text:
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
Email: firstname.lastname@example.com
Fetal MRIAntenatal diagnosisFetal surgeryEx utero intrapartum treatmentCongenital anomalies
5.1 Introduction
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 [1].
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 [2]. 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 [3]. 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 [4]. 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 [5].
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 [3]. Successful management of CHAOS has been achieved with a combination of fetal tracheostomy and delivery using the EXIT procedure [7].
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 [4], and these lesions often insinuate between multiple planes. Other rare neck masses within the differential diagnosis include goiter, hemangioma, neuroblastoma, and soft-tissue tumors [8].
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) [9].
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 [8]. 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 [8]. 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 [8].
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 [10]. 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 [11].
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 [12] or by EXIT procedure for establishment of an airway and tumor resection on uteroplacental support [13].
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).
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 [14]. 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 [15]. 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 [16]. 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 [22]. Generally, fetal lung volume increases considerably in late gestation [23]. 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 [24].
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 [25]. 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.
Fig. 5.3
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 [26]. 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 [27].
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 [28].
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 [29].
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 [30].
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 [28].
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 [31], 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.
Fig. 5.4
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 [41]. 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 [42].
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 [45]. 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 [46]. 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.
5.5 Myelomeningocele
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 [49]. 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 [50].
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 [51]. 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 [52].
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 [53].
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 [54]. 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) [55]. 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) [57].
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 [58]. 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 [59].
Finally, recent advances in fetal LUTO treatment include in utero cystoscopy and laser fulguration of PUV, with some clinical promising preliminary results [60].
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Dagger in the Heart Mr Y stated he really felt a sharp stabbing discomfort in his heart, when he discovered out that the woman he enjoyed had actually lately discovered a sweetheart. I claimed, " I comprehend that pain sensation. " Everyone who has actually gotten on the brink of shedding a romantic partner has felt this sharp stabbing discomfort. If you have not, then you have not loved with all your heart.
Each these items make it very easy to fall to the narcissist. It's important to be aware the idealizing stage is oftentimes referred to as the love bombing stage. That's exactly what the narcissist is doing, bombing their potential partner, Since you can readily see.
- - Bill Remember the fantastic old times, Dad- - the days before you left home? - - Sheila Children undergo a modification process similar to the procedure, but each rebuilding block's feelings and attitudes might be somewhat different for children. If we realize that our children are in process, using a mountain of their own to 21, it helps.
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Listen to them. I will also show you where you might be slipping up from winning a fantastic man, along with the scenarios that might be bothering you. My goal is to help you get rid of time- wasting habits and situations that won't be conducive to the connection you are striving to get into.
" Whoa, " he says, punching himself at the sternum. " This is not what I was expecting of tonight. " " I know, isn't it good? " " I think' she'. " He nods slowly like he is trying to work out a maths equation.
Let us examine two case studies, one where a long- distance relationship functioned and the other where it did not. You can spot elements.
Be skeptical of how long you proceed onto a different platform, as the more quickly you give a different program to chat on to them, the earlier they are asking for nudes. Usually Snapchat is the culprit for this, as I have previously discussed.
the Friendzone occurs if you don't want to wind up in the Friendzone, then you have to understand. Learn how to recognize patterns in your relationships which property you so which you can make the necessary adjustments.
Nevertheless, men can get intimidated by girls. My tall girlfriends state that guys can't deal with their stature. Harvard girls report on men's slumped shoulders and slack jaws when they think their alma mater does not step up. And lord knows I've gotten a bit dazzled before with a girl who's. The best explanation for this phenomenon stems from reader Frederica A. : The truth is some men are intimidated by women for a variety of reasons.
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Paying for a local sluts on dates, and always buying her things reduces your chances of succeeding with her brief and long- term. It sets you up asa'Supplier'! And there are reasons for this which you need to get your mind around.
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Whenyou're in a relationship and dating somebody, they ought to make you feel better about yourself. At first, the narcissist may build you but that isn't going to last very long. It's very likely that you feel much worse about yourself then you've in a very long time, if ever, ifyou're dating a narcissist.
Men, like you, have to be reminded they have somebody who cares and loves for them, a loving partner in you.
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In an catfishing swindle, the scammer goes from her or his way to make an alluring bogus profile utilizing literary names, or adopted real identities( as an example, a scammer may illegally adopt the good wlw dating apps of a CEO, military employees, professional working overseas, or even assist employees) with the intent of gaining your confidence.
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It may sound cruel, however, your spouse's death is an chance for self- examination. How do you see life, yourself, along with others? In which areas are you fallen into a rut or become stagnant? The death of your spouse is a method that you examine any ways in which you've taken life for granted.

