Congenital renal tract anomalies: outcome and follow-up of 402 cases detected antenatally between 1986 and 2001

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1 Ultrasound Obstet Gynecol 2005; 25: Published online 19 January 2005 in Wiley InterScience ( DOI: /uog.1788 Congenital renal tract anomalies: outcome and follow-up of 402 cases detected antenatally between 1986 and 2001 H. A. M. DAMEN-ELIAS*, T. P. V. M. DE JONG, R. H. STIGTER*, G. H. A. VISSER* and P. H. STOUTENBEEK* Departments of *Perinatology and Gynaecology and Paediatric Urology, University Hospital Utrecht, Utrecht and Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands KEYWORDS: follow-up; postnatal outcome; prenatal diagnosis; renal tract; ultrasonography ABSTRACT Objective To determine the long-term prognosis of antenatally detected renal tract anomalies in order to optimize parental counseling. Methods This was a follow-up study of all renal tract abnormalities detected antenatally in a Level 3 ultrasound department between 1986 and Follow-up data (median age, 8 years) were retrieved from the records of the Paediatric Urology Department or the attending pediatrician. Results A urinary tract anomaly was detected in 408 fetuses. There were four false-positive diagnoses. From two children follow-up data were incomplete, leaving 402 cases for analysis. A chromosomal abnormality was present in 7/81 (8.6%) fetuses that had karyotyping. Termination of pregnancy was performed in 55 (13.7%) cases and a further 66 (16.4%) children died during the perinatal period and up to 1 year of age. In 106/121 (26.4% of all fetuses) deceased children the cause of death was directly related to the renal tract anomaly. In the 281 surviving children a total of 545 renal tract anomalies were diagnosed postnatally, requiring a total of 381 surgical interventions in 156 infants. Outcome in survivors was generally good, with impaired renal function in nine infants and hypertension in three (4% of the survivors). Conclusions Congenital renal tract anomalies are associated with a high mortality rate, especially when they are structural developmental anomalies of the kidneys. Survivors require multiple operations, but the outcome is generally favorable. Ultrasound diagnosis, especially when made early, of non-lethal urinary tract anomalies may prevent additional renal damage by timing of delivery and early postnatal treatment. Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION High-resolution ultrasound equipment increasingly provides the opportunity to identify congenital anomalies prenatally. The prevalence of any detected congenital anomaly during pregnancy is approximately 1 2% 1 4. Abnormalities of the urinary tract account for 15 20% with a detection rate of approximately 89% 3,4. Evidence exists that the number of antenatally detected malformations of the urinary tract is increasing. This is attributed to the widespread use of ultrasound in pregnancy and not to epidemiological changes 5,6. Data on antenatal diagnosis and postnatal follow-up are important for assessing prognosis and counseling of parents. They may be helpful in making difficult decisions as to whether or not to terminate a pregnancy before viability, and in determining the need for further diagnostic procedures and the best management before and after birth. Data on large cohorts are scarce 7 and most follow-up data are confined to specific urological anomalies, such as hydronephrosis or multicystic dysplastic kidneys The aim of the present study was to determine the long-term prognosis of antenatally detected renal tract anomalies in order to optimize parental counseling. METHODS A cohort study was carried out by reviewing the database of the obstetric ultrasound unit of the University Medical Centre, Utrecht, The Netherlands. The unit is a tertiary Correspondence to: Dr H. A. M. Damen-Elias, University Medical Centre Utrecht, Wilhelmina Children s Hospital, Department of Perinatology and Gynaecology, KE , Lundlaan 6, 3508 AB Utrecht, The Netherlands ( H.Damen@dog.azu.nl) Accepted: 28 May 2004 Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 Fetal renal tract anomalies 135 referral center and the database contains all cases from the population attending the antenatal clinic of the hospital including those referred from district general hospitals. In The Netherlands, tertiary centers only provide Level 3 ultrasound facilities and examinations are performed for specific, well-defined indications without doing routine antenatal screening. The database was reviewed for urinary tract anomalies detected between 1 January 1986 and 31 December There were no exclusion criteria. The cut-off point we used for dilated pelves was > 5 mm for the anteroposterior diameter before 32 weeks in pregnancy and 10 mm thereafter. The diagnosis of polycystic kidney disease (PCKD) was made when there was the typical in-utero presentation of two enlarged hyperechogenic kidneys with loss of cortical differentiation and oligohydramnios 12,13. We defined kidneys as multicystic dysplastic when cysts of various size without connection between the