Denis A. Cozzi1 and Silvia Ceccanti1
Pediatric Surgery Unit, Sapienza University of Rome, Azienda Policlinico Umberto I, Viale Regina Elena, 324, Rome, RM, 00161, Italy
Denis A. Cozzi
Fetal MRIAntenatal diagnosisFetal surgeryEx utero intrapartum treatmentCongenital anomalies
Over the last decades, advances in imaging techniques contributed to elucidate the natural history of some anomalies in human fetuses. The accurate diagnosis of a fetal anomaly allows the physician and parents to choose the best way to manage the pregnancy. Although most prenatally diagnosed malformations are best managed by planned delivery near term with appropriate neonatal care, other therapeutic options include a change in the timing or mode of delivery or even in utero therapy. Fetal therapy is certainly the logical culmination of progress in fetal diagnosis of anatomical abnormalities with predictable and life-threatening prenatal pathophysiological consequences that may benefit from surgical correction before birth.
In the 1970s, experience with increasingly advanced ultrasound technology led to the accurate diagnosis before birth of many anatomical defects. Over the ensuing 10 years, the developmental pathophysiology of some potentially correctable anatomical malformations was studied in animal models. More recently, ultrafast fetal magnetic resonance imaging (MRI) was introduced to enhance prenatal diagnosis, and refinements in patient selection, along with initial available randomized clinical trials, allowed to improve safety and efficacy of fetal surgical therapy. The use of fetal MRI allows exquisite definition of fetal anatomy and facilitates treatment planning. However, fetal surgery carries considerable maternal risks such as preterm delivery and amniotic fluid leak and post-procedural chorioamniotic separation. Additionally, the umbilical cord and fetus extremities may become entangled in and compromised by frayed and detached membranes .
Therefore, fetal surgery initially had only a role for those fetuses with a very poor prognosis who were likely to die without intervention. With advances in imaging, endoscopic techniques, anesthesia, and novel interventions, fetal surgery is becoming a realistic option in some conditions with less severe prognoses, where the aim is now to improve quality of life rather than simply allow survival.
Ultrasonography (USS) remains the first and primary imaging modality for fetal assessment. However, in some instances, this tool may be not so accurate to guide prenatal or neonatal treatment options, and a complementary imaging technique such as MRI is often desirable to supplement or confirm USS findings . MRI does not require ionizing radiation and combines excellent contrast resolution and a large field of view. Additionally, no adverse fetal effects of MRI have been described to date, and thus pregnant patients can be offered MRI at any stage of pregnancy. However, this technique requires a dedicated scanning room and specialized technical support, which is at the expense of availability and a higher cost. Moreover, precise indications for fetal MRI in the setting of fetal surgery are not yet established, because both fetal MRI and fetal surgery are relatively new techniques that remain in evolution.
Herein, we will briefly describe some of the conditions in which fetal MRI has contributed to fetal surgical planning or management immediately after birth.
5.2 Fetal Tracheolaryngeal Airway Obstruction
5.2.1 Congenital High Airway Obstruction Syndrome (CHAOS)
Among the vast spectrum of congenital cervical masses, the so-called CHAOS represents a rare but life-threatening condition with substantial morbidity and reported mortality of 80–100 % if unrecognized before delivery. CHAOS is classified as intrinsic or extrinsic, according to the nature of existing obstruction.
Intrinsic causes include atresia and stenosis of the larynx or upper trachea, whereas extrinsic causes of obstruction include lymphatic malformation, cervical teratoma, or compression by a vascular ring. Fluid produced within the fetal lungs is trapped by the obstruction, and the lungs become abnormally distended, creating a characteristic picture of voluminous lungs that invert the leaflets of the diaphragm . The majority of the fetuses with CHAOS demonstrates findings consistent with the sonographic diagnosis of hydrops fetalis. Hyperexpansion of the lungs exerts a mass effect that is believed to impede venous return to the heart, which leads to the subsequent development of fetal hydrops and ascites [3, 4]. USS and MRI are useful tools to detect both extrinsic and intrinsic congenital airway obstructions and their consequences. The degree of correlation between MRI and tertiary prenatal USS is high, although the diagnosis of CHAOS may be overlooked on USS, especially in the setting of multiple additional anomalies. Given its larger field of view and the high soft-tissue contrast resolution, MRI provides a better definition of the anatomy of the fetal airway and produces images easily understood by clinicians . The appearance of the CHAOS malformation on MRI is remarkable and very constant such that the diagnosis can be established by imaging alone. Characteristic findings include large lung volumes, increased lung signal intensity, inverted diaphragm, and dilated fluid-filled lower airway, and usually identifies the obstruction level .