subset: commoncrawl


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Social Representations and Education: Anchoring, Objectification and Cognitive Polyphasia as Basic Processes
SR of history embrace shared images and knowledge about the past, elaborated, transmitted and conserved by a group through interpersonal (e.g. family transmission) and institutional communication (e.g. history education). These representations serve to preserve a sense of ingroup continuity and to cultivate values and norms that prescribe behaviors within the group (Pennebaker, Paez, & Rime, 1997). Importantly, SR imply a process where lay beliefs assimilate more elaborated, frequently scientific or philosophical, discourses (Jodelet, 2006). In consequence, both historiographical traditions (in a biased manner) and national narratives transmitted by history textbooks and teachers are reflected in a shared image of the world's past. Furthermore, understanding of such processes as anchoring, objectification and cognitive polyphasia, relevant in emergence of SR (Jodelet, 2011; Lautier, 2001; Tutiaux-Guillon, 2012), may also be necessary for strengthening competences in historical thinking.
Anchoring involves the ascribing of meaning to new information by means of integrating it into existing worldviews, so it can be interpreted and compared to the "already known". For instance, students learning history anchor the information they receive in their experience, group membership and values. Because of anchoring processes, young migrants are less interested in European nations' history than majority youth, and Muslim young migrants are more critical about Holocaust issues compared to non-Muslims (Grever, 2012; Lautier, 2001).
In turn, the process of objectification turns something abstract into something almost concrete. These processes are present in historical understanding: historical events are reified in figures (e.g. Hitler representing the Nazi evil in Second World War (WWII)) and images (e.g. Columbus's three ships as a figurative image of the "Discovery") (Lautier, 2001). In this text, we will examine the relationship between specific examples of such processes, which shape the content of SR, for competences in history education and learning.
Finally, cognitive poliyphasia implies a dynamic coexistence of the distinct modalities of knowledge. That is, cognitive polyphasia permits the coexistence of logical and a pre-logical thinking or causal and "magical" thinking (Moscovici, 1976).


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Announcement! Inception Workshop of UNDP/GEF project "Joint Actions to Reduce PTS and Nutrients Pollution in Lake Baikal through integrated basin management", Ulan-Ude, Russia, 9-11 April 2008
On 9-11 April 2008 an inception workshop of the preparatory stage (PPG) of the UNDP/GEF project "Joint Actions to Reduce PTS and Nutrients Pollution in Lake Baikal through integrated basin management" will be held in Ulan-Ude, Russia.
The workshop is organized by UNDP Russia in close cooperation with the Ministry of Natural Resources of the Russian Federation, Center for International Projects (Moscow, Russia), People's Khural of the Republic of Buryatia (Committee for economic policy, natural resources use and environmental protection), Baikal Ministry of Natural Resources of the Republic of Buryatia, Institute of Nature Management of the Siberian Branch of Russian Academy of Sciences. Among the participants of the workshop are: representatives of Russian Ministry of Natural Resources, Mongolian Ministry of Nature and Environment, the scientific community of Russia and Mongolia, UNESCO, UNDP Bratislava Regional Centre, UNDP Russia and UNDP Mongolia.
Lake Baikal, situated in eastern Siberia on the Russian border with Mongolia, is the world's oldest (>25 million years old) and deepest lake (1,637 m). It contains 20 percent of the Earth's fresh surface water and supports a diverse and highly endemic flora and fauna. Although the lake is in Russia, the catchment around this vast freshwater reservoir (Baikal Lake Basin, BLB) is a transboundary resource extending over a 500,000 km2 area shared between Russia and Mongolia, with over 300 rivers and streams. Ongoing pressure to expand the economy in both countries is driving the largely uncontrolled expansion of industrial, agricultural and urban developments within the watershed on both sides of the lake.
The PPG will finance the development of the preliminary Transboundary Diagnostic Analysis (TDA) that will identify major root causes and hot spots in the watershed through collection and analysis of baseline data on ecological and socio-economic context in the BLB. Implementation of the PPG will be shared between the Russian Federation and Mongolia. UNDP Russia will lead the project development process.
The purpose of the PPG Inception workshop will be to introduce all partners, to plan for the project preparation activities, to review the TORs for key experts/consultants and analyze information gaps, to agree on the project coordination mechanisms (national and regional Steering Committees.


