Fetal surgery for severe lower urinary tract obstruction

Fetal interventions have been proposed for treatment of severe lower urinary tract obstruction (LUTO), as this condition is associated with high rates of perinatal mortality and postnatal renal impairment. The rationale for in utero treatment for those cases is based on the possibility of relieving the obstruction, improving the amniotic fluid volume, and preventing renal and bladder damage. Candidates for fetal intervention should be rigorously selected based on the confirmation of severe LUTO (dilated bladder and bilateral hydronephrosis), oligohydramnios or anyhydramnios and ‘favorable’ fetal urinalysis (dependent on gestational age). Nowadays there are two different therapeutic options with specific technical approaches. Vesico-amniotic shunting is an easier procedure, but with a higher frequency of related complications. Fetal cystoscopy can be used for diagnostic purpose and for treatment of posterior urethral valves, with suggestive advantage of allowing a more physiological release of the obstruction. According to the literature, estimated survival rates and postnatal normal renal function frequencies are approximately 40 and 50% after vesico-amniotic shunting and 75 and 65% after fetal cystoscopy, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Further predictors of renal dysplasia in fetal obstructive uropathy: Bladder pressure and biochemistry of ‘fresh’ urine

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia. Urinary sodium (Na⁺) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na⁺ = −11.3 per cent; Osm= −13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na ⁺ concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false-positive diagnosis of dysplasia. Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18–28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function. Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.     

Invasive assessment of fetal renal abnormalities: urinalysis,fetal blood sampling and biopsy

There are a number of potential biochemcial markers that may have some role in predicting renal function postnatally. These include urinary sodium, calcium and β2‒microglobulin. The latter may also be measured in fetal serum. However, the accuracy of these parameters at a point in time is far from perfect as urinary tract obstruction is a progressive disease which may be best defined by repeated observations throughout pregnancy. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal laser therapy: applications in the management of fetal pathologies

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy. © 2015 John Wiley & Sons, Ltd.     

The making of fetal surgery

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. Copyright © 2010 John Wiley & Sons, Ltd.     

Fetal lower urinary tract obstruction: What should we tell the prospective parents?

Fetal lower urinary tract obstruction (LUTO), which often results in marked perinatal morbidity and mortality, is caused by a heterogeneous group of anatomical defects that lead to blockage of the urethra. The classic prenatal presentation of LUTO includes megacystis with hydronephrosis. While mild forms of the disease can be associated with favorable outcomes, more severe disease commonly leads to dysplastic changes in the fetal kidneys, and ultimately oligohydramnios, which can result in secondary pulmonary hypoplasia and renal failure at birth. The aim of this review is to provide practitioners with a general overview of the diagnosis and treatment of LUTO based on disease severity, along with some points to consider when counseling prospective parents of fetuses with this condition.     

Successful intrauterine shunting of a sacrococcygeal teratoma (SCT) causing fetal bladder obstruction

We report a case of a sacrococcygeal teratoma (SCT) diagnosed at 22 weeks with a substantial intrapelvic cystic extension leading to bladder outlet obstruction and hydronephrosis at 27 weeks. Prenatal percutaneous shunting of the cystic teratoma was performed at 28 weeks to avoid prolonged fetal pelvic compression by the tumour that could have adverse effects by stretching the pelvic plexus and sacral nerves. Urinary dilatation resolved completely after shunting and a 3880 g baby girl was delivered at 39 weeks. The potential benefits of in utero shunting to avoid urological complications of SCTs with intrapelvic extension are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1·8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.     

Prenatal evaluation of fetal renal function based on serum beta2-microglobulin assessment

The relationship between fetal renal function (FRF) and fetal serum beta₂-microglobulin (B2MG) was investigated by comparing its value in 112 unaffected fetuses with that of 23 fetuses presenting with urinary tract malformations (UTM). Fetal serum level of B2MG was totally unrelated to gestational age; its value increased in cases of severe impairment of FRF but was similar to controls in all mild uropathies (p<0.05). Evaluating serum B2MG could be beneficial in fetuses with severe renal damage, but is of no use in unilateral UTM since only the global FRF is tested and not the function of each single kidney. Copyright © 2001 John Wiley & Sons, Ltd.     

