Z-scores of fetal bladder size for antenatal differential diagnosis between posterior urethral valves and urethral atresia.

OBJECTIVE: To construct reference values for fetal urinary bladder distension in pregnancy and use Z-scores as a diagnostic tool to differentiate posterior urethral valves (PUV) from urethral atresia (UA). METHODS: This was a prospective cross-sectional study in healthy singleton pregnancies aimed at constructing nomograms of fetal urinary bladder diameter and volume between 15 and 35 weeks' gestation. Z-scores of longitudinal bladder diameter (LBD) were calculated and validated in a cohort of fetuses with megacystis with ascertained postnatal or postmortem diagnosis, collected from a retrospective, multicenter study. Correlations between anatomopathological findings, based on medical examination of the infant or postmortem examination, and fetal megacystis were established. The accuracy of the Z-scores was evaluated by receiver-operating-characteristics (ROC)-curve analysis. RESULTS: Nomograms of fetal urinary bladder diameter and volume were produced from three-dimensional ultrasound volumes in 225 pregnant women between 15 and 35 weeks of gestation. A total of 1238 urinary bladder measurements were obtained. Z-scores, derived from the fetal nomograms, were calculated in 106 cases with suspected lower urinary tract obstruction (LUTO), including 76 (72%) cases with PUV, 22 (21%) cases with UA, four (4%) cases with urethral stenosis and four (4%) cases with megacystis-microcolon-intestinal hypoperistalsis syndrome. Fetuses with PUV showed a significantly lower LBD Z-score compared to those with UA (3.95 vs 8.83, P < 0.01). On ROC-curve analysis, we identified 5.2 as the optimal Z-score cut-off to differentiate fetuses with PUV from the rest of the study population (area under the curve, 0.84 (95% CI, 0.748-0.936); P < 0.01; sensitivity, 74%; specificity, 86%). CONCLUSIONS: Z-scores of LBD can distinguish reliably fetuses with LUTO caused by PUV from those with other subtypes of LUTO, with an optimal cut-off of 5.2. This information should be useful for prenatal counseling and management of LUTO. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Urethroplasty with balloon catheterization in fetal lower urinary tract obstruction: observational study of 10 fetuses.

OBJECTIVE: To present the preliminary outcomes of fetal urethroplasty using a coronary angioplasty balloon catheter in lower urinary tract obstruction (LUTO). METHODS: We included 10 consecutive male fetuses diagnosed with LUTO caused by presumed isolated posterior urethral valves (PUVs), who underwent urethroplasty with a balloon catheter in our center between 2015 and 2018. During urethroplasty, the fetal urethra was dilated using a balloon catheter (diameter, 0.014 inches; balloon size, 2 × 9 mm) inserted under ultrasonographic guidance via an 18-gauge needle introduced into the fetal bladder. RESULTS: Mean gestational age at the time of urethroplasty was 17.8 (range, 16.5-20.4) weeks. All fetuses survived the procedure without any complications and there was no case of preterm prelabor rupture of the membranes. The procedure was successful in 5/10 (50%) fetuses, while in the other five (50%), we were unable to insert the balloon catheter into the urethra. In the five successfully treated cases, mean gestational age at delivery was 38 (range, 36-40) weeks and presence of PUVs was confirmed after birth. All five neonates micturated spontaneously and presented with normal urine output after birth. During the follow-up period, the parameters of kidney function were within normal limits in two neonates, whereas signs of impaired renal function were seen in another two. The other was diagnosed with renal insufficiency and required kidney transplant with bladder sparing at 2 years of age. CONCLUSIONS: Urethroplasty with a balloon catheter is a new prenatal treatment option for fetuses with PUVs. By restoring fetal micturition, the procedure can preserve normal urinary bladder and kidney function. Although data on its efficacy and potential to differentiate the etiology of LUTO are sparse, a significant advantage of this method is its safety for the fetus and the mother. Even if the neonates develop renal insufficiency, they may be eligible for kidney transplant with connection to their own bladder, without the need for urostomy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiac findings and hemodynamic changes associated with severe lower urinary tract obstruction in utero.

