FETAL RENAL ANOMALIES: diagnosis, management and outcome · Webb NJ, Lewis MA, Bruce J, Gough DC,...

FETAL RENAL ANOMALIES: diagnosis, management and outcome.

cover: Albert Damen sr. print Budde-Elinkwijk, Nieuwegein

FETAL RENAL ANOMALIES: diagnosis, management and outcome

Afwijkingen aan nieren en urinewegen bij de foetus: diagnose, behandeling en uitkomst.

(met een samenvatting in het Nederlands)

Proefschrift

ter verkrijging van de graad van doctor

aan de Universiteit Utrecht

op gezag van de Rector Magnificus, Prof. dr. W.H. Gispen,

ingevolge het besluit van het College voor Promoties

in het openbaar te verdedigen op

dinsdag 14 december 2004 des middags te 14.30 uur

door

Henrica Antonia Maria Damen – Elias

geboren te Tegelen, 27 mei 1941

Promotor: Prof. dr. G.H.A. Visser Department of Perinatology and Gynaecology

University Medical Centre Utrecht

Copromotores: Dr. T.P.V.M. de Jong Department of Paediatric Urology University Medical Centre Utrecht

Dr. P.H. Stoutenbeek Department of Perinatology and Gynaecology University Medical Centre Utrecht

ISBN: 90-9018851-7

CIP-DATA KONINKLIJKE BIBLIOTHEEK DEN HAAG Damen-Elias, Henrica Antonia Maria FETAL RENAL ANOMALIES: diagnosis, management and outcome Utrecht, Universiteit Utrecht, Faculteit Geneeskunde Thesis Universiteit Utrecht

Financial support for the publication of the this thesis is gratefully acknowledged: Stichting Kindernierziekten Easote Pie Medical Toshiba Medical Systems Europe Nierstichting Nederland

What does wisdom benefits us, if we do not possess love.

Referents: Prof. dr. F. van Bel Department of Neonatology

University Medical Centre Utrecht

Prof. dr. J.L.H.R. Bosch Department of Urology University Medical Centre Utrecht

Prof. dr. H.W. Bruinse

Department of Perinatology and Gynaecology University Medical Centre Utrecht

Prof. dr. J.M. Nijman

Department of Urology University Medical Centre Groningen

Prof. dr. J.W. Wladimiroff

Department of Obstetrics and Gynaecology Erasmus Medical Centre Rotterdam

Paranimfen: Drs. P.J. Damen

Mevr. M.J. Korenromp

Table of contents 7

Chapter 1 Introduction and aims of the thesis Chapter 2 Intra- and interobserver variability of fetal kidney and adrenal gland measurements

revised version resubmitted to Ultrasound in Obstetrics and Gynaecology

Chapter 3 Growth and size charts of the fetal kidney and the renal pelvis


Chapter 4 Growth and size charts of the fetal adrenal gland


Chapter 5 Congenital renal tract anomalies: outcome and follow-up of 402 cases detected antenatally over a period of 15 years.

in press: Ultrasound in Obstetrics and Gynaecology

Chapter 6 Concomitant anomalies in 100 children with unilateral multicystic kidney


Chapter 7 Mild pyelectasis diagnosed by prenatal ultrasound is not a predictor of urinary tract morbidity in childhood


Chapter 8 Variability in dilatation of the fetal renal pelvis during a bladder filling cycle


Chapter 9 Summary, discussion and conclusion

Nederlandse samenvatting

Dankwoord

Curriculum Vitae

Chapter 1 Introduction, aims and outline of the thesis

10 Chapter 1

introduction

Interest in fetal development has grown enormously in the past decades. Till then

non-invasive methods were used to asses fetal health such as the feeling of

movements by the pregnant woman, measuring growth by palpation of the fundal

height and auscultation of the fetal heart tones with a wooden stethoscope. X-ray

examination was used in search for fetal abnormalities and to diagnose multiple

pregnancies but the questionable safety of such investigation in pregnancy made this

method unsuitable for routine examinations.

All changed when it became possible to observe the fetus in utero by ultrasound. As

early as 1958, Donald et al1 showed the outline of the fetal skull. The technical and

methodological development of this technique made it possible to investigate the

fetus directly and the consequence of this quickly expanding and improving new

technique has been an increasing amount of information concerning fetal

morphological and physiological development during pregnancy. Further

improvement of the equipment with high-resolution real-time ultrasound has given the

possibility to more detailed information of the fetus and later on transvaginal

sonography has made it possible to obtain detailed information of early embryonic

development.

The introduction of routine prenatal ultrasound scanning since the early 1980’s in

several countries in Europe has increased our knowledge on morphology and

functional development of the fetus. Moreover it became possible to diagnose

anomalies in utero. In population studies minor or major structural anomalies are

detected in 2 to 3 % of cases2-5. Abnormalities of the urinary tract account for 15-20%

of these anomalies with a detection rate of approximately 90%2, 4.

The fetal kidneys can first be visualised by transabdominal ultrasound at 9 weeks

gestational age and can be seen in all cases from 12 weeks onwards. In early

pregnancy the echogenity of the fetal kidneys is high but this decreases in the course

of gestation when they become hypoechoic6. At about 28 weeks the renal pyramids

can be detected and also the borders of the kidneys can be seen more clearly with

progressing gestational age, since fat tissue is developing around the kidneys from

that moment on.

introduction, aims and outline 11

The fetal bladder can be visualised from the onset of urine production, which occurs

at about 10 weeks gestation7. At 11 weeks of gestation the bladder can be visualised,

both transvaginally and transabdominally, in 80% of fetuses and at 13 weeks

almost in all fetuses8, 9. It should always be possible to visualize the bladder when

the crown-rump length is more than 67 mm (13+ weeks).

The fetal adrenal glands are visible by ultrasonography as early as 9 weeks of

gestation and in all cases from 12 weeks onwards. In the second trimester they

appear as a disc-like structure in a transverse plane, cranially and medially to the

kidney. Three layers can clearly be distinguished of which the outer layer is

hypoechogenic and the central medulla hyperechoic. In the sagittal view they appear

as heart-shaped figures of low echogenicity.

During the last three decades numerous papers have dealed with the fetal renal

system and its anomalies. Follow-up studies on (long term) outcome are, however,

scarce and this hampers adequate counselling of parents and giving appropriate

treatment advice. Moreover, up to date charts on normal fetal kidney size and growth

are scarce. We therefore formulated the following aims of this thesis.

aims of the thesis

1 – To develop charts of size and growth of the fetal kidney, renal pelvis and adrenal

gland.

2 – To study long-term follow-up of a large cohort of infants with an antenatally

diagnosed renal tract anomaly.

3 – To answer the question whether mild pyelectasis (anteroposterior diameter of the

fetal renal pelvis of 5 – 10 mm) as diagnosed around 18 to 20 weeks of gestation

results in increased morbidity in childhood and therefore requires postnatal

treatment.

4 – To study the relationship between the size of the renal pelvis and the fetal

bladder-filling cycle, to answer the question if fixed cut-off values regarding renal

pelvis dilatation can be used or whether bladder filling has to be taken into account.

12 Chapter 1

outline of the thesis

In Chapters 2 to 4 a prospective longitudinal study is described on size and growth of

the fetal kidney, the fetal renal pelvis and the fetal adrenal gland in 111 fetuses from

16 weeks gestational age onwards till term. These studies were preceded by a study

on intra- and inter-observer variation.

In Chapter 5 we describe the findings and outcome of a large cohort of 402 fetuses in

which urogenital anomalies were detected antenatally. We could use the database of

the ultrasound unit of the department of obstetrics of the University Medical Centre,

Utrecht, The Netherlands, which was established in 1986. At follow-up the youngest

infant was 3 years and the oldest was 17 years (median 7 years 11 months).

In Chapter 6 we present the outcome of 100 fetuses with an antenatally detected

unilateral multicystic kidney. All additional urogenital and other anomalies are

described. According to the advice of the Dutch Society of Paediatric Urology the

non-functioning cystic kidney is removed at approximately 6 months of age to prevent

life-time follow-up of these children because of an increased risk of hypertension10,

infection11 or malignancy12, 13. When the parents decided to do so, each child

underwent a cystoscopy and girls also a colposopy prior to the operation. All these

findings are included in the follow-up of these children (median 5 years and 4

months).

For Chapter 7 we could use the data of the ultrasound department of the Amphia

Hospital, Oosterhout, The Netherlands, which was established since 1982. Two

hundred and eight children, who had had a mild pyelectasis of 5 – 10 mm at 18 to 20

weeks gestation, were compared with 416 matched controls regarding voiding and

defecation patrons and urinary tract infections. A validated questionnaire, as used in

the International Reflux Study in children, was used for this purpose.

In Chapter 8 we describe a study in which 18 third trimester pregnant women are

examined by ultrasound during several fetal bladder-filling cycles, to investigate if

there is a correlation between the size of the renal pelvis and the extent of bladder

filling.

In Chapter 9 a summary and general discussion is described.

introduction, aims and outline 13

references 1 Donald I, Macvicar J, Brown TG. Investigation of abdominal masses by pulsed ultrasound. Lancet 1958;1(7032):1188-95. 2. Grandjean H, Larroque D, Levi S. Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team. Ann N Y Acad Sci 1998;847:118-24. 3. Levi S. Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening for second trimester fetal malformations. Prenat Diagn 2002;22(4):285-95. 4. Levi S. Mass screening for fetal malformations: the Eurofetus study. Ultrasound Obstet Gynecol 2003;22(6):555-8. 5. Stoll C, Clementi M. Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe. Ultrasound Obstet Gynecol 2003;21(6):543-51. 6. Green JJ, Hobbins JC. Abdominal ultrasound examination of the first-trimester fetus. Am J Obstet Gynecol 1988;159(1):165-75. 7. McHugo J, Whittle M. Enlarged fetal bladders: aetiology, management and outcome.Prenat Diagn 2001;21(11):958-63. 8. Rosati P, Guariglia L. Transvaginal sonographic assessment of the fetal urinary tract in early pregnancy. Ultrasound Obstet Gynecol 1996;7(2):95-100. 9. Braithwaite JM, Armstrong MA, Economides DL. Assessment of fetal anatomy at 12 to 13 weeks of gestation by transabdominal and transvaginal sonography. Br J Obstet Gynaecol 1996;103(1):82-5. 10. Webb NJ, Lewis MA, Bruce J, Gough DC, Ladusans EJ, Thomson AP, et al. Unilateral multicystic dysplastic kidney: the case for nephrectomy. Arch Dis Child 1997;76(1):31-4. 11. Wacksman J, Phipps L. Report of the Multicystic Kidney Registry: preliminary findings. J Urol 1993;150(6):1870-2. 12. Elder JS, Hladky D, Selzman AA. Outpatient nephrectomy for nonfunctioning kidneys. J Urol 1995;154(2 Pt 2):712-4; discussion 714-5. 13. LaSalle MD, Stock JA, Hanna MK. Insurability of children with congenital urological anomalies. J Urol 1997;158(3 Pt 2):1312-5.

Chapter 2 Intra- and interobserver variability of fetal kidney and adrenal gland

measurements

H.A.M. Damen - Eliasa, G.H.A. Vissera, P. Westers b, L. Pistorius a

a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Centre for Biostatistics, Utrecht University, The Netherlands

16 Chapter 2

ABSTRACT

Objectives: To assess the intra- and interobserver variability of fetal kidney and fetal

adrenal gland measurement by ultrasound.

Methods: Data were obtained prospectively by experienced ultrasonographers. Thirty

fetuses were measured for the intraobserver analysis and 20 fetuses for the

interobserver analysis. Length, anteroposterior and transverse diameter from both

the right and left kidney and from the length of the right and left adrenal gland were

measured 3 times. Statistical analysis was performed by SPSS.

Results: The reproducibility of the measurements of the kidney and of the adrenal

gland were good with an intraclass correlation above 0,80 for all measurements for

both the intraobserver and interobserver analysis.

Conclusions: The high degree of intra- and interobserver reproducibility indicates that

the three dimensions of the kidney and adrenal gland length are technically feasible

to measure.

Intra- and interobserver variability 17

INTRODUCTION

Many reference curves of the fetal renal kidney have been published1-7. Knowledge of

the normal range of the measurements of the fetus is essential when during

screening an anomaly is identified. No intraobserver and interobserver variation

analysis was done prior to any of these studies. Only Bertagnoli2 in 1983 reported on

the differences in measurements between 3 operators who each used a different

ultrasound machine. Some studies describe the design, the patient selection and the

methods of analysis8-10 but do not involve differences in intraobserver and

interobserver measurements. The discriminatory ability of a diagnostic test is in large

extent depending on the repeatability of the test.

The aim of this study was to assess the intra- and interobserver reproducibility of the

length, the anteroposterior and the transverse measurements of the fetal kidney and

of the length of the adrenal gland by ultrasound.

MATERIALS AND METHODS

Thirty pregnant women were asked to participate in the study for the intraobserver

variation analysis and another twenty for the interobserver variation analysis. All

women consented to participate in the study There were no exclusion criteria. Two

experienced ultrasonographers, (HDE, LP) examined the fetuses. Each observer

attempted to obtain three measurements with different time intervals between each

measurement. The sonographers were not allowed to see their own measurements

or to watch each other performing the measurements to avoid any possible

influence.

In both investigations the length, the anteroposterior and transverse diameter of the

kidney and the length of the adrenal gland were measured transabdominally with the

multifrequency transducer PVM 375 AT of the Toshiba Power Vision 6000, type SSA

370 A (manufacturer Toshiba, Tokyo, Japan).

In a sagittal plane when the full length of the kidney with the renal pelvis was

visualised the length of the kidney was measured and in the same sectional plane

the length of the combination of the kidney and the adrenal gland. Subsequently the

length of the adrenal gland was determined by subtraction of the kidney length from

the combined length. Perpendicular to this plane in the largest sectional plane, the

anteroposterior and transverse diameter of both kidneys were measured. The data

18 Chapter 2

were recorded on a photograph and stored in a database.

Statistical analysis was performed by using SPSS, version 10.1 (Statistical Product

and Service Solutions, Chicago). The mean and standard deviation were calculated

to determine if there was a good consistency between the measurements. In addition

the range, the Cronbachs alpha (α) and the intra class correlation (ICC) were

calculated. The range is the distance between the highest and lowest value.

Cronbachs α is a statistical index for internal consistency between the

measurements. The index ranges from 0 = bad to 1 = excellent. The ICC is the

measure of concordance and is a statistic that describes the reproducibility of

repeated measures in the same subject and indicates true variance as a fraction of

the total variance. Landis and Koch11 have indicated the meaning of the different

values of the ICC and a value of 0.61-0.80 has a good agreement and larger > 0.81

an excellent one. The value of ICC of 1 for repeated measurements indicates perfect

reproducibility while a value of 0 is interpreted as no better or worse than that

expected by chance.

RESULTS

intraobserver variation analysis

The kidney length, kidney anteroposterior diameter, kidney transverse diameter and

adrenal gland length could be measured 3 times in all 30 women. Intraobserver

agreement is given in Table 1. Statistic analysis shows a high alpha above the 0,9

and also a high IC above 0,8 for all different measurements.

Table 1 – Intraobserver variation of length, anteroposterior and transverse diameter of the kidney and of length of the adrenal gland.

variable mean ± std.dev alpha intra class correlation (95% CI) RiKiL 22,706 ± 3.486 0.956 0.955 (0.924 – 0.976) LeKiL 22,413 ± 3.434 0.970 0.969 (0.947 – 0.983) RiKiAP 15,217 ± 2.292 0.912 0.911 (0.850 – 0.952) LeKiAP 15,190 ± 2.232 0.919 0.918 (0.862 – 0.956) RiKiTr 15,172 ± 2.238 0.933 0.931 (0.883 – 0.963) LeKiTr 15,412 ± 2.391 0.939 0.937 (0.893 – 0.967) RiGL 5,316 ± 1.259 0.935 0.931 (0.885 – 0.963) LeGL 5,275 ± 1.345 0.930 0.928 (0.879 – 0.962)

RiKiL = right kidney length, LeKiL = left kidney length, RiKiAP = right kidney anterior/ posterior diameter, LeKiAP = left kidney anterior/ posterior diameter, RiKiTr = right kidney transverse diameter, LeKiTr = left kidney transverse diameter, RiGL = right adrenal gland length, LeGL = left adrenal gland length.

Intra- and interobserver variability 19

interobserver variation analysis

Both investigators could take all measurements 3 times in all 20 women. The

interobserver analysis is given in Table 2. There was a high alpha above 0,9 for all

measurements as well as a high IC above 0,8. There was a high level of agreement

between the two observers.

Table 2 - Interobserver variation of length, anteroposterior diameter and transverse diameter of the kidney and of length of the adrenal gland.

HDE* = observer 1, LP# = observer 2 RiKiL = right kidney length, LeKiL = left kidney length, RiKiAP = right kidney anterior/ posterior diameter, LeKiAP = left kidney anterior/ posterior diameter, RiKiTr = right kidney transverse diameter, LeKiTr = left kidney transverse diameter, RiGL = right adrenal gland length, LeGL = left adrenal gland length. DISCUSSION

Measurements of the kidney are of importance when an anomaly is identified.

Measurements of the adrenal gland may be of importance in high-risk pregnancies

when intra uterine growth retardation is suspected12-14, when mothers use

glucocosteriods15 for a prolonged period of time or in case of congenital adrenal

hyperplasia16, 17. A valuable screenings test should be both feasible and repeatable.

An intra- and interobserver analysis should be evaluated and measurements should

only be introduced in routine setting if a good sensitivity and specificity is

demonstrated. It was technically feasible to take three measurements of the fetal

kidney and the length of the adrenal gland. We used various indices and coefficients

to assess intra- and interobserver variability and found a good agreement of both for

the intraobserver analysis and for the interobserver analysis. Comparison of our

results with those of others is not possible because there is no study in literature on

intra- and interobserver analysis of fetal kidney and adrenal gland measurements.

variable mean ± st.dev observer 1 observer 2

range .

alpha intraclass correlation 95% CI)

HDE* LP# HDE LP RiKiL 34.320 ± 8.155 34.530 ± 8.043 0.265 0.460 0.997 0.9822 (0.967 – 0.992) LeKiL 33.823 ± 7.782 34.115 ± 7.611 0.185 0.265 0.999 0.9928 (0.987 – 0.997) RiKiAP 19.936 ± 3.848 19.090 ± 3.907 0.315 0.100 0.992 0.9513 (0.912 – 0.978) LeKiAP 19.260 ± 4.271 18.960 ± 4.032 0.245 0.075 0.998 0.9392 (0.891 – 0.997) RiKiTr 23.411 ± 5.754 23.460 ± 5.955 0.992 0.110 0.996 0.9786 (0.961 – 0.990) LeKiTR 22.676 ± 5.043 22.045 ± 5.200 0.115 0.115 0.978 0.9445 (0.900 – 0.972) RiGL 8.916 ± 2.068 8.696 ± 1.841 0.996 0.973 0.986 0.9094 (0.841 – 0.957) LeGL 8.921 ± 1.975 8.738 ± 1.803 0.215 0.145 0.971 0.8481 (0.744 – 0.926)

20 Chapter 2

REFERENCES 1. Jeanty P, Dramaix-Wilmet M, Elkhazen N, Hubinont C, van Regemorter N. Measurements of fetal kidney

growth on ultrasound. Radiology 1982;144(1):159-62.

2. Bertagnoli L, Lalatta F, Gallicchio R, Fantuzzi M, Rusca M, Zorzoli A, et al. Quantitative characterization of

the growth of the fetal kidney. J Clin Ultrasound 1983;11(7):349-56.

3. Sagi J, Vagman I, David MP, Van Dongen LG, Goudie E, Butterworth A, et al. Fetal kidney size related to

gestational age. Gynecol Obstet Invest 1987;23(1):1-4.

4. Pruggmayer M, Terinde R. [Fetal kidney screening: growth curves and indices]. Geburtshilfe Frauenheilkd

1989;49(8):705-10.

5. Cohen HL, Cooper J, Eisenberg P, Mandel FS, Gross BR, Goldman MA, et al. Normal length of fetal

kidneys: sonographic study in 397 obstetric patients. AJR Am J Roentgenol 1991;157(3):545-8.

6. Scott JE, Wright B, Wilson G, Pearson IA, Matthews JN, Rose PG. Measuring the fetal kidney with

ultrasonography. Br J Urol 1995;76(6):769-74.

7. Chitty LS, Altman DG. Charts of fetal size: kidney and renal pelvis measurements. Prenat Diagn

2003;23(11):891-7.

8. Royston P, Wright EM. How to construct 'normal ranges' for fetal variables. Ultrasound Obstet Gynecol

1998;11(1):30-8

9. Altman DG, Chitty LS. Design and analysis of studies to derive charts of fetal size. Ultrasound Obstet

Gynecol 1993;3(6):378-84.

10. Altman DG, Chitty LS. Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994;101(1):29-34.

11. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics

1977;33(1):159-74.

13. Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal adrenal gland

in utero. Int J Gynaecol Obstet 1985;23(5):355-9.

14. Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal adrenal gland

in utero: clinical application. Gynecol Obstet Invest 1988;25(1):16-22.

15. Bronshtein M, Tzidony D, Dimant M, Hajos J, Jaeger M, Blumenfeld Z. Transvaginal ultrasonographic

measurements of the fetal adrenal glands at 12 to 17 weeks of gestation. Am J Obstet Gynecol

1993;169(5):1205-10.

Intra- and interobserver variability 21 16. Esser T, Chaoui R. Enlarged adrenal glands as a prenatal marker of congenital adrenal hyperplasia: a

report of two cases. Ultrasound Obstet Gynecol 2004;23(3):293-7.

17. Saada J, Grebille AG, Aubry MC, Rafii A, Dumez Y, Benachi A. Sonography in prenatal diagnosis of

congenital adrenal hyperplasia. Prenat Diagn 2004;24(8):627-30.

Chapter 3 Growth and size charts of the fetal kidney and the renal pelvis.

H.A.M. Damen - Eliasa, R.H. Stigtera,c, P. Westers b, G.H.A. Vissera

a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Centre for Biostatistics, Utrecht University, The Netherlands c Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands

24 Chapter 3

ABSTRACT

Objectives The aim of this study was to develop a reference curve for the size and

growth of the fetal kidney and of the fetal renal pelvis.

Methods Prospective longitudinal study including 111 fetuses. Ultrasound

examinations were made every four weeks beginning in one half of the cases at 16

weeks and in the other half at 18 weeks. Length, anteroposterior and transverse

diameter from both the right and left kidney and the anteroposterior diameter and

transverse diameter from the right and left renal pelvis were measured. Statistical

analysis was performed by multilevel analysis.

Results Fitted 5th, 50th and 95th centile charts are presented with the raw data.

Comparisons were made with previously published data.

Conclusions The new charts for size and growth are of use for the three dimensions

and for the perimeter of the fetal kidney and for the size of the renal pelvis.

Charts of fetal kidney and renal pelvis 25

INTRODUCTION

Knowledge of the normal range of the dimensions of the fetal kidney and renal pelvis

is essential. Various papers on the intrauterine growth of the renal size have been

published but many failed to validate gestational age by measuring crown-rump

length1-5, do not cover the whole of the second and third trimester of pregnancy1, 2, 6-8,

did not measure the kidney in three dimensions1, 2, 4-6 or used only pre-term born

children or post-mortem specimens9-11. Several studies used a mixture of cross-

sectional and longitudinal data1, 3-6, 8, 11.

Cross-sectional data obtained by measurements of each fetus on a single occasion

give information on size, whereas longitudinal data obtained by measurements of

fetuses on a series of occasions may be used for a reference curve for size and

growth12-15. The difficulty of any longitudinal study to construct nomograms is that

there are some missing data. This problem has been overcome by the approach of

multilevel analysis, which is able to correct for this problem16. This statistical

technique allows for the dependency of measurements in hierarchically structured

data, whereas traditional regression analysis presupposes the independence of

observations. Another advantage of this technique is that it can separately examine

the effects of variables of different levels (repeated measures) and can also be used

when measurements have been made at different times (e.g. recordings at 16

weeks, at 16 2/7 weeks or 16 6/7 weeks of gestation).

An intraobserver and interobserver variation analysis forms no part of any publication

of reference curves of the fetal renal kidney. Only Bertagnoli6 in 1983 performed an

interobserver analysis between 3 operators who each used a different ultrasound

machine. Some studies describe the design, the patient selection and the methods of

analysis but do not report on intra- or interobserver error12, 13, 15.

The aim of this study was to estimate a reference curve for the size and growth of the

fetal kidney and fetal renal pelvis.

26 Chapter 3

MATERIAL AND METHODS

One hundred and twelve low risk women with 116 fetuses (4 twin pregnancies) were

asked during an ultrasound scan for validating gestational age by measuring the

crown-rump length, to participate in the study. After written informed consent the

women were divided in two groups in order of registration. One half was examined at

around 16 – 20 – 24 - 28 - 32 - 36 and 40 weeks of gestational age and the other half

at around 18 – 22 – 26 – 30 – 34 - 38 and 42 weeks of gestational age. All

examinations were made by one ultrasonographer (HDE), using the multifrequency,

abdominal transducer PVM 375 AT of the Toshiba Power Vision 6000, type SSA 370

A with (manufacturer Toshiba, Tokyo, Japan). An intra- and interobserver variation

analysis preceded the study resulting in a good consistency in measurements.

