Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial

Abstract

SummaryBackgroundFetal 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.MethodsIn 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.Findings31 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.InterpretationSurvival seemed to be higher in the fetuses receiving vesico...

Cirurgia fetal no contexto atual

“…As duas malformações congênitas mais comuns que causam a obstrução são a válvula de uretra posterior (VUP) e a atresia uretral 49 . Ao exame ultrassonográfico, essas patologias costumam ser de difícil diferenciação 50,51 , apresentando-se com megabexiga, dilatação uretral proximal e hidronefrose bilateral, geralmente acompanhadas de oligoâmnio/ anidrâmnio, estando relacionadas a uma alta prevalência de hipoplasia pulmonar devido à ausência de líquido amniótico 49 .…”

“…Algumas séries de casos e revisões sistemáticas mostraram evidência de aumento na taxa de sobrevida após drenagem vesical, mas não havia nenhum ensaio randomizado até a realização do estudo PLUTO, iniciado em 2006 49 .…”

“…O desfecho primário era sobrevivência até 28 dias após o parto, e os desfechos secundários eram sobrevivência até 1 e 2 anos, e função renal com 28 dias, 1 ano e 2 anos. Entre os principais resultados, observouse maior sobrevivência no grupo dos fetos que recebeu a derivação, apesar de não significante, mas em ambos os grupos houve apenas duas crianças que chegaram à idade de 2 anos sem prejuízo à função renal 49 .…”

“…Os resultados do estudo PLUTO foram desanimadores e vieram reforçar a ideia de que a história natural dessa doença é muito grave, e que sua morbimortalidade é substancial apesar do tratamento, sugerindo que o dano ao parênquima renal já é irreversível no momento do diagnóstico 49 . Em outras palavras, o ganho em sobrevida não compensaria as morbidades trazidas pela doença à vida pós-natal.…”

Severe antenatally diagnosed renal disorders: background, prognosis and practical approach

“…Nevertheless, 33 % were dependent on dialysis after birth, and 39 % retained pulmonary symptoms, mainly asthma [33]. In 2013 a prospective randomized controlled trial was performed, but due to poor recruitment only 31 patients with LUTO were included in this study [34,35]. Survival was better-although not statistically-in fetuses with LUTO receiving vesicoamniotic shunting (8/16 vs. 4/15), and the overall long-term outcome was comparable; only two children survived for 2 years without renal impairment.…”