Current strategies to predict and manage sequelae of posterior urethral valves in children

Summary Background Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO. Methods In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. Findings 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. Interpretation Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. Funding UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).

One hundred and fourteen boys with posterior urethral valves were treated between 1966 and 1975. Four died during the first hospital admission, 6 died from renal failure during childhood, 1 died from other causes and 15 were lost to follow-up. Eighty-eight were reviewed 11 to 22 years after diagnosis and the renal outcome of 98 patients is therefore known. Approximately one-third of patients presented under 1 month of age, between 1 month and 1 year, and over 1 year respectively. Bilateral vesicoureteric reflux was observed in one-quarter of the boys, more frequently in those presenting in the first month of life. Half of the patients were treated by primary valve ablation and half underwent temporary upper tract diversion: the outcome was worse for the diverted group. One-third of the boys had a long-term bad outcome for renal function. This outcome was associated with early presentation, bilateral vesicoureteric reflux and day-time urinary incontinence after the age of 5 years. The association of bad outcome with incontinence points to continuing bladder dysfunction as a major determinant of long-term outcome for renal function.

We reviewed the literature to better elucidate the history behind our understanding of the anatomy, classification and embryology of posterior urethral valves. A directed MEDLINE literature review of the anatomy, classification and embryology of posterior urethral valves was performed. An effort was made to focus on the most frequently cited historical articles as well as those including detailed anatomical analyses of fetal specimens. Also included was the analysis of a specimen obtained at our institution in a novel manner that to our knowledge has not been previously described in the literature with respect to the anatomy of posterior urethral valves. The precise origins regarding the anatomy and embryology of posterior urethral valves remain undefined. However, the literature is abundant in theories regarding the origin of posterior urethral valves, based primarily on small uncontrolled series or case reports. There are a limited number of reports of the anatomy of posterior urethral valves in methodical fashion using reproducible scientific techniques such as histopathology. These reports are invaluable for providing a foundation of how to properly study and define the origins of posterior urethral valves. Elucidating this most fundamental feature of a congenital condition central to the practice of pediatric urology is essential. More well designed studies specifically with this goal in mind are necessary. Incorporating new reconstructive imaging modalities may assist us in pinpointing the elusive origins of the embryology and anatomy of posterior urethral valves.