Exclusion criteria were: mono-chorionic twin pregnancies, chromosomal or congenital

defects of the fetus, small for gestational age at birth (SGA = weight at birth <2.3%(17)

percentile for gestational age) and maternal disease which might effect fetal growth

(diabetes mellitus, hypertension requiring treatment).

The length of the kidney was measured when in a sagittal plane the full length with

the renal pelvis was visualised. Perpendicular to this, in the largest sectional plane,

the anteroposterior (AP) and transverse diameter of the kidney were measured by

placing the callipers from outer to outer border. In the same sectional plane the AP

and transverse diameters of the renal pelvis were measured by placing the callipers

on the inner borders of the renal tissue. All measurements were obtained three times

and the data were averaged and stored in a database.

Statistical analysis was performed by multilevel analysis with the software program

Mln (Multilevel Model Project, London, UK)16 and SPSS, version 10.1 (Statistical

Product and Service Solutions, Chicago) to construct nomograms (medians and the

5th and 95th centiles).

RESULTS

Five fetuses were excluded: small for gestational age (n=2), congenital anomalies

(n=3; triploidy, clubfoot and hydronephrosis >10mm anteroposterior diameter of the

renal pelvis). Of the remaining 107 woman and 111 fetuses all measurements could

be obtained from both kidneys and both renal pelves with a total of 628 data for each

separate measurement for length, anteroposterior diameter and transverse diameter


of both kidneys and for the anteroposterior and transverse diameter of both renal

pelves.

Statistical analysis was performed on all separate measurement from the right and

left fetal kidney. The charts of length, anteroposterior and transverse diameter and

perimeter of the left and right kidney were about identical with a high correlation

coefficient between the measurements from the right and left side: R = 0.993 for

length, R = 0.976 for AP-diameter, R = 0.969 for transverse diameter and R = 0.986

for perimeter.

There was no asymmetry between the right and left renal pelvic measurements

(Table 1: Kappa 0,459). The charts made of the anteroposterior and transverse

diameter of the right and left renal pelvis were similar with correlation coefficients

between measurements of the right and left side of: R = 0.777 for the AP-diameter

and R = 0.795 for the transverse diameter. In only 16 of 628 comparisons between

right and left pelvic size there was a difference of more than 2 millimetres between

the measurements (Table 1).

Table 1 – Partition of the dimensions of the right and left renal pelvis. Kappa 0,459

The data of all right and left kidney and renal pelvis measurements were averaged to

obtain the reference charts. The account of the nomograms of the 5th, 50th and 95th

fitted centiles of length, anteroposterior and transverse diameter and of the perimeter

from the kidney are shown in Table 2 with the corresponding charts (Figures 1 to 4).

right renal pelvis measurements (mm) 0–<2 mm 2–<4 mm 4–<6 mm 6–<8 mm 8–<10 mm total 0 – < 2 mm 93 34 2 - - 129 2 – < 4 mm* 23 240 71 7 1 342 4 – < 6 mm - 46 74 10 - 130 6 – < 8 mm 1 5 10 8 1 25 8 – <10 mm - - - 2 - 2

left renal pelvis measurements (mm)

total 117 325 157 27 2 628

28 Chapter 3

gestational age in weeks

4238343026221814

kidn

ey

leng

th (

mm

)

60

55

50

45

40

35

30

25

20

15

10

5

0

Figure 1 – Fitted 5th, 50th and 95th centiles for the kidney length and the raw data.


4238343026221814

kidn

ey

AP

-dia

me

ter

(mm

)

30

25

20

15

10

5

0

Figure 2 – Fitted 5th, 50th and 95th centiles for the anteroposterior kidney diameter and the raw data.



4238343026221814

kidn

ey t

rans

vers

e d

iam

eter

(m

m)

40

35

30

25

20

15

10

5

0

Figure 3 – Fitted 5th, 50th and 95th centiles of the transverse kidney diameter and the raw data.


4238343026221814

kidn

ey

perim

ete

r

100

90

80

70

60

50

40

30

20

10

0

Figure 4 – Fitted 5th, 50th and 95th centiles of the perimeter of the kidney and the raw data.

Tab

le 2

– F

itted

cen

tiles

of f

etal

ren

al k

idne

y le

ngth

, ant

erop

oste

rior

diam

eter

, tra

nsve

rse

diam

eter

and

per

imet

er w

ith th

e nu

mbe

r of

fetu

ses

for

exac

t wee

ks b

etw

een

16 a

nd 4

2 w

eeks

of g

esta

tiona

l age

.

wee

ks o

f ge

stat

ion

N

fetu

ses

fitte

d ce

ntile

s ki

dney

leng

th

fitte

d ce

ntile

s ki

dney

ant

erop

oste

rior

diam

eter

fit

ted

cent

iles

kidn

ey tr

ansv

erse

dia

met

er

fitte

d ce

ntile

s ki

dney

per

imet

er

5th

50

th

95th

SD

5th

50

th

95th

SD

5th

50

th

95th

SD

5th

50

th

95th

SD

16

55

12

,9

14,3

15

,7

0,70

7

,4

8,6

9

,8

0,

60

7,3

8,6

9,

9

0,

66

23,5

27

,0

30,6

1,

80

17

14

,3

15,7

17

,2

0,74

8

,2

9,5

10

,7

0,

64

8,3

9,7

11

,1

0,

70

26,2

29

,9

33,7

1,

91

18

56

15,6

17

,1

18,7

0,

79

9,0

10

,4

11,7

0,68

9,

3 10

,8

12,2

0,74

29

,2

33,2

37

,2

2,03

19

16,9

18

,5

20,2

0,

84

9,8

11

,2

12,6

0,71

10

,3

11,8

13

,2

0,

78

31,8

36

,0

40,2

2,

14

20

55

18,2

19

,9

21,6

0,

88

10,6

12

,1

13,5

0,75

11

,2

12,8

14

,4

0,

82

34,6

39

,1

43,5

2,

26

21

20

,0

21,8

23

,7

0,94

11

,3

12,8

14

,4

0,

79

12,1

13

,9

15,4

0,86

37

,9

42,3

46

,9

2,39

22

56

20

,7

22,6

24

,5

0,96

12

,0

13,6

15

,3

0,

83

13

14,8

16

,5

0,

90

39,8

44

,6

49,5

2,

48

23

22

,0

24,0

25

,9

1,00

12

,7

14,4

16

,1

0,

86

13,9

15

,7

17,6

0,94

42

,3

47,3

52

,4

2,59

24

55

23

,2

25,3

27

,3

1,05

13

,4

15,1

16

,9

0,

90

14,7

16

,6

18,6

0,99

44

,6

49,9

55

,2

2,71

25

24,5

26

,6

28,7

1,

10

14,0

15

,8

17,7

0,95

15

,5

17,5

19

,5

1,

03

46,8

52

,4

57,8

2,

84

26

56

25,6

27

,9

30,1

1,

14

14,6

16

,5

18,4

0,98

16

,3

18,4

20

,5

1,

07

49,1

54

,8

60,6

2,

93

27

26

,8

29,0

31

,3

1,19

15

,2

17,2

19

,2

1,

00

17

19,3

21

,4

1,

10

50,9

57

,2

62,8

3,

05

28

55

28,0

30

,4

32,8

1,

23

15,7

17

,8

19,9

1,05

17

,8

20,1

22

,3

1,

15

53,3

59

,5

65,7

3,

16

29

29

,2

31,7

34

,2

1,27

16

,3

18,4

20

,6

1,

10

18,5

20

,8

23,2

1,19

55

,3

61,7

68

,1

3,27

30

54

30

,3

32,9

35

,5

1,31

16

,8

19,0

21

,2

1,

13

19,2

21

,6

24

1,

23

57,2

63

,8

70,5

3,

38

31

31

,5

34,2

36

,8

1,35

17

,3

19,6

21

,8

1,

17

19,9

22

,4

24,9

1,27

59

,0

65,9

72

,7

3,50

32

55

32

,6

35,3

38

,1

1,40

17

,7

20,1

22

,5

1,

20

20,5

23

,1

25,7

1,31

60

,8

67,9

74

,9

3,61

33

34,3

36

,5

40,1

1,

43

18,4

20

,6

23,4

1,23

21

,2

23,7

26

,5

1,

35

63,1

69

,5

77,5

3,

71

34

53

35,0

37

,7

40,8

1,

49

18,6

21

,1

23,6

1,28

21

,8

24,5

27

,2

1,

40

64,1

71

,6

79,1

3,

83

35

36

,0

38,9

41

,9

1,52

19

,0

21,6

24

,1

1,

31

22,4

25

27

,9

1,

43

65,7

73

,4

81,2

3,

92

36

52

37,0

40

,0

43,1

1,

57

19,3

22

,0

24,7

1,35

22

,9

25,8

28

,7

1,

48

67,1

75

,0

83,0

4,

06

37

37

,9

41,0

44

,2

1,61

19

,7

22,4

25

,1

1,

39

23,5

26

,4

29,5

1,52

68

,5

76,7

84

,8

4,17

38

51

38

,8

42,0

45

,2

1,66

20

,0

22,8

25

,6

1,

43

23,9

27

30

1,56

69

,8

78,2

86

,6

4,29

39

39,6

42

,9

46,2

1,

71

20,3

23

,2

26,0

1,47

24

,4

27,5

30

,7

1,

60

71,0

79

,6

88,3

4,

40

40

21

40,4

43

,8

47,1

1,

75

20,6

23

,5

26,5

1,50

24

,8

28,1

31

,3

1,

64

72,2

81

,0

89,9

4,

51

41

41

,1

44,8

48

1,

79

20,8

23

,8

26,8

1,54

25

,2

28,5

31

,8

1,

68

73,3

82

,3

91,4

4,

61

42

2 41

,8

45,6

48

,8

1,81

21

,1

24,1

27

,2

1,

57

25,6

28

,9

32,2

1,72

74

,4

83,6

92

,9

4,68

to

tal

111


The account of the nomograms of the 5th, 50th and 95th fitted centiles of the

anteroposterior and transverse diameter from the renal pelvis are given in Table 3

with the corresponding charts (Figures 5 and 6).

Table 3 - Fitted centiles of the anteroposterior and transverse diameter of the fetal renal pelvis with the number of fetuses for exact weeks between 16 and 42 weeks of gestational age

weeks of gestation

N fetuses

fitted centiles pelvis anteroposterior diameter

fitted centiles pelvis transverse diameter

5th 50th 95th SD 5th 50th 95th SD 16 55 0,2 1,1 1,9 0,4 - 0,8 1,4 3,6 1,1 17 0,5 1,3 2,2 0,5 - 0,6 1,7 4,0 1,2 18 56 0,7 1,6 2,5 0,5 - 0,1 2,3 4,7 1,2 19 0,9 1,8 2,8 0,5 0,1 2,6 5,1 1,3 20 55 1,2 2,1 3,1 0,5 0,5 3,1 5,6 1,3 21 1,3 2,3 3,3 0,5 0,9 3,4 6,0 1,3 22 56 1,6 2,6 3,6 0,5 1,0 3,7 6,5 1,4 23 1,7 2,7 3,8 0,5 1,2 4,0 6,8 1,4 24 55 1,9 3,0 4,0 0,5 1,4 4,3 7,2 1,5 25 2,0 3,1 4,2 0,6 1,6 4,5 7,5 1,5 26 56 2,2 3,3 4,4 0,6 1,7 4,8 7,9 1,6 27 2,3 3,4 4,6 0,6 1,9 5,0 8,2 1,6 28 55 2,4 3,6 4,7 0,6 2,0 5,2 8,5 1,7 29 2,5 3,7 4,9 0,6 2,0 5,4 8,8 1,7 30 54 2,5 3,8 5,0 0,6 2,1 5,5 9,0 1,8 31 2,6 3,8 5,1 0,6 2,1 5,7 9,2 1,8 32 55 2,6 3,9 5,2 0,7 2,1 5,8 9,4 1,9 33 2,7 4,0 5,3 0,7 2,1 5,8 9,6 1,9 34 53 2,7 4,0 5,4 0,7 2,0 5,9 9,7 2,0 35 2,6 4,0 5,4 0,7 2,0 5,9 9,8 2,0 36 52 2,6 4,0 5,5 0,7 1,9 6,0 10,0 2,1 37 2,6 4,0 5,5 0,7 1,8 5,9 10,0 2,1 38 51 2,5 4,0 5,5 0,8 1,6 5,9 10,1 2,2 39 2,5 4,0 5,5 0,8 1,5 5,8 10,1 2,2 40 21 2,4 4,0 5,5 0,8 1,3 5,7 10,1 2,3 41 2,3 3,9 5,4 0,8 1,1 5,6 10,1 2,3 42 2 2,3 3,9 5,4 0,8 1,0 5,5 10,0 2,3

total 111

32 Chapter 3


4238343026221814

pye

lum

AP

-dia

me

ter

(mm

)10

8

6

4

2

0

-2

Figure 5 – Fitted 5th, 50th and 95th centiles of the A-P diameter of the renal pelvis and the raw data.


4238343026221814

tra

nsve

rse

pye

lum

dia

me

ter

(mm

)

14

12

10

8

6

4

2

0

-2

Figure 6 – Fitted 5th, 50th and 95th centiles of the transverse diameter of the renal pelvis and the raw data.


The centile charts were compared with previously published charts from Chitty and

Altman18 for length, AP-diameter, transverse diameter and renal pelvis

measurements and from Pruggmayer and Terinde3 for length and transverse

diameter. See figures 7, 8, 9 and 10.

0

10

20

30

40

50

60

14 16 18 20 22 24 26 28 30 32 34 36 38 40 42


kidn

ey le

ngth

(m

m)

Figure 7 – Comparison of 5th, 50th and 95th centiles for kidney length measurements obtained in this study (solid lines) and the 10th, 50th and 90th centiles of Chitty (dashed lines – – – – ) and the 5th, 50th and 95th centiles of Pruggmayer (dashed lines - - - - ).

0

5

10

15

20

25

30

35

14 16 18 20 22 24 26 28 30 32 34 36 38 40 42


kidn

ey A

-P d

iam

eter

(m

m)

Figure 8 – Comparison of 5th, 50th and 95th centiles for kidney anteroposterior diameter obtained in this study (solid lines) and the 10th, 50th and 90th centiles of Chitty (dashed lines – – – –).

34 Chapter 3

0

5

10

15

20

25

30

35

40

45

14 16 18 20 22 24 26 28 30 32 34 36 38 40 42


kidn

ey tr

ansv

erse

dia

met

er (

mm

)

Figure 9 – Comparison of 5th, 50th and 95th centiles for kidney transverse diameter obtained in this study (solid lines) and the 10th, 50th and 90th centiles of Chitty (dashed lines – – – –) and the 5th, 50th and 95th centiles of Pruggmayer (dashed lines - - - -).

0

1

2

3

4

5

6

7

8

16 20 24 28 32 36 40


rena

l pel

vis

(mm

)

Figure 10 – Comparison of 5th, 50th and 95th centiles for anteroposterior renal pelvis measurements obtained in this study (solid lines) and the 10th, 50th and 90th centiles of Chitty (dashed lines). DISCUSSION

Several charts of fetal kidney sizes have been published before, but some with

shortcomings in data collection or with methodological weaknesses. Our charts of the

fetal kidney and fetal renal pelvis were obtained from longitudinal data derived from

prospective investigations that were done specifically for the development of the

centile charts. The data were obtained from a large longitudinal sample and therefore

the charts are suitable for size and growth measurements i.e. for comparing renal

size at a known gestational age between 16 and 42 weeks of gestation and for


following the growth of the fetal kidney by comparing the measured data of the fetus

between two separate occasions with the fitted data. Until now there had not been a

chart published, which combines both possibilities, when taken into account

methodological pitfalls and incorrect methods in design such as not validating

gestational age1-5, only partly covering the second and third trimester1, 2, 6-8,

measuring only one or two dimensions of the kidney1, 2, 4-6 or averaging both cross-

sectional and longitudinal data1, 3-6, 8, 11. Moreover this study has the added

advantage that the statistical analysis used is able to correct for missing data.

We were limited in comparing our findings with previously published charts of kidney

size because several studies gave no raw data or when they did so they gave

evidence of methodological weakness or did not cover the whole second and third

trimester of pregnancy. None of the previous studies had carried out an intra- and

interobserver variation analysis before data collecting, as we did.

Chitty and Altman18 obtained their data in a cross-sectional study, including

approximately 15 to 20 cases per week. Measurements were only done once. They

published the 3rd, 10th, 50th, 90th and 97th centile. Pruggmayer and Terinde3 also

performed a cross-sectional study including 612 fetuses. They did not give data on

the number of fetuses measured each week and excluded 18.6% of infants because

they were either large or small for dates. The most obvious differences between our

kidney charts and those of the other two groups relate to the smaller ranges that we

found. The 50th centile of measurements of Chitty and Altman was higher than ours at

around 30 weeks of gestation, but almost the same near term. The 50th centile for the

transverse kidney diameter was about the same in the three studies, apart from term

age, when our data were in between those of the two other groups. It is difficult to

explain the differences between the findings of the three studies. The fact that we

have repeated the measurements three times may have resulted in narrowed ranges.

Regarding the fetal renal pelvic dimensions only two charts have been published

before. Chitty et al18 published a chart based on cross-sectional data from fetuses

measured only once for the purpose of the study but examined only a low number of

fetuses at each week of gestation (3 to 11: mean 7). Scott5 published a chart with a

mixture of cross-sectional and longitudinal data obtained during routine scanning and

36 Chapter 3

as a consequence some fetuses were only included once whereas others were

included at many ages; the resulting scatter diagrams of kidney and pelvis sizes

show many data at around 18-20 weeks and at around 32-34 weeks and a lack data

beyond 36 weeks of gestational age. They did not publish the raw data. We therefore

only compared our chart with the one published by Chitty and Altman. Their chart

suggests a linear growth of the renal pelvis size, with a wide range, whereas ours

shows a curved line, with no increase size from 32 weeks onwards, an a

considerable narrower range (especially, when taken into account the fact that we

gave the 5th, 50th and 95th centile and Chitty and Altman the 10th, 50th and 90th

centiles) (Figure 8).

Renal pathology often presents itself late in pregnancy. A chart for size and growth

chart of the kidney may be useful in case of diagnostic problems. The same holds for

renal pelvic dilatation, which is a common sonographic finding in pregnancy.


REFERENCES

1. Cohen HL, Cooper J, Eisenberg P, Mandel FS, Gross BR, Goldman MA, et al. Normal length of fetal kidneys: sonographic study in 397 obstetric patients. AJR Am J Roentgenol 1991;157(3):545-8. 2. Gloor JM, Breckle RJ, Gehrking WC, Rosenquist RG, Mulholland TA, Bergstralh EJ, et al. Fetal renal growth evaluated by prenatal ultrasound examination. Mayo Clin Proc 1997;72(2):124-9. 3. Pruggmayer M, Terinde R. [Fetal kidney screening: growth curves and indices]. Geburtshilfe Frauenheilkd 1989;49(8):705-10. 4. Sagi J, Vagman I, David MP, Van Dongen LG, Goudie E, Butterworth A, et al. Fetal kidney size related to gestational age. Gynecol Obstet Invest 1987;23(1):1-4. 5. Scott JE, Wright B, Wilson G, Pearson IA, Matthews JN, Rose PG. Measuring the fetal kidney with ultrasonography. Br J Urol 1995;76(6):769-74. 6. Bertagnoli L, Lalatta F, Gallicchio R, Fantuzzi M, Rusca M, Zorzoli A, et al. Quantitative characterization of the growth of the fetal kidney. J Clin Ultrasound 1983;11(7):349-56. 7. Bernaschek G, Kratochwil A. [Ultra-sound study on the growth of the fetal kidney in the second half of pregnancy (author's transl)]. Geburtshilfe Frauenheilkd 1980;40(12):1059-64. 8. Jeanty P, Dramaix-Wilmet M, Elkhazen N, Hubinont C, van Regemorter N. Measurements of fetal kidney growth on ultrasound. Radiology 1982;144(1):159-62. 9. Chiara A, Chirico G, Barbarini M, De Vecchi E, Rondini G. Ultrasonic evaluation of kidney length in term and preterm infants. Eur J Pediatr 1989;149(2):94-5. 10. Gonzales J. [Anatomical measurements during fetal growth of the kidney. Its value for the ultrasonographer and the anatomo-pathologist (author's transl)]. J Gynecol Obstet Biol Reprod (Paris) 1981;10(2):113-7. 11. Vries de L, Levene MI. Measurement of renal size in preterm and term infants by real-time ultrasound. Arch Dis Child 1983;58(2):145-7. 12. Altman DG, Chitty LS. Design and analysis of studies to derive charts of fetal size. Ultrasound Obstet Gynecol 1993;3(6):378-84. 13. Altman DG, Chitty LS.Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994;101(1):29-34. 14. Royston P, Altman DG. Design and analysis of longitudinal studies of fetal size. Ultrasound Obstet Gynecol 1995;6(5):307-12. 15. Royston P, Wright EM. How to construct 'normal ranges' for fetal variables. Ultrasound Obstet Gynecol 1998;11(1):30-8. 16. Goldstein H. Multilevel statistical models. 2nd ed. London: University of London. ed; 1995. 17. Kloosterman GJ. On intrauterine growth. Int J Gynaecol Obstet 1970;8:895-912. 18. Chitty LS, Altman DG. Charts of fetal size: kidney and renal pelvis measurements. Prenat Diagn 2003;23(11):891-7.

Chapter 4 Growth and size charts of the fetal adrenal gland H.A.M. Damen - Eliasa, R.H. Stigtera,c, P. Westers b, G.H.A. Vissera a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Centre for Biostatistics, Utrecht University, The Netherlands c Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands

40 Chapter 4

ABSTRACT

Objectives It was the aim of this study was to develop a reference curve for size and

growth of the length of the fetal adrenal gland.

Methods Longitudinal prospective study of one hundred eleven fetuses that were

scanned every four weeks. The ultrasound measurements started in one half of the

cases at sixteen weeks of gestation and in the other half at eighteen weeks.

Statistical analysis was performed by multilevel analysis.

Results Fitted 5th, 50th and 95th centile charts for the length of the adrenal gland are

presented with the raw data. There was a high correlation between adrenal and

kidney length (R = 0,932) with a ratio of 2 to 7.

Conclusions The chart for size and growth is of use for measurements of the length

and growth of the adrenal gland.

Charts of fetal adrenal gland 41

INTRODUCTION

Knowledge of the normal range of the growth and size of the fetal adrenal gland is of

importance for the identification of morphological changes once an anomaly is

suspected.

A number of reference values of adrenal gland measurements have been published1-

7, but none covers the whole second and third trimester of the pregnancy. Moreover

in none of these studies data were used with an ultrasound validated gestational age

and in some publications only post-mortem specimens were used1, 2. All studies used

cross-sectional data. Since 1990 there has been no study using abdominal

investigations. In 1993 a study has been published using transvaginal ultrasound

between 12 and 17 weeks of gestation.

It was the aim of this prospective study to develop a reference curve for the size and

growth of fetal adrenal gland length.

MATERIAL AND METHODS

Data of the length of the adrenal gland were collected in a longitudinal, prospective

study. Measurements of the fetal kidney and fetal renal pelvis were collected

simultaneously and will be published in a separate paper.

One hundred and twelve low risk women with 116 fetuses (4 twin-pregnancies) were

included after written informed consent had been obtained. They were divided in two

groups who were scanned at four weeks interval starting at 16 weeks or at 18 weeks

gestational age, respectively. All women had had a dating scan before 13 weeks of

gestation. One experienced ultrasonographer (HDE) made all the examinations using

the multifrequency transducer PVM 375 AT of the Toshiba Power Vision 6000, type

SSA 370 A (manufacturer Toshiba, Tokyo, Japan).

An intra- and interobserver variation analysis was performed before carrying out this

study. The results of which will be published elsewhere.

Women were excluded when they had a mono-chorionic twin pregnancy, a

chromosomal or congenital defect of the fetus, a small for gestational age infant

(SGA = birth weight according to growth charts <2.3% percentile8) or a maternal

disease which might effect fetal growth (diabetes mellitus, hypertension requiring

treatment).

42 Chapter 4

The suprarenal adrenal glands are heart-shaped structures located cranially to the

kidney like little helmets placed askew on top of the kidneys. They are imaged as

relatively anechoic pyramidal structures but sometimes the echogenicity of the

adrenal glands is similar to that of the adjacent kidney. In a transverse scan three

layers can usually be distinguished; the cortex is hypoechoic and the central medulla

hyperechoic. When visualising the full length of the kidney in a sagittal plane the

length of the kidney was measured and in the same plane the length of the kidney

including the adrenal gland was measured by placing the callipers from the outer to

outer border. The adrenal gland length was determined by subtraction of the kidney

length from the total length (Figure 1).

Statistical analysis was performed by using SPSS, version 10.1 (Statistical Product

and Service Solutions, Chicago) and by multilevel analysis using the software

program Mln (Multilevel Model Project, London, UK9) to construct nomograms

(medians and the 5th and 95th centiles). The latter method is able to rectify the

problem of missing data inherent to any study with longitudinal data.