The correct localization of the fetal upper airway obstruction helps treatment planning, i.e., to choose between fetal versus neonatal intervention using the ex utero intrapartum treatment (EXIT) procedure [5, 6]. The EXIT procedure can be used to deliver affected fetuses by cesarean section under deep maternal and fetal anesthesia, allowing for safe airway control and management and greatly improving outcome. The EXIT procedure involves partial delivery of the fetus via a hysterotomy, while both the placenta and umbilical cord remain intact. The fetus remains hemodynamically stable, as the uteroplacental gas exchange is maintained. A common strategy is to first attempt intubation via direct laryngoscopy. If the airway is not adequately visualized, then rigid bronchoscopy is attempted. If an endotracheal tube is unable to be passed, tracheotomy is the final option . Successful management of CHAOS has been achieved with a combination of fetal tracheostomy and delivery using the EXIT procedure .
5.2.2 Cervical Lymphangioma
Lymphangioma is a pretty rare lymphatic malformation occurring in 1:4000 pregnancies. This lesion is characterized from cystic lymphatic spaces, possibly secondary to local failure of lymphatic connections during development. Themajority of lymphangiomas occur in the head and neck, with the posterior cervical region as the most common site. Some of these malformations may be complicated by hydrops, likely caused by compression of neck vessels. Fetal differential diagnosis includes primarily teratomas, especially in large lesions. However, lymphangioma generally appears as septated fluid-filled collection with rare solid components. In contrast, a predominantly solid or a cystic lesion with solid nodules favors the diagnosis of teratoma. Location can also be helpful in differentiation of these lesions. Lymphatic malformations often arise posteriorly, and cervical teratomas are typically located anteriorly. Intrathoracic extension of the lesion favors the diagnosis of lymphatic malformation , and these lesions often insinuate between multiple planes. Other rare neck masses within the differential diagnosis include goiter, hemangioma, neuroblastoma, and soft-tissue tumors .
Fetal MRI seems very helpful in antepartum assessment of lymphangioma, complementing ultrasonographic images and providing a detailed view of anatomic relationships of the lesion to surrounding tissues. T2-weighted MR images may give information about the degree of concomitant airway compression exerted by the neck mass. This information may be useful in the decision to use the EXIT procedure and to help surgeons in planning their approach to establish airway control during delivery (Fig. 5.1) .
Giant cervical lymphangioma. Coronal (a), sagittal (b), and axial (c) HASTE MR images demonstrate a large anterior multicystic neck mass (arrow), with no compression to the airways in a fetus at 27 weeks’ gestation. Orotracheal intubation (d) under direct laryngoscopy performed during EXIT, i.e., by preserving uteroplacental blood flow. Note the partial delivery of the fetus through the hysterotomy and the untouched umbilical cord (asterisk). The fetus is monitored with a pulse oximeter attached to his left hand
5.2.3 Cervical and Mediastinal Teratoma
The head and neck is the second commonest site of teratoma in the fetus . These masses typically consist of both cystic and solid components and originate from the palate, nasopharynx, or thyrocervical area. The finding of calcifications is nearly diagnostic of teratoma, although these are present only in approximately 50 % of cases and might not be conspicuous on USS or MRI . A common and important associated finding seen with cervical and oral teratomas is the polyhydramnios, resulting from a direct mass effect, because swallowing can be compromised by occlusion of the mouth or compression of the esophagus .
The management of fetal giant cervical teratoma includes a spectrum of options. For the rare fetus who develops hydrops fetalis, fetal resection may be indicated . In patients with airway obstruction, EXIT procedure provides the luxury of time to obtain airway control either by intubation, tracheostomy, or, if necessary, tumor resection on placental support .
Fetal mediastinal teratomas are rare tumors that, if massive in size, may cause hydrops leading to fetal demise or fetal esophageal and airway compression causing late-gestation polyhydramnios and preterm labor. In some instances, the occurrence of hydrops fetalis has been managed successfully by in utero aspiration of the tumor cyst fluid and postnatal tumor resection  or by EXIT procedure for establishment of an airway and tumor resection on uteroplacental support .
