Key Points
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Most fetuses with a prenatal diagnosis of a congenital abnormality can be managed expectantly. For some conditions, in utero referral is mandatory for planned delivery and management after birth.
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Fetal surgery is only required for conditions that cannot await therapy after birth and when there is enough evidence that prenatal surgery partly reverses the natural course.
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Open fetal surgery (OFS) is one modality to perform operations on fetuses. OFS is invasive, with maternal morbidity and an impact on the uterus in the index and future pregnancies, and it increases the risk for preterm delivery.
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Open spina bifida is the only nonlethal condition operated in utero , yet it became the most frequent indication based on level I evidence. OFS improves the outcome of children with spina bifida, but it is not a cure.
Rationale of Open Fetal Surgery for Congenital Abnormalities
Pathophysiology and Natural History
Since the introduction of ultrasound (US) and later other imaging modalities and the increased interest for congenital anomalies (CAs) and their outcomes in relation to prenatal findings, it has become possible to define the natural history of several potentially correctable CAs. Also, researchers developed appropriate animal models for the disease of interest to study both the pathophysiology as well as the surgical interventions contemplated. These studies, particularly in primates, have been used for developing the anaesthetic, tocolytic and surgical protocols for hysterotomy and OFS.
Selection Criteria for Open Fetal Surgery
Open fetal surgery is currently being offered in highly specialised multidisciplinary fetal centres for highly selected fetuses with a condition that is, without any intervention, either lethal or in which the subsequent organ function loss leads to an extremely poor quality of life after birth. The International Fetal Medicine and Surgery Society (IFMSS) defined five criteria required to justify fetal surgery ( Table 38.1 ).
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Indications
A Nonlethal Condition: Spina Bifida Aperta
The epidemiology, pathophysiology and natural history have been addressed in Chapter 28 . Within routine screening US programs neural tube defects should be diagnosed prenatally. An invasive fetal procedure for spina bifida aperta (SBA) seems to be justified because of the significant lifelong neurologic disabilities, the prenatal progression of findings and the experimental validation of the two-hit pathophysiology. Experimental research and early clinical experience suggest that ongoing damage to the exposed malformed spinal cord and developing brain is alleviated by prenatal repair. The Management of Myelomeningocele Study (MOMS) was a multicentre randomized controlled trial that unequivocally demonstrated that prenatal surgery for SBA improves outcome compared with standard postnatal repair. Table 38.2 displays the initial and current indications and contraindications for in utero SBA repair. Fetal surgery was shown to lessen or reverse hindbrain herniation, reduce the postnatal ventriculoperitoneal shunt rate at 1 year of age and improve neurofunctional outcome at the age of 30 months.
| Indications for OFS | Type of Malformation | Rationale for In Utero Therapy | Inclusion Criteria | Exclusion Criteria |
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| Spina bifida aperta | MMC or myeloschisis with CM |
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| Congenital thoracic malformations (CCAM and BPS) | Large solid lesion complicated with fetal hydrops |
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| Sacrococcygeal teratoma | Large, fast-growing solid lesion complicated with fetal hydrops |
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Lethal Conditions
Congenital Thoracic Malformations Complicated With Fetal Hydrops
Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. As an accurate pathological prenatal diagnosis is not possible; a detailed prenatal description of the appearance of the lesion is sufficient and should follow the new CTM classification and nomenclature (see Chapter 30 ). This section focuses on the two most frequent CTMs that are also amenable to OFS: congenital cystic adenomatoid malformation (CCAM) and its related malformation, bronchopulmonary sequestration (BPS). It is important to realise that the exact nature of the condition (or their combination) may only be possible after resection. In fact, lung parenchymal malformations, although superficially heterogeneous in appearance, have significant overlap and seem to share a common embryologic origin. According to the European Surveillance of Congenital Anomalies (EUROCAT) registry, the prevalence of CTM between 2008 and 2012 was 4.13 per 10,000 live births. Among the CTMs, the estimated prevalence of CCAM was 1.05 per 10,000 live births, that is, about one quarter of all CTMs. The exact prevalence of BPS is unknown and probably lower than for CCAM. CTMs may spontaneously regress before birth; the ones that deteriorate in utero and may even lead to fetal death are of relevance to this chapter (see Table 38.2 ).