cysts were located in the mostly bright echogenic parenchyma of a structurally abnormal kidney in which no renal pelvis could be demonstrated 13. The term dysplastic kidney was used when the kidney was echogenic in isolation, had no normal parenchyma and was structurally abnormal without large cysts 13,14. The diagnosis of an isolated megabladder was made antenatally when the distended bladder reached the insertion of the umbilical vein independently of oligohydramnios. Prune belly syndrome was diagnosed postnatally when the triad of abnormalities 15,16 (abdominal wall deficient in muscular tissue, dilated urinary tract and bilateral cryptorchidism) with proven absence of urethral obstruction was present, thus excluding female fetuses. Follow-up data were obtained by chart review of the Department of Paediatric Urology and by contacting the pediatricians and general practitioners for information having obtained consent from the parents. Clinical findings and/or autopsy reports were used to determine postnatal outcome. Prenatal diagnosis was confirmed by postnatal ultrasound scans, radiological investigations, biochemical data on kidney function and surgical records. During the 15-year study period, 2070 fetuses were seen with confirmed congenital anomalies of which 408 (19.7%) cases were for urinary tract abnormalities. There were four infants in whom the urinary tract appeared normal at follow-up and two cases were lost to followup, due to relocation abroad, leaving 402 patients for further analysis. From all these cases follow-up data were available up to the age of between 3 and 17 years (median, 7 years 11 months). RESULTS Diagnosis (n = 402) Table 1 shows the antenatal diagnosis in the 402 fetuses. A total of 151/402 (37.6%) fetuses had a structural kidney anomaly, 247/402 (61.5%) had urinary tract dilatation and 4/402 (1.0%) had anomalies of miscellaneous origin. The anomaly was bilateral in 206/402 (51.2%) fetuses and unilateral in 173/402 (43.1%) fetuses. Some 20/402 (4.9%) fetuses had an isolated megabladder and 3/402 (0.8%) had postnatally confirmed prune belly syndrome. Forty-nine percent of the 173 unilateral anomalies were on the right side (n = 84) and 51% were on the left side (n = 89). The overall male : female ratio was 7 : 3. In the structural kidneys anomaly group this ratio was 5 : 3 and in the urinary tract dilatation group it was 9 : 3.4. The mortality rate was 30.1% (121/402). At the end of the follow-up, nine surviving infants had impaired renal function and three children had hypertension (i.e. 12/281, 4.3%). A total of 7/281 (2.5%) children had one dysplastic and one normal kidney left but they had overall normal renal function. Mortality (n = 121) In 106/402 (26.4%) deceased children the cause of death was directly related to the renal tract anomaly. Perinatal mortality (Table 1) was highest in the group with structural kidney anomalies (i.e. 87/150, 58%). Mortality in the group with urinary tract dilatation was 13.4% (33/247). Perinatal mortality included all cases with PCKD, bilateral renal agenesis and bilateral multicystic kidney disease (MCKD) and these cases accounted for 61.2% (74/121) of total mortality. Moreover, mortality in cases with an isolated megabladder was high (17/20). Autopsy in nine of these fetuses revealed three cases of urethral stenosis, four cases of urethral obstruction and two cases of urethral atresia. The parents of eight fetuses refused autopsy: in five cases stillbirth occurred, one fetus had caudal regression syndrome, one had a cloacal anomaly and another had no visible anomalies. A total of 10/64 children (15.6%) with unilateral MCKD died because of contralateral renal anomalies: renal agenesis in nine cases and renal dysplasia in one. In the miscellaneous group one child died with a unilateral pelvic kidney and Arnold-Chiari malformation. Table 2 lists all 121 deceased children with the main renal anomaly and additional renal and extrarenal anomalies. Autopsy was performed in 72/121 (59.5%) deceased fetuses, and in all but one of them the main antenatal diagnosis was confirmed. Fifty-five pregnancies were terminated on parental request (55/402, 13.7%) at a mean gestational age of 22.7 (range, 15 35) weeks. In 54/55 of these cases there was a lethal anomaly and in one case a suspected poor quality of life especially of the newborn (Table 2). 12/402 (3.0%) fetuses were stillborn, and a further 50/402 (12.4%) children died during the first 28 days after birth, and four others during the first year of life: one on account of the renal tract anomaly and three for other reasons (4/402, 1.0%). Sixty-nine percent of all perinatal deaths were of boys. Survivors (n = 281) Altogether 281 infants survived the perinatal period (Table 1). In these infants a total of 545 anomalies was