Fetal MRI has proven to be a useful complementary imaging tool to characterize cervical and mediastinal teratoma, helping to direct optimal prenatal and perinatal management of these lesions (Fig. 5.2).
Giant mediastinal teratoma. Coronal True Fisp (a), sagittal (b), and axial (c) T2-weighted HASTE MR sequences demonstrate a large heterogeneous mediastinal mass (arrow) that deviates the heart to the right in a fetus at 27 weeks’ gestation. Note the small lungs of relatively low signal intensity (thick arrows in c). Note pleural effusion, ascites, and generalized subcutaneous edema. The airway below the mass is dilated (short arrow in b). Macroscopic appearance (d) of the surgical resection specimen of the tumor
5.3 Congenital Diaphragmatic Hernia (CDH)
Congenital diaphragmatic hernia (CDH) is a common surgically correctable defect, occurring in 1:3000 pregnancies. Despite great strides in its management made in recent years, CDH continues to be associated with significant morbidity and mortality.
This disorder is characterized by a defect in the diaphragm allowing herniation of the abdominal viscera into the thorax that compromise normal lung development. The current mainstay of treatment of CDH involves stabilization and respiratory support at birth, followed by closure of the diaphragmatic defect, which returns the abdominal organs to the abdominal cavity and makes room in the chest for the hypoplastic lung to grow. Despite some recent series from specialized centers reporting a survival rate of close to 90 %, there is a significant divergence in survival data for CDH due to potential case selection bias, primarily because as many as 35 % of live-born infants with CDH do not survive to transport resulting in a “hidden mortality.” Hidden mortality is referred to patients who die before surgery, either during gestation or shortly after birth, and thus are not reported by individual institutions. Specific morbidities in survivors include neurodevelopmental, nutritional, sensorineural hearing, and pulmonary function deficiencies, all of which are most likely attributable to the severity of lung hypoplasia and pulmonary hypertension that accompany CDH [1, 2]. Marked hypoplasia and persistent pulmonary hypertension, in fact, complicate postnatal management in severe cases and are the justification for considering antenatal intervention in selected cases.
Now that two-thirds of CDH can be accurately diagnosed by mid-gestation, multiple attempts have been made to find accurate prenatal parameters that predict neonatal outcomes with much of the focus on measurements of lung size and vasculature, as well as on intrathoracic liver herniation.
The most commonly used parameter used to predict neonatal outcomes is the lung area to head circumference ratio (LHR), which is a sonographically obtained measurement reflecting the relative lung size contralateral to the diaphragmatic defect. Unfortunately, this parameter is highly operator dependent, can be measured in various formats, and has gestational limitations that make it only reliable when measured between 22 and 28 weeks’ gestation in the presence of liver herniation . These limits have been obviated by using the observed to expected LHR (o/e LHR). However, its sensitivity in predicting neonatal survival in left-sided CDH is still only 46 % with 10 % false-positive rate, likely a limitation of the two-dimensional measurement . Even with advances in three-dimensional USS, the contralateral lung volume is underestimated by 25 % with the ipsilateral lung not even visualized for measurement in nearly 45 % of evaluation.
Fetal magnetic resonance imaging (MRI) is an alternative imaging study with improved accuracy in fetal lung volume measurement. This modality provides improved soft-tissue contrast and is not affected by maternal body habitus or fetal position. Some studies have demonstrated total lung volume (TLV), observed to expected TLV (o/e TLV), and the percentage of predicted lung volume (PPLV) to be predictive of neonatal outcomes while alleviating some of the shortcomings of USS [16–21]. Busing et al. have demonstrated that TLV alone has acceptable prognostic ability to predict neonatal survival and need for extracorporeal membrane oxygenation (ECMO), comparable with o/e TLV . PPLV, which evaluates TLV in regard to the expected volume of the individual fetus, has also been shown to predict ECMO use, length of hospital stay, and neonatal survival . Generally, fetal lung volume increases considerably in late gestation . Bargy et al. analyzed postmortem lungs from CDH fetuses and found that pulmonary hypoplasia became progressively worse with advancing gestation, especially beyond 30 weeks’ gestation .