OBJECTIVES: To describe fetal echocardiographic findings associated with lower urinary tract obstruction (LUTO) and to compare anatomic and hemodynamic measurements between fetuses with LUTO and gestational age (GA)-matched controls, with an emphasis on quantitative indices of diastolic function and cardiac output. METHODS: This was a retrospective cohort study of fetuses diagnosed with severe LUTO with giant bladder, which underwent at least one fetal echocardiogram at our center between January 2005 and June 2018. Fetuses with major congenital heart disease were excluded. Control fetuses did not have any structural or functional abnormalities and were GA-matched to the LUTO fetuses based on the time of the first fetal echocardiogram. Cardiac anatomy and hemodynamic measurements were compared between fetuses with LUTO and controls. In infants with LUTO, serial fetal and postnatal echocardiographic data were assessed, when available, and clinical outcomes were reviewed. RESULTS: Twenty-six fetuses with LUTO and at least one fetal echocardiogram available were identified, one of which was excluded due to hypoplastic left heart syndrome, leaving 25 LUTO fetuses in the final cohort. The mean GA at the first fetal echocardiogram was 25.4 ± 5.1 weeks in the LUTO group and 25.3 ± 5.0 weeks in the control group. Common findings in fetuses with LUTO included cardiomegaly (40%), pericardial effusion (44%), right ventricular (RV) hypertrophy (64%) and left ventricular (LV) hypertrophy (48%). Compared with GA-matched controls, LUTO fetuses had lower ascending aorta Z-score (-0.10 ± 0.94 vs -0.93 ± 1.03; P = 0.02) and aortic isthmus Z-score (-0.14 ± 0.86 vs -1.62 ± 1.11; P < 0.001), shorter mitral valve inflow time indexed to cardiac cycle length (0.46 ± 0.04 vs 0.41 ± 0.06; P = 0.002), and worse (increased) LV myocardial performance index (0.39 ± 0.03 vs 0.44 ± 0.04; P < 0.001). In addition, the ratio of RV to LV cardiac index was higher in LUTO fetuses compared with controls (1.62 ± 0.13 vs 1.33 ± 0.11; P < 0.001). Of the 25 LUTO pregnancies, two were lost to follow-up, three underwent elective termination of pregnancy and three ended in intrauterine fetal demise. Four (16%) patients had mildly hypoplastic left-heart structures, comprising two with aortic arch hypoplasia and two with mitral and aortic stenosis. CONCLUSION: In addition to presenting with cardiomegaly, pericardial effusion and ventricular hypertrophy, fetuses with LUTO demonstrate LV diastolic dysfunction and appear to redistribute cardiac output as compared to control fetuses, which may contribute to the development of left-heart hypoplasia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Perinatal Outcomes of Fetal Lower Urinary Tract Obstruction After Vesicoamniotic Shunting Using a Double-Basket Catheter.

OBJECTIVES: To evaluate the perinatal survival and renal function of fetuses with lower urinary tract obstruction (LUTO) who underwent vesicoamniotic shunting using a double-basket catheter METHODS: We retrospectively reviewed 32 fetuses with LUTO who underwent vesicoamniotic shunting using a double-basket catheter between 1998 and 2013. RESULTS: Among the 32 fetuses examined, 5 died because of termination of pregnancy, and 2 died in utero. The median gestational age at diagnosis was 15.5 (range, 10.0-27.3) weeks, and that at initial shunting was 17.1 (range, 12.3-32.2) weeks. Shunt dislocation or occlusion occurred in 18 of 42 procedures (42.8%). The median gestational age at delivery for the 25 live births was 35.5 (range, 28-40) weeks. Postnatal diagnosis revealed posterior urethral valves in 15 fetuses, a cloacal anomaly in 7, and urethral stenosis in 3. Three neonatal deaths occurred, resulting in an overall perinatal survival rate of 68.8% (22 of 32). The rates of normal renal function were 40.6% (13 of 32) at 28 days and 40% (10 of 25) at 2 years after birth. The absence of oligohydramnios after shunting was the only prognostic factor for normal renal function at 2 years (P < .05). CONCLUSIONS: Vesicoamniotic shunting may be helpful for fetuses with LUTO.