3 136 Damen-Elias et al. Table 1 All children, alive or dead, with a structural developmental kidney anomaly, urinary tract dilatation or miscellaneous uropathy, together with prenatal and postnatal diagnosis, details of abnormalities, surgery and renal function Prenatal diagnosis Postnatal diagnosis All Dead Death not due to renal anomaly Alive Infants with surgery Operations Renal function Structural developmental anomaly (n = 151) Unilateral renal agenesis Unilateral renal agenesis normal Bilateral renal agenesis Bilateral renal agenesis NA Unilateral enlarged Unilateral MCKD normal, 1 mild failure echogenic/cystic kidney Unilateral dysplasia normal Bilateral enlarged Bilateral MCKD NA echogenic/cystic Bilateral dysplasia dialysis, 1 mild failure kidneys PCKD NA Meckel Gruber syndrome 5 5 NA Perlman syndrome 1 1 NA Bilateral echogenic Normal normal kidneys normal size Total Urinary tract dilatation (n = 247) Unilateral dilatation normal Bilateral dilatation transplant, 4 chronic failure, 3 hypertension, 109 normal Unilateral megaureter normal Bilateral megaureter normal Isolated megabladder Prune belly syndrome 3 3 Megabladder normal Total Miscellaneous anomaly (n = 4) Pelvic kidney normal Horseshoe kidney normal Total Overall total failure, 3 hypertension MCKD, multicystic kidney disease; NA, not applicable; PCKD, polycystic kidney disease. identified, resulting in 381 surgical interventions in 156 infants (55.5% of the 281 survivors). Indications for surgery were upper tract dilatation with split function on renal scan < 40%, deteriorating function at followup renography or renal colics based on pyeloureteric junction obstruction. Table 3 shows all diagnosed renal tract anomalies and all surgical interventions. Most children had more than one renal tract anomaly diagnosed and approximately half of the survivors needed on average two to three surgical interventions. Surviving infants with structural kidney anomaly (n = 64) Most (51/64, 79.7%) children in this group had unilateral MCKD and 12/51 (23.5%) infants had contralateral renal anomalies: a dysplastic kidney in three, pyelectasis in six, a megaureter in one (Tables 5 and 6) and vesicoureteral reflux (VUR) in two (one Grade IV and one Grade V). There was one fetus with bilateral echogenic kidneys of normal size and normal amniotic fluid at 24 weeks gestational age in which the renal echogenicity normalized during pregnancy. The child had normal function after birth. Surgery in the infants with a structural anomaly mainly consisted of unilateral nephrectomy (Table 1). In 43/45 cases with nephrectomy of the multicystic kidney there was no functioning at all on the renogram, whereas the other two cases had an overall function of less than 10%. At histology of the multicystic kidneys the diagnosis of MCKD was confirmed in all cases including the two cases with minimal function on the isotope scan. Of the 64 survivors 62 children have normal renal function at follow-up. The two cases with impaired outcome were as follows: 1. One child had bilateral, echogenic, dysplastic kidneys due to bilateral obstructive uropathy based on ectopic ureter with ureterocele, contralateral megaureter and bilateral VUR. The girl had several operations and eventually developed end-stage renal failure at the age of 8 years (in 2002) and started peritoneal dialysis. 2. One girl with bilateral, echogenic, dysplastic kidneys was finally diagnosed as having the hereditary

4 Fetal renal tract anomalies 137 Table 2 Overview of all the children who died, classified according to renal anomaly; data on additional renal and extrarenal malformations are given as well as time of death Renal anomaly Total Additional malformations Renal additional malformations Extrarenal additional malformations TOP Stillborn Neonatal death < 28 days Late infant death > 28 days Total (n (%)) Renal agenesis bilateral absent bladder, 1 urethral stenosis, 2 agenesis of the ureters MCKD bilateral cloacal malformations, 1 multiple anomalies of the renal tract MCKD unilateral agenesis contralateral, 1 dysplasia contralateral 1 hydrocephalus, 1 diaphragmatic hernia, 3 heart defects, 1 anal/esophageal atresia 2 sirenomelia, 3 heart defect, 1 anal/esophageal atresia 2 pulmonary hypoplasia, 1 preterm labor (27.3) (18.2) (10.7) PCKD Meckel Gruber, (15.7) Perlman syndrome Prune belly syndrome (2.5) 10* (15.7) Obstructive uropathy was reason for death Obstructive uropathy was not reason for death Uropathy was not reason for death cloacal malformation* 1 omphalocele, 1 caudal regression trisomy 13, 2 heart defects = Noonan, 1 hypoperistalsis syndrome, 1 intrauterine infection, 1 megabladder, cloacal anomaly and preterm labor, 1 Arnold Chiari malformation, 1 Dandy Walker malformation, 1 obstructive uropathy + anal/esophageal atresia = VACTERL association, 1 obstructive uropathy + anal atresia, genotype 46 XX, phenotype male = VACTERL association, 1 obstructive uropathy + anal/esophageal atresia, +VSD = VACTERL association (9.1) pelvic kidney + Arnold Chiari malformation 1 1 (0.8) Total (%) (45.5) 12 (9.9) 50 (41.3) 4 (3.3) 121 (100) MCKD, multicystic kidney disease; PCKD, polycystic kidney disease; TOP, termination of pregnancy (all had a lethal anomaly except one * ); VACTERL, vertebral defects (V), anal atresia (A), cardiac anomaly (C), tracheal-esophageal fistula with esophageal atresia (TE), renal defects (R), radial limb dysplasia (L); VSD, ventriculoseptal defect.