Coleman et al. have recently hypothesized that fetal lung growth rate is related to neonatal outcome. In their longitudinal study of isolated left CDH fetuses, a significant difference in lung growth (rate of change in TLV) was found between survivors and non-survivors . The authors found that the severity of pulmonary hypoplasia is dynamic and can worsen in the third trimester. Therefore, they concluded that all prenatal MRI-derived lung volumes are more predictive of outcome closer to term, facilitating prenatal counseling and focusing perinatal management.
MRI can also demonstrate the presence of intrathoracic liver herniation and quantify the degree of that herniation (Fig. 5.3). However, there is no clear consensus on the landmarks to define/quantify liver herniation at present. Although current published data suggest but are not conclusive whether the liver is truly an independent predictor of outcome, next to lung size measurements, at present, both variables should be considered when counseling the patient.
Prenatal diagnosis of left-sided CDH with intrathoracic liver herniation. Coronal True Fisp (a) and T1-weighted (b, c) MR images show upward herniation of part of the liver into the chest across the diaphragmatic defect of a left-sided CDH defect in a fetus at 24 weeks’ gestation. Note the dark T2 signal of the liver compared with the higher T2 signal of the lung. Note also the hyperintense signal of the herniated colon (arrow in c). Intraoperative view (d) of the “liver up” (asterisk) before its reduction into the abdominal cavity. Intraoperative view (e) of the left-sided CDH following complete reduction of herniated viscera. Note the markedly hypoplastic lung (asterisk) and the wide size of the defect that required patch repair
Novel methods, in particular those evaluating the pulmonary circulation – either by measurements at baseline or following maternal hyperoxygenation – as well as MRI diffusion imaging might help in the prediction of the second cause of death in CDH, which is pulmonary hypertension. A great advantage of USS is the possibility to visualize and measure blood flow without the need for contrast agents. Ruano et al. investigated the predictive value of 3D power Doppler of the entire lung vasculature in terms of survival as well as the occurrence of pulmonary hypertension . Thereafter, other authors found a strong correlation between the reduction in lung tissue perfusion, increased intrapulmonary artery impedance, and lung growth, as evaluated by o/e LHR .
Some authors have recently proposed the use of the diffusion-weighted imaging (DWI) for the assessment of fetal lung. DWI is an MRI modality that maps the microstructural characteristics of water diffusion, i.e., the random thermal (Brownian) motion of water molecules in capillaries and extravascular space.
The principal claim is that DWI–MRI might provide functional information of the fetal lung, such as increased interstitial tissue pressure or impaired capillarization. Preliminary work on the use of DWI–MRI as a tool to differentiate between normal and pathological lung development has shown a significant relationship between DWI–MRI parameters and gestational age in the normal fetus but failed to validate DWI–MRI as a tool to predict postnatal outcome in fetuses with CDH .
Finally, both USS and MRI can be used to plan the need and the results of fetal interventions for CDH. The first successful fetal surgery for severe CDH was performed at the University of California in San Francisco. Fetal surgery for CDH was originally proposed to involve an “open” approach to repair the diaphragmatic defect in mid-gestation. Indeed, today, there are a handful of survivors of open fetal CDH repair .
Thereafter, animal studies, mainly using the fetal lamb model of CDH, showed that temporary occlusion of the fetal trachea prevents the egress of lung fluid, thus promoting lung growth. The development and implementation of minimally invasive surgical techniques advanced at a rapid pace. Simultaneously, irritation of the uterus and the threat of preterm labor were identified as major hurdles in fetal interventions. Initially, a surgical clip was placed on the trachea through a neck incision. Although this technique effectively occluded the trachea, scarring and the development of tracheal stenosis were identified as significant adverse effects. Ultimately, fetal bronchoscopy with tracheal balloon occlusion emerged as an appropriate solution. Further refinements of this technique lead to a novel strategy – percutaneous fetoscopic endoluminal tracheal occlusion (FETO). Small endoscopes and video equipment are used to place a detachable balloon via fetal bronchoscopy around 28 weeks’ gestation with removal of the balloon at 34 weeks’ gestation. The advantage of this treatment is the lack of maternal hysterotomy and its associated morbidity.
After the FETO intervention, both USS and MRI can be used to confirm the adequate position of the balloon and to evaluate lung growth rate .
Finally, combination of lung volume parameters and the microstructural fetal lung evaluation using DWI may provide more information on lung growth and maturation in these cases to determine objective time frames for balloon release .