Fetoscopic laser surgery to decompress distal urethral obstruction caused by prolapsed ureterocele.

We report on the successful use of fetoscopic surgery to treat a case of prolapsed ureterocele in a female fetus. At 21 weeks' gestation, a double renal system with an intravesical ureterocele obstructing the bladder outlet was diagnosed, causing severe megacystis, bilateral hydronephrosis and progressive oligohydramnios. Ultrasound evaluation following referral to our center confirmed severe bilateral hydronephrosis with pelvic and calyceal dilatation, but amniotic fluid volume was normal and the ureterocele was not visualized in the bladder. Instead, a cystic mass within the external genitalia was observed, suggestive of a prolapsed ureterocele, causing intermittently severe obstruction of the urethra. The parents were counseled about the uncertain prognosis and fetal surgery to decompress the urinary system was proposed. The procedure involved firing a contact diode laser until perforation of the ureterocele was achieved. Following laser surgery, resolution of megacystis, reduction of hydronephrosis and normalization of amniotic fluid volume were observed. Our report demonstrates that fetoscopic decompression of a distal urethral obstruction is feasible in the rare event of congenital prolapsed ureterocele.

Fetal biomarkers for lower urinary tract obstruction secondary to posterior urethral valves.

Today, prenatal diagnosis of congenital urogenital malformations is mostly dependent on anatomical variations found on imaging. However, these findings can mislead us in telling us when to intervene, and about post-natal prognosis. Since many findings are dependent on multiple assessments, delayed diagnosis can occur, leading to less optimal outcomes compared to early intervention. Analyses of fetal urinary biomarkers have been proposed as a method of finding biological changes that are predictive for diagnosis and prognosis in fetuses at risk of kidney disease. We interviewed a group of researchers that have demonstrated that by combining multiple omics traits extracted from fetal urine, the biological variability found in single omics data can be circumvented. By analyzing multiple fetal urine peptides and metabolites at single time point, the prognostic power of postnatal renal outcome in fetuses with lower urinary tract obstruction is significantly increased. In this interview, we inquired about the technical aspects of the tests, challenges, and limitations the research group have come across, and how they envision the future for multi-omics fetal analysis in the clinic.

Fetal obstructive uropathy complicated by urinary ascites: outcome and prognostic value of fetal serum ß-2-microglobulin.

OBJECTIVES: To determine whether the prognostic value of fetal serum ß-2-microglobulin is altered and whether the occurrence of fetal urinary ascites prevents kidney damage in cases of fetal obstructive uropathy with urinary ascites. METHODS: This was a retrospective study of cases of fetal bilateral obstructive uropathy that occurred between 2006 and 2010, for which both fetal serum and ascites samples were sent to our laboratory for analysis. ß-2-microglobulin was assayed in both fetal serum and the corresponding ascites. Renal outcome was analyzed. Histological features of the kidney in cases of termination of pregnancy and renal function of liveborn infants were recorded. RESULTS: Fourteen cases with analysis of fetal serum and fetal ascites in a context of urinary obstruction were included. Renal outcome was unfavorable in eight cases (57%) and favorable in six (43%). When fetal serum ß-2-microglobulin was < 5 mg/L, renal outcome was favorable in all cases (4/4). When fetal serum ß-2-microglobulin was ≥ 5 mg/L, 8/10 cases (80%) had an unfavorable renal outcome (sensitivity, 100%; specificity, 66%). CONCLUSION: Fetal serum ß-2-microglobulin reliably predicts postnatal renal outcome in obstructive uropathy complicated by urinary ascites. Moreover, urine extravasation does not seem to protect fetal renal function.

Development of an animal model to study congenital urinary obstruction.