5 138 Damen-Elias et al. Table 3 Summary of all 545 renal tract anomalies diagnosed in the 281 survivors (most had more than one anomaly diagnosed) and details of the number and type of surgical procedures in 156 of these children Diagnosis of the renal tract n Surgery on the renal tract Pyeloureteric junction 113 Kidney transplant 1 obstruction Vesicoureteric junction 8 Nephrectomy 51 obstruction Multicystic kidney 51 Heminephrectomy 21 Posterior urethral 45 Reimplantation 53 valves (mega-) ureter Narrowed urethra 15 Ureterectomy 22 Megaureter 129 Pyeloplasty 36 Vesicoureteric reflux 46 Incision posterior urethral 64 valves Megabladder 45 Vesicostomy 6 Agenesis of the kidney 8 Pull-through vagina 3 (Mayer Rokitanski) Dysplastic kidney 4 Reconstruction vagina 2 (cloacal malformation) Duplex system 43 Ureterocele 19 excision/reconstruction lower tract Urinary ascites 3 Diverticulectomy 3 Unclear 35 Drainage of the upper tract 43 Vesicoureteric 13 reflux endoscopic treatment Closure of bladder rupture 1 Excision/incision syringocele 22 or utriculus cyst Miscellaneous small 21 interventions Total number of diagnoses 545 Total number of surgical interventions 381 branchio-oto-renal (BOR) syndrome 17, which includes renal failure and impaired hearing (creatinine, 71 µmol/l at age 7.5 years). Surviving infants with urinary tract dilatation (n = 214) Table 4 gives an overview of the age of diagnosis, size of the dilatation at diagnosis and outcome of the 118 surviving infants with an isolated uni- or bilateral renal pelvis dilatation. Forty-four infants needed a total of 84 interventions. One child has chronic renal failure and one has hypertension; both children had bilateral dilated pelves. Another 96 infants had a uni- or bilateral urinary tract dilatation in combination with a uni- or bilateral megaureter and/or megabladder. There was a high intervention rate of 227 interventions in 62 of these children (62/96, 64.6%). A total of 45/96 children had posterior urethral valves (PUV) with an intervention rate of 100%, leaving four infants with impaired function and one infant with hypertension. In 14 of these infants labor had been induced (Table 6). Moreover, the intervention rate was high (39/45, 86.6%) in cases of VUR. n Outcome in all 39 children with a unilateral renal tract dilatation was favorable. Most of the 54 infants with a bilateral dilatation had a good outcome. There were six infants with chronic renal failure, one requiring kidney transplant (Table 5) and two with hypertension. Impaired outcome was not related to the time of diagnosis or to the size of dilatation at diagnosis. In 21/119 (17.7%) cases with a bilateral dilatation labor was electively induced before 37 (mean, 34.9; range, 29 37) weeks of gestation because of the development of anhydramnios. Only one fetus had solitary bilateral hydronephrosis (Table 6). All 21 neonates (19 boys and two girls) had surgery within a few days after birth. Almost all children with impaired outcome can be found in this group (six chronic renal failure, one hypertension). VUR was diagnosed in 45/214 (21.0%) children with urinary tract dilatation after evaluation by voiding cystourethrography; 39 infants needed a total of 123 interventions (39/45, 86.6%). The male : female ratio was 7 : 2. Table 7 gives an overview of all cases with uniand bilateral VUR, surgical interventions and final renal function. Surviving infants with miscellaneous anomalies (n = 3) These three infants (Table 1) had a developmental kidney anomaly without consequences for renal function and all were normal at follow-up. Infants with chromosomal anomalies (n = 7) Karyotyping was done prenatally in 77 fetuses (in 13 cases because of maternal age > 36 years) and postnatally in another four children, in total 81/402 (20.2%). Seven children had a chromosomal anomaly (7/81, 8.6%) (Table 8). In another three stillborn fetuses a chromosomal anomaly was suspected but the parents refused karyotyping and autopsy. Four children had trisomy 21 and these four infants accounted for 1.8% of all 221 living children with uni- or bilateral renal tract dilatation. False-positive diagnosis (n = 4) There were 4/402 (1.0%) infants in whom the urinary tract appeared to be normal at follow-up. The antenatal diagnoses in these four cases were (a) pelvic kidney (appeared to be normal position), (b) extrarenal dilatation of the kidney (appeared to be adrenal gland hemorrhage), (c) cyst of upper moiety of a duplex kidney (appeared to be extralobar sequestration of the lung) and (d) dysplastic kidneys with increased echogenicity (appeared to be normal). DISCUSSION The population in the present study may not be representative of the overall obstetric population, since severe anomalies are likely to be referred more frequently to our

