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

Abstract

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).

Figure 1

Trial profile Normal renal function is defined as serum creatinine less than 50 μmol/L; mild renal impairment is defined as serum creatinine of 50 μmol/L or more, not requiring medical treatment; moderate renal impairment is defined as serum creatinine of 50 μmol/L or more, requiring medical treatment; end-stage renal failure is defined as need for transplant or dialysis. TOP=termination of pregnancy. *Two treatment related TOPs occurred secondary to spontaneous rupture of membranes after shunt insertion at 17 and 22 weeks. † Parental decision at 18–25 weeks. ‡After spontaneous rupture of membranes at 16 weeks. §Due to pulmonary hypoplasia.

Figure 2

Results of Bayesian analysis Bayesian prior and posterior estimates of relative risk of survival to age 28 days. The prior distribution (A) was obtained by eliciting prior distributions from 52 experts, averaging the distributions, and fitting a normal distribution. The posterior distribution (B) is based on combining the elicited prior with the intention-to-treat results. The posterior distribution (C) is based on combining a non-informative prior with the intention-to-treat results.

Figure 3

Kaplan-Meier estimates of survival from conception to end of follow-up Vertical dashes on the lines represent censored observations, either through parental choice to terminate pregnancy (before 36·5 weeks) or end of follow-up. Hazard ratios (HRs) were calculated for the period 0–36·5 weeks and from 36·5 weeks to the end of follow-up (conditional on survival to 36·5 weeks). These HRs are Bayesian estimates based on non-informative priors. The hazard rate comparison is of conservative management versus vesicoamniotic shunt, such that the interpretation of HRs greater than 1 as being indicative of benefit is consistent with the interpretation of the relative risk estimates. CrI=credibility interval.