Congenital Cystic Adenomatoid Malformation
Congenital cystic adenomatoid malformation is a benign cystic intrapulmonary nonfunctioning lung mass that is usually localised in one lobe of the lung and mainly unilateral. CCAM contains cysts ranging from smaller than 1 mm to larger than 10 cm in diameter. Most CCAMs derive their blood supply from the pulmonary circulation. CCAM is histologically characterised by an overgrowth of terminal respiratory bronchioles that form cysts and lack normal alveoli. Many pathologists consider it a hamartoma (i.e., a developmental abnormality with excess of one or several tissue components). Although nonfunctional for normal gas exchange, CCAM parenchyma has connections with the tracheobronchial tree as evidenced by air trapping that can develop during postnatal resuscitative efforts. There are different prenatal classifications; however, postnatally, typically four Stocker types (I–IV) are described.
Congenital cystic adenomatoid malformation growth usually reaches a plateau by 28 weeks of gestation and may even nearly disappear by birth. Others may cause fetal hydrops and in utero death. The impact on normal lung development and postnatal function has not been properly studied. Prenatally, the size of the lesion, the cyst size, the growth and perfusion and the secondary signs have all been used to describe the severity of the impact on the fetus. In general, fetal hydrops is the single accepted criterion for fetal therapy. A CCAM volume ratio (CVR) (CCAM volume by sonographic measurement using the formula for an ellipse, length × height × width × 0.52 divided by head circumference to correct for differences in fetal size) greater than1.6 has been shown to predict hydrops in 80% of fetuses with CCAM.
Bronchopulmonary Sequestration
Bronchopulmonary sequestration is defined as a nonfunctioning lung mass that receives a systemic blood supply rather than from a branch of the pulmonary artery. It belongs to the spectrum of congenital foregut malformations arising as an aberrant outpouching from the developing foregut. BPS is believed to be aberrantly located pulmonary mesenchyma that develops apart from the normal lung.
Bronchopulmonary sequestration is classified into intralobar and extralobar forms. The extralobar (25%) form consists of pulmonary tissue located outside the lung and enveloped in its own pleura without communication with the normal tracheobronchial tree. Around 90% are supradiaphragmatic and 10% infradiaphragmatic, usually left suprarenal. The intralobar form is found within the normal lung tissue with or without communication.
Other Rarer Lethal Conditions
We will not discuss these even rarer indications, some of which have been operated in utero :
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Hybrid lesions (CCAM and BPS)
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Bronchogenic and enteric cysts
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Mediastinal cystic teratoma
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Congenital lobar emphysema
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Haemangioma
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Bronchial atresia
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Pulmonary leiomyofibroma
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Intrathoracic gastric duplication cyst
Sacrococcygeal Teratoma With Hydrops Fetalis
Sacrococcygeal teratoma (SCT) is the most common tumour of newborns with a prevalence of about 0.37 to 0.93 per 10,000 live births. SCT is uniformly attached to the coccyx and has been classified into four types (I–IV) by the relative amounts of intrapelvic and external tumour. SCTs presenting postnatally have excellent long-term outcomes; conversely, prenatally diagnosed SCTs have a significant perinatal mortality ranging from 25% to 37%. Death occurs mainly in fetuses with fast-growing, solid and highly vascularised teratomas that lead to high-output cardiac failure or haemorrhage. The pathophysiological mechanism behind this is explained by the ‘vascular steal’ from the placenta and the fetus and by the mass effect :
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SCT acts as a large arteriovenous malformation that deviates high volumes of blood from the fetus and the placenta. Also, bleeding inside the tumour can cause anaemia. The consequence is high-output cardiac failure, which can then lead to placentomegaly, hydrops fetalis, intrauterine fetal demise, preterm birth and neonatal death. This may also cause Ballantyne syndrome (maternal mirror syndrome), which is a dangerous maternal complication.