A adrenal gland B D kidney ureter C Figure 1 – The length of the fetal adrenal gland is AC – BC.


RESULTS

Five fetuses were excluded, SGA (n=2), congenital anomalies (n=3; triploidy, clubfoot

and hydronephrosis >10mm anteroposterior diameter of the renal pelvis), leaving

data from 111 fetuses for analysis. At each gestational age all measurements could

be obtained from both the right and the left adrenal gland with a total of 628 data for

each side.

Statistical analysis was performed on the separate measurements of the length of the

right and left adrenal gland. The charts were virtually identical with a high correlation

of R = 0.979. (Figure 2).

rigth adrenal gland length (mm)

1412108642

left

adre

nal g

land

leng

th (

mm

)

14

12

10

8

6

4

2

Figure 2 – Scatter from the data of the right and left adrenal gland length with the fitted

correlation line (correlation R = 0,979).

The data of the length of right and left adrenal gland were averaged to construct the

reference chart. The account of the nomograms of the 5th, 50th and 95th fitted centiles

are given in Table 1 with the corresponding chart in Figure 3.

44 Chapter 4

Table 1 – Fitted centiles of the fetal adrenal gland with the number of fetuses for exact weeks between 16 and 42 weeks of gestational age. weeks of gestation

fetuses N

fitted centiles adrenal length

5th 50th 95th SD 16 3.6 4.2 4.8 0.3 17

55 4.0 4.6 5.2 0.3

18 4.4 5.0 5.6 0.3 19

56 4.8 5.4 6.1 0.3

20 5.2 5.8 6.4 0.3 21

55 5.6 6.2 6.8 0.3

22 6.0 6.6 7.2 0.3 23

56 6.3 7.0 7.6 0.3

24 6.7 7.3 7.9 0.3 25

55 7.0 7.6 8.3 0.3

26 7.3 8.0 8.6 0.3 27

56 7.6 8.3 9.0 0.3

28 7.9 8.6 9.3 0.3 29

55 8.2 8.9 9.6 0.3

30 8.5 9.2 9.8 0.4 31

54 8.7 9.4 10.1 0.4

32 9.0 9.7 10.4 0.4 33

55 9.4 9.9 10.8 0.4

34 9.5 10.2 11.0 0.4 35

53 9.6 10.3 11.0 0.4

36 9.9 10.6 11.3 0.4 37

52 10.1 10.8 11.5 0.4

38 10.3 11.0 11.7 0.4 39

51 10.4 11.2 12.0 0.4

40 10.6 11.3 12.1 0.4 41

21 10.7 11.5 12.3 0.4

42 2 10.9 11.7 12.5 0.4 total 111


4238343026221814

adre

nal g

land

leng

th (

mm

)

14

12

10

8

6

4

2

Figure 3 – Fitted 5th, 50th and 95th centiles for the adrenal gland and the raw data.


The adrenal-to-kidney length correlation was calculated using the data of the kidney

length chart (separate article) and those from the adrenal length. A strong linear

correlation was found between kidney length and adrenal gland length: R = 0,932

(Figure 4). The length of the adrenal gland was on average 27% (range 25 to 29%) of

that of the kidney (ratio 2 to 7) and this relation did not change with gestation/ kidney

size.

adrenal gland length in mm

14121086420

kidn

ey le

ngth

in m

m

60

50

40

30

20

10

0

Figure 4 - Scatter from the data of the length of the kidney and the adrenal gland with the

fitted correlation line (correlation R = 0,932).

DISCUSSION

Fetal adrenal glands are relatively large in comparison to early postnatal life. After

delivery their size rapidly decreases and increases again at the end of the first year

to attain their maximal weight and size by adulthood10. The fetal adrenal gland has

been the subject of only a few previous ultrasonographic investigations1-7, 11 with the

latest study published in the early 1990”s. Insufficient resolution of the equipment at

that time resulted in an inability to obtain accurate data especially during the second

trimester3 - 5, 7. In the early 1980’s Rosenberg et al7 could identify the adrenal glands

in only 12% of cases before 26 weeks gestational age and in 90% beyond that age.

In the same period, Jeanty et al5 were, not able to detect the adrenal gland in 30% of

cases before 25 weeks gestational age, decreasing to 6.5% in term fetuses.

46 Chapter 4

All previous charts have been made using cross-sectional data and several charts

showed evidence of methodological weaknesses such as the use of post-mortem

specimens1, 2 or the measurement of only one adrenal gland6.

We calculated the correlation between adrenal and kidney length since that may be

of significance in high-risk pregnancies. Naeye et al12 found in post mortem

examinations that fetal adrenal glands were relatively more reduced in weight than

body weight, in case of intra-uterine growth retardation. Hata et al3, 4 found a

decrease in the calculated adrenal gland surface in growth retarded fetuses and

others found small fetal adrenal glands when the mother was using glucocosteriods

because of congenital adrenal hyperplasia11. There are two case-reports on

ultrasound diagnosis of congenital adrenal hyperplasia13-14.

Our charts of the length of the fetal adrenal gland were obtained using longitudinal

data derived from a large prospective investigation that was done especially for the

development of a reference curve. The chart is suitable for size and growth of the

adrenal gland i.e. first of all for comparing adrenal size at a known gestational age

between 16 and 42 weeks of gestation and secondly for following the growth of the

adrenal gland by comparing the measured data of the fetus between two separate

occasions with the fitted data15-18. Until now there had not been a chart published,

which combines both possibilities.

Comparison of previously published charts with ours was not possible. Hata et al3, 4

published two studies: in one study he gave no raw data and in the other study the

data can not be used because he measured the length of the adrenal gland in

another way than we did by placing the callipers at A and D (Figure 1). We have

chosen for the distance A to B since this measure can be standardized better

because the borders of the adrenal gland are better visible at these points. Jeanty at

al5 gave averaged data with a range for every 5 weeks from 20 weeks gestation

onwards. Lewis et al6 published data between 30 and 39 weeks gestation but they

did only provide information on the length in comparison with kidney length and

biparietal diameter.


Fetal adrenal gland measurements can be an important ultrasonographic parameter

especially when a fetus is at risk for intra uterine growth retardation. The ratio of 2 to

7 between the adrenal gland and kidney length does not change with gestational age

and that may also be helpful.

48 Chapter 4

REFERENCES

1. Aragao de AH, Mandarim-de-Lacerda CA. Allometric growth of the adrenal gland in Brazilian fetuses. Okajimas Folia Anat Jpn 1990;67(2-3):165-8. 2. Gaillard DA, Lallemand AV, Moirot HH, Visseaux-Coletto BJ, Paradis PH. Fetal adrenal development during the second trimester of gestation. Pediatr Pathol 1990;10(3):335-50. 3. Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal adrenal gland in utero. Int J Gynaecol Obstet 1985;23(5):355-9. 4. Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal adrenal gland in utero: clinical application. Gynecol Obstet Invest 1988;25(1):16-22. 5. Jeanty P, Chervenak F, Grannum P, Hobbins JC. Normal ultrasonic size and characteristics of the fetal adrenal glands. Prenat Diagn 1984;4(1):21-8. 6. Lewis E, Kurtz AB, Dubbins PA, Wapner RJ, Goldberg BB. Real-time ultrasonographic evaluation of normal fetal adrenal glands. J Ultrasound Med 1982;1(7):265-70. 7. Rosenberg ER, Bowie JD, Andreotti RF, Fields SI. Sonographic evaluation of fetal adrenal glands. AJR Am J Roentgenol 1982;139(6):1145-7. 8. Kloosterman GJ. [Intrauterine growth and intrauterine growth curves]. Ned Tijdschr Verloskd Gynaecol 1969;69(5):349-65. 9. Goldstein H. Multilevel statistical models. 2nd ed. London: University of London. ed; 1995. 10. Potter EL, Craig JM. Pathology of the fetus and infant. St.Louis: A.S. Patterson; 1997. 11. Bronshtein M, Tzidony D, Dimant M, Hajos J, Jaeger M, Blumenfeld Z. Transvaginal ultrasonographic measurements of the fetal adrenal glands at 12 to 17 weeks of gestation. Am J Obstet Gynecol 1993;169(5):1205-10. 12. Naeye RL. Malnutrition: Probable Cause of Fetal Growth Retardation. Arch Pathol 1965;79:284-91. 13. Esser T, Chaoui R. Enlarged adrenal glands as a prenatal marker of congenital adrenal hyperplasia: a report of two cases. Ultrasound Obstet Gynecol 2004;23(3):293-7. 14. Saada J, Grebille AG, Aubry MC, Rafii A, Dumez Y, Benachi A. Sonography in prenatal diagnosis of congenital adrenal hyperplasia. Prenat Diagn 2004;24(8):627-30. 15. Altman DG, Chitty LS. Design and analysis of studies to derive charts of fetal size. Ultrasound Obstet Gynecol 1993;3(6):378-84. 16. Altman DG, Chitty LS. Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994;101(1):29-34. 17. Royston P, Altman DG. Design and analysis of longitudinal studies of fetal size.Ultrasound Obstet Gynecol 1995;6(5):307-12. 18. Royston P, Wright EM. How to construct 'normal ranges' for fetal variables. Ultrasound Obstet Gynecol 1998;11(1):30-8.

Chapter 5 Congenital renal tract anomalies: outcome and follow-up of 402 cases detected antenatally over a period of 15 years. H.A.M. Damen - Eliasa, T.P.V.M. de Jongb, R.H. Stigtera,c, G.H.A. Vissera, P.H. Stoutenbeeka a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Department of Paediatric Urology, University Hospital Utrecht, The Netherlands c Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands

50 Chapter 5

ABSTRACT

Objectives To determine the long-term prognosis of antenatally detected renal tract

anomalies in order to optimise counselling of the parents.

Methods Follow-up study of all renal tract abnormalities detected antenatally in a

level three-ultrasound department between 1986 and 2001. Follow-up data (medium

age 8 years) were retrieved from the records of the Paediatric Urology Department or

the attending paediatrician.

Results A urinary tract anomaly was detected in 408 fetuses. There were 4 false

positive diagnoses. From 2 children follow-up data were incomplete, leaving 402

cases for analysis. A chromosomal abnormality was present in 7 of 81 fetuses that

had karyotyping (8,6%). Termination of pregnancy occurred in 55 cases (13,7%) and

a further 66 children (16,4%) died during the perinatal period and up to 1 year of age.

In 106 of the 121 deceased children the cause of death was directly related to the

renal tract anomaly (26,4%). In the 281 surviving children a total of 545 renal tract

anomalies were diagnosed postnatally, requiring a total of 351 surgical interventions

in 160 infants. Outcome in survivors was generally good, with impaired renal function

in 9 infants and hypertension in 3 (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 outcome is generally favourable.

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.

Congenital renal tract anomalies: 402 cases 51

INTRODUCTION

High-resolution ultrasound equipment increasingly gives the opportunity to identify

congenital anomalies antenatally. 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 changes5,6.

Data on antenatal diagnosis and postnatal follow-up are important for assessing

prognosis and counselling of the parents. They may be helpful in making difficult

decisions as to whether or not to terminate a pregnancy before viability, in

determining the need for further diagnostic procedures and on the best management

before and after birth. Data on large cohorts are scarce7 and most follow-up data are

confined to specific urological anomalies, such as hydronephrosis or multicystic

dysplastic kidneys8-11.

The aim of this study was to determine the long-term prognosis of antenatally

detected renal tract anomalies in order to optimise counselling of the parents.


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

referral centre 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 centres 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 January 1st, 1986 and December 31st, 2000.

There were no exclusion criteria.

The cut-off point used in dilated renal pelves was >5 mm for the anteroposterior

diameter before 32 weeks in pregnancy and >10mm thereafter. The diagnosis of

polycystic kidney disease was made when there was the typical in utero presentation

of two enlarged hyperechogenic kidneys with loss of cortical differentiation and

oligohydramnios12,13. We defined kidneys as multicystic dysplastic when cysts of

52 Chapter 5

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 demonstrated13. The term dysplastic kidney was used when the kidney was

echogenic in isolation, had no normal parenchyma and was structurally abnormal

without large cysts13,14. 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 abnormalities15,16 (abdominal wall deficient 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 paediatricians 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 cases (19,7%) 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 follow-up, 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. 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. 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 (n=84) side and 51 percent were on the left side (n=89).

Table 1 – A list of all ch

ildren, alive or dead, with

a structural d

eve

lopmental k

idney anomaly, urinary tract dilatatio

n or misce

llaneous uropathy

along with

prenatal a

nd postnatal d

iagnosis, details of abnorm

alities, su

rgery and renal function.

prenatal d

iagnosis

postnatal d

iagnosis

all

dead

dead ≠

renal a

nomaly

alive

infants w

ith

surgery

No. of

operatio

ns

renal function

structural d

eve

lopmental a

nomaly n = 151

unila

teral renal a

genesis

unila

teral renal a

genesis

8

8 3

7 8 norm

al

bila

teral renal a

genesis

bila

teral renal a

genesis

33

33

n.a.

unila

teral e

nlarged

ech

ogenic/ cy

stic kidney

unila

teral M

CKD

64

10

351

45

54

50 norm

al

1 m

ild failu

reunila

teral d

ysplasia

2

2 1

1

2 norm

al

bila

teral e

nlarged

ech

ogenic/ cy

stic kidneys

bila

teral M

CKD

22

22

n.a.

bila

teral d

ysplasia

2

2 1

8

1 dialysis

1 m

ild failure

PKD

13

13

n.a.

Meck

el G

ruber sy

ndrome

5

5

n.a.

Perlman syn

drome

1 1

n.a.

bila

teral e

chogenic kidneys

norm

al s

ize

norm

al

11

1 norm

al

total

151

84

364

50

70

urinary tract dilatatio

n n = 247

unila

teral d

ilatation

94

391

51

133

91 norm

al

bila

teral d

ilatatio

n127

28

117

52

169

1 transp

lant

4 chronic failure

3 hyp

ertension

109 norm

al

unila

teral m

egaureter

1

1 1

2

1 norm

al

bila

teral m

egaureter

2

2 1

3

2 norm

al

isolated m

egabladder

Prune Belly

3

3megabladder

20

17

31

4

3 norm

al

total

247

22

11

214

106

311

misce

llaneous anomaly n = 4

pelvic kidney

2

1

1 1 norm

al

horseshoe kidney

2

2 2 norm

al

total

4

1

30

0

total

402

106

15

281

156

381

8 failure

3 hyp

ertension

MCKD = m

ulticy

stic kidney disease

, PKD = polycystic kidney disease

, n.a. = not applicable

54 Chapter 5

The overall male to 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 9 children of the 281 surviving infants had impaired renal

function and 3 children had hypertension, 12/281 (4,3%). 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, namely 87/150 (58%). Mortality in the group with urinary

tract dilatation was 13,4% (33/247). Perinatal mortality included all cases with

polycystic kidney disease, bilateral renal agenesis and bilateral multicystic kidney

disease (MCKD) and these cases accounted for 61,2% (74/121) of total mortality.

Moreover, mortality in case of an isolated megabladder was high (17 out of 20).

Autopsy in 9 of these fetuses revealed 3 cases of urethral stenosis, 4 cases of

urethral obstruction and 2 cases of urethral atresia. The parents of 8 fetuses refused

autopsy: 5 times stillbirth occurred, 1 fetus had caudal regression syndrome, 1 a

cloacal anomaly and another one no visible anomalies. Ten of 64 children (15,6%)

with unilateral MCKD died because of contralateral renal anomalies: renal agenesis

in 9 and renal dysplasia in one. In the miscellaneous group one child died with a

unilateral pelvic kidney and Arnold Chiari syndrome.

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 1 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 of those 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 (13,4%) children

died during the first 28 days after birth, and 4 others during the first year of life: 1 due

to the renal tract anomaly and 3 for other reasons, 4/402 (1,0%).

Sixty-nine percent of all perinatal deaths were boys.

Table 2 - O

verview of all ch

ildren who died, class

ified acc

ording to the anomaly. Data on additional renal a

nd extrarenal m

alfo

rmatio

ns are given as

well as the tim

e of death.

renal a

nomaly

total

No.

additional

malfo

rmations

renal

additional

malfo

rmations

extrarenal

additional

malfo

rmations

TOP

stillborn

neonatal death <

28 days

late in

fant death

> 28 days

total

renal

agenesis

bila

teral

33

10

1 absent bladder

1 urethral s

tenosis

2 agenesis of the ureters

1 hyd

roce

phalus

1 diaphragmatic

hernia

3 heart defects

1 anal/ oesophageal a

tresia

16

215

33 (27,3%)

MCKD bila

teral

22

9

2 cloacal m

alfo

rmation

1 m

ultiple anomalie

s of

the renal tract

2 sirenomelia

3 heart defect

1 anal/ oesophageal a

tresia

13

23

22 (18,2%)

MCKD unilateral

13

13

9 agenesis co

ntralateral

1 dys

plasia contralateral

2 pulm

onary hyp

oplasia

1 preterm

labour

51

713 (10,7%)

PKD

19

6

5 M

eck

el G

ruber

1 Perlman’s syn

drome

71

14

119 (15,7%)

Prune Belly syn

drome

31

2 3 (2,5%)

obstructive uropathy

= reaso

n death

19

3

1 cloacal m

alfo

rmation*

1 omphaloce

le1 caudal regress

ion

10*

36

19 (15,7%)

obstructive uropathy

≠ reaso

n death

11

11

1 triso

my 13

2 heart defects = N

oonan

1 hyp

operistaltis sy

ndrome

1 in

tra-uterine in

fection

1 m

egabladder, cloaca

l anomaly and preterm

labour

1 Arnold C

hiari m

alfo

rmation

1 D

andy Walker malfo

rmation

1 obstructive uropathy + anal/ oeso

phageal atresia =

VACTERL ass

ociation

1 obstructive uropathy + anal atresia, genotype 46 xx,

phenotype m

ale = VACTERL ass

ociation

1 obstructive uropathy + anal/ oeso

phageal atresia

+ VSD = VACTERL ass

ociation

31

43

11 (9,1%)

uropathy

≠

reaso

ndeath

11

1 pelvic kidney + Arnold C

hiari m

alfo

rmatio

n1

1 (0,8%)

total

121

53

18

35

55

(45,5%)

12

(9,9%)

50

(41,3%)

4 (3,3%)

121

(100%)

TOP = term

inatio

n of pregnancy

, all had a le

thal a

nomaly exc

ept one*, PKD = polycystic kidney disease

, VACTERL= vertebral d

efects (V

), anal a

tresia (A), cardiac

anomaly (C), trach

eal-eso

phageal fistula w

ith eso

phageal a

tresia (TE), renal d

efects (R

), radial lim

b dys

plasia (L), VSD = ventricle), septal d

efect

56 Chapter 5

survivors (n = 281)

Altogether 281 infants survived the perinatal period (Table 1). In these infants a total

of 545 anomalies was 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 follow-up renography or

renal colics based on UPJ obstruction. Table 3 shows all diagnosed renal tract

anomalies and all surgical interventions.

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 surgery on the renal tract pyelo-ureteric junction obstruction 113 kidney transplant 1 vesico-ureteric junction obstruction 8 nephrectomy 51 multicystic kidney 51 hemi-nephrectomy 21 posterior urethral valves 45 reimplantation (mega-) ureter 53 narrowed urethra 15 ureterectomy 22 megaureter 129 pyeloplasty 36 vesico ureteric reflux 46 incision posterior urethral valves 64 megabladder 45 vesicostomy 6 agenesis kidney 8 pull through vagina (Mayer Rokitanski) 3 dysplastic kidney 4 reconstruction vagina (cloacal malformation) 2 duplex system 43 ureterocele excision /reconstruction lower tract 19 urinary ascites 3 diverticulectomy 3 unclear 35 drainage of the upper tract 43 VUR - endoscopic treatment 13 closure of bladder rupture 1 excision/ incision syringocele or utriculus cyst 22 miscellaneous small interventions 21 number of diagnosis 545

total number of surgical interventions 381

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 3, pyelectasis in 6, a

megaureter in 1 and vesicoureteral reflux (VUR) in 2 (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 of which the 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 of 45 cases with nephrectomy of the multicystic kidney

there was no functioning at all on the renogram, whereas the other 2 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 63

survivors 61 children have normal renal function at follow-up. The two cases with

impaired outcome are:

1 - One child with 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 (2002) and started peritoneal dialysis.

2 - One girl with bilateral echogenic, dysplastic kidneys, who was finally diagnosed as

having the hereditary branchio-oto-renal (BOR)-syndrome(17), which includes renal

failure and impaired hearing (Creatinine 71 µmol/l at 7½ years).

58 Chapter 5

surviving infants with urinary tract dilatation (n = 214)

Table 5 gives an overview of the age of diagnosis, size of the dilatation at diagnosis

and outcome of the 118 surviving infants with a solitary uni- or bilateral renal pelvis

dilatation. Forty-five infants needed a total of 88 interventions. One child has chronic

renal failure and 1 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%). Forty-five of these 96

children had posterior urethral valves (PUV) with an intervention rate of 100%,

leaving 4 infants with impaired function and 1 infant with hypertension. In 14 of these

infants labour had been induced (Table 7). Moreover the intervention rate was high

(39/45 (86,6%)) in case of VUR.

Outcome in all 39 children with a unilateral renal tract dilatation was favourable. 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 4) and 2 with

hypertension. Impaired outcome was not related to the time of diagnosis or to the

size of dilatation at diagnosis.

Table 4 - Children with obstructive uropathy and impaired renal function. Induced labour = No. corresponding with those in Table 7 2 Boy with bilateral pyelectasis = 5/ 5 mm, megaureter and megabladder in week 16 of gestational

age. He had PUV and bilateral VUR (gr IV and IV). After two years of renal dialysis and multiple operations he had a kidney transplant at the age of five. 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 9½ years old with creatinine levels of 81 µmol/l.

8 Boy with bilateral hydronephrosis =10/ 10 mm, megaureter and megabladder in week 27 of gestational age. He had PUV and extensive surgery with temporary diversion by vesicostomy and drainage of the upper tract. He is 9 years old with creatinine levels of 74 µmol/l.

9 Boy with bilateral hydronephrosis =10/ 13 mm, megaureter and megabladder in week 23 of gestational age. He had PUV and bilateral VUR (gr IV and V). He has dysplastic kidneys with immature parenchyma and underwent ample surgical reconstructions. At 10 years of age he has a preterminal renal failure (creatinine 179 µmol/l).

18 Boy with bilateral hydronephrosis= 25/ 25 mm, megaureter and megabladder in week 34 of gestational age. 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 in week 34 of gestational age. He had bilateral VUR (gr III and IV). At 10 years and after multiple operations he has mild renal failure = reflux nephropathy (creatinine 74 µmol/l) and hypertension.

No induced labour Boy with bilateral pyelectasis = 9/ 7 mm in week 29 of gestational age. He had bilateral VUR (gr V

and V) and developed pyelonephritis in spite of antibiotic prophylaxis. He underwent bilateral reimplantation and recalibration of the ureter. He has a creatinine of 74 µmol/l at three years of age.

Table 5

- C

hildren w

ith solitary u

ni- o

r bila

teral renal pelvis d

ilatatio

n a

long w

ith g

estatio

nal age a

nd size o

f dilatatio

n a

t first d

iagnosis. F

igures in

parenthese

s indicate operated children. Total n

umber of su

rgical interventio

ns and renal failu

re after su

rgery are prese

nted in

the la

st columns.

5 -10 m

munilateral

2

2 ( 1)

13

11

10 ( 1 = 10 %)

2

bilateral

11

42 ( 1)

118 ( 1 = 5,5 %

) 5

1 chronic renal failure

10 -15 m

munilateral

2 ( 1)

1 ( 1)

3 ( 1)

5 ( 2)

3 ( 1)

14 ( 6 = 42,9 %

) 11

bilateral

5 ( 1)

6 ( 2)

66

23 ( 3 = 13,0 %

) 5

15– 20 m

munilateral

1 ( 1)

4 ( 3)

6 ( 2)

11 ( 6 = 54,5 %

) 7

bilateral

21

3 ( 2)

3 ( 2)

9 ( 4 = 44,4 %

) 8

20– 25 m

munilateral

1 ( 1)

2 ( 2)

2 5 ( 3 = 60 %)

5

bilateral

14 ( 1)

2 ( 2)

7 ( 3 = 42,9 %

) 8

1 hyp

ertension

25– 30 m

munilateral

2 ( 2)

1 ( 1)

1 4 ( 3 = 75 %)

10

bilateral

1 ( 1)

1 ( 1 = 100 %)

1

30– 35 m

munilateral

11 ( 1)

2 ( 1 = 50 %)

1

bilateral

1 ( 1)

11 ( 1)

3 ( 2 = 66,6 %

) 3

> 35 m

munilateral

2 ( 2)

3 ( 3)

1 ( 1)

6 ( 6 =100 %

) 8

bilateral

1 ( 1)

1 ( 1)

2 ( 2 =100 %

) 5

unilateral

1 ( 1)

1 ( 1 =100 %

) 2

solitaire

megaureter

bilateral

11 ( 1)

2 ( 1 = 50 %

) 3

total

14

13 ( 3)

16 ( 8)

26 (10)

30 (16)

22 ( 8)

118 (44 = 37,3 %

) 84

60 Chapter 5

In 21 of the 119 cases (17,7%) with a bilateral dilatation labour was electively

induced before 37 weeks of gestation (mean 34,9 weeks: range 29 – 37) because of

the development of anhydramnios. Only one fetus had solitary bilateral

hydronephrosis (Table 7). All 21 neonates (19 boys and 2 girls) had surgery within a

few days after birth. Almost all children with impaired outcome can be found in this

group (6 chronic renal failure, 1 hypertension).

