if the gestational age is less than 28 weeks of gestation. After that gestational age, early delivery following steroid administration would be reasonable [88].

Both minimally invasive interventions using laser ablation or radiofrequency ablation, and open fetal surgery, have been attempted [90], [91]. Both approaches aim at decreasing the vascularity of the tumor and the cardiovascular consequences of the arteriovenous fistulas within the tumor, allowing for recovery of the fetus. Conflicting outcomes have been reported.

Tips and tricks:

1. Identify fetuses with evidence of cardiac dysfunction prior to development of hydrops as candidates for open fetal surgery.

2. Follow generalized approach in Table 6 if open fetal surgery is indicated.

3. Make hysterotomy large enough to exteriorize lesion.

4. Spend as little time as is necessary to debulk exterior portion of tumor only.

5. Achieve complete skin coverage of remaining tumor.