PURPOSE: We outline the development of a reliable model of obstructive uropathy in fetal lambs highlighting our understanding of the critical time points for interventions and the variability of any such model. We identify some discoveries that may have clinical implications. METHODS: The model requires 60-day-gestation fetal lambs. In lambs, glomerulogenesis is complete by 90 days gestation. (Term is 145 days.) The ability to develop a reliable method of creating bladder outlet obstruction in females, ligating both the urethra and urachus was critical. The lambs are bred to an accuracy of ±24 h. RESULTS: Creating the model at 50-60 days gestation, produces different expressions of renal dysplasia in groups of lambs undergoing identical interventions at the same stage of gestation. Early complete urethral obstruction can produce the Potter phenotype. An appropriately timed vesico-amniotic shunt preserves renal development, producing a shrunken, non-compliant bladder. Shunting the normal fetal bladder at 80 days gestation produces a similar bladder. Provision of a low-pressure valve in the shunt preserves bladder development and compliance. Using a high-pressure shunt produces results similar to non-shunted lambs. DISCUSSION: We developed a reliable animal model for obstructive uropathy. Being alert to peripheral results can lead to new findings.

Effectiveness of fetal cystoscopy as a diagnostic and therapeutic intervention for lower urinary tract obstruction: a systematic review.

OBJECTIVE: To determine the effectiveness of fetal cystoscopy in the prenatal diagnosis of and intervention for congenital lower urinary tract obstruction. METHODS: This study was a literature search using MEDLINE, Embase, Cochrane Library, MEDION, Web of Science reference lists and contact with experts. All studies reporting on fetal cystoscopy in lower urinary tract obstruction with data for a 2 × 2 table were selected for review. No language restrictions were applied. There was independent selection of studies, data extraction and quality assessment by two reviewers. Peto odds ratios were calculated as a summary measure of effect. RESULTS: A total of 2071 citations were identified and 66 papers selected for detailed evaluation, from which four papers with a total of 63 patients were selected for inclusion. Two papers had results for the use of cystoscopy in diagnosis, showing that fetal cystoscopy altered the ultrasound diagnosis of the underlying pathology in 36.4 and 25.0% of fetuses, respectively. Compared to no treatment, fetal cystoscopic intervention demonstrated an odds ratio for improved perinatal survival of 20.51 (95% CI, 3.87-108.69). However, comparing vesicoamniotic shunt (VAS) with fetal cystoscopy there appeared to be no significant improvement in the perinatal survival odds ratio of 1.49 (95% CI, 0.13-16.97). These results had wide CIs and for cystoscopy vs. VAS, all results crossed the line of no effect. CONCLUSION: There is little published evidence for the effectiveness of therapeutic fetal cystoscopy as an intervention for congenital lower urinary tract obstruction and the quality of this evidence is poor. It should thus be considered to be an 'experimental intervention' and subjected to further investigation.

Fetal cardiovascular effects of lower urinary tract obstruction with giant bladder.

OBJECTIVE: Lower urinary tract obstruction (LUTO) with massive bladder distension impacts on a variety of developing organ systems with consequent morbidity and mortality. The impact of LUTO on the fetal cardiovascular system has not previously been investigated. We hypothesize that a giant, distended bladder within the pelvis may cause vascular compression with observable consequences. METHODS: Fetal echocardiography was performed in 42 fetuses with LUTO and compared with 35 normal controls matched for gestational age. Parameters investigated included cardiothoracic ratio, presence or absence of ventricular hypertrophy and pericardial effusion. Doppler echocardiographic examination of mitral and tricuspid valve inflow and the ductus venosus was performed. To assess arterial vascular impedance, pulsatility indices (PIs) were calculated for segments of the descending aorta and right and left iliac arteries (RIA and LIA). RESULTS: In the LUTO group an increased cardiothoracic ratio was seen in nine (21%), ventricular hypertrophy in 12 (29%) and small pericardial effusion in 15 (36%). Filling characteristics of the right ventricle in the LUTO group demonstrated greater dependency upon atrial contraction, and ductus venosus flow demonstrated higher downstream impedance to filling, than in controls, suggesting altered compliance. The LUTO group also had lower distal descending aorta PI (1.53 ± 0.38 vs. 1.76 ± 0.44, P = 0.04), lower RIA-PI (1.31 ± 0.29 vs. 1.76 ± 0.44, P < 0.001) and lower LIA-PI (1.41 ± 0.44 vs. 1.73 ± 0.31, P < 0.01) than controls, suggesting vascular compression and increased impedance to flow. CONCLUSIONS: LUTO with giant urinary bladder compresses the iliac arteries, which may lead to increased afterload. Further study is warranted to examine the impact of fetal treatment such as bladder drainage on these cardiovascular parameters.