VUR was diagnosed in 45 of the 214 children (21,0%) 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 6 gives an

overview of all cases with uni- and bilateral VUR, surgical interventions and final

renal function.

Table 6- Summary of interventions and outcome in 45 infants with unilateral or bilateral VUR. urinary tract anomaly with VUR

children with surgery

No. of operations

final renal function

13 = unilateral urinary tract anomaly with VUR

11 26 1 unilateral reflux nephropathy 2 dysplasia in operated kidney

10 = bilateral urinary tract anomaly with unilateral VUR

10 13* 1 hypertension and mental delay

22 = bilateral urinary tract anomaly with bilateral VUR

18

84 1 kidney transplant 1 peritoneal dialysis 1 hypertension, bilateral reflux nephropathy, unilateral hypoplasia 1 chronic renal failure 1 preterminal insufficient 1 hypertension 1 dysplasia in operated kidney

*7 in reflux kidney, 6 in the contralateral hydronephrotic kidney.

surviving infants with miscellaneous anomaly (n = 4)

These four infants (Table 1) had a developmental kidney anomaly without

consequences for renal function and were all normal at follow-up.

Table 7 - C

ase

s in w

hich labour was induce

d along w

ith sex, gestatio

nal age, antenatal diagnosis, typ

e of anomaly, su

rgery and renal function after

surgery. (PUV = posterior urethral v

alves)

in

duce

d la

bour n =21

No.

sex

inducing

labour

antenatal d

iagnosis

postnatal a

nomaly - surgery

renal function after su

rgery

1

xy32 w

eeks

bilateral h

ydronephrosis and m

egaureters

PUV - excision urethral v

alves

good

2

xy36 w

eeks

bilateral h

ydronephrosis, m

egaureter-megabladder

PUV-bilateral V

UR (gr IV + IV) -extensive

surgery

kidney transp

lant

3

xy33 w

eeks

bilateral h

ydronephrosis and m

egaureters

PUV - extensive

surgery

good

4

xy35 w

eeks

bilateral h

ydronephrosis

bilateral h

ydronephrosis - bilateral p

yeloplasty

good

5

xy36 w

eeks

bilateral h

ydronephrosis, m


PUV - extensive

surgery

good (unila

teral d

ysplasia)

6

xy35 w

eeks

bilateral h

ydronephrosis and urinary asc

ites

PUV - extensive

surgery

good

7

xy36 w

eeks

unilateral m

egaureter and contralateral M

CKD

unilateral m

egaureter and contralateral M

CKD –

ureter reim

plantatio

n and nephrectomy

mild failure

8

xy37 w

eeks

bilateral h

ydronephrosis, m


PUV - extensive

surgery

mild failure

9

xy33 w

eeks

bilateral h

ydronephrosis, m


PUV-bilateral V

UR (gr IV + V) - extensive

surgery

preterm

inal failure

10

xy29 w

eeks

bilateral h

ydronephrosis, m


premature la

bour after amnion in

fusion - PUV -

extensive

surgery

good

11

xy35 w

eeks

megabladder and urinary asc

ites

PUV and spontaneous bladder rupture -

extensive

surgery

good

12

xy33 w

eeks

bilateral h

ydronephrosis, m


PUV - extensive

surgery

good

13

xy37 w

eeks

unilateral h

ydronephrosis,co

ntralateral m

egaureter

and utereoce

lePUV - extensive

surgery

good - hyp

ertension

14

xy36 w

eeks

bilateral h

ydronephrosis, m

egabladder - urinary

asc

ites

bilateral h

ydronephrosis

died during heart su

rgery –

DORV, TGA

15

xy36 w

eeks

bilateral h

ydronephrosis, megabladder - urinary

asc

ites

PUV and bila

teral V

UR (gr III and IV)

extensive

surgery

good

16

xy37 w

eeks

unilateral h

ydronephrosis with

megaureter,

contralateral M

CKD

UVJ stenosis with

unilateral M

CKD, unilateral

megaureter with

VUR gr V- extensive

surgery

good

17

xy36 w

eeks

bilateral h

ydronephrosis, m

egabladder

PUV- excision urethral v

alves

good

18

xy34 w

eeks

bilateral h

ydronephrosis, m


PUV- extensive

surgery

mild failure

19

xy37 w

eeks

bilateral h

ydronephrosis, m


bilateral V

UR (gr III and IV) and m

egaureter

– bila

teral u

reteral reim

plantatio

nbilateral

reflu

x nephropathy

and hyp

ertension

20

xx

34 w

eeks

bilateral h

ydronephrosis and m

egaureters

bilateral h

ydronephrosis - extensive

surgery

good

21

xx

37 w

eeks

unilateral h

ydronephrosis with

megaureter,

contralateral M

CKD

unilateral M

CKD, co

ntralateral V

UR gr V -

extensive

surgery

good

DORV = double outle

t of the right ve

ntricle, TGA = transp

ositio

n of the great arteries

62 Chapter 5

infants with chromosomal anomalies (n=7)

Karyotyping was done antenatally in 77 fetuses (in 13 cases because of maternal

age >36 years) and postnatally in another 4 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 parents refused

karyotyping and autopsy.

Four children had trisomy 21 and these 4 infants accounted for 1,8% of all 221 living

children with uni- or bilateral renal tract dilatation.

Table 8 - Overview of fetuses with a chromosomal anomaly. No.

urinary tract anomaly chromosomal anomaly

extra renal anomaly

postnatal management renal function

1 bilateral MCKD Klinefelter syndr. XXY none n.a. n.a. 2 bilateral pyelectasis,

Ø 8 mm trisomy 13 multiple n.a. n.a.

3 bilateral hydronephrosis >20 mm and megaureter

mosaicism chromosome 8

none resection urethral valve normal

4 hydronephrosis >20mm, megaureter,megabladder

trisomy 21 none resection urethral valve diverticulectomy

normal

5 bilateral megaureter trisomy 21 hydrops foetalis polyhydramnios

prophylactic antibiotics normal

6 bilateral hydronephrosis > 15 mm and megabladder

trisomy 21 VSD, stenosis of pulmonary artery, unilateral clubfoot

closure VSD defect clubfoot correction

normal

7 bilateral hydronephrosis L > 30 mm, R > 6 mm

trisomy 21 VSD prophylactic antibiotics normal

n.a. = not applicable, VSD = ventricle septal defect

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 haemorrhage),

c) cyst of upper moiety of a duplex kidney (appeared to be extralobar sequestration

of the lung),

d) dysplastic kidneys with increased echogenicity (appeared to be normal).


DISCUSSION

The population in this study may not be representative of the overall obstetric

population, since severe anomalies are likely to be referred more frequently to our

tertiary centre, than minor ones. Nevertheless, our data may be helpful in assessing

the prognosis of the various anomalies and be of help in counselling parents.

Urinary tract anomalies accounted for 20% of all congenital anomalies, detected

antenatally, with a very low false positive rate of 1,0% that never caused

inappropriate treatment. Mortality due to the renal tract anomaly was high,

approximately one quarter of all cases and was mainly restricted to the perinatal

period (including TOP in half of these cases). The mortality rate, almost 60%, was

especially high in infants with a structural kidney anomaly and relatively low, with

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 9

children and hypertension in 3 (12 out of 281 survivors = 4,3%). This favourable

outcome applied both to infants with a structural anomaly and to these with a urinary

tract dilatation. There were seven children with one dysplastic and one normal kidney

left but they all have overall normal renal function at follow-up. We did not include

data on the incidence of urine incontinence.

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 polycystic kidney disease are well documented12 and the

typical multicystic kidney usually does not present a diagnostic problem7,13,18,19.

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 function14, 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 our series structural anomalies

represented approximately one third 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

64 Chapter 5

the Dutch Society for Paediatric Urology21,22. Fetuses with a unilateral MCKD had 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 case of urinary tract dilatation different thresholds are used for

measurements of the antero-posterior 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 criteria23-26. Some authors suggest that the risk of surgery is

minimal when the dilatation is <10 mm in late pregnancy26,27 but Thomas28 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 antero-posterior

diameter of > 10 mm is usually considered of significance27,29 but the Great Ormond

Street Experience30 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 out of 65 infants with an isolated uni- or bilateral mild

dilatation (<15 mm) still required surgery.

It is the policy in our clinic that in case of an early and mild pyelectasis (<10 mm) and

after scanning for 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 our 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 due to VUR and when their

child feels listless or has fever of unknown origin a urinary tract infection must be ruled

out. With such a policy unnecessary parental anxiety may be prevented as well as

unnecessary costs of follow-up.

Surgery can be needed in case of an isolated uni- or bilateral dilatation of the renal

renal pelvis of >10 mm and in our study nearly half of these infants had surgery.

Especially high was the intervention rate in the 45 boys with PUV (100%). Labour

was induced in 14 of these infants and 6 have impaired renal function and 1


hypertension. The overall conclusion for obstructive uropathy that can be drawn from

this series is that, regardless of the presence of 1 or 2 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 were located in the group with progressive

oligohydramnios in which labour was induced preterm (6 of 21 infants). Poor

outcome of fetuses with bilateral urinary tract dilation combined with prolonged

periods of oligohydramnios has been repeatedly described31-33. Intrauterine therapy

still has a poor outcome with about 50% fetal loss and 40% end-stage renal disease

in the survivors34,35 but such a therapy is only a possible option when there is a

megabladder at midgestation. Our policy of preterm induction of labour when

oligohydramnios develops seems to result in a relatively favourable outcome

although the timing of induction is still uncertain and the proof that we actually gave

them better chances is non-existent.

Isolated megabladder was diagnosed in 23 cases antenatally, of which 3 boys had

Prune Belly syndrome diagnosed postnatally. In literature usually a high number of

Prune Belly is given15,16 without looking for urethral obstruction. Our number is low

because of the definitions we use for the Prune Belly syndrome15, 16 with proven

patent ureter and excluding female fetuses.

VUR accounted for approximately 21% of antenatally diagnosed urinary tract

dilatations, which is slightly higher than the 15% described by others36-39. There was

a high surgical intervention rate in 86,6% of the infants who needed approximately

one third of all surgical interventions (Table 6). VUR predisposes to urinary tract

infection and can lead to renal scarring and chronic renal failure but approximately

60% of kidneys with reflux already have an abnormal renogram even in the absence

of urinary tract infection40-42. Therefore all children with an anteroposterior renal

pelvis dilatation >10 mm around 32 weeks of gestation should be carefully managed

postnatally (low-dosed antibiotics, voiding cystourethrography).

We did antenatal karyotyping only when additional anomalies next to that of the

urogenital tract were found and postnatally only when there was a suspicion of

chromosomal abnormalities. Also at autopsy it is not routine in our unit to karyotype

the child. Seventeen parents refused autopsy and/ or karyotyping. Seven of 81

66 Chapter 5

fetuses, which were karyotyped, had a chromosomal disorder, 8,6%. See Table 8.

Others mentioned chromosomal disorders in 11-12%1,43 and even 25%44. However,

these studies are not quite comparable with ours because Stoll et al1 did not mention

the percentage of cases in which karyotyping was carried out, Nicolaides et al45

performed karyotyping at all children with the prenatal diagnosis of urogenital tract

anomalies and Isaksen et al44 described a selected group of deceased children.

Fetuses with a pyelectasis have a higher chance of having chromosomal anomalies

(mostly trisomy 21 followed by trisomy 13 and 18)43,46,47. In our series all the 7

fetuses (3,2%) with a chromosomal defect had a uni- or bilateral pyelectasis which is

in accordance with the 3,2 till 5,4% as reported in literature43,46,47. However, it is the

prevalent opinion that there is not an indication for fetal karyotyping in isolated

pyelectasis45.

Autopsy was performed in 72 of the 121 deceased fetuses (59,5%). The main

urological, prenatal diagnosis was confirmed in all but one of these fetuses (98,6%).

A suspected bilateral MCKD was a unilateral one with a normal contralateral kidney.

The child had also severe idiopathic pulmonary hypoplasia and anhydramnios and

did not die as a result of the inappropriate diagnosis. In 18 fetuses additional autopsy

findings, such as anal atresia in 5 fetuses, had not been found antenatally by

ultrasonography mostly due to the anhydramnios. Isaksen et al found a slightly lower

91% agreement between prenatal diagnosis of severe urogenital tract anomalies and

autopsy findings.

CONCLUSIONS

The overall value of antenatal diagnosis 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 shows 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 has no therapeutic consequences at all

but still causes unnecessary anxiety in many cases. This study was undertaken to

ameliorate insight into which parents should have anxiety and which can be

congratulated with the fact that they can expect a healthy child with, possibly, a minor

problem without consequences for life or life expectancy. More studies about this will

be needed in future.


REFERENCES

1. Stoll C, Clementi M. Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe. Ultrasound Obstet Gynecol 2003;21(6):543-51. 2. Levi S. Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening for second trimester fetal malformations. Prenat Diagn 2002;22(4):285-95. 3. Levi S. Mass screening for fetal malformations: the Eurofetus study. Ultrasound Obstet Gynecol 2003;22(6):555-8. 4. Grandjean H, Larroque D, Levi S. Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team. Ann N Y Acad Sci 1998;847:118-24. 5. Alladi A, Agarwala S, Gupta AK, Bal CS, Mitra DK, Bhatnagar V. Postnatal outcome and natural history of antenatally-detected hydronephrosis. Pediatr Surg Int 2000;16(8):569-72. 6. Barker AP, Cave MM, Thomas DF, Lilford RJ, Irving HC, Arthur RJ, et al. Fetal pelvi-ureteric junction obstruction: predictors of outcome. Br J Urol 1995;76(5):649-52. 7. Dillon E, Ryall A. A 10 year audit of antenatal ultrasound detection of renal disease. Br J Radiol 1998;71(845):497-500. 8. Broadley P, McHugo J, Morgan I, Whittle MJ, Kilby MD. The 4 year outcome following the demonstration of bilateral renal pelvic dilatation on pre-natal renal ultrasound. Br J Radiol 1999;72(855):265-70. 9. Feldman DM, DeCambre M, Kong E, Borgida A, Jamil M, McKenna P, et al. Evaluation and follow-up of fetal hydronephrosis. J Ultrasound Med 2001;20(10):1065-9. 10. Thomas DF, Madden NP, Irving HC, Arthur RJ, Smith SE. Mild dilatation of the fetal kidney: a follow-up study. Br J Urol 1994;74(2):236-9. 11. Onen A, Jayanthi VR, Koff SA. Long-term followup of prenatally detected severe bilateral newborn hydronephrosis initially managed nonoperatively. J Urol 2002;168(3):1118-20. 12. Reuss A, Wladimiroff JW, Stewart PA, Niermeijer MF. Prenatal diagnosis by ultrasound in pregnancies at risk for autosomal recessive polycystic kidney disease. Ultrasound Med Biol 1990;16(4):355-9. 13. Winyard P, Chitty L. Dysplastic and polycystic kidneys: diagnosis, associations and management Prenat Diagn 2001;21(11):924-35. 14. Wellesley D, Howe DT. Fetal renal anomalies and genetic syndromes. Prenat Diagn 2001;21(11):992-1003. 15. Jennings RW. Prune belly syndrome. Semin Pediatr Surg 2000;9(3):115-20. 16. Sutherland RS, Mevorach RA, Kogan BA. The prune-belly syndrome: current insights. Pediatr Nephrol 1995;9(6):770-8. 17. Rodriguez Soriano J. Branchio-oto-renal syndrome. J Nephrol 2003;16(4):603-5. 18. Aubertin G, Cripps S, Coleman G, McGillivray B, Yong SL, Van Allen M, et al. Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management. Prenat Diagn 2002;22(5):388-94. 19. Lam BC, Wong SN, Yeung CY, Tang MH, Ghosh A. Outcome and management of babies with prenatal ultrasonographic renal abnormalities. Am J Perinatol 1993;10(4):263-8.

68 Chapter 5

20. Estroff JA, Mandell J, Benacerraf BR. Increased renal parenchymal echogenicity in the fetus: importance and clinical outcome. Radiology 1991;181(1):135-9. 21. Oliveira EA, Diniz JS, Vilasboas AS, Rabelo EA, Silva JM, Filgueiras MT. Multicystic dysplastic kidney detected by fetal sonography: conservative management and follow-up. Pediatr Surg Int 2001;17(1):54-7. 22. Webb NJ, Lewis MA, Bruce J, Gough DC, Ladusans EJ, Thomson AP, et al.Unilateral multicystic dysplastic kidney: the case for nephrectomy. Arch Dis Child 1997;76(1):31-4. 23. Kent A, Cox D, Downey P, James SL. A study of mild fetal pyelectasia - outcome and proposed strategy of management. Prenat Diagn 2000;20(3):206-9. 24. Langer B. Fetal pyelectasis. Ultrasound Obstet Gynecol. 2000;Jul;16(1):1-5. 25. Ismaili K, Hall M, Donner C, Thomas D, Vermeylen D, Avni FE. Results of systematic screening for minor degrees of fetal renal pelvis dilatation in an unselected population. Am J Obstet Gynecol 2003;188(1):242-6. 26. Sairam S, Al-Habib A, Sasson S, Thilaganathan B. Natural history of fetal hydronephrosis diagnosed on mid-trimester ultrasound. Ultrasound Obstet Gynecol 2001;17(3):191-6. 27. Dremsek PA, Gindl K, Voitl P, Strobl R, Hafner E, Geissler W, et al. Renal Pyelectasis in fetuses and neonates: Diagnostic value of renal pelvis diameter in pre and postnatal sonographic screening. AJR Am J Roentgenol 1997(Apr;168(4)):1017-9. 28. Thomas DF. Prenatal diagnosis: does it alter outcome? Prenat Diagn 2001;21(11):1004-11. 29. Adra AM, Mejides AA, Dennaoui MS, Beydoun SN. Fetal pyelectasis: is it always 'physiologic'? Am J Obstet Gynecol 1995(Oct;173(4)):1263-6. 30. Dhillon HK. Prenatally diagnosed hydronephrosis: the Great Ormond Street experience. British Journal of Urology 1998(81,Suppl.2):39-44. 31. Brumfield CG, Guinn D, Davis R, Owen J, Wenstrom K, Mize P. The significance of non-visualization of the fetal bladder during an ultrasound examination to evaluate second-trimester oligohydramnios. Ultrasound Obstet Gynecol 1996;8(3):186-91. 32. Eckoldt F, Woderich R, Gellermann J, Hammer H, Tennstedt C, Heling KS. Survival in second trimester oligohydramnios secondary to bilateral pelviureteral junction obstruction. Urology 2003;61(5):1036. 33. Winn HN, Chen M, Amon E, Leet TL, Shumway JB, Mostello D. Neonatal pulmonary hypoplasia and perinatal mortality in patients with midtrimester rupture of amniotic membranes--a critical analysis. Am J Obstet Gynecol 2000;182(6):1638-44. 34. Freedman AL, Johnson MP, Smith CA, Gonzalez R, Evans MI. Long-term outcome in children after antenatal intervention for obstructive uropathies. Lancet 1999;354(9176):374-7. 35. Holmes N, Harrison MR, Baskin LS. Fetal surgery for posterior urethral valves: long-term postnatal outcomes. Pediatrics 2001;108(1):E7. 36. Anderson NG, Abbott GD, Mogridge N, Allan RB, Maling TM, Wells JE. Vesicoureteric reflux in the newborn: relationship to fetal renal pelvic diameter. Pediatr Nephrol 1997;11(5):610-6. 37. Arena F, Romeo C, Cruccetti A, Centonze A, Basile M, Arena S, et al. Fetal vesicoureteral reflux: neonatal findings and follow-up study. Pediatr Med Chir 2001;23(1):31-4.


38. Herndon CD, McKenna PH, Kolon TF, Gonzales ET, Baker LA, Docimo SG. A multicenter outcomes analysis of patients with neonatal reflux presenting with prenatal hydronephrosis. J Urol 1999;162(3 Pt 2):1203-8.

39. Shapiro E, Elder JS. The office management of recurrent urinary tract infection and vesicoureteral reflux in children. Urol Clin North Am 1998;25(4):725-34, x. 40. Anderson PA, Rickwood AM. Features of primary vesicoureteric reflux detected by prenatal sonography. Br J Urol 1991;67(3):267-71. 41. Gordon AC, Thomas DF, Arthur RJ, Irving HC, Smith SE. Prenatally diagnosed reflux: a follow-up study. Br J Urol 1990;65(4):407-12. 42. de Jong TP, van Gool JD, Van Wijk AA, Stoutenbeek P, Van Isselt HW. Antenatally diagnosed obstructive uropathy--kidney imaging vs kidney function. Acta Urol Belg 1989;57(2):413-6. 43. Nicolaides KH, Cheng HH, Abbas A, Snijders RJ, Gosden C. Fetal renal defects: associated malformations and chromosomal defects. Fetal Diagn Ther 1992;7(1):1-11. 44. Isaksen CV, Eik-Nes SH, Blaas HG, Torp SH. Fetuses and infants with congenital urinary system anomalies: correlation between prenatal ultrasound and postmortem findings. Ultrasound Obstet Gynecol 2000;15(3):177-85. 45. Nicolaides KH. Screening for chromosomal defects. Ultrasound Obstet Gynecol 2003;21(4):313-21. 46. Benacerraf BR, Mandell J, Estroff JA, Harlow BL, Frigoletto FDJ. Fetal pyelectasis: a possible association with Down syndrome. Obstet Gynecol 1990(Jul;76(1)):58-60. 47. Corteville JE, Dicke JM, Crane JP. Fetal pyelectasis and Down syndrome: is genetic amniocentesis warranted? Obstet Gynecol 1992;79(5 ( Pt 1)):770-2.

Chapter 6 Concomitant anomalies in 100 children with unilateral multicystic kidney Henny A.M. Damen - Eliasa, Philip H. Stoutenbeeka, Gerard H.A. Vissera, Peter G.J. Nikkelsb, Tom P.V.M. de Jongc.

a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Department of Pathology, University Medical Centre Utrecht, The Netherlands. c Department of Paediatric Urology, University Medical Centre Utrecht, The Netherlands.

72 Chapter 6

ABSTRACT

Objectives To determine the incidence and type of associated urogenital anomalies

in children with unilateral multicystic kidney disease and to assess the additional

diagnostic value of cystoscopy and colposcopy (in girls) in children with

nephrectomy.

Methods Follow-up study of 100 children with antenatally detected unilateral

multicystic kidney disease. After ultrasound confirmation of the diagnosis a voiding

cystourethrography and isotope scan were done in each child to exclude vesico

ureteral reflux and to establish renal function. Eighty-one children had a nephrectomy

and prior to surgery all had a cystoscopy and girls also had a colposcopy.

Results Seventy-five children had one or more additional urogenital anomalies: 39

infants of the contralateral kidney, 42 of the ipsilateral kidney and 28 one or more on

the lower urogenital tract. With cystoscopy 54 anomalies of the genitourinary tract

were detected in 48 children and with colposcopy 3 anomalies in 35 girls. Eighty-one

children had a (hemi-) nephrectomy and 33 of them needed other urological

interventions. Thirteen fetuses died (mostly on agenesis of the contralateral kidney)

and 6 infants had no surgery at all.

Conclusion Children with unilateral multicystic kidney disease have a considerable

risk of having other urogenital anomalies. When cystoscopy and colposcopy are

added to the routine investigations the rate of detected anomalies is 75%, twice as

much as reported in literature.

Concomitant anomalies with unilateral multicystic kidney 73

INTRODUCTION

MCKD gives only rarely diagnostic dilemmas on prenatal ultrasound1 due to the

typical manifestation with in general multiple non-communicating cysts that are

randomly arranged with a size of less than 1 mm up to several centimetres in

diameter. The multicystic kidney is frequently enlarged, misshapen and irregularly

cystic with often a pyelo-calyceal occlusion and an atretic ureter and may go into

involution, pre- or postnatally and may become a small non-functional solid mass

with or without cystic lesions in the retroperitoneum2.

A multicystic dysplastic kidney is an aberrant developmental disturbance secondary

to an early obstruction3-8. They can be of any size ranging between kidneys with

multiple large cysts, commonly termed as multicystic dysplastic kidneys (MCKD), to

normal or small kidney remnants without cysts. A severe pyeloureteric junction

obstruction with dilated calices and hardly visible parenchyma may mimic a

multicystic kidney so in strictest terms renal dysplasia can only be diagnosed at

histology5.

The multicystic kidney can be affected unilateral, bilateral or as segmental part of a

duplex kidney. The incidence of unilateral MCKD is between 1 in 2500 - 4300 live

births9. Rarely inheritance10 has been reported but in that case it can be a feature of

syndromes or chromosomal disorders11. An abnormal karyotype has only been found

in cases with associated non-urological anomalies12, 13.