The complications after FETO include difficulty in balloon retrieval and postnatal tracheomegaly. However, fetal tracheal occlusion for CDH remains an investigational therapy for which the long-term benefits have yet to be proven.
5.4 Congenital Pulmonary Airway (Cystic Adenomatoid) Malformation
Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation (CCAM), is a rare developmental anomaly of the lower respiratory tract, occurring approximately in 1:30,000 pregnancies. Despite its rarity, CPAM is still the most common congenital lung lesion.
Although the underlying cause for CPAM is unknown, they are thought to result from an early abnormal development of the airway from intrauterine airway obstruction , supported by histologic and pathologic changes of exuberant primary bronchiolar overgrowth in communication with an abnormal bronchial tree lacking cartilage.
In CPAM, usually an entire lobe of lung is replaced by a nonworking cystic piece of abnormal lung tissue. This abnormal tissue will never function as normal lung tissue.
Basing on clinical and pathologic features, CPAMs can be classified into five types (revised Stocker classification) that take into account also the size of the lesions:
· Type 0: Severe acinar dysgenesis affecting all lung lobes, uniformly fatal.
· Type 1: Solitary or multiple macrocysts (>2 cm); this type is of bronchial or bronchiolar origin.
· Type 2: Single or multiple cysts of bronchiolar origin, measuring between 0.5 and 2 cm.
· Type 3: Multiple microcysts measuring 0.5 cm; they are predominately solid. This type is the only adenomatoid type and has a bronchiolar–alveolar duct origin.
· Type 4: Large air-filled cysts, with a distal acinar origin. Notably, they are indistinguishable by imaging from type 1 pleuropulmonary blastoma, appearing as a large cystic lesion.
Large-cyst subtypes account for about 70 % of CPAMs (Fig. 5.4). In most of the cases, the outcome of a fetus with CPAM is very good. However, in rare cases, the cystic mass grows so large as to limit the growth of the surrounding lung and cause pressure against the heart. In these situations, the CPAM can be life-threatening for the fetus.
Congenital pulmonary airway (cystic adenomatoid) malformation. HASTE oblique sagittal (a), axial HASTE (b), and True Fisp (c) MR images obtained at 28 weeks’ gestation showing a large high signal mass in the right chest (arrows). The lesion causes mediastinal shift of the heart to the left (short arrow in c). Intraoperative view (d) of a large-cyst subtype CPAM affecting the right lower lobe, requiring lobectomy few days after birth
The prenatal diagnosis of lung pathologies has considerably increased in recent years due to the generalization and technical improvements of USS screening during pregnancy. Prenatal USS may assess the overall mass size and associated compressive effects on the adjacent normal lung and mediastinal structures. Macrocystic CPAMs (types 1 and 2) appear on prenatal USS as echogenic masses with variable-sized cysts, while type 3 CPAMs appear as a homogenous echogenic mass on USS, being indistinguishable from other solid congenital lung anomalies.
Although USS enables a first recognition of the lesions and detection of adverse prognostic factors, their complete characterization in utero may be difficult or inconclusive, mainly because of technical problems, maternal habitus, or fetal position. Complementary fetal MRI has been increasingly performed over the last few years [32–35] as an adjunct to USS in the imaging of fetuses with congenital lung malformations as early as 18 weeks’ gestation [36, 37]. Compared to USS, fetal MRI allows for multiplanar imaging and may be superior at characterization of the boundaries of the malformed lung and how it relates to the normal lung lobar anatomy and surrounding thoracic structures [38–40].
The prenatal natural history of CPAM varies: in many cases, the lesions actually regress, and some disappear completely. Most of the remaining lesions will have a stable prenatal course and can be treated after birth. However, a minority of cases may develop worrisome signs such as mediastinal shift, polyhydramnios, and hydrops fetalis. These events are secondary to the mass effect exerted by the enlarging fetal CPAM. Hydrops, in itself, is harbinger of impending fetal death and is characterized by edema in two or more fetal compartments, e.g., subcutaneous collection, pleural effusion, pericardial effusion, ascites. Therefore, fetuses with congenital lung lesions resulting in a significant intrathoracic mass effect and risk for pulmonary hypoplasia and/or hydrops without other anatomical or chromosomal abnormalities may be candidates for fetal intervention. The mode of intervention is dependent on the type of lesion as well as the gestational age. Open fetal surgery was, and still is, being done for hydropic fetuses, especially for microcystic CPAM lesions. Following fetal lobectomy, survival rates of 60 % have been reported with resolution of hydrops, in utero lung growth, and normal postnatal development . More recently, early delivery with controlled resection of large fetal lung lesions using an EXIT strategy has been performed in hydropic fetuses of greater than 32 weeks’ gestation .
