Efficacy of prenatal ultrasonography in diagnosing urogenital developmental anomalies in newborns.

BACKGROUND: Showing a prevalence rate of 0.5-0.8%, urogenital malformations discovered in newborns is regarded relatively common. The aim of this study is to examine the efficacy of ultrasound diagnostics in detecting developmental disorders in the urogenital system. METHODS: We have processed the prenatal sonographic and postnatal clinical details of 175 urogenital abnormalities in 140 newborns delivered with urogenital malformation according to EUROCAT recommendations over a 5-year period between 2006 and 2010. The patients were divided into three groups; Group 1: prenatal sonography and postnatal examinations yielded fully identical results. Group 2: postnatally detected urogenital changes were partially discovered in prenatal investigations. Group 3: prenatal sonography failed to detect the urogenital malformation identified in postnatal examinations. Urogenital changes representing part of certain multiple disorders associated with chromosomal aberration were investigated separately. RESULTS: Prenatal sonographic diagnosis and postnatal results completely coincided in 45%, i.e. 63/140 of cases in newborns delivered with urogenital developmental disorders. In 34/140 cases (24%), discovery was partial, while in 43/140 patients (31%), no urogenital malformation was detected prenatally. No associated malformations were observed in 108 cases, in 57 of which (53%), the results of prenatal ultrasonography and postnatal examinations showed complete coincidence. Prenatally, urogenital changes were found in 11 patients (10%), whereas no urogenital disorders were diagnosed in 40 cases (37%) by investigations prior to birth. Urogenital disorders were found to represent part of multiple malformations in a total of 28 cases as follows: prenatal diagnosis of urogenital malformation and the findings of postnatal examinations completely coincided in three patients (11%), partial coincidence was found in 22 newborns (79%) and in another three patients (11%), the disorder was not detected prenatally. In four newborns, chromosomal aberration was associated with the urogenital disorder; 45,X karyotype was detected in two patients, trisomy 9 and trisomy 18 were found in one case each. CONCLUSION: In approximately half of the cases, postnatally diagnosed abnormalities coincided with the prenatally discovered fetal urogenital developmental disorders. The results have confirmed that ultrasonography plays an important role in diagnosing urogenital malformations but it fails to detect all of the urogenital developmental abnormalities

Noninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanism

Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high-resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high-grade VUR

EXPERIMENTAL SHORT-TERM PARTIAL OBSTRUCTION OF THE FETAL SHEEP BLADDER OUTFLOW: II. COMPLIANCE AND CONTRACTILITY ASSOCIATED WITH URINARY FLOW IMPAIRMENT

Purpose Posterior urethral valves (PUV) is the commonest cause of congenital bladder outlet obstruction. Despite valve ablation in the neonatal period, up to 70% of patients develop renal failure by their teenage years, and progressive bladder dysfunction. This study forms part of a continuing project examining the relationship between severity and duration of obstruction and urinary tract dysfunction. Here is the assessed result of short-term (9-day) obstruction. Materials and methods Fourteen male fetal lambs at 75 days' gestation were assigned to one of three groups: urachal ligation, urachal ligation with partial urethral obstruction, sham-operated controls. Pregnancy proceeded for 9 days. At autopsy, filling cystometry was performed with the urinary tract in situ and the bladder harvested for nerve counts using PGP 9.5 immunohistochemistry, or in vitro measurement of contractile function. Results Obstruction was associated with an increase in bladder:fetal weight ratio. Compliance was variable in the obstructed bladders, but the calculated wall stress per unit strain was either similar or less than controls. Nerve-mediated or agonist-induced contraction magnitude in tissue from obstructed bladders and nerve counts did not differ from controls. Conclusions Nine days of outflow obstruction at mid-gestation generated a bladder of increased weight but without evidence of contractile failure. An increase in bladder compliance as a function of bladder growth was observed even at this stage, and represents one of the initial responses to outflow tract obstruction

EXPERIMENTAL SHORT-TERM PARTIAL OBSTRUCTION OF THE FETAL SHEEP BLADDER OUTFLOW: II. COMPLIANCE AND CONTRACTILITY ASSOCIATED WITH URINARY FLOW IMPAIRMENT