The function of the affected kidney is absent or poor. Therefore, bilateral MCKD is

invariably associated with a fatal outcome. The prognosis of unilateral MCKD is

favourable and depends on the integrity of the contralateral kidney14, 15. Contralateral

ureteropelvic junction (UPJ) stenosis, vesico ureteral reflux (VUR) and renal

agenesis have been reported in 15 – 50% of children2, 16, 17 and extrarenal associated

anomalies in 16 - 35%1, 12.

Removal of the multicystic kidney as standard procedure is still under debate. In

some studies the affected kidney is removed because of fear for potential

complications such as hypertension18, infection15 or malignancy17, 19 and in others the

children were examined periodically because their opinion is that the risk of

developing a malignancy or hypertension is considered very low or even non-

existing2, 15.

74 Chapter 6

It was the aim of our study to determine the incidence and type of associated

urogenital anomalies when prenatally a unilateral MCKD was diagnosed and to

assess the additional diagnostic value of cystoscopy and colposcopy (in girls) when a

nephrectomy was performed.


One hundred children with a prenatally diagnosed unilateral MCKD, between January

1986 and December 2001, were evaluated. Data were obtained by reviewing the

database of the obstetric ultrasound department and of the paediatric urology

department of the University Medical Centre Utrecht, The Netherlands. In all children

postnatal ultrasound examination within a few days after birth confirmed the

presence and location of the multicystic kidney. Within four weeks all infants had a

voiding cystourethrography (VCUG) without anaesthesia to exclude reflux in the

opposite kidney and a MAG3 renography or DMSA scan to measure function. In case

of VUR antibiotic prophylaxis was given. All surviving children were offered a

nephrectomy at the age of approximately six months, under general anaesthesia,

combined with cystoscopy and the girls were also offered a colposcopy.

RESULTS

Unilateral MCKD was diagnosed in 100 fetuses between 15 and 42 weeks of

gestation: 21% before 20 weeks gestation, 49% between 20 and 30 weeks gestation

and 30% thereafter (mean 26.7 weeks). The left to right affected kidney ratio was 47 :

53. There were 58 boys, 41 girls and 1 fetus with unknown sex because of

sirenomelia. Thirteen fetuses died in the perinatal period: 9 with an agenesis of the

contralateral kidney, 1 with a contralateral dysplastic kidney, megabladder and

arrhythmia, 1 with a contralateral dysplastic kidney, pulmonary hypoplasia and

sirenomelia and 2 with idiopathic pulmonary hypoplasia. Autopsy was performed in 7

of these infants and the diagnoses were confirmed.

The other 87 infants survived and were between 0 -16 years (mean 5 years and 4

months) at follow-up. All living infants were morphologically normal. Four parents

refused investigations after birth. In the remaining 83 an ultrasonography, a VCUG

and an isotope scan were performed within a few weeks after birth. The multicystic

kidney was non-functional in 80 children and had a function of 3% to 7% of total renal


function in the other three. Seventy-five of the 100 children had one or more

additional anomalies. Thirty-nine of these infants had 52 renal anomalies of the

contralateral kidney of which agenesis, hydronephrosis and pyelectasis as most

occurring. Forty-two infants had 56 renal anomalies of the ipsilateral kidney so

besides the multicystic kidney an ectopic or megaureter as most common and

another 28 infants had altogether 32 anomalies of the lower urogenital tract with as

most diagnosed an infravesical obstruction (Table 1). No differences were made

between minor or major anomalies neither between primary or secondary developed

abnormalities. Reflux was seen in 9 children, 7 boys and 2 girls. It was bilateral in 3

cases. Three children had a reimplantation of the ureter and 1 endoscopic treatment

by subureteric injection of a bulking agent.

Table 1 – 100 infants with unilateral MCKD. Total number of minor and major anomalies ofthe contralateral kidney (39 infants), ipsilateral kidney (42 infants) and of the lower urogenitaltract (27 infants), which were primary or secondary developed.

contralateral kidney ipsilateral kidney lower urogenital tract

kidney agenesis 9

kidney non-cystic dysplasia 5

duplex system 1 4

ectopic pelvic kidney 1 3

horseshoe kidney 1

spider kidney 1

hydronephrosis* 7

VUR 9 3

megaureter 5 10

ectopic ureter 32

partially doubled urethra 2

ureterocele 2 2

infravesical obstruction 18

megabladder↑

3

diverticulum of the bladder wall 3

urethral meatus stenosis 5

multicystic testicle 1

Mayer-Rokitansky syndrome 1

hymen imperforates 1

total anomalies 41 56 32

* renal pelvis diameter >10mm anteroposterior, # renal pelvis diameter 5-10 mm anteroposterior, ↑ topof the bladder reached the umbilical height

Two of the 5 infants with a contralateral kidney dysplasia died perinatally. The other

three are 2, 4 and 10 years old and have creatinine levels of 94, 35 and 75 µmol/l.,

respectively. The two-year-old boy is mentally and motor retarded with syndromal

76 Chapter 6

anomalies without a specific diagnosis, the 4-year-old boy is idiopathic motor

retarded and the 10-year-old boy is otherwise healthy.

Nine infants had also extra renal anomalies (Table 2). One of the latter died

neonatally and four are mentally and/ or motor retarded.

Table 2 - Associated extrarenal anomalies in 9 cases with unilateral MCKD

infant alive anomaly 1 anomaly 2 anomaly 3 structural anomalies male yes anus atresia partial sacral agenesis male yes multiple congenital spina bifida neurogenic bladder male yes pulmonary valve male* no cheilo-gnatho- - - functional anomalies male yes hypertension mental retardation motor retardation female yes dimorphism hypotonic motor retardation female yes dimorphism mental retardation motor retardation male yes panhypopituitarism male yes mental retardation motor retardation - * Fetus died; there was a contralateral kidney agenesis.

In general, anomalies were divided equally between boys and girls except for

predominance in males of contralateral kidney agenesis (8 out of 9), ectopic ureter

(23 out of 32) and infravesical obstruction (18 out of 21).

Eighty-one infants were operated: 79 had a nephrectomy and 2 a hemi-nephrectomy

and thirty-seven of these 81 children needed 53 other interventions for urological

anomalies (Table 3). At histology of the 81 multicystic kidneys the diagnosis of

MCKD was confirmed in all cases including the three cases with minimal function on

the isotope scan. Cartilage was found in 54 specimens (66,6%) and a nephrogenic

rest lesion in 6 kidneys (7,4%).

Table 3 - Interventions in 81 children with unilateral MCKD surgery No. nephrectomy 79 hemi-nephrectomy 2 reimplantation of a ureter 7 pyeloplasty 4 resection of urethral valves 18 meatotomy 5 excision ureterocele/ diverticulum 6 incision partial double urethra 1 excision multicystic testis 1 endoscopic treatment by subureteric injection of a bulking agent in VUR 1 orchidopexy 1 other small incisions/ excisions 9 total interventions 134


In two cases there was a bladder incision made to remove the distal segment of the

ectopic ureter that ended in both cases in an ureterocele. In all other cases the ureter

was removed as far as possible at the nephrectomy. Reimplantation of a ureter was

performed in 7 cases: 3 times because of VUR (grade III, IV and V), twice the

remaining ureter after heminephro-urethrectomy, once it was a solitary obstructive

megaureter and once it was together with a pyeloplasty and ureteral obstruction.

Directly before nephrectomy cystoscopy was performed. Thirty-six of the 81 infants

(44,4%) had one or more anomalies: 18 had urethral obstruction, 5 meatal stenosis,

3 a secondary diverticulum of the bladder and 32 an ectopic ureter of which 1 ended

in a utricular cyst and 2 in an ectopic ureterocele. In 10 of the 18 children with a

urethral obstruction an excision of urethral valves was performed and in the other 8

an incision was done because of a narrow bladder neck or mid-urethral stenosis. In 2

of the 5 children with a meatal stenosis the meatus was obstructive for the

cystoscope and in three other girls calibration of the meatus was narrow for age and

the jet of urine was anomalous.

In 35 girls colposcopy was performed. In 3 of them (8,6%) anomalies of the genital

tract were found. One girl had Mayer-Rokitansky’s syndrome (vaginal atresia, uterus

duplex, abnormal pelvic blood vessels) and 1 child had an imperforate hymen.

Another 4 girls had an ectopic ureter ending into a Gartner’s duct of (in 1 case with

an opening into the vagina, diagnosed at colposcopy). Six girls had no colposcopy: 3

had died perinatally and 3 had no surgery at all.

The diagnosis of an ectopic ureter was made at the cystoscopy by seeing a

hemitrigonum and an absent orifice. At nephrectomy 10 ureters could not be traced

and the histology of the remaining 22 ectopic ureters showed that 2 had a double

lumen, that 7 were atretic, that 1 was fibrotic, that 6 were mega dilated (2 ending in a

ureterocele, 1 ending in a seminal vesicle), that 1 was totally obstructed, that 4 ended

in the duct of Gartner and that 1 ended in a ureterocele. There was one boy with a

scrotally located multicystic testicle removed from the same side as the multicystic

kidney.

Six children had no surgery at all because two parents refused surgery, two children

have one moiety of a well functioning duplex system affected and 2 were under

control elsewhere and conservative management was recommended by their

paediatricians.

78 Chapter 6

DISCUSSION

Children with unilateral MCKD have an increased risk of abnormalities of the

contralateral kidney and the lower urogenital tract9, 14, 15, 20. The finding of a unilateral

MCKD must therefore lead to meticulous screening of the complete urinary tract,

both pre- and postnatally, as most studies also recommend, which implies a full

urologic investigation to verify the diagnosis, to assess renal functioning and to

exclude or confirm additional anomalies, which may require additional urologic

treatment.

There is no uniformity of opinion on the role of nephrectomy in the management of

MCKD. Most authors stated that indications for surgery include a large mass

compromising respiration or feeding, pain or an enlarging mass. The increased

incidence of hypertension warrants routine blood pressure monitoring by some

authors and others stated that there is no increased risk2, 8, 15, 21, 22. An every 3 to 6

months ultrasound scan is recommended by some authors because of a higher risk

on malignant degeneration18 while others claimed the opposite2, 15. Webb et al18

recommend nephrectomy because of a higher risk on hypertension and malignancy

and Ranke et al23 advices the same because of money saving on the long-term.

Manzoni et al8 describe indications for management but admitted that long-term

follow-up is requested and because of poor parental compliance nephrectomy should

strongly be considered.

The view of the Dutch Society for Paediatric Urology is that nephrectomy done at the

early age of approximately six months, because flank musculature is hardly used at

that time because most of the children cannot yet sit, is as a minor operation with

negligible morbidity. This allows for day-care nephrectomy or short stay due to limited

need of post operation analgesia. There will be no need for the lifetime follow-up in

case the kidney is left in place because this long-term follow-up will easily be

neglected in the course of years. Furthermore parents need not to be anxious when

their child has abdominal pain.

Different to all referred sources we performed a cystoscopy and in girls a colposcopy

prior to nephrectomy. With these examinations a high number of anomalies of the


urinary tract and of the internal genital organs was detected with ectopic ureters in

40% of the children, infravesical obstructions in 26% and - in girls - an ectopic ending

ureter into the duct of Gartner in 11%, as most common findings. Some may argue

that only 3 anomalies discovered by colposcopy can lead to the conclusion that this

examination is superfluous. But an atresia of the vagina and hymen imperforates

would not have been found at the standard investigation after birth (department of

neonatology: personal communication) and probably not earlier than the beginning

of the puberty. In our opinion colposcopy is a minor intervention in a child already

under anaesthesia and every anomaly found is of importance for the child and for her

parents. Moreover we found 4 ectopic ending ureters into a Gartner’s duct, one with

an opening into the vagina, which otherwise would not have been detected.

Nephrectomy, preferably at the age of approximately six months was proposed to all

parents according to the guidelines of the Dutch Society for Paediatric Urology.

At histology cartilage was found in 66,6% of the removed multicystic kidneys which is

thought to be a sign of dysplasia as a result of obstruction11, 24. A nephrogenic rest

lesion was found in 7,4% of the removed MCKD kidneys and is considered a risk

factor for developing a Wilms tumor25 later in life. A similar percentage (6,4%) was

found by Dimmick et al26.

The differences in outcome for anomalies on the contralateral or ipsilateral kidney

and the lower urogenital tract are remarkable when we compare our series with

others. In our study 39 children had 41 anomalies of the contralateral kidney. We

found agenesis of the kidney in 9% of cases comparable with Lazebnik et al12 but

higher than the 2,3 to 2,6% of others14, 20. A hydronephrosis was seen in 18% of

children higher than the 7,9 to 12 % of others12. In approximately 11% of the children

VUR was diagnosed hardly higher than the 8% of van Eijk et al20 but lower than the

14 to 20% of others20, Wacksman et al15 mentioned even 43%.

In our study 42 children had 56 abnormalities on the ipsilateral side with an ectopic

ureter in 38,6% and a megaureter in 12,1% as most common. Those anomalies are

mentioned sporadically or not at all in the literature in which VUR and UPJ stenosis

Table 4 – An ove

rview of co

nco

mita

nt anomalies in children with

a unila

teral m

ulticy

stic kidney in seven studies.

anomaly

contralateral

ipsilateral

lower tract

extrarenal

author

total

No.

N (%) with

additional renal

anomalies

total N

o.

agenesis

dys

plasia

hyd

ronephrosis

/ pye

lectasis

VUR

Atiy

eh 1992

49

25 = 51 %

39%

4%

12%

18%

6,1%

6,1%

Al-Khaldi

1994

30

17 = 57 %

23,3%

2,3%

20%

13,3%

Rudnik –

Sch

onebőrn

1998

204

? = 27 %

27%

14%

Laze

bnik

1999

102

27 = 23 %

32%

9%

9,8%

3,8%

3,8%

35%

Aubertin

2002

54

18 = 33 %

24,1%

5,5%

3,7%

16%

Eijk van 2002

38

8 = 21 %

13%

2,6%

7,9%

8%

8%

5,3%

prese

nt

study

100

75 = 75 %

48,1%

9%

5%

18%

10,8%

48,3%

33%

10%


were mostly mentioned9, 20. We found ureteroceles in 4 cases (4,8%) comparable

with Lazebnik et al12 with an incidence of 3.8%. VUR was found in 9 children (10,8%)

comparable with the 8% of van Eijk et al20 but lower than the 14% till 43% mentioned

by others2, 9, 14, 15.

A lower urinary tract anomaly was only mentioned by Atiyeh et al9, 12 in 6% of cases.

This study found 32 anomalies in 26 infants (31.3%): an infravesical obstruction in

21,7% (18 infants), a diverticulum in 3,6% (3 infants) and a stenosis of the urethral

meatus in 6,0% (5 infants) as most common. Posterior urethral valve incision was

done at the judgment of the paediatric urologist at the time of cystoscopy and we are

aware that the incidence of infravesical obstruction and consequently incision of

urethral valves is high compared to other studies. There was no urodynamic study

done routinely before the valve incision to proof the obstruction and it was up to the,

subjective, judgment of the surgeon whether or not to incise the folds.

Associated extrarenal anomalies were found with an incidence of 10%, less than the

16% of Aubertin et al1, 12 and the 35% as reported by Lazebnik et al1, 12. Outcome,

however, is not comparable because in most studies another target group was

included e.g. both bilateral and unilateral MCKD or a different population limited to

fetuses with chromosomal analysis. Only van Eijk et al20 described a comparable

population and reported an incidence of 5,3% of extrarenal anomalies. Mental and

motor retardation in 4 cases was the most common extrarenal anomaly in our study

followed by a cardiac abnormality in 2 children. Table 4 shows an overview of all

additional anomalies found in our study in comparison with literature.

The male to female ratio (58 : 41) showed a predominance of males similar to the

literature.

The left to right affected kidney ratio in our series was 47 : 53. This is in contrast with

literature that reports more left-sided multicystic kidneys identical with the explanation

that the left kidney is more often associated with primary obstruction(27, 28). We have

no explanation for this difference and It is probably “simply chance” that our ratio is

the opposite.

82 Chapter 6

We agree that the benefice for the child is not demonstrated with our invasive

management. The problem is that a large randomised controlled study is needed to

prove whether a nephrectomy or an expectant policy has the preference. In addition

follow-up will be needed during several decades because hypertension or

malignancy can develop later in life.

CONCLUSIONS

Children with unilateral MCKD have a considerable chance of having other

congenital anomalies of the urinary tract and therefore they need to be precisely

screened pre- and postnatally. We recommend that a routine postnatal examination

consist of an ultrasound examination, an isotope scan and a VCUG and when a

nephrectomy is done also a cystoscopy and a colposcopy to detect possibly hidden

anomalies of the genitourinary tract.


REFERENCES

1. Aubertin G, Cripps S, Coleman G, McGillivray B, Yong SL, Van Allen M, et al. Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management. Prenat Diagn 2002;22(5):388-94. 2. Rudnik-Schoneborn S, John U, Deget F, Ehrich JH, Misselwitz J, Zerres K. Clinical features of unilateral multicystic renal dysplasia in children. Eur J Pediatr 1998;157(8):666-72. 3. Beck AD. The effect of intra-uterine urinary obstruction upon the development of the fetal kidney. J Urol 1971;105(6):784-9. 4. Peters CA. Animal models of fetal renal disease. Prenat Diagn 2001;21(11):917-23. 5. Winyard P, Chitty L. Dysplastic and polycystic kidneys: diagnosis, associations and management. Prenat Diagn 2001;21(11):924-35. 6. Felson B, Cussen LJ. The hydronephrotic type of unilateral congenital multicystic disease of the kidney. Semin Roentgenol 1975;10(2):113-23. 7. Peters CA, Carr MC, Lais A, Retik AB, Mandell J. The response of the fetal kidney to obstruction. J Urol 1992;148(2 Pt 2):503-9. 8. Manzoni GM, Caldamone AA. Pediatric Surgery and Urology: Long Term Outcome. London: W.B. Saunders; 1998. 9. Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities in multicystic-dysplastic kidney disease. J Pediatr 1992;121(1):65-7. 10. Srivastava T, Garola RE, Hellerstein S. Autosomal dominant inheritance of multicystic dysplastic kidney. Pediatr Nephrol 1999;13(6):481-3. 11. Zerres K, Volpel MC, Weiss H. Cystic kidneys. Genetics, pathologic anatomy, clinical picture, and prenatal diagnosis. Hum Genet 1984;68(2):104-35. 12. Lazebnik N, Bellinger MF, Ferguson JE, 2nd, Hogge JS, Hogge WA. Insights into the pathogenesis and natural history of fetuses with multicystic dysplastic kidney disease. Prenat Diagn 1999;19(5):418-23. 13. Nicolaides KH, Cheng HH, Abbas A, Snijders RJ, Gosden C. Fetal renal defects: associated malformations and chromosomal defects. Fetal Diagn Ther 1992;7(1):1-11. 14. Al-Khaldi N, Watson AR, Zuccollo J, Twining P, Rose DH. Outcome of antenatally detected cystic dysplastic kidney disease. Arch Dis Child 1994;70(6):520-2. 15. Wacksman J, Phipps L. Report of the Multicystic Kidney Registry: preliminary findings. J Urol 1993;150(6):1870-2. 16. Lippert MC. Renal Cystic Disease. In: (eds) LWW, editor. Adult and Pediatric Urology. Philadelphia; 2002. p. 829-878. 17. Elder JS, Hladky D, Selzman AA. Outpatient nephrectomy for nonfunctioning kidneys. J Urol 1995;154(2 Pt 2):712-4; discussion 714-5. 18. Webb NJ, Lewis MA, Bruce J, Gough DC, Ladusans EJ, Thomson AP, et al. Unilateral multicystic dysplastic kidney: the case for nephrectomy. Arch Dis Child 1997;76(1):31-4. 19. LaSalle MD, Stock JA, Hanna MK. Insurability of children with congenital urological anomalies. J Urol 1997;158(3 Pt 2):1312-5.

84 Chapter 6

20. Eijk van L, Cohen-Overbeek TE, den Hollander NS, Nijman JM, Wladimiroff JW. Unilateral multicystic dysplastic kidney: a combined pre- and postnatal assessment. Ultrasound Obstet Gynecol 2002;19(2):180-3. 21. Sukthankar S, Watson AR. Unilateral multicystic dysplastic kidney disease: defining the natural history. Anglia Paediatric Nephrourology Group. Acta Paediatr 2000;89(7):811-3. 22. Oliveira EA, Diniz JS, Vilasboas AS, Rabelo EA, Silva JM, Filgueiras MT. Multicystic dysplastic kidney detected by fetal sonography: conservative management and follow-up. Pediatr Surg Int 2001;17(1):54-7. 23. Ranke A, Schmitt M, Didier F, Droulle P. Antenatal diagnosis of Multicystic Renal Dysplasia. Eur J Pediatr Surg 2001;11(4):246-54. 24 Glassberg KI, Stephens FD, Lebowitz RL, Braren V, Duckett JW, Jacobs EC, et al. Renal dysgenesis and cystic disease of the kidney: a report of the Committee on Terminology, Nomenclature and Classification, Section on Urology, American Academy of Pediatrics. J Urol 1987;138(4 Pt 2):1085-92. 25. Beckwith JB. Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet 1998;79(4):268-73. 26. Dimmick JE, Johnson HW, Coleman GU, Carter M. Wilms tumorlet, nodular renal blastema and multicystic renal dysplasia. J Urol 1989;142(2 Pt 2):484-5; discussion 489. 27 Glassberg KI. Dilated ureter. Classification and approach. Urology 1977;9(1):1-7. 28. Johnston JH, Evans JP, Glassberg KI, Shapiro SR. Pelvic hydronephrosis in children: a review of 219 personal cases. J Urol 1977;117(1):97-101.

Chapter 7 Mild pyelectasis diagnosed by prenatal ultrasound is not a predictor of urinary tract morbidity in childhood H.A. Damen–Eliasa, S.E. Luijnenburga, G.H.A. Vissera, P.H. Stoutenbeeka, T. P.V.M. de Jongb a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Department of Paediatric Urology, University Hospital Utrecht, The Netherlands

86 Chapter 7

ABSTRACT

Objectives To determine children whether with an antenatally diagnosed mild

pyelectasis have more urinary tract morbidity during childhood than children without

this finding.

Methods Case-control study in children with pyelectasis (anteroposterior diameter of

the fetal renal pelvis of 5-10 mm) detected at about 20 weeks of gestational age by

ultrasound. A validated questionnaire, regarding voiding and defecation habits and

urinary tract infections (UTI), was send to the parents of 208 cases and 416 matched

controls.

Results The questionnaire was returned by 146 cases and 250 controls. There was a

male predominance in the case group as compared to the controls (p=<0,000). There

were neither differences in voiding habits nor in incidence of UTI. The incidence of

infections was high in both groups: 11,6% in cases and 10,0% in controls. The only

difference between the groups was a higher incidence of constipation (stools

frequency of 2 times a week or less) in the case group (p=0,003).

Postnatally forty-one children had an ultrasound examination and 16 were referred to

a paediatrician or urologist: 3 had persisting pyelectasis, 3 had a recurrent urinary

tract infection (one girl also VUR grade I) and 1 required surgery (a pyeloplasty).

Four of the controls were referred to a paediatrician or urologist: 3 had recurrent UTI

and 1 was urinary incontinent.

Conclusion Children with a mild fetal pyelectasis do not have more urinary tract

morbidity during childhood than children without this finding. Therefore, there seems

to be no need for additional investigation after birth.

Mild pyelectasis 87

INTRODUCTION

Mild uni- or bilateral fetal pyelectasis is a frequent finding at prenatal ultrasound

examination, with a considerable variation in the reported incidence, from 0,6% to

5,5%1-4. This wide variation is likely to be due to differences in criteria as to the

definition of pyelectasis, in particular regarding size and gestational age at diagnosis.

The clinical significance of mild fetal pyelectasis is still unclear; it may resolve,

stabilize or be the first indicator of significant urinary tract pathology. The

anteroposterior diameter of the renal pelvis above which further investigation during

or after pregnancy is required is still controversial3, 5-7. Some investigators consider

an anteroposterior diameter of the renal pelvis <10 mm as physiological, since this

will resolve or improve within a couple of years after birth8-11. Others recommend a

full postnatal investigation for all fetuses with mild pyelectasis1, 12-14. In their opinion a

significant percentage of these infants will have vesico ureteral reflux (VUR) or need

postnatal surgery, when the pyelectasis persists at a follow-up scan around 32 weeks

of gestation.

Evidence exists that pyelectasis may result in clinical complications such as

obstructive uropathy or VUR. A single observation of a pyelectasis puts the fetus at

risk for VUR but a normal scan does not exclude the possibility of VUR13, 15. So far no

correlation has been found between antenatal and postnatal dilatation and the

severity of VUR13. There is a suggestion of a between-pregnancy consistency in fetal

pyelectasis in subsequent pregnancies and this emphasizes the possibility that

genetic and/or environmental factors play a role in its development16-19.

Counselling the parents is difficult due to our limited understanding of the natural

history of pyelectasis. False positive diagnosis of fetal pyelectasis may lead to

unwarranted anxiety, as well as unnecessary and expensive diagnostic investigations

after delivery.