6 Fetal renal tract anomalies 139 Table 4 Children with isolated uni- or bilateral renal pelvis dilatation together with gestational age and size of dilatation at first diagnosis Renal Gestational age (weeks) Total number and Surgical Renal failure after AP diameter pelvis n (%) of children interventions surgery or (mm) dilatation < operated on hypertension 5 10 Unilateral 2 2 (1) (1, 10) 2 Bilateral (1) 1 18 (1, 5.5) 5 1 chronic renal failure Unilateral 2 (1) 1 (1) 3 (1) 5 (2) 3 (1) 14 (6, 42.9) 11 Bilateral 5 (1) 6 (2) (3, 13.0) Unilateral 1 (1) 4 (3) 6 (2) 11 (6, 54.5) 7 Bilateral (2) 3 (2) 9 (4, 44.4) Unilateral 1 (1) 2 (2) 2 5 (3, 60.0) 5 Bilateral 1 4 (1) 2 (2) 7 (3, 42.9) 8 1 hypertension Unilateral 2 (2) 1 (1) 1 4 (3, 75.0) 10 Bilateral 1 (1) 1 (1, 100) Unilateral 1 1 (1) 2 (1, 50.0) 1 Bilateral 1 (1) 1 1 (1) 3 (2, 66.6) 3 > 35 Unilateral 2 (2) 3 (3) 1 (1) 6 (6, 100) 8 Bilateral 1 (1) 1 (1) 2 (2, 100) 5 Isolated Unilateral 1 (1) 1 (1, 100) 2 megaureter Bilateral 1 1 (1) 2 (1, 50.0) 3 Total (3) 16 (8) 25 (10) 29 (16) 22 (8) 118 (44, 37.3) 84 Figures in parentheses indicate children in whom operations were performed. Total number of surgical interventions and renal failure after surgery are presented in the final columns. AP, anteroposterior. tertiary center than minor ones. Nevertheless, our data may be helpful in assessing the prognosis of the various anomalies and be of help in counseling parents. Urinary tract anomalies accounted for 20% of all congenital anomalies detected prenatally, with a very low false-positive rate of 1.0% for which no inappropriate treatment was performed. Mortality due to renal tract anomaly was high, approximately one quarter of all cases and was mainly restricted to the perinatal period (including termination of pregnancy in half of these cases). The mortality rate, almost 60%, was especially high in infants with a structural kidney anomaly and relatively low, at 13.3%, in the group with urinary tract dilatation. Approximately half of the survivors needed an average of two to three surgical interventions. Outcome in the surviving infants was generally good, with impaired renal function in 4.3% of cases. This favorable outcome applied both to infants with a structural anomaly and to those with a urinary tract dilatation. There were seven children with one dysplastic and one normal kidney but they all had overall normal renal function at follow-up. The incidence of urine incontinence was not examined. One may rightly argue that the incidence of impaired outcome may increase with increasing age, but the median duration of follow-up was already considerable (almost 8 years). Large, bright kidneys in PCKD are well documented 12 and the typical multicystic kidney usually does not present a diagnostic problem 7,13,18,19. Increased echogenicity of the renal parenchyma may represent significant disease with poor outcome especially when there is oligo- or anhydramnios but with normal amniotic fluid there may be normal function 14,20. The degree of echogenicity had to be judged by comparing the kidneys to the echogenicity of the liver because normally they should appear with similar brightness. In the present series structural anomalies represented approximately onethird of anomalies. Postnatally most of the multicystic kidneys had a non-functioning parenchyma and they were removed to avoid the need for lifetime follow-up when the kidney is left in place, according to the guidelines of the Dutch Society for Paediatric Urology 21,22.Fetuses with a unilateral MCKD had a 34% chance of having contralateral renal anomalies with a high mortality rate of 15.6%. Thus, the finding of a unilateral MCKD must lead to meticulous screening of the complete urinary tract, both pre- and postnatally. Agreement exists that in cases of urinary tract dilatation different thresholds are used for measurements of the anteroposterior diameter of the renal pelvis in the second and third trimester of pregnancy but the size and gestational age at diagnosis vary because of the lack of diagnostic criteria Some authors suggest that the risk of surgery is minimal when the dilatation is < 10 mm in late pregnancy 26,27 but Thomas 28 has stated that the size of the prenatal dilatation is not a sensitive predictor of pathology but that increasing dilatation is associated with morbidity and mortality. An anteroposterior diameter of > 10 mm is usually considered to be of significance 27,29 but the Great Ormond Street experience 30 showed that there is a very low risk of clinically significant obstruction when the dilatation does not exceed 15 mm at any gestational age. However, in our series 11/65 infants with an isolated uni- or bilateral mild dilatation (< 15 mm) still required surgery. It is the policy in our clinic that in cases of early and mild pyelectasis (< 10 mm) and after scanning for

