Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb.

BACKGROUND: Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques. METHOD: OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10. RESULTS: Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model. DISCUSSION: PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.

Muscle imbalance as a cause of scoliosis: a study in a fetal lamb abdominal wall defect model.

BACKGROUND: We created abdominal wall defects (AWD) in fetal lambs to investigate possible causes of scoliosis. METHODS: We incised the upper abdominal wall (including Rectus) in 60-day gestation fetal lambs, from the midline to either the right (Group A) or left (Group B) costal margin, in 14 lambs carried by 7 ewes. They were delivered by cesarean section at term (about 145 days). Scoliosis was evaluated by anterio-posterior X-rays, determining the Cobb angle. RESULTS: Four fetuses in Group A and 3 in Group B survived. There were 3 successful AWD lambs Group A and 2 in Group B. One lamb in each group survived with the AWD covered with a thick capsule. The convexity of spinal curve was the direction of scoliosis. Right scoliosis was only seen in the 4 Group A lambs. Left scoliosis was only seen in Group B lambs (2/3, 67%). The mean Cobb angle was 41.7 ± 11.5° in Group A and in Group B the Cobb angles were 59.6o and 60.6°. Overall, 4/5 lambs with organ prolapse (80%) and both lambs without organ prolapse had scoliosis. CONCLUSION: Muscle imbalance may contribute to the development of scoliosis in a fetal lamb AWD model.

The Expression of Transcription Factors in Fetal Lamb Kidney.

(1) Background: Renal development involves frequent expression and loss of transcription factors, resulting in the activation of genes. Wilms' tumor 1 (WT1), hepatocyte nuclear factor-1-beta (HNF1ß), and paired box genes 2 and 8 (Pax2 and Pax8) play an important role in renal development. With this in vivo study, we examined the period and location of expression of these factors in renal development. (2) Methods: Fetal lamb kidneys (50 days from gestation to term) and adult ewe kidneys were evaluated by hematoxylin and eosin staining. Serial sections were subjected to immunohistochemistry for WT1, HNF1ß, Pax2, and Pax8. (3) Results: Pax2, Pax8, and HNF1ß expression was observed in the ureteric bud and collecting duct epithelial cells. We observed expression of WT1 alone in metanephric mesenchymal cells, glomerular epithelial cells, and interstitial cells in the medullary rays and Pax8 and HNF1ß expression in tubular epithelial cells. WT1 was highly expressed in cells more proximal to the medulla in renal vesicles and in C- and S-shaped bodies. Pax2 was expressed in the middle and peripheral regions, and HNF1ß in cells in the region in the middle of these. (4) Conclusions: WT1 is involved in nephron development. Pax2, Pax8, and HNF1ß are involved in nephron maturation and the formation of peripheral collecting ducts from the Wolffian duct.

A new approach using image analysis to assess pulmonary hypoplasia in the fetal lamb diaphragmatic hernia model.

BACKGROUND: In congenital diaphragmatic hernia (CDH), there is pulmonary hypoplasia (PH) and also pulmonary vascular and bronchial abnormalities. Few studies have investigated bronchial maldevelopment in CDH. We evaluated bronchial area (BA) by bronchography in a fetal lamb DH model to develop a measure of PH. METHODS: We created DH in fetal lambs at 75 days gestation, delivering by cesarean section and killing them at term (DH, n = 12). Normal term fetuses provided controls (C, n = 5). We measured total lung volume (TLV) and performed barium bronchography. Using image analysis, BA, total lung area (TLA) and bronchial area/lung area ratio (B/L ratio) were calculated. Student's T test (p < 0.05; significant) and Spearman's correlation coefficient were performed. RESULTS: TLV (ml) was 133.3 ± 41.2 in DH and 326 ± 22.5 in C (p = 0.0000001). TLA (cm2) was 78.8 ± 17.4 in DH and 107.1 ± 10.3 in C (p = 0.006). BA (cm2) was 39.6 ± 11.9 in DH and 52.2 ± 7.7 in C (p = 0.019). The B/L ratio was 0.45 ± 0.06 in DH and 0.49 ± 0.05 in C (p = 0.28). There are correlations in DH between TLV and TLA (r = 0.79), TLV and BA (r = 0.73) and in C between TLV and TLA (r = 0.97) and TLV and BA (r = 0.67). CONCLUSION: It may be possible to assess PH on fetal MRI, given the correlation between TLV and TLA, and TLV and BA.

The role of the ureteric bud in the development of the ovine fetal kidney.