Pyelectasis is still a controversial problem since renal pelvis measurements are not

well standardized and since there are no consistent guidelines in relating the severity

of pyelectasis to appropriate perinatal and postnatal management. Because of the

lack of data on possible long-term morbidity in late childhood in infants who had been

antenatally diagnosed as having mild pyelectasis, it was the aim of this study to

investigate the occurrence of urinary tract morbidity in childhood in these infants in

88 Chapter 7

comparison to a control group, to assess if there is an indication for postnatal

follow-up of these children.

METHODS

In the Netherlands standard screening for fetal anomalies has not yet been

introduced, in spite of an extensive debate. Nonetheless, in the Amphia hospital (a

District General Hospital, location Oosterhout, The Netherlands), the anomaly scan

has been introduced for all pregnant women in the early 1980’s. Two midwives–

ultrasonographer examined all women at 18 – 20 weeks gestational age using the

same ultrasound machine. Data were recorded in a standardized way.

When a pyelectasis was noticed, defined as an anteroposterior diameter (A-P

diameter) of the renal pelvis of 5–10 mm, the anteroposterior diameter of the renal

pelvis was measured when in a sagittal plane the full length with the renal pelvis was

visualised and perpendicular to this, in the largest sectional plane, the

anteroposterior diameter of the pelvis by placing the callipers on the inner borders of

the renal tissue. No dilatation of the calices was noticed unless the pyelectasis

exceeded 10 mm. All examinations were carried out during daytime. Maternal fluid

intake was not specified because it is questionable whether maternal hydration

influences fetal pyelectasis20-22.

When a mild pyelectasis was found, it was customary to re-exam the women at

approximately 32 weeks of gestation. When the A-P diameter exceeded 10 mm, the

child was referred to a paediatrician or urologist for urological follow-up during the

first weeks of life. When the mild pyelectasis had stabilized or resolved, the parents

were advised to refrain from further investigations before or after birth and were told

that their child might have an increased risk for urinary tract infection (UTI) due to

VUR and that, in case of feeling listless or fever of unknown origin, UTI should be

ruled out. This advice corresponds to the current opinion about pyelectasis in the

Netherlands.

The archives of the obstetric ultrasound department were reviewed over the period

January 1st, 1994 till December 31st, 1998. All accounts of fetuses with an isolated

mild uni- or bilateral pyelectasis were extracted, in common with the notes of controls

(two per case) seen on the same day, in which no anomaly had been found.

Mild pyelectasis 89

The local ethical review board and the board of the University Medical Centre

Utrecht, The Netherlands, authorized the study.

After written informed consent was obtained, the parents of the cases and controls

were asked, to fill out a standardized questionnaire (Appendix 1) regarding voiding

and defecation patrons and urinary tract infections. The questionnaire, we used, was

based on the validated questionnaire used in the International Reflux Study in

Children(23). Simultaneously they answered questions about day and night potty

training of the child and consultations of the general practitioner or other doctors

(Appendix 2). We choose the study period 1994-1998 because for answering the

questionnaires the children had to be potty-trained.

Statistical analyses were performed using Statistical Product and Service Solutions

package 10.1 (SPSSR)24. For the calculations the t-test, the chi-square test or the

Fisher’s exact test (we appropriate) were used, with p<0.05 considered significant.

RESULTS

During the 5-year study period the 18-20 weeks anomaly scan was performed in

4532 pregnant women. Uni- or bilateral pyelectasis was diagnosed in 208 fetuses,

giving an incidence of 4,6 %. In 164 fetuses (78,8%) there was a bilateral pyelectasis

and in 44 (21,2%) a unilateral pyelectasis. The ratio of bilateral to unilateral affected

kidneys was 4 : 1 and in the group with a unilateral pyelectasis the ratio of the right to

left kidney was 1 : 1.

One hundred and seventy-nine fetuses with pyelectasis, 179/208 (86,1%), were

rescanned at approximately 32 weeks (range 28 till 38 weeks). The pyelectasis was

resolved in 67 fetuses (37,4%) was stable in 96 fetuses (53,6%) and had progressed

to >10 mm in 16 fetuses (8,9%). These 16 cases were excluded from the present

study since these children were referred for urological follow-up during the first week

of life. In 20 fetuses (11,2%) the pyelectasis had changed from bilateral to unilateral

and in 4 children (2,2%) from unilateral to bilateral.

The response rate was 146 out of 192 cases (208 – 16 excluded cases) and 250 out

of 416 controls. Five cases and 4 controls could not be traced and were lost to

follow-up, giving corrected response rates of 76,0% (146/192) and 60,7% (250/412),

respectively. In the case group another 17 fetuses were excluded because no repeat

90 Chapter 7

scan had been made at 32 weeks gestation and we therefore lacked information

about dilatation of the renal pelvis during the third trimester. So, finally the

calculations were made on 129 cases and 250 controls. There were no significant

differences between responders and non-responders except for maternal age at the

first ultrasound examination (p=0,005; see Table 1).

Table 1 - Comparison between patient characteristics of responders and non-responders inthe casegroup.

variable respondersn = 146

non-respondersn = 57

significantdifference?

mean maternal age at time of the firstgestational ultrasound examination

30 years, 10months

28 years, 11months

p =0,005 *

mean age (wks) of detection of pyelectasis 21,6 22,1 p = 0,449mean number of antenatal ultrasoundexaminations

2,5 2,7 p = 0,221

mean number of previous deliveries of themother

0,77 0,75 p = 0,939

unilateral pyelectasis at time of detection 31 12 p = 0,977bilateral pyelectasis at time of detection 115 45 p = 0,977no follow-up ultrasound examination± 32 weeks

17 12 p = 0,085

pyelectasis resolved (<5mm) duringpregnancy

47 18 p = 0,933

pyelectasis stabilized (5-10mm) duringpregnancy

72 21 p = 0,109

pyelectasis progressed (>10mm) duringpregnancy

10 6 p = 1,000

pyelectasis changed from bilateral tounilateral

11 8 p = 0,153

pyelectasis changed from unilateral tobilateral

4 0 p = 0,578

* significant difference

The responders in the case and control group were comparable on the most

important items (Table 2).

Table 2 - Comparison between patients’ characteristics of the responders in the case andcontrol group.

variable case-groupn = 146

control-groupn = 250

significantdifference?

mean maternal age at time of delivery 31 years, 2months

30 years, 5months

p = 0,057

mean number of pregnancies 1,98 1,84 p = 0,207mean number of previous deliveries 0,77 0,63 p = 0,094mean current age of the children 6 years, 1month 5 years, 9

monthsp = 0,314

mean number of antenatal ultrasoundexaminations

2,52 1,63 p = <0,000*


Mild pyelectasis 91

As expected, the only variable that showed a significant difference was the number of

antenatal ultrasound examinations (p=<0,000) because of the repeated ultrasound

scan in the third trimester of pregnancy in the case group; median of number of

examinations in the case group 2,52 and in the control group 1,63.

Data on voiding and defecation habits and urinary tract infections are shown in Table

3. On three items there were significant differences: a) the male to female ratio in the

case group was 2,17:1 and in the control group 1:1,02 (p=<0,000), b) children in the

case-group were more often constipated, when constipation was defined as a stool

frequency of 2 times a week or less (p=0,003), c) children in the case group were

potty trained during daytime at a slightly higher age (p=0,026).

Table 3 - Voiding and defecation habits and urinary tract infections in the case and controlgroup.

variable case-group

n = 129

control-group

n = 250

significant

difference?

number of males 88 124

number of females 41 126

Male : Female ratio 2,17 : 1 1 : 1,02 p = <0,000*

daytime urinary incontinence 22 = 17,1% 34 = 13,6% p = 0,476

nocturnal enuresis 30 = 23,3% 49 = 19,6% p = 0,794

urinary tract infection 17 = 11,6 % 25 = 10 % p = 0,601

soiling 17 = 11,6 % 45 = 18,0% p = 0,095

constipation A = stool frequency of <2 times a

week

9 = 7,0% 2 = 0,8% p = 0,003*

constipation B = hard stools 9 = 7,0% 14 = 5,6% p = 0,811

constipation C = stool frequency of <2 times a

week and hard stools

1 = 0,8% 0 p = 0,368

constipation treatment 4 = 3,1% 2 = 0,8% p = 0,195

mean number of months in which the children

were trained in voiding during daytime

3 years,

1 month

2 years,

10 months

p = 0,026*


were trained in voiding during nighttime

3 years,

4 months

3 years,

2 months

p = 0,128


were trained in stools

3 years,

0 months

2 years,

11 months

p = 0,108


92 Chapter 7

In Table 4 data are presented separately for males and females. There were no

significant differences between the boys and girls except for a higher incidence of

constipation A in the females in the case group (p=0,005). The incidence of UTI was

not different in boys and girls of case and control groups: 17 cases, 17/129 (13,2%):

6 males and 11 females and in 25 controls, 25/250 (10,0%): 6 males and 19 females.

Table 4 - Voiding and defecation habits and urinary tract infections (in numbers or mean agein years and months) in males and females from the case and control group.

malesn = 212

females n = 167

variable

casen = 88

controln = 124

p-value casen = 41

controln = 126

p-value

daytime urinary incontinence 17 17 p=0,743 5 17 p = 0,873

nocturnal enuresis 24 30 p=0,993 6 19 p = 0,737

urinary tract infection 6 6 p=0,699 11 19 p = 0,177

soiling 12 21 p=0,314 5 24 p = 0,198

constipation A = stool frequency

of <2 times a week

3 0 p=0,088 6 2 p =0,005*

constipation B = hard stools 5 6 p=1,000 4 8 p = 1,000

constipation C = stool frequency

of <2 times a week or less and

hard stools

0 0 ---- 1 0 p = 0,267

constipation treatment 3 1 p=0,321 1 1 p = 1,000

mean age (n of years/ months) of

potty-training during daytime

3 years,

1 month

3 years,

0 months

p=0,420 3 years,

4 months

2 years,

9 months

p = 0,245

mean age (n of years/ months) of

potty-training during nighttime

3 years,

5 months

3 years,

4 months

p=0,256 3 years,

0 months

3 years,

0 months

p = 0,915

mean age (n of years/ months) at

which the children were trained in

stools

3 years,

1 month

3 years,

0 months

p=0,543 2 years,

10 months

2 years,

9 months

p = 0,464


In spite of our advice to refrain from any investigation postnatally, 41 children, 41/129

(31,8%), in the case-group received a postnatal ultrasound examination of the urinary

tract. Sixteen of them were subsequently referred to a paediatrician or urologist. Nine

of these infants received prophylactic antibiotics, 9/129 (7,0%). The dilatation

resolved spontaneously in 7 of the 16 referred children; in 3 infants the dilatation

persisted but no further treatment was necessary; 3 infants had recurrent UTI (with a

Mild pyelectasis 93

VUR grade I in one female); 1 child had a dilatation of an extrarenal pelvis; 1 child

had transient haematuria but normal anatomy of the urinary tract and 1 infant

required surgery. This child, a boy, showed a unilateral pyelectasis at 20 weeks

gestational age of 8mm, which had stabilized (9 mm) at the 31 weeks ultrasound

scan. The boy required surgery 36 months after birth because of progressive

pelvicalyceal dilatation and deterioration of the renal function. In the control group 4

children were referred to a paediatrician or urologist: 3 had recurrent UTI and 1 had

problems with urinary incontinence. All infants in the case and control group are

doing well and have normal renal function.

Thirty children of the remaining 88 children (129-41) in the case group consulted a

general practitioner 48 times, mindful of our advice to have the urine checked

because of lethargy or fever of unknown origin and 5 were treated with antibiotics

because of a proven UTI.

DISCUSSION

Little is known about urinary tract morbidity during childhood in children who had a

mild prenatal pyelectasis. Fetuses with a mild fetal pyelectasis are frequently

encountered during ultrasound examination, but the aetiology and clinical

significance are unclear. Distinguishing cases in which the pyelectasis has no clinical

consequences from those with underlying renal pathology is not yet possible and

consistent guidelines about antenatal and postnatal follow up are absent.

Questionnaires, which are a good method of studying large groups or to study a

population, were used to interview the children. A drawback is that the physical

examination and other tests are lacking and that the parents or guardians have to fill

in the test, which implies the possibility of subjective opinion. But an advantage is

that the information can be gathered without too much bother for the children and

their parents. Questionnaires can be used to screen on health, on the prevalence of

diseases or to investigate the quality of life25, 26. They should be tested before for

reproducibility and should be validated23.

Studies on antenatal detection of pyelectasis show considerable differences in

outcome3, 15, 27-31. Percentages for resolving of the pyelectasis range from 5 to 51%,

for remaining stable from 21 to 39% and for worsening from 9 till 27% (Table 5).

These wide variations are understandable given the different criteria for pyelectasis.

94 Chapter 7

Some authors have stated that the size of the prenatal dilatation is not a sensitive

predictor of pathology but that an increasing size during pregnancy is associated with

morbidity and mortality32. An A-P diameter of >10 mm is usually considered of

significance9, 15, but the Great Ormond Street Experience33 showed that there is a

very low risk of clinically significant obstruction when the dilatation does not exceed

15 mm at any gestational age.

We found hardly any (significant) differences in morbidity between children with or

without mild prenatal pyelectasis. There was a male predominance in the case group,

which is in concordance with findings of others (Table 5).

Table 5 - An overview of studies about mild fetal pyelectasis: definitions, course during pregnancy, sex ratio and advice given.

No. of fetuses

cut-off points pyelectasis

resolution stable progression ♂ : ♀ ratio

advice

Adra 1997 68 ≥4mm <33wks

≥7mm ≤10mm

at ≥33wks

31% ? ? 2 : 1 repeat scan 28 wks

gestation; full post natal

investigation in case

>8mm

Feldman

2001

347 ≥4mm ≤7mm

at ≤21wks

≥5mm ≤8mm

at >20wks

51% 39% 10% ? ?

Harding

1999

70 <10mm 30,4 21,4 19,6 2,2 : 1 repeat scan 34wks

gestation

ultrasound week 1 and 6

after birth

Morin

1996

122 ≥4mm ≤10mm

at < 20wks

≥5mm ≤10mm

at ≥20wks

29% 25% 9% ? ultrasound after >72 hours

after birth

Persutte

1997

294 ≥4mm ≤10mm

4,7% ? 27,1% 2,3 : 1 antibiotic prophylaxis -

ultrasound < 1 month after

birth + voiding

cystourethrography

present

study

208 ≥5mm ≤10mm 37,4% 53,6% 8,9% 2,2 : 1 repeat scan 32wks

gestation - after birth: urine

check in case of lethargy

or fever of unknown origin

Mild pyelectasis 95

Furthermore we found in the case group a low stool frequency and a higher age at

toilet training. There are no reports published in literature suggesting a correlation

between mild fetal pyelectasis and constipation during childhood.

There was no statistical significant difference in UTI between both groups, although

the incidence of 11,6% in cases and 10,0% in controls is higher than the 3,3% - 8,6%

found by others9, 34 and also higher than Dutch figures obtained from general

practitioners’ practices. Accordingly to those data the incidence of UTI’s in the

Netherlands is 2,9% (♂ 0,5%, ♀ 2,4%) in infants of 0 – 4 years of age and 3,2% (♂

0,4%, ♀ 2,8%)(35) in children of 5-9 years of age. It might be that the higher

incidence of UTI’s that we found in this study is due to the very detailed questions on

voiding and defecation habits in the questionnaire. De Kort et al36 have used the

same questionnaire in a study of hypermobility of joints in children of the same age

as in our study and found an incidence of UTI 15,7% in cases and 7,8% in controls.

Another reason for the high incidence of UTI – at least in the case group – might be

that general practitioners in this area are more focused on a UTI because of the

advice given to the parents to have the urine checked if their child is lethargic or

develops a fever of unknown origin. Earlier studies have reported that UTI’s are

underdiagnosed in children and concluded that a greater awareness of the

importance of investigation and management of UTI in children is needed because

as already known infections may lead to renal scarring37-39. Shaw et al40 reported that

even the presence of another potential source of fever, such as otitis media or

respiratory infection, does not reliably exclude UTI.

In spite of our advice, corresponding to the current opinion about pyelectasis in the

Netherlands, that in case of a mild fetal pyelectasis no further investigations were

needed after birth, 41 infants of these infants still had an ultrasound examination at

request of the general practitioner or gynaecologist. Sixteen children were referred to

a paediatrician or urologist (12,4%). Finally 1 child underwent surgery at the age of 3

years, because of an UPJ-obstruction. This resulted in a surgical intervention rate of

2,5% (1/41), or may be 0,8% (1/129), although we cannot completely exclude renal

pathology requiring surgery in the other infants. Anyhow the intervention rate seems

much lower than reported by others (3,6%-24,3%)1, 3, 27.

96 Chapter 7

CONCLUSIONS

The finding of fetal pyelectasis often generates considerable parental anxiety32, 34. At

birth the “affected” infants seem healthy and outwardly normal, but parental relief is

short-lived if their asymptomatic infant is then required to undergo intensive and

invasive investigations. Our study demonstrated similar incidence UTI’s. Therefore,

there seems to be no need for postnatal investigations. In case of a mild renal

pyelectasis at 20 weeks of gestation we suggest a single follow-up scan in the third

trimester to determine if the pyelectasis has resolved, stabilized or progressed. The

child should only be referred for postnatal examination if there is progression >10mm.

With this policy there is only a very small chance of missing an occasional case of

VUR or potential obstruction. On the other hand, however, this policy may reduce

parental anxiety and minimizes the burden of unnecessary invasive investigations in

healthy infants as well as unnecessary costs. Parents should be advised to visit their

general practitioner if their child is lethargic or has fever of unknown origin to have

urine tested to rule out UTI or treat infection effectively in order to prevent renal

damage.

Mild pyelectasis 97

APPENDIX 1

Questionnaire for children with voiding dysfunction and/or urinary tract infection,

translated from Dutch.

A2 Age .. years

A3 Gender □ boy

□ girl

A4 Date of filling out questionnaire .. .. ….

B Daytime incontinence

B1 Does your child wet his pants □ yes

□ no >> go to question B2

B1a If yes, at what age started the wetting

B1b If yes, how often does it happen □ < 3 times a week

□ 3-4 times a week

□ > 4 times a week

B1c If yes, are the pants □ damp

□ soaking

□ variable

□ don’t know

B1d If yes, wet pants □ all day

□ in the afternoon

□ variable

□ with physical activity

□ don’t know

B1e If yes, only in certain situations (playing) □ yes

□ no

□ don’t know

B1f If yes, does your child ignore the wet pants □ yes

□ no

□ don’t know

Continue with question C1

B2 When dry at daytime, at what age did your child

achieve continence .. years and .. months

98 Chapter 7

C Voiding habits yes no don’t know

C1 Is there normal early morning voiding □ □ □

C2 Do you have to send your child to the bathroom □ □ □

C3 Does your child void hasty and sloppy □ □ □

C4 Does your child strain during voiding □ □ □

C5 Is the stream interrupted or staccato □ □ □

C7 Is voiding painful □ □ □

C8 For girls: does she wet the toilet seat □ □ □

C9 For girls: is the meatus irritated □ □ □

C6 How often does your child void during day time □ < 4 □ 4-7 □ >7

D Urge and reaction on urge never sometimes always don’t know

D1 Does your child have difficult to suppress urgency □ □ □ □

D2 If yes, does your child take an urge position, like

squatting, crossing the legs, hand to the genitals □ □ □ □

D3 Is there adequate reaction to urge (timely voiding) □ □ □ □

D4 Does your child postpone voiding □ □ □ □

E Bedwetting

E1 Does your child wet the bed or diaper □ yes >> go to question E1b

□ no

E2 If no, at what age was your child continent at night .. years and .. months

E1b If yes, how many times a week . . times

E1c Are the sheets/diapers □ damp

□ soaking

E1d If yes, has your child been dry for > ½ year □ yes

□ no >> E2

E1da If yes, at what age started the bedwetting .. years and .. months

yes no sometimes don’t know

E2 Are there family members who wet their beds □ □ □ □

E3 Does your child wake up by itself to void □ □ □ □

E4 Is it hard to wake up your child to void □ □ □ □

Mild pyelectasis 99

F Urinary tract infection

F1 Has your child ever been treated by medication □ yes

for urinary tract infection □ no >> go to question G

F1a If yes, how often □ < 3

□ 3-10

□ > 10

F1b Since when …. (year)

F1c If yes, when was the last infection .. (month) …. (year)

F1d Does your child have low dose antibiotics □ yes

At the moment to prevent new infections □ no

F1da If yes, what kind of medication □ nitrofurantoin

□ norfloxacin

□ trimethoprim

□ other

G Defecation

G1 Frequency of defecation/stools □ once a day or more often

□ every 2 days

□ 1-2 a week

□ less than once a week

yes no sometimes don’t know

G2 Is defecation painful □ □ □ □

G3 Does your child feel urge to defecate □ □ □ □

G4 Form of stools □ soft but molded

□ firm and dry

□ very soft, not molded

□ otherwise, explain…

G5 Does your child have abdominal pain □ yes

□ no

G6 Is there fecal soiling □ yes

□ no >> go to question G8

G6a If yes, how often a week □ < 3 times a week

□ 3-4 times a week

□ > 4 times a week

G6b If yes, at what age started the soiling .. years and .. months

G7 Does your child ever defecate in its pants □ yes

□ no

100 Chapter 7

G8 Is your child being treated for constipation □ yes

□ no >> go to question G10

G8a If yes, in what way □ high fiber diet

□ lactulose

□ suppository

□ enema

□ bowel lavage

□ otherwise

G10 At what age did your child achieve fecal continence .. years and .. months

G11 How many cups does your child drink a day .. cups a day

Thank you for filling out the questionnaire.

Mild pyelectasis 101

APPENDIX 2

Does a mild dilatation of the urinary tract give morbidity in childhood? Last name mother:__________________________________________________________________ Date of birth mother: �� Ultrasound investigation: date �� year�� Code-number: �� Name child (forename + family name) _____________________________________ boy / girl Address: _________________________________________________________________________ Zip code/ residence: ________________________________________________________________ Phone number: ______________________ Date of birth child: �� Is your child healthy? Yes O No O Don’t know O Is your child toilet trained? by day Yes O No O

at night Yes O No O

At what age your child was toilet trained? by day ______ year _____ months

at night ______ year _____ months

Had your child a little bit liquid in one or both kidneys??

Yes O No O → Go further on the next page.

If, yes, this was the right kidney O left kidney O both kidneys O You became the advice that if your child was lethargic to go to your general practitioner to have the

urine checked. Was did ever necessary? Yes O No O

If so, how often? 1 time O 2 times O 3 till 5 times O more than 5 times O

Has your child been to a doctor to have his kidneys checked? Yes O No O If so, did you become an advice? Yes O No O If so, which advice? ________________________________________________________________ _____________________________________________________________________________________________________ Became your child medication? Yes O No O Is your child still under control? Yes O No O If so, do you agree that we asked for information? Yes O No O If so, put your signature please? ______________________________________________________ What is the name of the doctor? ______________________________________________________ In which hospital? ______________________________________________________

Thank you for filling out the questionnaire.

102 Chapter 7

REFERENCES

1. Kent A, Cox D, Downey P, James SL. A study of mild fetal pyelectasia - outcome and proposed strategy of management. Prenat Diagn 2000;20(3):206-9. 2. Langer B, Simeoni U, Montoya Y, Casanova R, Schlaeder G. Antenatal diagnosis of upper urinary tract dilation by ultrasonography. Fetal Diagn Ther 1996;11(3):191-8. 3. Persutte WH, Koyle M, Lenke RR, Klas J, Ryan C, Hobbins JC. Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically significant. Ultrasound Obstet Gynecol 1997;10(1):12-8. 4. Scott JE, Renwick M. Antenatal renal pelvic measurements: what do they mean? BJU Int 2001;87(4):376-80. 5. Ismaili K, Hall M, Donner C, Thomas D, Vermeylen D, Avni FE. Results of systematic screening for minor degrees of fetal renal pelvis dilatation in an unselected population. Am J Obstet Gynecol 2003;188(1):242-6. 6. Langer B. Fetal pyelectasis. Ultrasound Obstet Gynecol 2000;16(1):1-5. 7. Ouzounian JG, Castro MA, Fresquez M, al-Sulyman OM, Kovacs BW. Prognostic significance of antenatally detected fetal pyelectasis. Ultrasound Obstet Gynecol 1996;7(6):424-8. 8. Broadley P, McHugo J, Morgan I, Whittle MJ, Kilby MD. The 4 year outcome following the demonstration of bilateral renal pelvic dilatation on pre-natal renal ultrasound. Br J Radiol 1999;72(855):265-70. 9. Dremsek PA, Gindl K, Voitl P, Strobl R, Hafner E, Geissler W, et al. Renal Pyelectasis in fetuses and neonates: Diagnostic value of renal pelvis diameter in pre and postnatal sonographic screening. AJR Am J Roentgenol 1997(Apr;168(4)):1017-9. 10. Grignon A, Filion R, Filiatrault D, Robitaille P, Homsy Y, Boutin H, et al. Urinary tract dilatation in utero: classification and clinical applications. Mild dilatation of the fetal kidney: a follow-up study. Radiology 1986;160(3):645-7. 11. Thomas DF, Madden NP, Irving HC, Arthur RJ, Smith SE. Mild dilatation of the fetal kidney: a follow-up study. Br J Urol 1994;74(2):236-9. 12. Corteville JE, Gray DL, Crane JP. Congenital hydronephrosis: correlation of fetal ultrasonographic findings with infant outcome. Am J Obstet Gynecol 1991;165(2):384-8. 13. Jaswon MS, Dibble L, Puri S, Davis J, Young J, Dave R, et al. Prospective study of outcome in antenatally diagnosed renal pelvis dilatation. Arch Dis Child Fetal Neonatal Ed 1999;80(2):F135-8. 14. Wilson RD, Lynch S, Lessoway VA. Fetal pyelectasis: comparison of postnatal renal pathology with unilateral and bilateral pyelectasis. Prenat Diagn 1997;17(5):451-5. 15. Adra AM, Mejides AA, Dennaoui MS, Beydoun SN. Fetal pyelectasis: is it always "physiologic"? Am J Obstet Gynecol 1995;173(4):1263-6. 16. Chertin B, Puri P. Familial vesicoureteral reflux. J Urol 2003;169(5):1804-8. 17. Degani S, Leibovitz Z, Shapiro I, Gonen R, Ohel G. Fetal pyelectasis in consecutive pregnancies: a possible genetic predisposition. Ultrasound Obstet Gynecol 1997;10(1):19-21. 18. Hollowell JG, Greenfield SP. Screening siblings for vesicoureteral reflux. J Urol 2002;168(5):2138-41.