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I have to say the the Active Rain re-blog is a beautiful thing. It gives me the opportunity to have my Outside Blog readers get introduced to Kim Daugherty, a McKinney TX REALTOR, Broker and wonderful writer. Kim's post put a cool aid grin on my face. Sometimes people need a gentle reminder that we all have a life to live and Kim reminds us with humor and style.
I have been in real estate since 2001. Since then, I have spent a good part of my time in my career devoted to being a BUYER'S AGENT. I know buyers. I like buyers. I LOVE first-time home buyers. But with every client I work with, I am continuously reminded how little the general public knows about how real estate agents operate.
Myths abound as to the secret lives of Realtors. So, in an effort to clear things up, I decided to let you in on a few important facts about my career.
1. I don't can't work 24/7. If I did that, I would be no good to you. I have a family. I like to get to bed at a decent hour. I celebrate holidays. This would seem like a given, but I've had clients call me at 11:30 at night. Would you call your CPA at that time? Your doctor? No. Please respect the time of day you call. I'm happy to listen to your message, but understand that it might be during normal business hours that I get back to you.
2. Not all Realtors are Millionaires. We do not work on salary. If we don't sell something one month, we don't bring home any money. We are not paid hourly, by the mile, or by the number of showings we do. So, when you wonder why we ask a few "intrusive" questions before putting you in our car to show homes, it's just that we want to make sure you can actually afford to buy a home, and that we aren't wasting either of our time by looking at the wrong homes.
3. Clients are not HANDED to us. Our company does not simply hand us clients ready to sign a contract. This was a big misconception that I had to overcome. When I left RE/MAX and Keller Williams to start my own brokerage, some people said - "Well, where will you get your business from?". Answer: the same place I've always gotten my business - through referrals,networking, and smart marketing. I like to ask my clients when I first begin working with them to keep me in mind for anyone they know who needs my services. That way, I'm not spending all of my time working to get more business, I can focus on the clients I have and do a better job for them in the end.
4. My Crystal Ball is Not Working. Oh, wait...I don't have a crystal ball. I don't know what price the seller will take. I don't know how long it will take a home to sell. I don't know how many houses we'll have to look at before you find the right one. It is my job, though to find out as much information as possible and give that to you. It is my due diligence to research a property, to obtain disclosures and as much info as I can get from the other agent to help you make the most informed decision possible.
5. I'm working for YOU! Now, I know there are some not-so-truthful agents out there that spoil it for the rest of us, which is why you need to do a thorough job of selecting your agent. It is my JOB to protect YOUR best interests. I will not go behind your back. I will not lie or decieve you. It is not in my best interest. It would only hurt my relationship with you, in turn, stopping any kind of referrals you might send my way. I'm bound by the Realtor's Code of Ethics on this one!
6. I can sell homes not listed by me or my company....That is the benefit of belonging to the local MLS. By being an MLS member I participate in broker reciprocity - we can all show each other's listings, thus allowing us to uphold our duties in #5.
7. ...And in other cities OUTSIDE of the city that my office is located in. Just because my office is physically located in McKinney, TX, doesn't mean I can't sell outside these limits. Ask your agent what areas they serve. Chances are, they can help you in that city or help you find a reputable agent that does.
Whew, now that I've got that off my chest I feel a lot better.
Bottom line is this - I love my job. I do my job well. I just want you to understand the basics of how I work, so I can help you better! So let's do it - interest rates couldn't be better, and McKinney, TX and the surrounding areas are a Buyer's Market right now! Now is the best time to find your dream home...
Disclaimer: Any comments and contributions provided on ActiveRain.com (or other electronic or print media) does not establish an agency relationship with any third party. Blog posts are intended to be informational only. Please be advised that real estate practices vary in regions and from state to state and market to market. The information contained herein does not constitute legal advice. All parties in need of legal, accounting, tax, or real estate guidance are directed to consult with the licensed professional of their choice. Please seek specific guidance from a retained professional in the specific field(s) required to service your interests. I and/or team blog writers make no claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained in or linked to this web site and its associated sites inclusive of but not limited to CarolynTannStarr.com MySpace/TannStarr 46486 NY Working Moms Examiner ActiveRain Group Club Chaos ClubChaosAgents.com CyberMinions.net CTannStarr Outside Blog CTannStarr Localism Blog TannStarr.net UberMental.com
© Carolyn Tann-Starr, 2008-2015. Unauthorized use and/or duplication of this material without express and written permission from the re-blog authors (when appropriate)and Carolyn Tann-Starr is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Carolyn Tann-Starr, (the re-blog authors when appropriate) and Wordy C's Blog with appropriate and specific direction to the original content.
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Felix Lipov, Official Photographer, Ambassadors of Chaos