Fetal cystoscopy for severe lower urinary tract obstruction--initial experience of a single center.

OBJECTIVE: To report the experience with fetal cystoscopy and laser fulguration of posterior urethral values (PUV) for severe lower urinary tract obstruction (LUTO). METHODS: Between July 2006 and December 2008, fetal cystoscopy was offered to 23 patients whose fetuses presented with severe LUTO, favorable urinary analysis and gestational age <26 weeks. Fetal urinary biochemistry was evaluated before and after cystoscopy. All infants were followed 6-12 months after birth. Abnormal renal function was defined when serum creatinine higher than 50 micromol/L (2 Standard Deviation) or the necessity of dialysis or renal transplantation. Autopsy was always performed whenever fetal or neonatal deaths occurred. RESULTS: Eleven patients decided to undergo fetal therapy and 12 elected to continue with expectant observation. There was no difference between both groups in gestation age at diagnosis and referral examinations. Urethral atresia was diagnosed in 4/11 (36.4%) fetuses by fetal cystoscopy. At 26 weeks, fetuses that were managed expectantly presented with worse urinary biochemistry results (p < 0.05). Survival rates and percentage of infants with normal renal function were significantly higher in the cystoscopic group than in the expectant group (p < 0.05). CONCLUSIONS: Percutaneous fetal cystoscopy is feasible using a thinner special cannula for prenatal diagnosis and therapy of LUTO. Prenatal laser ablation of the PUV under cystoscopy may prevent renal function deterioration improving postnatal outcome.

Genetic and developmental basis for urinary tract obstruction.

Urinary tract obstruction results in obstructive nephropathy and uropathy. It is the most frequent cause of renal failure in infants and children. In the past two decades studies of transgenic models and humans have greatly enhanced our understanding of the genetic factors and developmental processes important in urinary tract obstruction. The emerging picture is that development of the urinary tract requires precise integration of a variety of progenitor cell populations of different embryonic origins. Such integration is controlled by an intricate signaling network that undergoes dynamic changes as the embryo develops. Most congenital forms of urinary tract obstruction result from the disruption of diverse factors and genetic pathways involved in these processes, especially in the morphogenesis of the urinary conduit or the functional aspects of the pyeloureteral peristaltic machinery.

An overview of the literature on congenital lower urinary tract obstruction and introduction to the PLUTO trial: percutaneous shunting in lower urinary tract obstruction.

Congenital lower urinary tract obstruction (LUTO) comprises a heterogeneous group of pathologies causing obstruction to the urethra, the most common being posterior urethral valves. Such pathology is often associated with high perinatal mortality and varying degrees of perinatal and infant morbidity. A high proportion of LUTO may be visualised during routine second trimester (and first trimester) ultrasound giving rise to the possibility of determining individual fetal prognosis and treatments such as vesico-amniotic shunting, with a view to altering pathogenesis. The aims of the percutaneous shunting in low urinary tract obstruction (PLUTO) trial are to determine the effectiveness of these treatments and accuracy of the investigations with the primary outcome measures being perinatal mortality and postnatal renal function.

Prenatal extravasation of urine seems to preserve renal function in boys with posterior urethral valves.