However, in utero thoracoamniotic (TA) shunt is the fetal intervention most frequently advocated for CPAM detected before 32 weeks’ gestation and carrying a dismal prognosis [43, 44].
The largest experience with this fetal procedure has been recently published by the Children’s Hospital of Philadelphia (CHOP) group, who reported 97 shunts placed in 75 fetuses . Average gestational age at shunt placement was 25 weeks and survival was 68 %, which depended on GA at birth, reduction in mass size, and hydrops resolution. Surviving infants had prolonged intensive care needs and often required either surgical resection or tube thoracostomy in the perinatal period. Despite the survival benefit, shunt placement is not without the risk of complications including shunt failure by occlusion or migration. Another known fetal complication of shunt placement is the production of chest wall deformities when shunts are placed for large macrocystic CCAMs at 18–20 weeks’ gestation . Finally, an initial experience with the use of steroid therapy given during the second trimester of pregnancy has been successfully reported in fetuses with hydrops fetalis and predominantly microcystic CPAM [47, 48].
Fetuses with CCAM but without hydrops have a good chance for survival with maternal transport and planned delivery for immediate neonatal care. Postnatal treatment options include either a lobectomy or segmentectomy for symptomatic patients. Treatment for asymptomatic patients is still controversial, as some authors suggest an elective resection, given the associated risks of hemorrhage, recurrent infection, and potential risk for malignancy.
Myelomeningocele (MMC) – the most common of spina bifida – is a congenital defect of the central nervous system characterized by protrusion of the meninges and spinal cord through open vertebral arches leading to lifelong paralysis and hydrocephalus. This condition affects 1 in 2000 live births, which translates to nearly 1500 cases occurring in the USA each year. Additionally, not included in these figures are the estimated 25–40 % of women seeking termination of pregnancy for prenatal diagnosis of MMC.
The natural history of MMC includes a constellation of findings which correlate with the proximal anatomic extent of the defect. Despite aggressive postnatal treatment, nearly 14 % of all MMC neonates do not survive past 5 years of age, with the mortality rising to 35 % in those with symptoms of brainstem dysfunction secondary to the Arnold–Chiari malformation.
The most serious associated problem is hydrocephalus and 85 % of children require a ventriculoperitoneal (VP) shunt and 45 % need one or more shunt revisions and hindbrain herniation can be fatal. Quality of life is affected by motor and cognitive impairments, bladder and bowel incontinence, renal failure, orthopedic disabilities, and of course many social and emotional challenges.
Although the etiology of MMC remains poorly understood, primary failure of neural tube closure at the caudal neuropore in the embryonic period results in exposure of the developing spinal cord to the uterine environment . Without protective tissue coverage, secondary destruction of the exposed neural tissue by trauma, hydrodynamics, or amniotic fluid may occur throughout gestation (“two-hit hypothesis”).
Advances in prenatal diagnosis now permit diagnosis of MMC as early as the first trimester, and extensive research into the etiology of neural tube defects has elucidated both genetic and micronutrient causes .
Fetal MRI has been helpful in characterizing other lesions of central nervous system with a greater detail of its anatomy. An optimal benefit of MRI may be its role as an adjunct to ultrasound at a later gestational age, when bony attenuation may complicate sonographic evaluation. Other advantages of MRI over US are its excellent soft-tissue contrast resolution and the ability to visualize the fetus despite maternal obesity, fetal lie, or oligohydramnios. Finally, MRI may help to detect factors thought to influence prognosis such as the level of the lesion and the presence of a covering membrane. It is well documented that higher lesion level, lesion size, and lack of a covering membrane were associated with several adverse outcomes in children with MMC.