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SCT compresses the abdominal and thoracic organs, leading to polyhydramnios (oesophageal and gastric compression) inducing uterine irritability, premature rupture of the membranes (PPROM) and preterm delivery. The tumour may also have an effect on nearby organs, such as obstructive uropathy. Dystocia in undiagnosed large masses is frequently associated with traumatic tumour rupture and haemorrhage during delivery, which is usually fatal.
Assessment of tumour size, growth rate and fetal cardiac function by fetal imaging allows the identification of fetuses at particular risk for decompensation. Ultrafast fetal magnetic resonance imaging (MRI) is superior to US in delineating the intrapelvic extent of the tumour, yet this does not contribute to the indication for fetal surgery. The currently accepted indications for OFS for this condition are detailed in Table 38.2 .
Surgical Technique
Pre- and Intraoperative Management
Open fetal surgery is recommended to take place in tertiary medical centres that have a multidisciplinary team experienced with the anaesthetic and surgical techniques described later; familiar with the management of the potential postoperative complications such as amniotic fluid leakage, fetal membrane separation and preterm labour; and with proven track record of managing the condition of interest postnatally. Any candidate OFS centres should follow a specific training with expert centres. We did so in a mixed training model, in-house training by physicians familiar with OFS, as well as exported training (i.e., short stay of selected team members at a large volume OFS centre). We performed our first five local surgeries under direct supervision.
Preoperative Management
A multidisciplinary OFS team of specialists will perform a complete prenatal evaluation and counselling of the parents. Surgery should not proceed until full informed consent is obtained. The maternal-fetal evaluation includes detailed prenatal US to confirm the diagnosis and severity and exclude other abnormalities as well as technical aspects such as placental location and maternal assessment. A fetal echocardiogram is mandatory to measure the haemodynamic impact of the condition while also ruling out congenital heart defects. Ultrafast fetal MRI today seems to be standard of care for most conditions eligible for fetal surgery. If no genetic testing was done yet, this should be undertaken first. Moreover, the expectant mothers undergo psychological evaluations and extensive counselling on the postnatal impact of the condition as well as that of OFS. Any nonmedical, socioeconomic issues should also be discussed and when necessary dealt with. Some centres organise a consult with the whole multidisciplinary team present.
Intraoperative Management
Control of Labour
The OFS team usually consists of one anaesthesiologist and an assistant, two general surgeons (either general paediatric surgeons or obstetricians, depending on the centre), another paediatric surgeon from the discipline of relevance to the condition, a maternal-fetal specialist, a specialist in echocardiography, one to two scrub nurses or midwifes, a circulating nurse and a perfusionist.
Patients are admitted before the operation for obstetric monitoring, including measurement of the cervix, and initiation of tocolysis. Most centres use an aggressive prophylactic tocolytic regimen. Drugs used are indomethacin (50 mg per rectum or orally) and atosiban in countries where it is available. Adequate analgesia in the peri- and postoperative period is also important; this is why an epidural anaesthesia is combined with the general anaesthesia. Prophylactic antibiotics are also given (e.g., cephazolin 1000 mg IV).
Maternal-Fetal Anaesthesia and Analgesia
The general anaesthesia ensures good uterine relaxation and is also anaesthetic for the fetus. Preoxygenation, rapid-sequence induction with cricoid pressure is used before intubation. Maintenance anaesthesia is with a combination of volatile agents, nitrous oxide and intravenous (IV) anaesthetics (e.g., propofol). Systolic arterial blood pressure is maintained over 100 mm Hg, and IV fluids are limited to 0.9% sodium chloride (rate 100 mL/hr), the latter to avoid pulmonary oedema. Maternal neuromuscular blockade is provided with a short-acting muscle relaxant (rocuronium 0.6mg/kg). After hysterotomy, fetal analgesia and immobilisation is performed using intramuscular injection of fentanyl (10 ug/kg), atropine sulphate 0.01 mg/kg and a muscle relaxant (cisatracurium, 0.4 mg/kg).