Intrauterine manometry: Technique and application to fetal pathology

A technique is described for measuring pressure within the amniotic cavity and within fetal vessels and/or body compartments. Two saline-filled catheters were connected at one end to needles inserted during indicated invasive procedures and at the other to silicon strain gauge transducers. In 36 pregnancies with normal liquor volume, stable intra-amniotic pressure (IAP, range 1–14 mmHg) increased with gestation (r=0·48, p<0·01). In pregnancies complicated by severe oligohydramnios, IAP was ≤ 1 mm Hg and rose to normal levels with saline amnioinfusion. Raised IAP (range 17–26 mm Hg), found in pregnancies with gross polyhydramnios, fell with drainage of amniotic fluid. Subtraction manometry was used to determine supra-amniotic pressure within the intervillus space, umbilical vein, umbilical artery, abdominal and thoracic cavities, and the urinary tract in normal and/or pathological fetuses. Low intravesical and intrapelvicalyceal pressures (median 6·5, range 2–10 mmHg) were noted in fetuses with obstructive uropathies. Intrauterine subtraction manometry appears to be a useful tool in the understanding of fetal pathophysiology and may be of clinical benefit in the therapeutic drainage and infusion of amniotic fluid and in the assessment of certain fetal disease states.     

Etiology and management of early pregnancy renal anhydramnios: Is there a place for serial amnioinfusions?

Early pregnancy renal anhydramios (EPRA) comprises congenital renal disease that results in fetal anhydramnios by 22 weeks of gestation. It occurs in over 1 in 2000 pregnancies and affects 1500 families in the US annually. EPRA was historically considered universally fatal due to associated pulmonary hypoplasia and neonatal respiratory failure. There are several etiologies of fetal renal failure that result in EPRA including bilateral renal agenesis, cystic kidney disease, and lower urinary tract obstruction. Appropriate sonographic evaluation is required to arrive at the appropriate urogenital diagnosis and to identify additional anomalies that allude to a specific genetic diagnosis. Genetic evaluation variably includes karyotype, microarray, targeted gene testing, panels, or whole exome sequencing depending on presentation. Patients receiving a fetal diagnosis of EPRA should be offered management options of pregnancy termination or perinatal palliative care, with the option of serial amnioinfusion therapy offered on a research basis. Preliminary data from case reports demonstrate an association between serial amnioinfusion therapy and short-term postnatal survival of EPRA, with excellent respiratory function in the neonatal period. A multicenter trial, the renal anhydramnios fetal therapy (RAFT) trial, is underway. We sought to review the initial diagnosis ultrasound findings, genetic etiologies, and current management options for EPRA.     

Prenatal diagnosis of hemoglobinopathies in twin pregnancies by double simultaneous fetoscopy

A new technique for sampling fetal blood in twin pregnancies using two fetoscopes simultaneously is described. Two fetoscopes were inserted, one after the other, into both amniotic cavities and fetal blood samples were obtained from either the chorionic plate vessels or the umbilical cord insertion area. The observation of the bright tip of the second fetoscope behind the septum using the first fetoscope assured the successful entry of the two fetoscopes into the two different amniotic sacs. This technique was performed on 15 out of 17 patients. In all patients the fetuses were at risk of β-thalassemia major. Sampling was successful in all cases. Double simultaneous fetoscopy seems to be a safe and accurate technique without technical problems or complications. The simultaneous use of two fetoscopes opens new possibilities in intrauterine fetal surgery and research.     