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About my practice
My goal is to advise clients on how to strategically plan ahead for their future. I want to provide you with peace of mind in the present so that we are planning ahead for the future. This will include allocating finances in the most tax efficient way. Together, we'll develop a roadmap to make your dreams become a reality. Please let me know how I can help.
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To learn more about Northwestern Mutual Investment Services, LLC and its financial representatives, visit FINRA BrokerCheck


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Get E-Book on COVID-19
Hello doctor,
My 22-month-old niece is strictly eating baby food. She attempts to eat food but gives up before it reaches her mouth. She also is still on a bottle and occasionally drinks water out of a solo cup or sippy cup. She is also slightly behind in her speech, but interacts and usually plays. Kindly help.
Welcome to icliniq.com.
According to me stop milk from 8 am to 8 pm and give semisolid diet like dal, dalia, khichdi aloo kela rice, apple, upma, halwa, patolia, raab, kadi idli poha satu custard etc., And from 8 pm to 8 am give mother milk is preferable if not give top milk without water and add sugar as per your taste. To start with stop milk for 4 hours for 15 days and give semisolid diet next 15 days stop milk for 8 hours and provide semisolid food lastly stop milk from 8 am to 8 pm and provide semisolid diet. Give your kid following supplements,
1. Vitanova drops (Vitamin D3) one ml once a day.
2. Feris drops one ml once a day.
3. Zincovit drops one ml once a day.
4. Syrup Ostebon one teaspoon full twice a day.
All above for six months.
Was this answer helpful?|
Is my chest pain due to vitamin D3 deficiency?
Query: Hello doctor,Four months ago, I consulted you on this platform for premature complexes which I was having without any other symptoms. Below is my query and your answer - I am a male of 48 years of age. I have a lean build and do regular exercise. Since childhood, I had a tendency for heart palpitat... Read Full »
What is the proper diet chart for a 6-month-old baby?
Query: Hello doctor, My infant is turning 6 months this month and we are moving to a different place. I am looking for a complete diet chart for an infant. Can you please help me get a diet chart and how to make the baby food for my baby, please? Also, can we preserve food in the freezer? My son's current... Read Full »
Why do I feel weak while sitting and working?
Query: Hi doctor, From past few days, I feel very weak while sitting and working. I do not feel energetic, and most of the time I feel sleepy and lazy. I have a little pain in the body, so I am not able to concentrate properly on anything. My blood pressure is 119/72 mmHg, and pulse is 72. I even have pa... Read Full »
Ask your health query to a doctor online?Ask a Paediatrician Now