7 140 Damen-Elias et al. Table 5 Children with obstructive uropathy and impaired renal function Case* Case description Induced labor 2 Boy with bilateral pyelectasis = 5/5 mm, megaureter and megabladder at GA 16 weeks. He had PUV and bilateral VUR (Grade IV and IV). After 2 years of renal dialysis and multiple operations he had a kidney transplant at the age of 5 years. At the time of writing he is 16 years of age and doing well. 7 Boy with unilateral megaureter and contralateral MCKD. He had MCKD nephrectomy and reimplantation of the ureter at the opposite side, excision of ureterocele and relief of urethral obstruction. He is now 9.5 years old with creatinine levels of 81 µmol/l. 8 Boy with bilateral hydronephrosis = 10/10 mm, megaureter and megabladder at GA 27 weeks. He had PUV and extensive surgery with temporary diversion by vesicostomy and drainage of the upper tract. He is now9yearsoldwithcreatininelevelsof74 µmol/l. 9 Boy with bilateral hydronephrosis = 10/13 mm, megaureter and megabladder at GA 23 weeks. He had PUV and bilateral VUR (Grade IV and V). He has dysplastic kidneys with immature parenchyma and underwent ample surgical reconstructions. At 10 years of age he has preterminal renal failure (creatinine, 179 µmol/l). 18 Boy with bilateral hydronephrosis = 25/25 mm, megaureter and megabladder at GA 34 weeks. He had PUV. After multiple operations he has mild chronic renal failure (creatinine, 80 µmol/l) and a renal urine concentration defect at 10 years of age. 19 Boy with bilateral hydronephrosis = 10/10 mm, megaureter and megabladder at GA 34 weeks. He had bilateral VUR (Grade III and IV). At age 10 years and after multiple operations he has mild renal failure = reflux nephropathy (creatinine, 74 µmol/l) and hypertension. No induced labor Boy with bilateral pyelectasis = 9/7 mm at GA 29 weeks. He had bilateral VUR (Grade V and V) and developed pyelonephritis despite antibiotic prophylaxis. He underwent bilateral reimplantation and recalibration of the ureter. He has a creatinine level of 74 µmol/l at the age of 3 years. *Numbers correspond with those in Table 6. GA, gestational age; MCKD, multicystic kidney disease; PUV, posterior urethral valves; VUR, vesicoureteral reflux. additional anomalies, patients are advised to have the ultrasound investigation repeated at around 32 weeks of gestation and when the dilatation is the same or less to refrain from further investigations before or after birth. (The two cases with a dilatation < 10 mm and surgery postnatally had both a dilatation > 10 mm at the 32- week ultrasound scan.) Low-grade VUR may be missed, although in the present series none of the infants with VUR had a dilatation less than 10 mm. We inform the parents that there may be an enhanced risk for urinary tract infection (UTI) due to VUR and when their child feels listless or has fever of unknown origin a UTI must be ruled out. With such a policy unnecessary parental anxiety may be prevented, as well as unnecessary costs of follow-up. Surgery may be needed in cases of an isolated unior bilateral dilatation of the renal pelvis of > 10 mm and in the present study nearly half of these infants had surgery. Especially high was the intervention rate in the 45 boys with PUV (100%). Labor was induced in 14 of these infants and six have impaired renal function and one hypertension. The overall conclusion for obstructive uropathy that can be drawn from the present series is that regardless of the presence of one or two kidneys and regardless of the degree of urinary tract dilatation, the prognosis for renal function is excellent when oligohydramnios is absent before birth and when proper urological care is given postnatally. Almost all renal failures occurred in the group with progressive oligohydramnios in which labor was induced preterm (6/21 infants). Poor outcome of fetuses with bilateral urinary tract dilation combined with prolonged periods of oligohydramnios has been repeatedly described Intrauterine therapy still has a poor outcome with about 50% fetal loss and 40% end-stage renal disease in the survivors 34,35 but such a therapy is only a possible option when there is a megabladder at mid-gestation. Our policy of preterm induction of labor when oligohydramnios develops seems to result in a relatively favorable outcome, although the timing of induction is still uncertain and the proof that we actually gave the neonates a better chance of survival is non-existent. Isolated megabladder was diagnosed in 23 cases antenatally, of which three boys had prune belly syndrome diagnosed postnatally. In the literature usually a high