Prenatal incision of ureterocele causing bladder outlet obstruction: a multicenter case series

We reviewed data from a cohort of fetuses with ureterocele diagnosed and operated prenatally in four fetal therapy centers. Inclusion criteria were (1) ureterocele confirmed on detailed fetal ultrasound examination, (2) absence of additional fetal malformations, and (3) fetal intervention to decompress the ureterocele with local institutional review boards' approval. Data on sonographic follow-up, obstetrical, neonatal outcome, and postnatal evaluation were collected. Ten cases of prenatally treated ureterocele are described. Six cases benefited from a fetoscopy for laser incision and decompression, two cases had an ultrasound guided puncture before resorting to a fetoscopy with laser incision, one case had a balloon catheterization under ultrasound guidance, and one case had an ultrasound-guided opening of the ureterocele with a laser fiber passed through a 20-gauge needle. Mean gestational age at diagnosis was 21.6 GW. Two cases underwent termination of pregnancy. The remaining eight cases recovered normal amniotic fluid volume and delivered a liveborn child at a mean gestational age of 38.6 GW with normal creatinine levels during the first week of life. Prenatal incision provided complete treatment of severely obstructive ureteroceles in 80% of the cases and allowed improvement of urinary electrolytes, renal size and echogenicity, bladder filling in all survivors, and recollection of normal amniotic fluid volume, in case of oligoanhydramnios. © 2017 John Wiley & Sons, Ltd.     

Feto-amniotic shunting—report of the experience of four european centres

Few reports concerning intrauterine shunting are available. We investigated the impact of this method. In order to evaluate intrauterine shunting and the complication rate for different indications, we sent a questionnaire to all German-speaking level 3 centres. In four level 3 centres, 52 intrauterine catheters were inserted in 34 fetuses. The indications were uni- or bilateral hydrothorax in nine cases, cystic adenomatoid malformation of the lung in four cases, infravesical stenosis in 13 cases, and fetal ascites in eight cases. In three cases (6 per cent), difficulties occurred when the drain was inserted. In 15 cases (29 per cent), the function of the drain was reduced by dislocation or occlusion. The mortality rate caused by shunting was as high as eight per cent (four cases). The application of an intrauterine shunt currently represents a rarely performed ultrasound-guided therapeutic intervention in the fetus. In all cases, the indication for shunting is to avoid compression of normal tissue by cystic structures. A high complication rate restricts the application of drainage to selected cases.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

Animal models of fetal renal disease

Fetal models of urinary tract disease have been used for many years and have provided unique and important insights into the pathophysiology of these conditions. This review will summarize the principal model systems used and the current directions of investigation. These models (including rabbit, opossum, sheep and recently swine) have demonstrated that in utero obstruction of the urinary tract alters renal growth, differentiation and produces stereotypical patterns of tissue response, particularly fibrosis. New molecular understanding of these processes has identified specific mechanisms that may be key elements in the development of renal dysfunction due to obstruction. These factors include the renin–angiotensin system (RAS) and its interaction with TGF-β in altering growth regulation and tissue fibrosis. These factors offer the prospect of clinical utility as markers of disease progression as well as pharmacologic therapy. Gene knockout systems have opened a new horizon of molecular models of congenital obstructive uropathy with insights into the role of the RAS in particular. It remains to be defined how closely these knockouts represent the human conditions they resemble. Continued application of fetal models of urinary obstruction, integrating large animal and knockout systems offers promise for improved diagnosis and treatment in these challenging conditions. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal ultrasonic findings in congenital chloride diarrhoea

In 3 fetuses affected by congenital chloride diarrhoea there were characteristic prenatal ultrasonic findings. In all cases the fetal abdominal cavity was filled with distended loops of fetal intestine, the fetal stomach was of normal size and polyhydramnios was present. The prenatal ultrasonic findings in this metabolic inherited disease are identical to those caused by mechanical obstruction of the distal fetal intestine. Whenever these findings are encountered prenatally, the possibility of chloride diarrhoea should be considered, because therapy with electrolytes is needed rather than the surgical intervention required in mechanical intestinal obstruction.     

