International Journal of Nephrology 28 weeks of gestation, shunts have limited obstetric compli- cations; however there are still a high percentage of mechan- ical complications [38]. Fetal cystoscopy through the same needle trocar used to place vesicoamniotic shunts was ﬁrst reported in 1995 [39]. With advances in endoscopic instrumentation, there have now been case reports of fetal cystoscopy and valve ablation [40]. Despite being introduced over 25 years ago, literature regarding antenatal intervention consists of case reports and small series. In a recent meta-analysis Morris et al. [5] iden- tiﬁed 20 studies of suﬃcient quality, representing a total pop- ulation of 369 fetuses, of which 261 had undergone ante- natal intervention. The majority underwent vesicoamniotic shunting; however patients undergoing cystoscopic ablation or open procedures were also included. The authors report an overall survival advantage when intervention is compared to no intervention. However, when renal function was examined, the odds of being born with normal renal function were decreased in the population undergoing fetal intervention. It has been postulated that this ﬁnding is due to the survival of fetuses that would otherwise have died without antenatal intervention. While intriguing, this study includes no randomized controlled trials (RCTs) and key data such as the age at which intervention was performed and the indications for antenatal intervention were largely unavailable. The percutaneous shunting in lower urinary tract ob- struction (PLUTO) trial [41] is an international multicenter study which began enrolling patients in 2008. The goal is to identify 150 male fetuses with ultrasound evidence of lower urinary tract obstruction and to randomize them to undergo vesicoamniotic shunting or observation. While the ﬁrst RCT will be a valuable study with appropriate endpoints, several key variables such as standardized criteria for ultrasound diagnosis and fetal age were not included in the study design and may limit meaningful conclusions if these variables are not controlled for properly. 7. Conclusion Congenital outlet obstruction continues to be a signiﬁcant source of fetal morbidity with little progress in its prenatal treatment or management over the last 25 years. Advances in the understanding of pathogenesis make it clear that the mechanical stretch of a dilated system leads to decreased nephrogenesis and renal dysplasia through altered diﬀeren- tiation, apoptosis, and inﬂammation. In fetal lamb models bladder outlet obstruction leads to acute tubular necrosis within 48 hours and dilation of developing tubules and interstitial widening within 5–7 days of obstruction [42]. When bladder outlet obstruction, in fetal lambs, induced on day 60 is relieved with a vesicoamniotic shunt on day 90, nephrogenesis is recoverable. Kidneys in which the obstruc- tion was reversed will have a 5% loss of total nephrons compared to 20% loss in those with persistent obstruc- tion [7]. Fetal urine production begins as early as eight weeks; however a muscular bladder capable of transmitting in- 3 creased intravesicle pressures to the developing kidney is not developed until 13 weeks. Based on animal models and the new understanding of the eﬀect of obstruction on nephrogenesis, it is likely that renal damage in congenital bladder outlet obstruction occurs as early as 14 weeks. The crucial period for lung development is also between 16 and 25 weeks. 14 days of persistent severe oligohydraminos prior to 25 weeks is associated with a fetal mortality of 90%. It is now possible to identify radiographic changes indica- tive of outlet obstruction as early as 11–14 weeks; however our current screening recommendations are initiated four to six weeks after this key developmental stage. New biologic markers and improved instrumentation will allow for more eﬀective diagnosis and intervention at earlier stages of fetal development. Until intervention close to the onset of obstruction is possible, there will likely be little impact in the overall morbidity and progressive loss of renal function in infants with congenital bladder outlet obstruction. References [1] S. A. Zderic and D. A. Canning, “Posterior urethral valves,” in The Kelalis-King-Belman Textbook of Clinical Pediatric Urology, S. G. Docimo, D. A. Canning, and A. E. A. Khoury, Eds., vol. 1, chapter 63, pp. 1059–1081, Thompson Publishing Services, 5th edition, 2007. [2] T. R. Gunn, J. D. Mora, and P. 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