Maternal Conditioning and Installation
The mother is positioned supine on a mouldable mattress usually slightly on her left side to avoid compression of the vena cava. Maternal perioperative monitoring, cannulisation and catheterisation includes blood pressure, electrocardiogram leads, two large IV catheters, a bladder catheter, leg compression boots, a transcutaneous pulse oximeter and if required a central radial arterial catheter and central venous catheter.
Fetal Resuscitation
Drugs for fetal resuscitation should be prepared and transferred in a sterile fashion into individually labelled syringes held by the scrub nurse for immediate fetal administration by the surgeon in case of fetal distress. These drugs include single-unit doses of atropine (20 mcg/kg), epinephrine (10 mcg/kg) and crystalloid (10 mL/kg). In the rare case of maternal circulatory collapse, if fetal resuscitation has been unsuccessful after 4 minutes, the fetus should be delivered immediately and managed by a neonatology team according to her or his gestational age and the country’s legislation.
The Surgical Procedure
Elective Open Fetal Surgery for Spina Bifida Aperta Repair
In the MOMS trial, the operation was scheduled between 19 weeks + 0 days to 25 + 6 days. Subsequent experience showed that the risk for membrane rupture was lower when the operation is deferred until 23 weeks (see Table 38.2 and 
). The duration of the surgery should be as short as possible because operating time is directly related to risks of prematurity.
Skin Opening and Uterus Exposition
A low transverse abdominal skin incision is made. If the placenta is posterior, an anterior hysterotomy will be required. In these, a vertical midline fascial incision is sufficient because the uterus can remain in the abdomen. If the placenta is anterior, a posterior hysterotomy will be necessary. To enable comfortable exteriorisation of the uterus, the rectus muscles may need division. This will prevent compression on the lateral uterine vessels because the uterus is tilted out of the abdomen. Then a large abdominal ring retractor maintains exposure.
Determining the Incision
Sterile intraoperative US delineates fetal position and placental location. The fetus may need to be manipulated. The edge of the placenta is marked under US guidance using electrocautery. The position and orientation of the hysterotomy are planned to stay parallel to, and at least 6 cm from, the placental edge.
Hysterotomy
Standard full-thickness haemostatic hysterotomy is performed, facilitated by the placement of two 0 monofilament slowly resorbable polydioxanone sutures (PDS), with a uterine stapling device loaded with absorbable polyglycolic acid staples (Poly CS 57 mm stapler; Covidien, Mansfield, MA, USA). This is to minimise blood loss and anchor the membranes, and in contrast with the use of metal staples, does not impair subsequent fertility. Since the MOMS trial, some modifications have been made in the United States such as clamping of the myometrium before stapling. A Brazilian group uses a homemade trocar to enter the uterus, and a Polish group has good outcomes with nonstapled hysterotomy ( Table 38.3 ).
| Fetal Centre | Aim | Steps | Results |
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| MOMS | Reference point |
| PPROM rate: 44% CMS rate: 30% |
| Philadelphia technique | To avoid jamming of the uterine stapler in thick uterine tissue |
| Lower rate of PPROM (32.3%) Lower CMS rate (23%) |
| Vanderbilt technique | To control uterine bleeding and avoid CMS |
| Lower rate of PPROM (22%) Lower rate of CMS (0%) |
| Brazilian technique | To perform a faster and less traumatic uterine entry |
| NS |
| Polish technique | To substitute the stapler |
| NS |
Fetal Monitoring and Amniotic Fluid Replacement
Continuous intraoperative fetal echocardiography is performed to monitor fetal myocardial performance (i.e., fetal heart rate and ventricular function). Initially, a strict maintenance of amniotic fluid volume was kept by using a ‘level I rapid infusion device’. This perfuses Ringer lactate solution at 38° to 40°C and keeps the fetus warm and buoyant. Others have meanwhile moved to replacing the amniotic fluid with warmed normal saline manually.