BACKGROUND: The kidney develops from an intimate interaction between the ureteric bud and the metanephric mass. We attempted to differentially stain the derivatives of the ureteric bud and the metanephric mass in ovine fetuses. METHODS: After appropriate approval, 47 fetal lambs' kidneys at 50 (4), 60 (6), 70 (5), 80 (4), 100 (10), 110 (8), 145 (10) days' gestation (term is 140-145 days) were obtained. After confirming the pregnancy, the sheep were anesthetized, and the fetuses sacrificed. The fetal kidneys were prepared for histological examination, using immunostaining for ß-catenin, Laminin, CK34ßE12, CK7, E-cadherin, and EMA. RESULTS: In the nephrogenic zone, positive staining was only seen for ß-catenin and Laminin. Areas with linear ß-catenin expression increased with increasing gestational age, whereas cytoplasmic granular expression in the nephrogenic zone diminished. At 50 days, Laminin-positive cells appeared in the ureteric bud epithelial cells, but not in the proximal tubule epithelium. They were found only in the immature collecting duct at 60 days. CONCLUSION: We have shown that the distribution of ß-catenin and Laminin positive-stained cells initially appearing in the ureteric bud changes with gestational age. Further studies may help inform the optimal timing of fetal shunt insertion in obstructive uropathy.

Evaluation of alveolar epithelial cells in the sheep model of congenital diaphragmatic hernia: Type 1 alveolar epithelial cells and histopathological image analysis.

BACKGROUND: There are few reports comparing type 1 alveolar epithelial cell development with histopathological image analysis. We investigated these as indicators of maturity in fetal lambs' lungs in a congenital diaphragmatic hernia (CDH) model. METHODS: We created left CDH in 4 fetal lambs at 75 or 76days' gestation (Group A). Controls were 5 sham-operated lambs (Group B); both groups delivered at term. The right lower lung lobe (RLL) and left lower lobe (LLL) were sampled. Using histopathological image analysis, alveoli/air sacs count (AC), alveoli/air sacs area percentage (AP), average area (AA), total area (TA), and perimeter (PM) were determined. We also evaluated total lung volumes, radial alveolar count (RAC), and Type 1 alveolar epithelial cells ratio (AT1 ratio), which we previously reported. Regression analysis was performed, with p<0.05 considered significant. RESULTS: RLL and LLL AT1 ratio and LLL RAC in Group A were lower than in Group B. There are no significant differences demonstrated by histopathological image analysis. In Group A, the AT1 ratio in the LLL was lower than in the RLL. There were no differences between LLL and RLL in Group B. CONCLUSION: AT1 ratio was superior to the other indicators evaluating lung maturity.

Does a large abdominal wall defect affect lung growth?

BACKGROUND/PURPOSE: Respiratory distress in babies with large abdominal wall defects suggests a relationship to decreased diaphragmatic movement. We evaluated pulmonary development in a fetal lamb gastroschisis model. METHODS: We created gastroschisis in 25 fetal lambs at 60days gestation (group A). Controls were 14 nonoperated lambs. (Group B) were all delivered at term. Lung volume, histology, and type 1 (AT1)/type 2 (AT2) cell ratios (AT1 ratio) were determined. We subdivided group A, comparing lambs with a large defect and scoliosis [group A (S)] with the remainder [group A (NS)]. RESULTS: Twenty-five lambs survived (11 fetuses in group A and 14 fetuses in group B). Lung volume in group A (S) was less than in group A (NS) (p<0.05). The AT1 ratio in group A was lower than in group B (p<0.01), without any difference in radial alveolar counts (RACs) or alveolar growth, and no association between scoliosis and alveolar differentiation. CONCLUSION: Gastroschisis in a sheep model reduces the AT1 ratio but not the RAC. Severe scoliosis affects lung volume but not the AT1 ratio, suggesting reduced diaphragmatic movement in fetuses with large abdominal defects.

Intestinal perforation in premature neonates: The need for subsequent laparotomy after placement of peritoneal drains.

AIM: In view of recent studies questioning the usefulness of peritoneal drainage (PD) in premature neonates with pneumoperitoneum, suggesting approximately 75% of those treated with PD needed delayed laparotomy, we reviewed the requirement for laparotomy after initial PD at our institution. METHODS: Retrospective cohort of all premature infants with a diagnosis of intestinal perforation (ICD Code P78.0) from 1995 to 2012. Inclusion criteria were pneumoperitoneum on x-ray (isolated perforation or necrotising enterocolitis), birthweight <1800 g and gestational age <33 weeks. RESULTS: Fifty patients met the criteria (38 PD, 12 primary laparotomy). Thirty-two per cent (95% CI 18-49%) received secondary laparotomy after initial PD. There was no significant difference when stratified according to isolated perforation (24%) versus necrotising enterocolitis (56%, P = 0.11). There was no significant difference between PD and primary laparotomy for time to full enteral nutrition, hazard ratio (HR) 0.99 (95% CI 0.48-2.04) or mortality, HR 2.15 (95% CI 0.48-9.63). The HR for mortality was partly confounded by birthweight, birthweight-adjusted HR 1.52 (95% CI 0.32-7.23). CONCLUSIONS: Thirty-two per cent of neonates treated with primary PD received secondary laparotomy, with no significant difference in key outcomes. Primary PD still appears to be of benefit for those without features of necrotising enterocolitis.