Mild pyelectasis 103 19. Scott JE, Swallow V, Coulthard MG, Lambert HJ, Lee RE. Screening of newborn babies for familial ureteric reflux. Lancet 1997;350(9075):396-400. 20. Allen KS, Arger PH, Mennuti M, Coleman BG, Mintz MC, Fishman M. Effects of maternal hydration on fetal renal pyelectasis. Radiology 1987;163(3):807-9. 21. Babcook CJ, Silvera M, Drake C, Levine D. Effect of maternal hydration on mild fetal pyelectasis. J Ultrasound Med 1998;17(9):539-44; quiz 545-6. 22. Robinson JN, Tice K, Kolm P, Abuhamad AZ. Effect of maternal hydration on fetal renal pyelectasis. Obstet Gynecol 1998;92(1):137-41. 23. Gool van JD, Hjalmas K, Tamminen-Mobius T, Olbing H. Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children. J Urol 1992;148(5 Pt 2):1699-702. 24. SPSS Inc. Chicago. 2004. 25. Hellstrom AL, Hanson E, Hansson S, Hjalmas K, Jodal U. Micturition habits and incontinence in 7-year-old Swedish school entrants. Eur J Pediatr 1990;149(6):434-7. 26. Jones MA, Breckman B, Hendry WF. Life with an ileal conduit: results of questionnaire surveys of patients and urological surgeons. Br J Urol 1980;52(1):21-5. 27. Dudley JA, Haworth JM, McGraw ME, Frank JD, Tizard EJ. Clinical relevance and implications of antenatal hydronephrosis. Arch Dis Child Fetal Neonatal Ed 1997;76(1):F31-4. 28. Feldman DM, DeCambre M, Kong E, Borgida A, Jamil M, McKenna P, et al. Evaluation and follow-up of fetal hydronephrosis. J Ultrasound Med 2001;20(10):1065-9. 29. Harding LJ, Malone PSJ, Wellesley DG. Antenatal minimal hydronephrosis: is its follow-up an unnecessary cause of concern? Prenat Diagn 1999(19):701-705. 30. Mandell J, Blyth BR, Peters CA, Retik AB, Estroff JA, Benacerraf BR. Structural genitourinary defects detected in utero. Radiology 1991;178(1):193-6. 31. Morin L, Cendron M, Crombleholme TM, Garmel SH, Klauber GT, D'Alton ME. Minimal hydronephrosis in the fetus: clinical significance and implications for management. J Urol 1996;155(6):2047-9. 32. Thomas DF. Prenatal diagnosis: does it alter outcome? Prenat Diagn 2001;21(11):1004-11. 33. Dhillon HK. Prenatally diagnosed hydronephrosis: the Great Ormond Street experience. British Journal of Urology 1998(81,Suppl.2):39-44. 34. Harding LJ, Malone PS, Wellesley DG. Antenatal minimal hydronephrosis: is its follow-up an unnecessary cause of concern? Prenat Diagn 1999;19(8):701-5. 35. Wolfhagen MJ, Weezenlanden HM. Incidentie en sterfte naar leeftijd en geslacht in: Volksgezondheid. Toekomst Verkenning, Nationaal Kompas Volksgezondheid, Bilthoven, RIVM, Gezondheidstoestand/ Ziekten en aandoeningen/ Urinewegen en de geslachtsorganen/ acute urineweginfecties, 2001(24 sept.2001). 36. de Kort LM, Verhulst JA, Engelbert RH, Uiterwaal CS, de Jong TP. Lower urinary tract dysfunction in children with generalized hypermobility of joints. J Urol 2003;170(5):1971-4. 37. Jadresic L, Cartwright K, Cowie N, Witcombe B, Stevens D. Investigation of urinary tract infection in childhood. Bmj 1993;307(6907):761-4.

104 Chapter 7

38. van der Voort J, Edwards A, Roberts R, Verrier Jones K. The struggle to diagnose UTI in children under two in primary care. Fam Pract 1997;14(1):44-8. 39. Van Der Voort JH, Edwards AG, Roberts R, Newcombe RG, Jones KV. Unexplained extra visits to general practitioners before the diagnosis of first urinary tract infection: a case-control study. Arch Dis Child 2002;87(6):530-2. 40. Shaw KN, Gorelick M, McGowan KL, Yakscoe NM, Schwartz JS. Prevalence of urinary tract infection in febrile young children in the emergency department. Pediatrics 1998;102(2):e16.

Chapter 8 Variability in dilatation of the fetal renal pelvis during a bladder filling cycle H.A.M. Damen - Eliasa, R.H. Stigterb, T. P.V.M. de Jong c, G.H.A. Vissera. a Department of Perinatology and Gynaecology, University Hospital Utrecht, The Netherlands b Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands c Department of Paediatric Urology, University Hospital Utrecht, The Netherlands

106 Chapter 8

ABSTRACT

Objective To investigate the variation of the dimensions of the fetal renal pelvis in

relation to the degree of bladder filling in fetuses with mild pyelectasis.

Methods Eighteen third trimester pregnant women with mild uni- or bilateral fetal

pyelectasis, defined as an anteroposterior diameter of the renal pelvis between 5-10

mm, were recruited for the study. The women were examined for 2 – 3 hours by

ultrasound. The anteroposterior and transverse dilatation of the renal pelvis and the

bladder dimensions (to calculate fetal bladder volume) were measured at 2 to 3

minutes intervals.

Results In 6 of the 18 fetuses a consistent relationship between size of the renal

pelvis and bladder filling was found, with a mean difference in renal pelvis diameter

between before and after voiding of 6,7mm and a largest observed difference of

14,3mm. In the other two third of infants no such relationship was found. Postnatally

all children had an ultrasonography and 5 infants were referred to the paediatric

urologist. The investigations in these 5 children could not confirm the hypothesis that

variation in renal pelvis size in relation to bladder size may predict prenatal

vesicoureteral reflux.

Conclusions In case of mild pyelectasis, the size of the renal pelvis is highly variable

in one third of cases. The association with bladder volume and micturition suggests

evidence of vesicoureteral reflux, but this could not be proven. If cut-off values are

used to differentiate between normal and abnormal renal pelvis size than not only

gestational age but also the degree of bladder filling at the time of measurement

should be taken in account. Caution should be expressed when the diagnosis of a

possible urological anomaly is based on one single measurement during only one

investigation.

Variability in dilatation of the fetal renal pelvis 107

INTRODUCTION

A mild uni- or bilateral fetal pyelectasis is a frequent finding with a considerable

variation in the reported incidence of 0,6-5,5%1-4 due to different criteria being used to

define pyelectasis, in particular regarding size and gestational age at diagnosis.

Evidence exists that the antenatal detection of pyelectasis can predict postnatal

complications such as obstructive uropathy or vesico ureteral reflux (VUR) and is

related to an increased risk of aneuploidy (1.6 tot 3.9%)5-8. During routine

examinations we have often noted that the size of the renal pelvis varies considerably

over time. This variation may be relevant, since a diagnosis of abnormal dilatation of

the urinary system is usually based on fixed cut-off values. So far two studies had

addressed the relationship between dimensions of the renal pelvis in relation to the

degree of bladder filling9,10. In one study such a relationship was found and in the

other one not.

It was the aim of the present study to investigate systematically the variation in the

dimensions of the fetal renal pelvis in relation to the degree of bladder filling in fetuses

with a mild pyelectasis.

108 Chapter 8

METHODS

Eighteen women participated in the study. Measuring crown-rump length by

ultrasound validated gestational age. None of the women used any medication and

all had an uncomplicated, singleton pregnancy. No congenital anomaly was present

except a uni- or bilateral pyelectasis at the 18 - 20 week anomaly scan. Pyelectasis

was defined as an anteroposterior diameter (A-P diameter) of the fetal renal pelvis of

5-10 mm. All women were rescanned at approximately 32 weeks gestational age and

were included in the study, only, when the A-P diameter of the renal pelvis did not

exceed 10mm. (In the institution this is the cut-off point where the child was referred

for urological follow-up during the first weeks of life.) The parents were advised to

refrain from further investigations before or after birth and were told that their child

might have an increased risk for urinary tract infection (UTI) due to VUR and that, in

case of feeling listless or fever of unknown origin, UTI should be ruled out. This

advice is in accordance with the policy in our institution.

All investigations were done between 36 and 38 weeks gestational age since it has

been shown that fetuses at that age have prolonged cycles of bladder filling/

emptying, related to fetal behavioural states11,12. All examinations were carried out

between 8 and 12 a.m. after a normal breakfast. Maternal fluid intake was not

specified because it is questionable whether maternal hydration influences fetal

pyelectasy13-15.

Every scan was made by one midwife-ultrasonographer (HDE), using the abdominal

multifrequency transducer PVM 375 AT of the Toshiba Power Vision 6000, type SSA

370, Toshiba Medical Systems Europe, Zoetermeer, The Netherlands. As part of

another study the same investigator carried out an intra-observer study before the

data of this study were collected (Article in preparation). After obtaining informed

consent, measurements of the renal pelvis and the bladder were taken during a 2 to

3 hour period with 2 to 3 minutes intervals. After identification of the fetal spine or the

aorta and perpendicular on this plane with both kidneys in the largest sectional

plane, the diameters of the renal pelvis were obtained by placing the callipers on the

inner borders of the renal pelvis. In every fetus the right and left renal pelvis was

measured in A-P and transverse diameter. The area of the bladder was measured,


by hand tracing, in a longitudinal plane with the largest outline to calculate the

volume of the bladder as previously described by Stigter et al16.

Data from all measurements were plotted in a graph separately for every bladder

filling cycle. The A-P and transverse diameter of the right and left renal pelvis and the

perimeter derived from these measurements (mathematical formula for an ellipse =

(.(½a+½b), where a = the long axis and b= the short axis), together with the

calculated bladder volumes were all marked against time and standardized according

to the moment of fetal voiding. All graphs were printed and visually judged by a

gynaecologist who did not participate in the study, to assess if there was relationship

between the various measurements obtained from the renal pelvis and the degree of

bladder filling, especially around the moment of bladder emptying. Statistical

analyses were performed using Statistical Product and Service Solutions version

10.1 (SPSSR).

Postnatally, all children were investigated by ultrasound within 3 or 4 months after

birth by the same investigator (HDE). Parents were asked to take care of a large fluid

intake by their child so that the examination could be done both before and after

voiding comparatively the same investigation as the investigations at approximately

37 weeks gestational age.

Table 1 - O

verview of all antenatal m

easu

rements and postnatal findings of the 18 children.

*Measu

red at 20 and 32 w

eeks

and postnatally ۲

numbers corresp

ond to the anteroposterior diameter of the renal p

elvis befio

re and after vo

iding

Patie

nt

number

and sex

Dilatation Dilatatio

nright kidney* le

ft kidney*

±20 ±32 pn ±20 ±32 pn

No. of

fillin

gcy

cles

No. of

measu

-rements

Right renal

pelvis positiv

eco

rrelatio

n

Left renal

pelvis positiv

eco

rrelatio

n

Postnatally ultraso

nographic in

vestigatio

n۲

1 ♂

7

8

0

6

10

7

139

Right 8>6 m

m, left 7>6 m

m referred beca

use

of restless

ness

crying,

VUR L=gr I R=gr II = 1 year antib

iotic

prophylaxis

2 ♂

7

9

0

7

10

8

269

+ both cyc

les

+ both cyc

les

Right 10>6 m

m and le

ft 20>8 m

m U

rine conce

ntratio

n problem ju

st like

his older brother and m

other

3 ♂

6

9

0

6

6

0

259

+ both cyc

les

+ both cyc

les

No dilatatio

n of renal p

elves, nl b

ladder wall

4 ♂

10

10

5

0

7

0

136

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

5 ♀

0

10

0

7

8

5

256

No dilatatio

n of renal p

elves, nl b

ladder wall

6 ♀

7

10

5

8

9

7

245

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

7 ♂

6

9

8

6

7

3

367

Right 8>4 m

m, left no dilatatio

n of renal p

elvis, residue after vo

iding,

renogram: high press

ure voiding, incision urethral v

alve

8 ♂

8

7

0

6

7

8

480

Right < 5 m

m dilatatio

n, left 10>8 m

m, nl b

ladder wall

9 ♂

8

7

1

6

5

8

254

+ both cyc

les

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

10 ♂

6

9

4

8

6

4

248

No dilatatio

n of renal p

elves, nl b

ladder wall

11 ♂

8

7

3

7

9

0

358

Right 3>9 m

m, left no dilatatio

n, nl b

ladder wall

12 ♀

7

8

3

10

7

2

353

+ three cyc

les

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

13 ♂

6

5

1

0

7

2

134

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

14 ♂

7

8

2

10

6

2

350

+ three cyc

les

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

15 ♂

0

5

3

8

7

2

242

No dilatatio

n of renal p

elves, nl b

ladder wall

16 ♂

0

0

5

8

8

5

258

Right < 5 m

m dilatatio

n, left 22>18 m

m, no high press

ure, under co

ntrol

17 ♂

8

6

5

7

7

3

232

< 5 m

m dilatatio

n of the renal p

elves, nl b

ladder wall

18 ♂

6

7

17

8

10

29

365

+ three cyc

les

Right 16>15 m

m, left 29>28 m

m w

ith dilated calices, residue after

voiding, no VUR, nl renogram, rese

ction urethral v

alve

Total =

3 girls

15 boys

40

945

7 cycles =

3 kidneys

12 cyc

les =

5 kidneys


RESULTS

In the 18 patients 40 bladder filling/emptying cycles (range 1 – 4) could be evaluated.

In 4 patients it was not possible to record more than one filling cycle because of a

maternal supine hypotension syndrome. All measurements were obtained from all 18

fetuses with a total of 945 measurements of the right as well as of the left kidney

(Table 1). The mean interval between first and last measurement in one cycle was 33

minutes (range 11 - 64) with an average of 17 renal pelves and bladder volume

measurements per cycle (range 7 - 33).

Assessed visually, in 6 of the 18 fetuses (33,3%) there were concomitant volume

changes of the renal pelvis in association with those of the bladder (data: Table 2).

Twice this concerned both kidneys (Number 2 and 3, Table 1) and in four fetuses one

kidney (Number 9, 12, 14, 18, Table 1). In these fetuses these associations occurred

during all the observed bladder cycles and this concerned for the A-P diameter, for

the transverse diameter and for the perimeter of the renal pelvis as well, each

separately, by comparison with the bladder volume.

Figure 1 (a) gives an example of such a correlation between fetal renal pelvis

dimensions and bladder volumes and figure 1 (b) shows the same measurements in

a fetus in whom no such correlations were present.

(a) (b)

0

5

10

15

20

25

-12 -8 -4 0 -4 -8 -12

time

mm

/ cm

/ cm

3 .

pyelum L anteroposterior w idth L pyelumperimeter L pyelum volume bladder

0

5

10

15

20

25

-12 -8 -4 0 4 8 12time

mm

/ cm

/ cm

3 .

pyelum R anteroposterior w idth R pyelumperimeter re pyelum volume bladder

Figure 1 a = Example of a case in which there is a concomitant variation in renal pelvis size and fetal bladder filling/ emptying. Figure 1 b = Example in which no such association was found. The x-axis is the time in minutes to the time of fetal micturition (point 0). The y-axis shows the size of the anterior/ posterior pelvis diameter and of the width of the pelvis, in millimetres. As to the perimeter of the pelvis in cm and bladder volume in cubic mm, respectively.

112 Chapter 8

Figure 2 (a) shows the measurements of decreasing and increasing size of renal

pelves, in relation to bladder filling and micturition (figure 2 b) of the 19 cycles in the 6

children in whom changes in renal pelvis dilatation were related to the bladder

filling/emptying cycle. It concerned 7 times the right kidney and 12 times the left

kidney (Table 1) in 6 fetuses.

(a) (b)

0

5

10

15

20

25

-10 -8 -6 -4 -2 0 2 4 6 8 10time

mill

imet

res

pyelum

0

5

10

15

20

25

-10 -8 -6 -4 -2 0 2 4 6 8 10

time

cent

imet

res3

volume bladdervolume bladder

Figure 2 a = Diameter of the pelvis in relation to the time of fetal micturition (0 minutes; 19 observations) Figure 2 b = The corresponding lines of bladder volume in these cases.

The x-axis is the time in minutes to the time of fetal micturition (point 0). The y-axis shows the size of the anterior/ posterior pelvis diameter and of the width of the pelvis, in millimetres. As to the perimeter of the pelvis in cm and bladder volume in cubic mm, respectively.

The mean difference between renal pelvis diameter 4 minutes before voiding and

directly after voiding was 6,7 millimetre, range 2,9 to 14,3. In five of these cases the

diameter was more than 15 mm before voiding, 16,8/ 18,1/ 18,0/ 18,9/ 19,8 mm,

respectively and 9,1/ 3,8/ 10,6/ 8,9 and 10,8 mm, respectively, thereafter. The

maximal renal pelvis diameter 4 minutes before voiding was related to the maximal

bladder volume (r=0,95) and the minimal renal pelvis diameter after voiding was

related to the minimal bladder volume (r=0,91).

Postnatally all children had an ultrasound scan at the age of approximately 3 or 4

months to measure renal pelvis size once again before and after voiding (Table 1).

None of the children were reported to have had urinary tract problems and all were

clinically well. Only one child had visited a paediatrician because of excessive crying

and restlessness at night but no conclusive diagnosis had been made.


Five of the eighteen investigated infants (27,7%) were referred to the paediatric

urologist because of dilated renal pelves and/or hydronephrosis (n=3), residual

bladder volume after voiding (n=1) or restlessness and excessive crying (n=1).

Table 1.

Antenatally, two of these children (No. 2 and 18) had shown a clear correlation

between the dilatation of the renal pelvis and bladder volume during a filling cycle in

contrast to the three others (No 1, 7 and 16). The referred children were:

- No. 1, a boy, referred because of restlessness and crying at night, to exclude an

underlying renal cause. A voiding cystourethrography (VCUG) showed grade I VUR

on the left and grade II on the right side. The child was put on antibiotic prophylaxis

for one year.

- No. 2, a boy, referred because of visible reduction of the dilated renal pelves

(before and after voiding, left 20 mm>5mm, right 10>6mm) and excessive drinking.

The child drank 2 litres per day and even 500 ml by night. Further information from

the mother, led to the diagnosis of a renal concentration disorder that also affected

her other son and also herself. No VUR was demonstrable during VCUG in this

infant.

- No. 7, a boy referred because of residual urine after voiding. An urodynamic study

notified suspicion on a urethral obstruction and high pressure at voiding. No VUR

was noted at VCUG. Posterior urethral valves were resected during a subsequent

cystoscopy.

- No. 16, a boy referred because of a unilateral hydronephrosis with a renal pelvis of

>20mm and dilated calices. An ultrasound showed a kidney with a plump collecting

system and no evidence for high pressure. The child will be followed up at 3 months

intervals.

- No. 18, a boy referred with bilateral hydronephrosis (right 17 and left 30 mm) with

dilated calices. A renogram showed normal function and no important obstruction. A

VCUG showed no VUR but a megabladder with significant residual urine after

voiding and a suspicion for obstruction of the bladder neck. At cystoscopy no

obstruction was found and the child will be followed up at 3 months intervals.

Table 2 – The distributio

n of measu

rements, 10 m

inutes before till 10 m

inutes after vo

iding, of the fetuse

s with

a correlatio

n between the pelvis of the

right and/ or left kidney and bladder vo

lume plotted against the tim

e in

minutes.

patië

nt

/ cycle

time

min.

renal p

elvis

dilatatio

n right left

bladder

volume

patië

nt

/ cycle

time

min.

renal p

elvis

dilatatio

n right le

ft

bladder

volume

patië

nt

/ cycle

time

min.

renal p

elvis

dilatatio

n right left

bladder

volume

patië

nt

/ cycle

time

min.

renal p

elvis

dilatatio

n right left

bladder

volume

2 / 1

-10

9,9

12,2

10,65

9 / 1

-10

8,7

25,07

12 / 3

-10

15,9

17,32

18 / 1

-10

16,8

12,46

- 8

10,3

12,1

10,22

- 8

9,1

26,06

- 8

16,3

15,35

- 8

17,1

13,07

- 6

10,1

11,3

9,34

- 6

9,9

26,18

- 6

15,6

13,76

- 6

17,4

13,13

- 4

9,3

11,8

7,32

- 4

10,2

28,02

- 4

17,9

12,35

- 4

18

13,88

- 2

8,8

12,2

7,01

- 2

10,6

16,34

- 2

16,8

11,89

- 2

17,5

14,12

0

5,7

7,7

1,61

0

3,4

5,74

0

9,1

2,35

0

10,6

6,31

2

6,4

7,7

2,57

2

6,9

8,18

2

10,2

3,51

2

11,1

7,17

4

6,8

9,5

3,34

4

7,4

10,45

4

11,1

5,55

4

12

7,81

6

6,7

9,2

4,51

6

8,8

10,70

6

13,6

6,41

6

13,1

8,13

8

8,2

9,7

6,17

8

10,2

14,62

8

14,2

9,22

8

14,2

8,98

10

8,9

10,0

6,85

10

11,1

14,99

10

15,1

10,86

10

16,8

9,81

2 / 2

-10

9,5

10,5

9,04

9 / 2

-10

8,8

14,62

14 / 1

-10

8,7

9,91

18 / 2

-10

19

12,11

- 8

9,4

11,3

9,13

- 8

10,2

14,99

- 8

7,8

10,94

- 8

18,9

12,92

- 6

10,4

11,4

9,54

- 6

11,1

15,97

- 6

9,1

11,34

- 6

17,9

13,39

- 4

10,2

10,6

10,69

- 4

11,4

18,31

- 4

10,6

12,22

- 4

19,3

13,51

- 2

10,5

10,6

11,02

- 2

12,6

17,69

- 2

10,3

12,32

- 2

18,9

14,12

0

7,6

5,8

2,01

0

6,2

2,51

0

6,4

2,56

0

8,9

2,09

2

8,2

6,4

3,42

2

7,4

3,46

2

7,1

3,79

2

9,8

2,75

4

8,9

7,6

4,10

4

8,8

4,15

4

7,8

4,05

4

11,8

3,16

6

8,7

8,1

5,00

6

9,2

4,65

6

8,7

6,09

6

12,4

3,79

8

9,9

8,6

5,38

8

9,4

4,92

8

9,4

7,08

8

13,1

5,32

10

9,6

10,1

5,92

10

9,8

5,71

10

9,6

7,70

10

16,2

5,29

3 / 1

-10

7,5

9,5

10,10

12 / 1

-10

13,9

13,48

14 / 2

-10

12,9

10,19

18 / 3

-10

18,6

14,12

- 8

7,8

10,7

10,36

- 8

13

11,13

- 8

13,8

11,14

- 8

20,1

13,39

- 6

8,3

11

10,24

- 6

14,3

9,48

- 6

14,6

17,81

- 6

19,8

13,51

- 4

9,4

11,6

11,52

- 4

15

7,13

- 4

16,8

20,40

- 4

17,3

14,37

- 2

9,4

11,5

7,72

- 2

10,6

6,74

- 2

18,1

21,14

- 2

19,8

14,37

0

5,7

8,1

1,80

0

7,4

4,42

0

3,8

2,80

0

10,8

4,47

2

6,4

8,8

2,82

2

8,9

6,12

2

4,5

3,60

2

11,6

6,31

4

6,9

93,08

4

12,2

7,49

4

6,2

4,17

4

12,6

7,19

6

7,7

9,6

4,32

6

14,6

8,93

6

6,9

4,43

6

13,3

8,29

8

7,9

9,5

4,51

8

15,3

10,21

8

7,1

5,18

8

15,4

8,90

10

89,9

6,39

10

15,6

12,34

10

7,2

6,79

10

14,9

10,99

3 / 2

-10

8,7

10,8

9,22

12 / 2

-10

14,6

12,54

14 / 3

-10

8,3

7,17

- 8

7,8

10,9

9,91

- 8

15,3

12,14

- 8

8,9

7,97

- 6

9,1

11

10,94

- 6

15,6

10,21

- 6

9,1

9,45

- 4

10,6

11,2

12,32

- 4

16

8,93

- 4

9,9

10,70

- 2

10,3

11,8

12,22

- 2

12,7

7,49

- 2

9,9

11,85

0

6,4

7,9

2,56

0

4,6

2,29

0

5,6

4,19

2

7,1

8,6

3,79

2

6,7

2,49

2

75,98

4

7,8

9,5

4,05

4

7,5

3,66

4

9,7

10,13

6

8,7

10,2

6,09

6

11,4

5,34

6

10,4

13,76

8

9,4

10,8

7,08

8

12

5,74

8

10,9

14,74

10

9,6

11,4

7,70

10

13,3

6,95

10

13,8

16,58


DISCUSSION

This study shows that in approximately one-third of term fetuses with a mild

pyelectasis the diameter of the renal pelvis varies according to bladder volume, with

a mean difference in renal pelvis diameter before and after voiding of 6,7 mm and a

largest observed difference of 14,3 mm. So the volume of the bladder should be

considered when fetal hydronephrosis is suspected. In the other two-third of fetuses

with a mild pyelectasis no changes in dilatation of the renal pelvis in relationship to

voiding were observed.