number of cases of prune belly is cited 15,16 without looking for urethral obstruction. Our number is low because of the definitions we used for prune belly syndrome 15,16 with proven patent ureter and excluding female fetuses. VUR accounted for approximately 21% of prenatally diagnosed urinary tract dilatations, which is slightly higher than the 15% described by others There was a high surgical intervention rate in 86.6% of the infants who needed approximately one-third of all surgical interventions (Table 7). VUR predisposes to UTI and can lead to renal scarring and chronic renal failure, however approximately 60% of kidneys with reflux already have an abnormal renogram even in the absence of UTI Therefore all children with an anteroposterior renal pelvis dilatation > 10 mm around 32 weeks of gestation should be carefully managed postnatally (low-dose antibiotics, voiding cystourethrography). We carried out antenatal karyotyping only when additional anomalies were found and postnatally only when there was a suspicion of chromosomal abnormalities. It is not routine in our unit to karyotype the child at autopsy. Seventeen parents refused autopsy and/or karyotyping. Some 7/81 (8.6%) fetuses that were karyotyped had a chromosomal disorder. Others mentioned chromosomal disorders in 11 12% 1,43 and even 25% of cases 44. However, these studies are not quite comparable with the present study because Stoll et al. 1 did not mention the percentage of cases in which karyotyping was carried out,

8 Fetal renal tract anomalies 141 Table 6 Cases in which labor was induced (n = 21) together with sex, gestational age, antenatal diagnosis, type of anomaly, surgery and renal function after surgery Case Sex Labor induced (weeks) Antenatal diagnosis Postnatal anomaly/surgery Renal function after surgery 1 XY 32 Bilateral hydronephrosis and megaureters PUV/excision urethral valves 2 XY 36 Bilateral hydronephrosis, PUV, bilateral VUR (Grade IV and IV)/extensive surgery 3 XY 33 Bilateral hydronephrosis and PUV/extensive surgery megaureters 4 XY 35 Bilateral hydronephrosis Bilateral hydronephrosis/bilateral pyeloplasty 5 XY 36 Bilateral hydronephrosis, PUV/extensive surgery 6 XY 35 Bilateral hydronephrosis and PUV/extensive surgery urinary ascites 7 XY 36 Unilateral megaureter and Unilateral megaureter and contralateral MCKD contralateral MCKD/ureter reimplantation and nephrectomy 8 XY 37 Bilateral hydronephrosis, PUV/extensive surgery 9 XY 33 Bilateral hydronephrosis, PUV, bilateral VUR (Grade IV 10 XY 29 Bilateral hydronephrosis, and V)/extensive surgery Premature labor after amnion infusion, PUV/extensive surgery 11 XY 35 Megabladder and urinary ascites PUV and spontaneous bladder rupture/extensive surgery 12 XY 33 Bilateral hydronephrosis, PUV/extensive surgery 13 XY 37 Unilateral hydronephrosis, PUV/extensive surgery contralateral megaureter and utereocele 14 XY 36 Bilateral hydronephrosis, megabladder, urinary ascites 15 XY 36 Bilateral hydronephrosis, megabladder, urinary ascites 16 XY 37 Unilateral hydronephrosis with megaureter, contralateral MCKD 17 XY 36 Bilateral hydronephrosis, megabladder 18 XY 34 Bilateral hydronephrosis, 19 XY 37 Bilateral hydronephrosis, 20 XX 34 Bilateral hydronephrosis and megaureters 21 XX 37 Unilateral hydronephrosis with megaureter, contralateral MCKD Bilateral hydronephrosis PUV and bilateral VUR (Grade III and IV)/extensive surgery UVJ stenosis with unilateral MCKD, unilateral megaureter with VUR Grade V/extensive surgery PUV/excision urethral valves PUV/extensive surgery Bilateral VUR (Grade III and IV) and megaureter/bilateral ureteral reimplantation Bilateral hydronephrosis/extensive surgery Unilateral MCKD, contralateral VUR Grade V/extensive surgery Kidney transplant (unilateral dysplasia) Mild failure Mild failure Preterminal failure, hypertension Died during heart surgery, DORV, TGA Mild failure Bilateral reflux nephropathy and hypertension DORV, double outlet of the right ventricle; MCKD, multicystic kidney disease; PUV, posterior urethral valves; TGA, transposition of the great arteries; UVJ, uteric vesico junction stenosis; VUR, vesicoureteral reflux. Nicolaides 45 performed karyotyping in all children with the prenatal diagnosis of urogenital tract anomalies and Isaksen et al. 44 described a selected group of deceased children. Fetuses with pyelectasis have a higher chance of having chromosomal anomalies (mostly trisomy 21 followed by trisomy 13 and 18) 43,46,47. In the present series all seven (3.2%) fetuses with a chromosomal defect had unior bilateral pyelectasis which is in accordance with the % reported in the literature 43,46,47. However, it is the prevalent opinion that isolated pyelectasis does not constitute an indication for fetal karyotyping 45.