INTRODUCTION: A posterior urethral valve (PUV) may lead to extravasation of urine, resulting in prenatal ascites and/or perirenal urinoma. Extravasation has been presumed to act as a pop-off mechanism, preserving renal function, but previous reports addressing this presumption have been inconclusive. AIM OF STUDY: The present study compares renal function in patients with PUV with and without extravasation. MATERIAL AND METHODS: Sixty boys with a confirmed diagnosis of PUV as neonates (gestational age [GA]<44 weeks) throughout 2001-2016 were included. Clinical data were collected from medical records. Renal function was assessed by nadir plasma creatinine, creatinine at the last follow-up, and glomerular filtration rate (GFR) at the last follow-up. The GFR was estimated using the Schwartz formula. Renal function was classified according to the kidney disease: improving global outcomes (KDIGO) guidelines' grades of chronic kidney disease (CKD). Glomerular filtration rate > 90 ml/min/1.73m2 at the last follow-up was classified as normal renal function. RESULTS: Twelve patients (20%) had ascites and/or urinoma, and 48 (80%) did not. GA and birth weight were not different in patients with and without extravasation. PUV was suspected from prenatal ultrasound findings in 66.7% of the patients in both groups. Median nadir creatinine was 21 (range, 11-33) µmol/L in boys with ascites/urinoma, and all values were within the age-adjusted reference values. Nadir creatinine was 23 (14-199) µmol/L in boys without extravasation, and it was above the normal range in 14 boys. The incidence of elevated nadir creatinine was significantly different in the two groups (p < 0.025). One of the 12 patients with extravasation developed chronic renal failure (CKD 3). In the group of 48 patients without extravasation, 20 (42%) had chronic renal failure grade 2-5, and among these, 5 patients have had a renal transplant (CKD grade 5). The prevalence of CKD grade 2-5 was statistically different in the two groups (p = 0.03). These findings are presented in the summary figure. CONCLUSION: Extravasation of urine was found in 12 of 60 (20%) boys with PUV. These patients had significantly lower prevalence of CKD at the last follow-up than patients without extravasation. This finding is important in prenatal counseling. It also indicates that prenatal decompression of the bladder and upper tract is beneficial in patients with PUV, which is relevant to the discussion of prenatal intervention in these fetuses.

Endoscopic fetal urethrotomy for anterior urethral valves: a preliminary report.

Anterior urethral valves are a rare congenital anomaly associated with distal urethral obstruction, which can result in a poor prognosis. We report on the endoscopic creation of a fetal urethrotomy for obstructive uropathy resulting from anterior urethral valves. A 33-year-old woman was evaluated at 17 weeks gestation due to fetal megacystis. The diagnosis of anterior urethral valves was confirmed by the characteristic sonographic feature of a dilated membranous penile urethra. Oligohydramnios with normal-appearing kidneys and favorable urinary electrolytes led to fetal intervention. Ablation on the ventral site of the fetal penis for a cutaneous urethrotomy was performed using a YAG laser under a 1-mm fetoscope at 19 weeks gestation. Urine was drained from the incision and the dilated penis and the distended bladder shrunk with an increase in amniotic fluid. However, the fetus died unexpectedly on postoperative day 3, and chorioamnionitis was suspected as the etiology. While the outcome was unfavorable, our preliminary experience shows that fetal urethrotomy for obstructive uropathy can be achieved in utero using an endoscopic laser approach. Further experience will be required to evaluate the therapeutic value of this new procedure in the management of fetal anterior urethral valves.

Pulmonary endocrine cells in hypoplastic lungs due to foetal urinary tract obstruction: a microscopic immunohistochemical study.

METHODS: We performed a urinary tract obstruction (UTO) surgical procedure at 93-107 days' gestation in lambs to investigate the relationship between pulmonary hypoplasia and the appearance of pulmonary endocrine cells by quantitative analysis of respiratory tract cells using light microscopic immunohistochemistry. RESULTS: UTO produced a significant reduction in lung weight, lung/body weight ratio, air capacity, air capacity/body weight ratio (p < 0.01) and radial alveolar count (p < 0.05), which indicated the presence of lung hypoplasia. These foetuses also showed a significant increase in the number of neuron-specific enolase (NSE)-positive pulmonary endocrine cells, expressed as the number of NSE-positive cells per bronchus (p < 0.01) or bronchiole (p < 0.05), the number of NSE-positive cells per unit perimeter of bronchus or bronchiole (p < 0.01), and the number of NSE-positive cells per unit bronchial or bronchiolar surface area (p < 0.01). CONCLUSION: These results suggest that UTO significantly retards and modifies the structural growth and functional development of pulmonary endocrine cells in NSE expression. We speculate that pulmonary endocrine cells and their mediators may play a role in the problems associated with UTO during intrauterine life.

Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy.