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.

Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney?

BACKGROUND: In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal 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 renal histology in 4 groups: group A-OU without shunt, group B-low-pressure shunt (15-54mmH2O), group C-high-pressure shunt (95-150mmH2O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS: We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group. CONCLUSIONS: V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells.

Position statement on fetal myelomeningocele repair.

Following the promising multicenter randomized trial results of in utero fetal myelomeningocele repair; we anticipate that an increasing number of tertiary care centers may want to offer this therapy. It is essential to establish minimum criteria for centers providing open fetal myelomeningocele repair to ensure optimal maternal and fetal/pediatric outcomes, as well as patient safety both short- and long-term; and to advance our knowledge of the role and benefit of fetal surgery in the management of fetal myelomeningocele. The fetal myelomeningocele Maternal-Fetal Management Task Force was initially convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to discuss the implementation of maternal fetal surgery for myelomeningocele. The decision was made to develop the optimal practice criteria presented in this document for the purpose of medical and surgical leadership. These criteria are not intended to be used for legal or regulatory purposes.

Valved shunt as a treatment for obstructive uropathy: does pressure make a difference?

PURPOSE: A valved ventriculo-peritoneal shunt (V-P shunt) as a vesico-amniotic shunt (V-A shunt) preserves the filling/emptying cycle and normal bladder development in fetal lambs with bladder outlet obstruction. The optimal pressure for such shunts is unknown. MATERIALS AND METHODS: We created obstructive uropathy in 60-day gestation fetal lambs. A V-A shunt was placed 3 weeks later, using a low-pressure (Group L: 15-54 mmH2O) or a high-pressure (Group H: 95-150 mmH2O) V-P shunt. We included non-shunted (obstructive uropathy, Group O) and control lambs (Group C). All were delivered at 130 days. Bladder volumes, bladder thickness, renal and bladder histology were compared. RESULTS: Seventeen lambs had an obstructive uropathy created. Five Group L (four survived), four Group H (three survived) and five Group O survived. Body weight and crown-to-rump lengths of the three groups were not significantly different. Group H lambs had a dilated urachus, urinary ascites and severe ureteral dilatation similar to Group O lambs. There were four Group C lambs. Bladder volume was 10, 15 and 1,150 ml in Group H, 115 ± 67.9 ml in Group L, 128 ± 99.8 ml in Group O and 24.5 ± 3.84 ml in Group C. Unlike Group O lambs, Group L did not have urinary ascites, urinomas or renal dysplasia. CONCLUSION: Low-pressure shunts preserved both bladder volume and renal development. High-pressure shunts did neither.

Bladder development following bladder outlet obstruction in fetal lambs: optimal timing of fetal therapy.

BACKGROUND: Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity. METHODS: We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain. RESULTS: The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent. CONCLUSION: The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.

Can a pressure-limited vesico-amniotic shunt tube preserve normal bladder function?

INTRODUCTION: We have previously shown that a vesico-amniotic shunt (V-A shunt) produces fibrotic bladders with poor compliance in normal fetal lambs. We hypothesized that using a ventriculo-peritoneal shunt (V-P shunt) as a V-A shunt in normal bladders may preserve the filling/emptying cycle and normal bladder development. MATERIALS AND METHODS: The V-A shunting in normal fetal lambs was performed at 74 days of gestation using a V-P shunt (group A) and a free-draining shunt tube (group B). Sham-operated lambs were used as controls (group C). They were all delivered at term (145 days), and the pressure-volume curve, bladder volume, and histologic features of the bladder wall were compared. RESULT: The mean bladder volume in group B (n = 5), 5 +/- 2.4 mL, was significantly smaller (P < .01) than that in group A (n = 6), 53 +/- 14 mL, and group C (n = 10), 57.3 +/- 12 mL. The bladder wall thickness in group A was 338 + 94.2 microm; group B, 741 +/- 128 microm; and group C, 374 +/- 120 microm. Group B bladders had very poor compliance with thick bladder wall (P < .01). Histologically, group B bladders showed prominent submucosal fibrotic change, but group A bladders were similar to controls. CONCLUSION: This study shows that a pressure-limited shunt tube for V-A shunting preserves the normal fetal bladder development.

Evaluation of sonographic diagnostic criteria for placenta accreta.