9 142 Damen-Elias et al. Table 7 Summary of interventions and outcome in 45 infants with unilateral or bilateral vesicoureteral reflux (VUR) Urinary tract anomaly with VUR Children undergoing surgery Operations Final renal function Unilateral urinary tract anomaly with VUR (n = 13) Bilateral urinary tract anomaly with unilateral VUR (n = 10) Bilateral urinary tract anomaly with bilateral VUR (n = 22) unilateral reflux nephropathy, 2 dysplasia in operated kidney 10 13* 1 hypertension and mental delay kidney transplant, 1 peritoneal dialysis, 1 hypertension, bilateral reflux nephropathy, unilateral hypoplasia, 1 chronic renal failure, 1 preterminal renal failure, 1 hypertension, 1 dysplasia in operated kidney *Seven in reflux kidney, six in the contralateral hydronephrotic kidney. Table 8 Overview of fetuses with a chromosomal anomaly Case Urinary tract anomaly Chromosomal anomaly Extrarenal anomaly Postnatal management Renal function 1 Bilateral MCKD Klinefelter syndrome XXY None NA NA 2 Bilateral pyelectasis Trisomy 13 Multiple NA NA Ø8mm 3 Bilateral hydronephrosis Mosaicism chromosome 8 None Resection urethral valve Normal > 20 mm and megaureter 4 Bilateral hydronephrosis Trisomy 21 None Resection urethral valve Normal > 0 mm, megaureter and megabladder diverticulectomy 5 Bilateral megaureter Trisomy 21 Hydrops fetalis Prophylactic antibiotics Normal 6 Bilateral hydronephrosis > 15 mm and megabladder 7 Bilateral hydronephrosis: L > 30 mm, R > 6 mm Trisomy 21 polyhydramnios VSD, stenosis of pulmonary artery, unilateral clubfoot Closure VSD defect, clubfoot correction Normal Trisomy 21 VSD Prophylactic antibiotics Normal L, left; MCKD, multicystic kidney disease; NA, not applicable; R, right; VSD, ventriculoseptal defect. Autopsy was performed in 72/121 (59.5%) deceased fetuses. The main urological, prenatal diagnosis was confirmed in all but one of these fetuses (98.6%). Suspected bilateral MCKD turned out to be unilateral with a normal contralateral kidney. The child also had severe idiopathic pulmonary hypoplasia and anhydramnios and did not die as a result of the inaccurate diagnosis. In 18 fetuses additional autopsy findings, such as anal atresia in five fetuses, had not been found prenatally by ultrasonography mostly due to the anhydramnios. Isaksen et al. 44 found a slightly lower 91% agreement between prenatal diagnosis of severe urogenital tract anomalies and autopsy findings. CONCLUSIONS The overall value of antenatal diagnosis of renal tract anomalies is that it indicates early termination of fetuses with fatal renal disease, prepares parents and medical staff for the likelihood of serious neonatal problems, and identifies dangerous abnormalities of the urinary tract that may not easily be detected postnatally. The drawback of antenatal diagnosis is that the majority of detected mild dilatations have no therapeutic consequences at all but still cause unnecessary anxiety in many cases. This study was undertaken to provide insight into which parents should be anxious and which can be reassured that they can expect a healthy child with, possibly, minor problems without consequences for life or life expectancy. REFERENCES 1. Stoll C, Clementi M. Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe. Ultrasound Obstet Gynecol 2003; 21: Levi S. Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening for second trimester fetal malformations. Prenat Diagn 2002; 22: Levi S. Mass screening for fetal malformations: the Eurofetus study. Ultrasound Obstet Gynecol 2003; 22: Grandjean H, Larroque D, Levi S. Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team. AnnNYAcadSci1998; 847: Alladi A, Agarwala S, Gupta AK, Bal CS, Mitra DK, Bhatnagar V. Postnatal outcome and natural history of antenatallydetected hydronephrosis. Pediatr Surg Int 2000; 16: Barker AP, Cave MM, Thomas DF, Lilford RJ, Irving HC, Arthur RJ, Smith SE. Fetal pelvi-ureteric junction obstruction: predictors of outcome. Br J Urol 1995; 76:

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