Until the modern era of fetal therapy, treatment of MMC consisted of surgical closure of the spinal canal at birth and lifelong supportive care. The “two-hit hypothesis” formed the rationale for antenatal intervention. It was speculated that if the spinal cord was covered, the secondary damage could be minimized. Beginning in 1993, a series of experiments conducted at the Children’s Hospital of Philadelphia by Martin Meuli, Scott Adzick, and colleagues demonstrated the similarities between a surgically created large animal model and human MMC and documented neurologic improvement following in utero repair . A sheep model was created in fetal lambs at 75 days’ gestation (term 145 days) by excision of skin, paraspinal musculature, vertebral arches of lumbar vertebrae 1 through 4, and the exposed dorsal dura mater. The pregnancy was then continued to near term, and cesarean section was performed at 140 days’ gestation. Clinically, the lambs demonstrated incontinence of urine and stool, flaccid paraplegia, as well as lack of sensation in the hindlimbs, which was confirmed by somatosensory evoked potentials.
In 1997, initial reports on fetoscopic and open fetal repair of MMC opened the door to the prenatal intervention for this disorder. In 2011, Adzick et al. reported on the results of the Management of Myelomeningocele Study (MOMS), a randomized trial that compared the efficacy of prenatal repair of MMC with that of postnatal repair. This study showed a significant reduction of VP shunt from 82 to 42 % and substantial improvement in overall neuromotor function at 30 months. Additionally, hindbrain herniation also resolved, and most children had minimal or no brain stem dysfunction .
Despite these promising results, the MOMS trial also revealed that fetal MMC surgery increases the risks for spontaneous rupture of membranes, oligohydramnios, and preterm delivery.
Therefore, current fetal therapy for MMC is still suboptimal. Further research is in need to decrease the risks to the mother and fetus by testing minimally invasive fetoscopic techniques and tissue-engineered components for prenatal MMC coverage, respectively .
5.6 Lower Urinary Tract Obstruction
Fetal lower urinary tract obstruction (LUTO) is a heterogeneous group of pathologies with a reported incidence of 2.2 in 10,000 births . The two most common congenital malformations causing LUTO are posterior urethral valves (PUV) and urethral atresia. Fetal LUTO can lead to severe prenatal renal impairment, especially when associated with clinically significant oligohydramnios. Such an ultrasound presentation, between 16 and 24 weeks, is associated with a high prevalence of pulmonary hypoplasia, resulting in high perinatal mortality and morbidity. Typical ultrasonographic features in the fetus are megacystis (enlarged bladder with a dilated proximal urethra) and bilateral hydronephrosis with or without renal parenchymal cystic appearances (cystic kidney disease) . Although USS is still the antenatal imaging modality of choice for the initial screening of the vast majority of fetal urogenital anomalies, there remain certain circumstances in which ultrasonography is limited, particularly when the method is indicative but not conclusive or technically difficult [56, 57]. During the last years, fetal MRI has shown to be a valuable, noninvasive, and well-tolerated complementary imaging technique. The advent of faster sequences of MRI has revolutionized ability to assess the fetus, and to date, there is no evidence that short-term exposure to electromagnetic fields harms the fetus when a field strength of 1.5 T is used [56, 57]. Therefore, fetal MRI has proven to be a correlative imaging modality that provides a more detailed anatomic description and better soft-tissue resolution in the vast majority of cases where USS has been inconclusive, especially if oligohydramnios altered fetal anatomy or pathologic findings of the pelvic structures are present (Fig. 5.5) .
Posterior urethral valves. Coronal (a) and sagittal (b) T2 HASTE MR images obtained at 29 weeks’ gestation showing a hugely distended fetal abdomen secondary to ascites. Note the dilated and thick-walled bladder associated with dilatation of the posterior urethra (arrow)
When significant oligohydramnios and renal cystic changes occur, bladder drainage by serial vesicocentesis or by continuous drainage into the amniotic cavity by placement of a vesicoamniotic shunt has been used to relieve fetal LUTO by bypassing the urethral blockage. Fetal vesicoamniotic shunting attempts to reduce or avoid renal parenchymal damage and chronic oligohydramnios that can adversely affect pulmonary development . A recent randomized trial comparing the placement of vesicoamniotic shunt versus conservative management found that survival seemed to be higher in the fetuses receiving vesicoamniotic shunting. However, the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Therefore, the authors concluded that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done .
Finally, recent advances in fetal LUTO treatment include in utero cystoscopy and laser fulguration of PUV, with some clinical promising preliminary results .
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