PURPOSE: To compare the diagnostic value of reported sonographic criteria for placenta accreta and to develop a composite score system for antenatal evaluation. METHOD: Sixty-six women at risk for placenta accreta were examined for 9 cases of placenta accreta that were confirmed at delivery. The performance of previously reported gray-scale and Doppler sonographic criteria for the diagnosis of placenta accreta was analyzed individually. A composite score system was developed by combining selected sensitive or specific sonographic criteria, and its performance was evaluated. RESULTS: The criteria of obliteration of retroplacental clear space, a myometrial thickness of <1 mm, presence of vessels bridging placenta and uterine margin, disruption of the placental-uterine wall interface, and vessels crossing the sites of interface disruption showed a statistically significant association with placenta accreta. The disruption of the placental-uterine wall interface and the presence of vessels crossing these sites were the only 2 individual criteria that could distinguish placenta accreta from non-accreta, which could also be achieved by our composite score system using a cutoff value of 40, with a sensitivity of 89% and specificity of 98%. CONCLUSION: The diagnostic performance of the sonographic diagnostic criteria used in the diagnosis of placenta accreta varies, and a composite score system improves the overall accuracy.

The maternal outcome in placenta accreta: the significance of antenatal diagnosis and non-separation of placenta at delivery.

AIM: To evaluate the effects of antenatal diagnosis and subsequent placental non-separation at delivery on the maternal outcome in confirmed cases of placenta accreta. METHOD: The perinatal database and medical records for women who delivered in the period 2000-6 in a teaching hospital in New Zealand with a diagnosis of placenta accreta or postpartum haemorrhage or hysterectomy were reviewed. In confirmed placenta accreta cases, the amount of blood loss and blood transfused at delivery and subsequent emergency hysterectomy were analysed in respect to the presence/absence of antenatal diagnosis and the management at delivery. RESULTS: 16 women had placenta accreta confirmed (15 histologically and 1 visually). Antenatal diagnosis was made in 7 women, elective Caesarean delivery planned in all, hysterectomy to follow in 5 (4 elective, 1 emergency preterm), and elective placental separation in 2 women. When an antenatal diagnosis was not made (n=9), attempted placental separation led to emergency hysterectomy for all (p=0.001). Antenatal diagnosis and placental non-separation resulted in less mean blood loss (1.4 L vs 3.6 L, p=0.003; 1.0 L vs 3.4 L, p<0.001) and mean units of blood transfused (1.2 vs 5.1, p=0.005) in the latter. CONCLUSION: In placenta accreta, antenatal diagnosis and avoidance of placental separation may result in better maternal outcome.

Is a vesicoamniotic shunt intrinsically bad? Shunting a normal fetal bladder.

INTRODUCTION: We previously demonstrated that in utero vesicoamniotic shunting of obstructive uropathy in fetal lambs produces a shrunken noncompliant bladder. We hypothesized that the normal fetal bladder filling and emptying cycle in fetal life is critical to the development of normal bladder function. MATERIALS AND METHODS: We placed vesicoamniotic shunts in 4 normal fetal lambs at 74 days' gestation. The fetuses were delivered at term (145 days), and bladder volume and compliance were measured and compared with those measurements in 3 normal term fetuses. The lambs were then killed and the renal tracts and bladders removed submitted to histologic examination. RESULTS: All shunted lambs survived to term. Three normal control lambs were delivered at term. The mean bladder volume in shunted lambs was 4 +/- 2.8 mL (n = 4) compared with 60 +/- 17 mL (n = 3) in control lambs (P < .05). Bladders in the shunted lambs had very poor compliance compared with normal lambs' bladders. Histologic examination of the shunted bladders showed increased fibrosis and distortion of the muscle layers compared with control bladders. CONCLUSION: Even in the absence of obstruction, preventing normal bladder filling and emptying in fetal life produces fibrotic bladders with poor compliance.

Pressure-limited vesico-amniotic shunt tube for fetal obstructive uropathy.

INTRODUCTION: In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development. MATERIALS AND METHODS: We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology. RESULTS: Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 +/- 41 mL with a valve shunt and 8.8 +/- 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 +/- 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt. CONCLUSION: A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb.

Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick-walled, poorly compliant bladder. We report the early histological changes in the obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. Vesicostomy or vesico-amniotic shunt tube insertion and biopsy of the bladder wall were performed 21 days later. The fetuses were delivered at term (145 days) and the kidneys and bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle actin (alpha-SMA) immunohistochemical stains were used for these samples. Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt failure or missed urachal ligation) were excluded. All biopsies taken at shunting had positive Col Fe and alpha-SMA. Term lambs had mild multicystic dysplastic kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All bladders had small volume and were severely fibrotic. Fetal shunt operations 3 weeks after the creation of obstructive uropathy provided partial preservation of renal histology but did not preserve normal bladder histology. We suggest that the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts in the dilated fetal bladder wall at the time of shunting results in irreversible damage to the developing bladder muscle and fibrosis.

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective.

PURPOSE: The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention. METHODS: We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination. RESULTS: Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 +/- 5 mL) compared with controls (71 +/- 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis. CONCLUSIONS: In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.