Purpose Posterior urethral valves (PUV) is the commonest cause of congenital bladder outlet obstruction. Despite valve ablation in the neonatal period, up to 70% of patients develop renal failure by their teenage years, and progressive bladder dysfunction. This study forms part of a continuing project examining the relationship between severity and duration of obstruction and urinary tract dysfunction. Here is the assessed result of short-term (9-day) obstruction. Materials and methods Fourteen male fetal lambs at 75 days' gestation were assigned to one of three groups: urachal ligation, urachal ligation with partial urethral obstruction, sham-operated controls. Pregnancy proceeded for 9 days. At autopsy, filling cystometry was performed with the urinary tract in situ and the bladder harvested for nerve counts using PGP 9.5 immunohistochemistry, or in vitro measurement of contractile function. Results Obstruction was associated with an increase in bladder:fetal weight ratio. Compliance was variable in the obstructed bladders, but the calculated wall stress per unit strain was either similar or less than controls. Nerve-mediated or agonist-induced contraction magnitude in tissue from obstructed bladders and nerve counts did not differ from controls. Conclusions Nine days of outflow obstruction at mid-gestation generated a bladder of increased weight but without evidence of contractile failure. An increase in bladder compliance as a function of bladder growth was observed even at this stage, and represents one of the initial responses to outflow tract obstruction

EXPERIMENTAL SHORT-TERM FETAL BLADDER OUTFLOW OBSTRUCTION: I. MORPHOLOGY AND CELL BIOLOGY ASSOCIATED WITH URINARY FLOW IMPAIRMENT

Purpose: In fetal sheep, combined urethral and urachal obstruction initiated at 75 days gestation and maintained for 30 days led to dysmorphic bladders similar to those found in humans with prune belly syndrome and to uniformly-disrupted kidney development. We aimed to create a less-severe model of fetal bladder outlet obstruction, more closely resembling infants with posterior urethral valves, and additionally to further our understanding of the role of the urachus. We hypothesized that milder morphological renal tract changes would occur after shorter-term experimental obstruction. Materials and Methods: Male fetal lambs were assigned to urachal and urethral ligation, urachal-only ligation or sham operations. Analyses were performed after nine days. Results: Concurrent urachal and urethral obstruction resulted in increased bladder weight, protein and DNA content. Detrusor smooth muscle was well-maintained, as assessed by light and electron microscopy, although urothelia showed basal apoptosis. Bladder obstruction led to hydronephrosis but failed to produce significant perturbations in urine osmolality. The nephrogenic cortex was either well-preserved or was replaced by glomerular cysts: the latter group tended to have heavier bladders. Urachal obstruction alone produced similar changes suggesting that the male sheep fetal urethra is a high-resistance conduit in midgestation. Conclusions: Concurrent urachal and urethral obstruction, or urachal obstruction alone, initiated in midgestation and maintained for nine days leads to bladder overgrowth but preserved renal tubular function. In future, it will be interesting to determine whether bladder decompression around this stage leads either to reversal of bladder overgrowth and/or ameliorates severe renal tract damage described after longer term fetal bladder outflow obstruction

EXPERIMENTAL SHORT-TERM FETAL BLADDER OUTFLOW OBSTRUCTION: I. MORPHOLOGY AND CELL BIOLOGY ASSOCIATED WITH URINARY FLOW IMPAIRMENT

Purpose: In fetal sheep, combined urethral and urachal obstruction initiated at 75 days gestation and maintained for 30 days led to dysmorphic bladders similar to those found in humans with prune belly syndrome and to uniformly-disrupted kidney development. We aimed to create a less-severe model of fetal bladder outlet obstruction, more closely resembling infants with posterior urethral valves, and additionally to further our understanding of the role of the urachus. We hypothesized that milder morphological renal tract changes would occur after shorter-term experimental obstruction. Materials and Methods: Male fetal lambs were assigned to urachal and urethral ligation, urachal-only ligation or sham operations. Analyses were performed after nine days. Results: Concurrent urachal and urethral obstruction resulted in increased bladder weight, protein and DNA content. Detrusor smooth muscle was well-maintained, as assessed by light and electron microscopy, although urothelia showed basal apoptosis. Bladder obstruction led to hydronephrosis but failed to produce significant perturbations in urine osmolality. The nephrogenic cortex was either well-preserved or was replaced by glomerular cysts: the latter group tended to have heavier bladders. Urachal obstruction alone produced similar changes suggesting that the male sheep fetal urethra is a high-resistance conduit in midgestation. Conclusions: Concurrent urachal and urethral obstruction, or urachal obstruction alone, initiated in midgestation and maintained for nine days leads to bladder overgrowth but preserved renal tubular function. In future, it will be interesting to determine whether bladder decompression around this stage leads either to reversal of bladder overgrowth and/or ameliorates severe renal tract damage described after longer term fetal bladder outflow obstruction