Standard Spina Bifida Aperta Fetal Repair
Most surgeons perform this surgery using loupes or even a microscope. The technique consists of eight steps whatever the type of SBA (i.e., myelomeningocele in two thirds and myeloschisis in one third of the cases; Figs. 38.1 and 38.2 ).
Closure of Uterus and Skin
A watertight two-layer uterine closure is performed with double-armed full-thickness 0 PDS interrupted stay sutures followed by a running 2-0 PDS suture. Warmed Ringer lactate is infused until normal fluid levels are obtained, and 500 mg of oxacillin or cefazolin is instilled into the amniotic cavity just before completing the running layer. The stay sutures are then tied, and an omental flap can be mobilised and secured over the hysterotomy site. The maternal laparotomy incision is closed in layers. A subcuticular maternal skin closure covered with a transparent dressing is used, allowing US.
Other Procedures in Open Fetal Surgery for Lethal Conditions
The procedures discussed in this section have a higher impact on fetal haemodynamics, so additional measures need to be taken. A fetal IV line is placed to check fetal blood gases and haematocrit, and if necessary, resuscitate the fetus with medication (atropine), fluid and fresh warm blood. If possible, this access can be complemented with intraoperative fetal monitoring. When a fetal limb can be exposed, a miniaturised pulse oximeter is placed around it. This oximeter is wrapped around the fetal palm or foot and protected with aluminium foil and Tegaderm (3M Company, St. Paul, MN, USA) to minimise light exposure.
Congenital Thoracic Malformations
Complete mass resection by fetal lobectomy is performed. The fetal chest is entered by a fifth intercostal space thoracotomy. The CTM readily decompresses out through the incision, consistent with increased intrathoracic pressure from the mass. The appropriate pulmonary lobe(s) containing the lesion is resected. The fetal thoracotomy is closed in layers, the fetus is returned to the uterus and warmed Ringer lactate containing antibiotics is instilled into the amniotic cavity.
Sacrococcygeal Teratomas
A fetal debulking procedure for external SCT is performed. The objective of this OFS is to occlude the tumour vascular supply and arrest the steal effect. No attempt is made to dissect the intrapelvic SCT component or to remove the coccyx. Completion of the removal is done postnatally. Hence, the SCT is exposed through an appropriate hysterotomy, and a Hegar dilator is placed in the rectum. The skin is incised circumferentially around the base of the SCT, and a tourniquet applied to constrict blood flow. The tumour is debulked externally usually with a 90-mm-thick tissue stapler (US Surgical Corporation). The fetal sacral wound is finally closed in layers.
Postoperative Management
Postoperative Prevention of Preterm Labour
In the United States, the tocolytic regimen for SBA repair is complex and includes IV magnesium sulphate (MgSO 4 ), which is started from closure of the hysterotomy and continued for about 18 to 24 hours (6-g loading dose followed by a continuous infusion at 2–4 g/hr), together with indomethacin rectal suppositories (50 mg) every 6 hours postoperatively for 48 hours. After the MgSO 4 , nifedipine (10–20 mg every 6 hours) is started and continued until the time of delivery. Careful monitoring of muscular function recovery is needed because MgSO 4 potentiates nondepolarising neuromuscular blockers. Adverse effect screening comprises monitoring of serum magnesium levels and observing for clinical signs of magnesium toxicity and daily fetal echocardiography to detect adverse fetal effects of indomethacin, including ductal constriction, tricuspid regurgitation and oligohydramnios. In Europe, atosiban is used, which has fewer side effects.
Postoperative Maternal-Fetal Monitoring
Cardiotocography externally records fetal heart rate and uterine activity. Daily US is performed to screen for fetal movements, anatomic evaluation, fetal membrane position and amniotic fluid volume status.
Postoperative Complications
Open fetal surgery is invasive hence has inherent maternal-fetal risks. There is the maternal morbidity due to the hysterotomy, the general anaesthesia and the medication used. To our knowledge, no maternal deaths have been reported. There are also fetal risks. The most frequent events are reduced ventricular contractility of the heart, with subsequent bradycardia and cardiac arrest. The main complications of OFS are listed in Table 38.4 .
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