BACKGROUND: In our fetal lamb model of lower urinary tract obstruction, a pressure limited shunt preserves bladder function and renal development. This study investigates the effects on pulmonary histology. METHODS: We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared pulmonary histology in 4 groups: group A, OU without shunt; group B, pressure limited shunt; group C, non-valved shunt. Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS: We compared 27 fetuses: 7 fetuses in group A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There was no significant difference in lung volume in any group. In group A, there were some areas of atelectasis and incomplete alveolar formation histologically. The alveoli in group A lambs lungs had a predominance of type II cells, whereas group B lambs lungs were lined by type I epithelial cells and were essentially indistinguishable from controls. CONCLUSIONS: This study suggests that using a pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the lungs.

Biochemical diagnosis in prenatal uropathy.

Thirty-two fetuses, six with prune-belly syndrome, seven with renal cyst, 19 with obstructive uropathy, underwent intrauterine fluid aspiration during weeks 15-37 of gestation. Fluid samples were analysed for Na, K, creatinine, urea, alpha 1-, and beta 2-microglobulin. Aspirate concentrations of sodium below 130 mmol/L and creatinine above 115 mumol/L indicate an active kidney and exclude a renal cyst. However, aspirates from fetal cysts or fetuses with obstructive uropathy showed analyte concentrations for sodium, potassium, creatinine, and urea corresponding to extracellular fluid (ECF). In conclusion fluid aspirates of fetuses with ultrasonographically detectable cystic cavities in the abdomen should be examined for sodium and creatinine to assess remaining renal function for planning of obstetric management.

A fetal lamb model of partial urethral obstruction: experimental protocol and results.

The functional effects of bladder outlet obstruction in the developing urinary tract are well recognized in patients born with posterior urethral valves, in whom a spectrum of bladder dysfunction has been described. To better understand the changes occurring in the partially obstructed developing lower urinary tract, a fetal lamb model of partial urethral obstruction was developed. Fetal lambs at 90 days' gestation underwent surgical placement of a silver ring (ex utero) at the level of the proximal bladder neck, with concomitant ligation of the urachus. Control animals underwent urethral ligation only. The lambs were then allowed to go through normal gestation, and ewes were delivered spontaneously. The animals were studied between 2 and 7 days after birth. The postmortem examination showed that the ring was just distal to the bladder neck, around the proximal urethra. This resulted in gradual, partial occlusion of the urethra. Bladder weights, bladder wall thickness, and bladder capacity were significantly increased in the partially obstructed animals as compared with the controls. There was little or no upper tract dilatation in the obstructed group. This animal model, the first to produce gradual outflow obstruction in the fetus, provides a reproducible model of partial urethral obstruction. The model can be used to assay the biochemical and physiological changes found in the developing urinary tract of fetal lambs submitted to intravesical obstruction.

Creation of experimental urethral obstruction in utero: evaluation of fetal renal function.

Management of obstructive uropathy diagnosed in utero would be markedly enhanced by the availability of a simple, safe and quantitative fetal renal function test to predict postnatal renal function. In order to allow experimental evaluation of such a parameter, we adjusted a model of complete urethral obstruction with urachal ligation in 30 fetal lambs at 79 or 99 days of gestation. The method described allows obstruction in male and female fetuses as early as 79 days of gestation, with an overall high survival rate (control: 12/14; obstructed: 23/29), although lower (6/12) when obstruction is performed early (79 days) during gestation. Consequences of obstruction were examined on the 121st day of gestation. Severe hydronephrosis, ureteral and calyceal dilatation, with or without ascites and pulmonary hypoplasia were observed in all fetuses; creatinine clearance determined in utero was decreased in both groups with obstruction (early and late) vs control group: 1.15 +/- 0.5, NS, and 0.58 +/- 0.4, p < 0.01 vs 1.61 +/- 0.8 ml/min/kg respectively. In both obstructed groups, fetuses with ascites displayed lower plasma creatinine concentration and higher creatinine clearance values when compared to fetuses without ascites. In conclusion, the experimental model of obstructive uropathy described appears efficient and easily reproducible, allowing therefore the evaluation of a predictive parameter of postnatal renal function. Our preliminary results suggest that renal fetal function is more dependent on the degree of obstruction than on the term of its creation.