Isolated fetal hydrothorax with hydrops: a systematic review of prenatal treatment options

Objective To evaluate the effect of prenatal therapeutic interventions on perinatal outcome in pregnancies complicated by isolated fetal hydrothorax with hydrops. Methods A systematic review of the literature from January 1982 to January 2006 of perinatal outcome in pregnancies with isolated fetal hydrothorax with hydrops with any form of prenatal treatment was conducted. Results Forty-four articles met our selection criteria, reporting a total of 172 fetuses treated prenatally. Reported treatment options were single (n = 13) or serial thoracocentesis (n = 18), thoraco-amniotic shunt placement (n = 100) or a combination of thoracocentesis and shunting (n = 36). Four case-reports described pleurodesis with OK-432, (n = 3) and intrapleural injection of autologous blood (n = 2). Overall survival rate was 63%, ranging from 54% for single thoracocentesis to 80% in the 5 cases treated with pleurodesis, without statistically significant differences between the treatment modalities. Shunt-placement with or without prior thoracocentesis was most often described, with survival rates of 67 and 61% respectively. Discussion The available literature consists exclusively of case reports and case series. This systematic review suggests that with prenatal intervention, perinatal survival rates around 63% are possible. There is a need for prospective, adequately controlled studies with long-term follow-up to determine the best treatment and more reliable outcome data in pregnancies complicated by fetal hydrothorax with hydrops. Copyright © 2007 John Wiley & Sons, Ltd.     

Alpha-fetoprotein and acetylcholinesterase are not predictive of fetal junctional epidermolysis bullosa,Herlitz variant

Junctional epidermolysis bullosa, Herlitz variant (junctional EB-Herlitz) is a lethal autosomal recessive skin disorder currently amenable to prenatal diagnosis only by direct analysis of fetal skin. However, elevated levels of alpha-fetoprotein, as well as the presence of acetylcholinesterase in amniotic fluid, have been associated with other severe fetal genodermatoses. Fetal skin samplings were performed in ten pregnancies at risk for fetal junctional EB-Herlitz, with three fetuses affected on the basis of electron microscopic detection of blisters within the lamina lucida and abnormal hemidesmosomes. In neither affected nor unaffected pregnancies were maternal serum or amniotic fluid alpha-fetoprotein levels elevated. Moreover, alphafetoprotein levels in both maternal serum and amniotic fluid were not statistically different comparing affected and unaffected fetuses. Acetylcholinesterase was not present in the amniotic fluid samples of the three affected pregnancies. Unlike other severe fetal genodermatoses, neither alpha-fetoprotein nor acetylcholinesterase was predictive of junctional EB-Herlitz.     

Detection and enumeration of colonic mucosal cells in amniotic fluid using a colon epithelial-specific monoclonal antibody

Since its introduction, prenatal diagnosis of chromosomal and metabolic disorder by mid-trimester amniocentesis has relied upon the use of a mixture of fetal cells obtained from amniotic fluid. Little knowledge has been gained in the sorting of these cells for diagnosis of tissue-specific disorders. In an attempt to determine the contribution of fetal colonic mucosal cells to the overall amniocyte population, we used the colonic epithelial-specific monoclonal antibody (MC-Ab) 7E₁₂H₁₂, IgM isotype. Specimens of the small intestine, colon, buccal mucosa, kidney, urinary bladder, and umbilical cord were obtained from electively aborted normal fetuses of 12–28 weeks' gestation. All of these specimens were examined with 7E₁₂H₁₂ by the immunoperoxidase technique. The MC-Ab reacted with the colonic epithelial cells but not with any of the other tissues. In addition, 40 amniotic fluid samples obtained from women between 16 and 18 weeks of gestation, who underwent amniocentesis because of advanced maternal age, were tested using a fluorescent activated cell sorter. Among the amniotic fluid specimens examined, 18·4 ± 10·3 percent cells reacted with 7E₁₂H₁₂. Double immunofluorescence studies revealed that all Mc-Ab-stained cells contained secretory component, confirming that they were epithelial in origin. All fetuses whose amniotic fluid was analysed had normal karyotypes and amniotic fluid alpha-fetoprctein levels that were also normal. This study demonstrates that cell-specific Mc-Ab can be used to detect colon cells in the amniotic fluid and that colon cells contribute significant numbers in the mixture of amniotic fluid cells. This technique could be helpful in the prenatal diagnosis of disorders in which the flow of amniotic fluid through the fetal intestine is impaired, such as cystic fibrosis, imperforate anus, Hirschsprung aganglionic megacolon, and intestinal atresia.