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Efficacy and complications of prenatal in utero treatment
Lower urinary tract obstruction (LUTO) is a heterogeneous group of pathologies, most commonly urethral atresia and posterior urethral valves (PUVs)1 that accounts for one third of renal tract anomalies detected at autopsy after termination for ultrasound-diagnosed fetal anomaly.2 The affected fetus is typically male unless associated with bladder hypoperistalsis syndromes which carry a worse prognosis. PUV accounts for about half of the cases presenting with ultrasonic features of LUTO3 in some case cohorts. In 2005, data from the Northern Region Congenital Anomaly register were reported. Over a 14-year period, 113 cases of LUTO were identified, giving an incidence of 2.2 in 10 000 births.4
The importance of LUTO in terms of perinatal outcome lies in its clinical course, with long-term urethral obstruction being potentially associated with cystic renal dysplasia, abnormal renal (glomerular and tubular) function leading to severe oligohydramnios, pulmonary hypoplasia and positional limb anomalies.5 Animal studies have shown a causal link between the distal renal tract obstruction in the fetus and these abnormalities. The fetal phenotype has been variously described as the effects of potential in utero treatment.
Fetal LUTO, if untreated, carries a mortality of up to 45% mainly due to the severe oligohydramnios in the mid-trimester6 being associated with pulmonary hypoplasia. Even in those that survive the neonatal period, up to one third may develop end-stage chronic renal impairment, necessitating dialysis or transplantation.7 Congenital obstructive uropathy accounts for up to 60% of all paediatric renal transplants.8 It is therefore a morbid condition, although data informing this comes from small, uncontrolled selected series. For this reason, prenatal in utero treatment has been considered in “selected” cases in an attempt to bypass the congenital urinary tract obstruction, modify pathogenesis and attenuate the secondary …
Competing interests: RKM is a research fellow sponsored by Wellbeing of Women. All investigators are coordinators of the PLUTO trial.