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Mouse called
The most dangerous Night … of the Games!
Scrooge, along with his nephews and Ponka, fall into the ancient pyramid, their movement to the treasure is stopped by a deep hole. However, for Willy with Ponochka this is not a problem: they jump to the other side and Willy activates a hidden button. Now the rest can also cross over to the other side, you just need to calculate the frequency of the trap and find the window. Billy and Scrooge do this without any problems and safely overcome darts, a little later Dilly joins the company, already pretty tired of the adventures. Travelers safely get to the Golden Idol, but Dilly is already tired of this – he learned the script by heart and knows what will happen next. He predicts further events accurately, and now the family has to escape from the boulder. Barely alive, Dilly returns home, but they do not give him a long rest: Scrooge Continue reading
Pluto (English Pluto) – an animated character who became famous in a series of short cartoons by Walt Disney Studios. Most often, he appears on screens as Mickey Mouse's pet dog.
Pluto looks like a yellow-orange dog. He has black ears and a tail. Usually he wears a red or green collar.
Pluto is a really well trained dog. He has enough considerations to get out of a difficult situation. He acts as an assistant to Mickey, a best friend, and sometimes even a conscience in some cases. Pluto is Continue reading
Donald and Lina are expecting the return of Scrooge and the company from another expedition. Donald tries to break the long pause when the noise from the hall announces the return of the travelers. While Donald helps his nephews to bear a heavy coin, Mrs. Cluvdia reports to Scrooge that the Board of Directors is concerned that his treasure hunt is doing more harm than good. Scrooge dismisses, assuring the maid that all his efforts are only for the good of the city and goes to rest. Lina, meanwhile, creeps up to the treasure trolley and lays a magic ruby and almost comes across Ponochka, who appeared with the statue. She greets her friend, enthusiastically telling what a fun night awaits them, and the girls run upstairs. Some time later, the handyman takes the mined gold to the Vault, the thrown gem is activated, Continue reading


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Xeropan: Learn English 4+
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App translation in 15 languages and counting
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SO WHAT IS XEROPAN GOOD FOR? Learn English, learn words, creative English learning, free language lessons, effective English learning for free, English language learning online, learning English, fun ESL games online for adults, personalised learning, english videos, grammar, pronunciation, vocabulary, exams, IELTS study, TOEFL study
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We made some minor corrections in the app to make it faster, better and simply nicer. This way you can focus only on developing your English skills, this is our most important goal.
Ratings and ReviewsSee All
Fun and interesting
Finally I can train my level of English in a more various way with this app! Congrats for the app makers! Cheers!
Easy to use, innovative, useful.
The app is fine but I think it's expensive. After I running out of starter coins I won't buy any.
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Requires iOS 11.0 or later. Compatible with iPhone, iPad and iPod touch.
- Languages
English, Arabic, French, German, Hindi, Hungarian, Indonesian, Italian, Japanese, Korean, Portuguese, Russian, Spanish, Turkish, Vietnamese
- Age Rating
- 4+
- Copyright
- © Xeropan International Kft. — Learn English through PLAY
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- 12 months of Xeropan PRO HUF17,790.00
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Family Sharing
Up to six family members will be able to use this app with Family Sharing enabled.


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Vax S86-SF-CC Steam Fresh Combi Classic Steam Cleaner - White
- Product Description
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Product Features
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With the 9 piece accessory kit you are able to clean floors and above the floor. You can successfully clean ovens, taps, tiles, kitchen surfaces, hobs, grout, windows and more at your own convenience. This ensures you are able to complete a total home clean with ease.
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Using detergent with steam helps break down grime faster than with steam alone (tested on four different substances and floor types treated with Vax steam+ detergent) Steam + detergent tackles stubborn dirt and stains and leaves the room smelling fresh.You have the option to turn the detergent on and off at your own convenience.
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Heating up in less than 30 seconds, the Steam Fresh Combi delivers 12 minutes of cleaning time and leaves floors and surfaces dry within a matter of minutes, making this steam cleaner perfect for use in homes with children and pets.
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|Product Type
|Steam cleaner
|Cleaner Type
|Cleaning Method
|Max Power Consumption
|3.7 kg
|Manufacturer Warranty
|2 years


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In three years, Isaac Mbatha got used to the lack of space, running water and electricity in a tent he shared with his wife and three children in Wilgespruit, a township on the outskirts of Johannesburg.
But he never got used to the rain. The coronavirus brought an unexpected respite to those harsh sleepless nights.
Since the pandemic, 70 families have been re-housed for free in nearby wooden chalets.


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