Petrikosky et al10 studied the overall relationship between renal pelvis diameter and

bladder volume in 43 fetuses with hydronephrosis between 18 and 24 weeks

gestational age. No criteria of the definition of hydronephrosis were given. The

anterior posterior diameter of the fetal renal pelvis diminished from 6,8 to 4,5 mm

when the bladder was emptied and the size of the fetal renal pelvis was correlated to

the bladder area (r=0,55). They only studied the overall effect in the total group and

did not distinguish between fetuses in which a relationship with bladder volume was

present or not. This explains the low correlation coefficient between pelvic size and

bladder volume as compared to our data but they also concluded that the volume of

the bladder should be considered when fetal hydronephrosis is diagnosed.

In contrast, Persutte et al9 found no relationship between bladder size and

pyelectasis (A-P diameter >4 mm and <10mm), but they took their measurements

every 15 minutes and therefore may have missed the changes in diameter, which

occur specifically around fetal micturition. However, they did find a highly variable

size of the fetal renal collecting system.

These studies are not quite comparable with ours because of the differences in

intervals of the measurements and the use of the data of all the fetuses for the

calculations instead of a selected part of the total group were the diameter of the

renal pelvis varies according to bladder volume, as we did.

One of the reasons of the variations in dilatation has been suggested to be an

association between maternal hydration and fetal renal pyelectasis14,15 although

another study has claimed the opposite13. Another possible reason for the

association between renal pelvis size and bladder filling, might be the presence of

116 Chapter 8

VUR, a renal tract anomaly that can be diagnosed antenatally only by the invasive

procedure of adding cystourethrography to a diagnostic puncture of the fetal

bladder17.

Pyelectasis, hydronephrosis or a dilated ureter suggests the need for postnatal

investigations to rule out VUR. However, thus far no correlation has been found

between antenatal and postnatal dilatation and the severity of VUR18. Even postnatal

ultrasound is falsely negative in 18 to 30% of the infants with VUR19-21 and until now

the golden standard for the diagnosis of VUR is a VCUG.

We had not the possibility to offer all 18 children a VCUG and so we could not

confirm the hypothesis that cyclic variation in bladder and renal pelvis size are

diagnostic regarding VUR.

After the postnatal ultrasound investigation only 5 children in our study group showed

abnormal dilatation of the renal pelvis and had subsequent investigations. Two of

these children (No 2 and 18; Table1) showed a correlation between the size of the

renal pelvis dilatation and the bladder volume but a VCUG did not confirm the

diagnosis of VUR. In another fetus (No 1) no correlation between bladder and renal

pelvis fluctuations had been found and nevertheless the child appeared to have

bilateral VUR.

We suggest another study in a greater cohort of third trimester pregnant woman with

measurements of the fetal renal pelves every 2 or 3 minutes from 15 minutes before

till 15 minutes after fetal voiding occurs and, if concomitant changes in size of the

renal pelvis in relation to that of the fetal bladder volume occur a postnatal VCUG.


REFERENCES 1. Kent A, Cox D, Downey P and James SL: A study of mild fetal pyelectasis - outcome andproposed strategy of management. Prenat Diagn. 20: 206-9, 2000. 2. Langer B, Simeoni U, Montoya Y, Casanova R and Schlaeder G: Antenatal diagnosis of upper urinary tract dilation by ultrasonography. Fetal Diagn Ther. 11: 191-8, 1996. 3. Persutte WH, Koyle M, Lenke RR, Klas J, Ryan C and Hobbins JC: Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically significant. Ultrasound Obstet Gynecol. 10: 12-8, 1997. 4. Scott JE and Renwick M: Antenatal renal pelvic measurements: what do they mean? BJU Int . 87: 376-80, 2001. 5. Aviram R, Pomeranz A, Sharony R, Beyth Y, Rathaus V, Tepper R and Pomeran A: The increase of renal pelvis dilatation in the fetus and its significance. Ultrasound Obstet Gynecol. 16: 60-2, 2000. 6. Chudleigh PM, Chitty LS, Pembrey M and Campbell S: The association of aneuploidy and mild fetal pyelectasis in an unselected population: the results of a multicenter study. Ultrasound Obstet Gynecol. 17: 197-202, 2001. 7. Corteville JE, Dicke JM and Crane JP: Fetal pyelectasis and Down syndrome: is genetic amniocentesis warranted? Obstet Gynecol. 79: 770-2, 1992. 8. Nicolaides KH, Cheng HH, Abbas A, Snijders RJ and Gosden C: Fetal renal defects: associated malformations and chromosomal defects. Fetal Diagn Ther. 7: 1-11, 1992. 9. Persutte WH, Hussey M, Chyu J and Hobbins JC: Striking findings concerning the variability in the measurement of the fetal renal collecting system. Ultrasound Obstet Gynecol. 15: 186-90, 2000. 10. Petrikovsky BM, Cuomo MI, Schneider EP, Wyse LJ, Cohen HL and Lesser M: Isolated fetal hydronephrosis: beware the effect of bladder filling. Prenat Diagn. 15: 827-9, 1995. 11. Visser GH, Goodman JD, Levine DH and Dawes GS: Micturition and the heart period cycle in the human fetus. Br J Obstet Gynaecol. 88: 803-5, 1981. 12. Stigter RH, Mulder EJ and Visser GH: Hourly fetal urine production rate in the near-term fetusis it really increased during fetal quiet sleep? Early Hum Dev. 50: 263-72, 1998 . 13. Allen KS, Arger PH, Mennuti M, Coleman BG, Mintz MC and Fishman M: Effects of maternal hydration on fetal renal pyelectasis. Radiology. 163: 807-9, 1987. 14. Babcook CJ, Silvera M, Drake C and Levine D: Effect of maternal hydration on mild fetal pyelectasis. J Ultrasound Med. 17: 539-44; quiz 545-6, 1998. 15. Robinson JN, Tice K, Kolm P and Abuhamad AZ: Effect of maternal hydration on fetal renal pyelectasis. Obstet Gynecol. 92: 137-41, 1998. 16. Stigter RH, Schelven van LJ, Bruinse HW, Mulder EJH, Gemert van MJC. On the measurement of fetal bladder volume and urine production: methodological consideration. Prenat Neonat Med 2000; 5: 169-76. 17. Stoutenbeek P, de Jong TP, van Gool JD and Drogtrop AP: Intra-uterine cystography for evaluation of prenatal obstructive uropathy. Pediatr Radiol. 19: 247-9, 1989. 18. Jaswon MS, Dibble L, Puri S, Davis J, Young J, Dave R and Morgan H: Prospective study of outcome in antenatally diagnosed renal pelvis dilatation. Arch Dis Child Fetal Neonatal Ed. 80: F135-8, 1999. 19. Najmaldin A, Burge DM and Atwell JD: Fetal vesicoureteric reflux. Br J Urol. 65: 403-6, 1990

118 Chapter 8

20. Tibballs JM and De Bruyn R: Primary vesicoureteric reflux--how useful is postnatal ultrasound? Arch Dis Child. 75: 444-7, 1996. 21. Zerin JM, Ritchey ML and Chang AC: Incidental vesicoureteral reflux in neonates with antenatally detected hydronephrosis and other renal abnormalities. Radiology. 187: 157-60, 1993.

Chapter 9 Summary and discussion Nederlandse samenvatting Dankwoord Curriculum Vitae

120 Chapter 9

SUMMARY, DISCUSSION AND CONCLUSION

introduction

In two to three percent of fetuses structural anomalies can be found with prenatal

ultrasound investigation1-4. Anomalies of the urinary tract account for 15 to 20% of

these anomalies with a detection rate of approximately of 90%3, 4. During the latest

decades numerous papers have been published on the fetal renal system and its

anomalies. However, follow-up studies on long-term outcome are still scarce and this

hampers adequate counselling of parents and of giving adequate treatment advises.

Moreover, up-to-date charts on normal fetal kidney and adrenal gland development

are scarce. We therefore formulated the following aims of this thesis (Chapter 1):

1 – To develop charts of size and growth of the fetal kidney, renal pelvis and adrenal

gland.

2 – To study long-term follow-up of a large cohort of infants with a prenatally

diagnosed renal tract anomaly.

3 – To answer the question whether mild pyelectasis (anteroposterior diameter of the

fetal renal pelvis of 5 – 10 mm) as diagnosed around 18 to 20 weeks of gestation

results in increased morbidity in childhood and therefore requires postnatal

treatment.

4 – To study the relationship between the size of the renal pelvis and the fetal

bladder-filling cycle, to answer the question if fixed cut-off values regarding renal

pelvis dilatation can be used or whether bladder filling has to be taken into account.

charts for size and growth of kidney, renal pelvis and adrenal gland

A reference curve for size and growth of fetal kidney, renal pelvis and adrenal gland

is of importance to judge the growth of these organs during pregnancy, especially

when during an ultrasound investigation an anomaly is suspected. Several charts of

fetal kidney sizes have been published, but mostly with shortcomings in data

collection or with methodological weaknesses i.e. not validating gestational age5-9,

not covering the whole of the second and third trimester of pregnancy5, 6, 10-12, not

measuring the kidney in three dimensions5, 6, 8-10 or using data from infants born

preterm or from post-mortem specimens13-15. Moreover several studies averaged

both cross-sectional and longitudinal data5, 7-10, 12, 15. In none of these publications an

intraobserver and interobserver variation analysis had preceded the study.

Summary, discussion and conclusion 121

We performed an intraobserver and interobserver variation analysis for the

measurements of length, anteroposterior diameter and transverse diameter of the

kidney and for length of the adrenal gland (Chapter 2). Data regarding an

intraobserver variation were obtained from 30 fetuses and by comparing three

measurements with different time intervals between each measurement. Statistical

analysis showed that there was a high intraobserver agreement with Cronbach’s

alpha (α) above 0.9 and the intra class correlation (IC) above 0.8. Interobeserver

agreement was studied in 20 fetuses by two experienced ultrasonographers. Also

these data were satisfactory (α above 0.9, IC above 0.8). All measurements could be

taken in each fetus both in the intra- and interobserver study.

In a prospective longitudinal study in 111 low risk fetuses we measured length,

anteroposterior diameter and transverse diameter of both kidneys, anteroposterior

and transverse diameter of both renal pelves and the length of both adrenal glands

(Chapter 3 and 4). Data were obtained every 4 weeks from 16 weeks onwards.

Data obtained in a longitudinal study by measurements of a considerable cohort of

fetuses on a series of occasions may be used for a reference curve for size and

growth. Cross-sectional data obtained by measurements of each fetus on a single

occasion give only information on size21-24.

Statistical analysis was performed by multilevel analysis a recently developed new

technique that can be used when some data are missing and when measurements

have been made at variable times16. It allows for the dependency in hierarchically

structured data in contrast to multiple regression analysis that presupposes the

independency of observations. Repeated measurements in the same individual with

investigations at different gestational ages belong to a low level. Computed means of

an individual measurement (e.g. kidney length) belong to a higher level.

There was hardly any difference between the curves of the right and left kidney, the

right and left renal pelvis and the right and left adrenal gland. Definitive charts were

made after averaging the data from both sides.

It was difficult to compare our charts with those of others because several studies did

not cover the whole second and third trimester of pregnancy or gave no raw data or

when they did so they gave evidence of methodological weakness. We compared our

122 Chapter 9

charts with those of Chitty and Altman7, 17 and of Pruggmayer and Terinde7. Both

studies used cross-sectional data and measured every fetus only once. Chitty et al

measured every week approximately 15 to 20 fetuses while Pruggmayer et al gave

no data on numbers/ week and excluded nearly 20% of infants because they were

either large or small for dates. Our charts differ from theirs in having smaller ranges.

This may be due to the fact that we did each measurement three times whereafter

we averaged the data.

A strong linear correlation was found between adrenal gland length and kidney length

with a ratio 2 to 7 and this relation did not change with gestation/ kidney size.

Comparing our chart of the length of the adrenal gland with others was not possible

because another measure of the adrenal was measured18 or data were published

only for every 5 weeks19 or were compared with biparietal diameter and kidney length

and not with weeks of gestation20.

structural anomalies of the fetal renal tract

The prevalence of any congenital anomaly that can be detected by ultrasound during

pregnancy is approximately 1 to 2% 1-4. Urinary tract abnormalities account for 15 to

20% of these anomalies with a detection rate of approximately 90%3, 4. Data on

antenatal diagnosis and postnatal follow-up are important for assessing prognosis of

the individual fetus with a diagnosed anomaly and for subsequent counselling of the

parents. Such data may also 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 best management before and after birth.

In Chapter 5 we describe the ultrasound findings and outcome of a large cohort of

402 fetuses with a prenatally diagnosed urinary tract anomaly. We could use the

database of the ultrasound unit of the department of obstetrics of the University

Medical Centre, Utrecht, and The Netherlands, which was established in 1986. At

follow-up the youngest infant was 3 years and the oldest was 17 years (median 7

years 11 months).


We made a distinction between a structural kidney anomaly and urinary tract

dilatation to gain insight into the prognosis and outcome of these two district groups

of anomalies. A structural anomaly exists when in the very beginning aberrant

development or defects in maturation have taken place in the embryologic urinary

tract. Dilatation of the urinary tract may result from slow maturation and canalisation

of the excretory system25.

One hundred and twenty-one of the 402 fetuses died before or after birth in 106

cases the reason of death was directly related to the renal tract anomaly (26,4%).

Eighty-four of these fetuses had a structural anomaly and died mostly due to bilateral

renal agenesis (33 fetuses), bilateral multicystic kidneys (22 fetuses) or bilateral

polycystic kidneys (19 fetuses). Another 22 fetuses had a urinary tract dilatation and

they died mainly due to an isolated megabladder (17 fetuses).

Two hundred and eighty-one fetuses survived of which 64 had a structural anomaly

and 213 had a urinary tract dilatation. The structural anomaly was in approximately

80% a unilateral multicystic kidney and 12 of these infants had a contralateral

anomaly. Surgery consisted mainly of nephrectomy of the multicystic kidney. Only

two children, both with bilateral echogenic dysplastic kidneys, had impaired function

at follow-up (one with peritoneal dialysis, one with an increased creatinine level of 71

µmol/l at 7½ years of age).

The dilatation in the 213 fetuses was approximately equally divided in uni- or

bilaterally. One hundred and eighteen fetuses had a solitary uni- or bilateral dilatation

of the renal pelvis while the 95 others had a combination with a uni- or bilateral

megaureter and/ or megabladder. Approximately 50% of these children had surgery

with a total of 315 interventions. Especially high was the intervention rate in 45

children with posterior urethral valves (100%) as in the 45 cases of vesico ureteral

reflux (86,6%). In 21 cases with a bilateral dilatation labour was electively induced

before 37 weeks of gestation (mean 34,9 weeks: range 29 – 37) because of the

development of anhydramnios. Almost all children with impaired outcome can be

found in this group (6 chronic renal failure, 1 hypertension). The overall conclusion

for obstructive uropathy that can be drawn from this series is that, regardless of the

presence of 1 or 2 kidneys and regardless of the degree of urinary tract dilatation, the

124 Chapter 9

prognosis for renal function is excellent when oligohydramnios is absent before birth

and when proper urological care is given postnatally.

All in all, at follow-up 9 of the 281 surviving infants had impaired renal function and 3

children had hypertension, 12/281 (4,3%). So, overall outcome in the children was

generally good.

In Chapter 6 a large cohort of 100 fetuses with unilateral multicystic kidney disease

(MCKD), prenatally diagnosed between 15 and 42 weeks of gestation (mean 26.7

weeks), is described. Data were obtained by reviewing the databases of the obstetric

ultrasound department and of the paediatric urology department of the University

Medical Centre Utrecht, The Netherlands. The children were at follow-up 0 -16 years

of age (mean 5 years and 4 months).

MCKD only gives rarely diagnostic dilemmas on prenatal ultrasound(26) due to its

typical manifestation with (in general) multiple non-communicating cysts. The

function of the affected kidney is absent or poor. Therefore, bilateral MCKD is

invariably associated with a fatal outcome. The prognosis of unilateral MCKD is

favourable and depends on the integrity of the contralateral kidney27, 28

It is known from literature that children with unilateral MCKD have an increased risk

of abnormalities of the contralateral kidney and of the lower urogenital tract27-30. The

finding of a unilateral MCKD must therefore lead to meticulous screening of the

complete urinary tract, both pre- and postnatally, as most studies also recommend.

There is no unanimous opinion as to whether the multicystic kidney should be

removed. In some studies the children are examined periodically28, 31 after birth while

others remove the affected kidney because of possible higher risks of hypertension,

infection or malignancy28, 32-34. It is the view of the Dutch Society for Paediatric

Urology to remove the non-functioning cystic kidney to prevent lifetime follow-up of

these children, which could easily be neglected in the course of years. Furthermore

parents need not to be anxious when their child has abdominal pain. In our

population nephrectomy has been performed in 93% of surviving children and this

operation was combined with cystoscopy and in the girls also with colposcopy.


Comparing our results with others is difficult because in some studies another target

group was included e.g. both the uni- and bilateral MCKD27 or a different population

limited to fetuses with a chromosomal anomaly35. We found an additional anomaly in

75% of the fetuses. This is much higher than the 21 to 57% as found by others26, 27,

29-31, 35. There were anomalies in the contralateral kidney in 48% of cases, as

compared to 13 to 39% in literature, in the ipsilateral kidney in 48% of cases (4 to

14% in literature) and in the lower urogenital tract in 33% as compared to 4 to 6% in

literature. We have no real explanation for the higher incidence of anomalies that we

found in the contralateral kidney and in the lower urogenital tract.

The higher incidence of anomalies of the ipsilateral kidney is probably the result of

the cystoscopy and the colposcopy in girls and concerned mainly an ectopic ureter or

a megaureter. Other studies only mentions an ureteral reflux or an ureteropelvic

junction stenosis27, 29, 30.

Once a multicystic kidney is diagnosed we advice a thorough screening both pre-

and postnatally since the chance of having other congenital anomalies of the urinary

tract appears high. Moreover we recommend a routine postnatal examination

consisting of an ultrasound examination, an isotope scan and a VCUG and when a

nephrectomy is done also cystoscopy and colposcopy to detect possibly hidden

anomalies of the genitourinary tract.

pyelectasis

In Chapter 7 a study is described that was done to investigate urinary tract morbidity

in late childhood in infants with a prenatally diagnosed mild pyelectasis. We defined

pyelectasis as an anteroposterior diameter of the fetal renal pelvis of 5-10 mm

without a specified gestational age at diagnosis. In literature there is no consensus

as to the cut-off points to use before birth to diagnose pyelectasis36-39.

Mild uni- or bilateral fetal pyelectasis is a frequent finding at prenatal ultrasound

examination, with a considerable variation in the reported incidence, from 0,6% to

5,5%(36-39), due to differences in criteria of the definition of pyelectasis, in particular

regarding size and gestational age at diagnosis. Guidelines relating the severity of

pyelectasis to perinatal and postnatal management are not well standardized. The

clinical significance of mild fetal pyelectasis is still unclear; it may resolve, stabilize or

126 Chapter 9

be the first indicator of significant urinary tract pathology. Evidence exists that

pyelectasis may result in clinical complications such as obstructive uropathy or

vesico ureteric reflux.

Because of the lack of data on possible long-term morbidity we investigated the

occurrence of urinary tract morbidity in childhood. We could use the data of the

Amphia hospital (a District General Hospital, location Oosterhout, The Netherlands).

All women in that region have an anomaly scan at 18 – 20 weeks gestation. It was

customary to reexam the women at approximately 32 weeks of gestation when at the

first ultrasound scan a uni- or bilateral pyelectasis was found. When the dilatation

had progressed to > 10 millimetres the child was referred to a paediatrician or

urologist for urological follow-up during the first weeks of life. When the dilatation was

stable or disappeared parents were advised to refrain from follow-up before and after

birth and were told that their child might have an increased risk for urinary tract

infection due to vesico ureteral reflux and that, in case of feeling listless or of fever of

unknown origin, urinary tract infection should be ruled out.

A large group of 208 cases and 416 matched controls were examined by a validated

questionnaire, developed by a group of The International Reflux Study in Children(40),

containing questions about urinary tract infections, incontinence, voiding and bowel

patrons. No significant differences in morbidity between children with or without mild

prenatal pyelectasis were found. Of interest is the higher incidence of urinary tract

infections in both the cases and controls as compared to literature41, 42. This high

incidence of infections was also found in another study of our group43. The surgical

intervention rate in our case-group was only 0,8% much lower than reported by

others (3,6%-24,3%) 36, 38, 44.

Based on these findings we advocate in case of a mild renal pyelectasis at about 20

weeks of gestation a single follow-up scan in the third trimester to determine if the

pyelectasis has resolved, stabilized or progressed. The child should only be referred

for postnatal examination if there is progression of the pyelectasis to >10mm. With

this policy there seems to be only a very low chance of missing an occasional case of

VUR or potential obstruction. Parents should be advised to visit the general

practitioner in case their child is lethargic or has fever of unknown origin to have the


child’s urine tested to rule out urinary tract infection or treat infection effectively in

order to prevent renal damage.

In Chapter 8 a study is described on the variation of the dimensions of the fetal renal

pelvis in relation to the degree of bladder filling in fetuses with mild pyelectasis.

Pyelectasis, defined as an anteroposterior diameter of the fetal renal pelvis of 5-10

mm, might predict postnatal complications such as obstructive uropathy or vesico

ureteral reflux.

Until now two studies have been published on the variation over time of the fetal

renal pelvis in relation to bladder filling45, 46. In one study such a relationship had been

found, in the other not. This existence – or not – of a variation in pelvic size in relation

to bladder filling is relevant since the diagnosis of abnormal dilatation of the upper

tract is usually based on fixed cut-off values.

We investigated 18 pregnant women who had fetus with a uni- or bilateral pyelectasis

at the 18 – 20 weeks anomaly scan, which did not exceed 10 mm at the repeat scan

at approximately 32 weeks of gestation. Investigations were made in the late third

trimester since it has been shown that fetuses at that age have prolonged cycles of

bladder filling/ emptying, related to fetal behavioural states47, 48. We found in one third

of the fetuses that the dilatation of the renal pelvis varied according to bladder

volume with a mean difference of 6,7 mm and a largest observed difference of 14,3

mm. So the filling state of the bladder should be taken into account when fetal

hydronephrosis is suspected.

CONCLUSION

The mortality rate in fetuses is high once a renal anomaly is identified. The prognosis

for the surviving children is relatively good and these infants have only a little chance

on lifelong damage, if during pregnancy the right diagnosis has been made and if

these children have had good urological care after birth. It is important that

paediatricians and urologists are acquainted with the advices, which were given

when antenatally anomalies at the urinary tract are diagnosed, because they will be

consulted often about these anomalies after birth.

128 Chapter 9

REFERENCES

1. Stoll C, Clementi M. Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe. Ultrasound Obstet Gynecol 2003;21(6):543-51. 2. Levi S. Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening for second trimester fetal malformations. Prenat Diagn 2002;22(4):285-95. 3. Levi S. Mass screening for fetal malformations: the Eurofetus study. Ultrasound Obstet Gynecol 2003;22(6):555-8. 4. Grandjean H, Larroque D, Levi S. Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team. Ann N Y Acad Sci 1998;847:118-24. 5. Cohen HL, Cooper J, Eisenberg P, Mandel FS, Gross BR, Goldman MA, et al. Normal length of fetal kidneys: sonographic study in 397 obstetric patients. AJR Am J Roentgenol 1991;157(3):545-8. 6. Gloor JM, Breckle RJ, Gehrking WC, Rosenquist RG, Mulholland TA, Bergstralh EJ, et al. Fetal renal growth evaluated by prenatal ultrasound examination. Mayo Clin Proc 1997;72(2):124-9. 7. Pruggmayer M, Terinde R. [Fetal kidney screening: growth curves and indices]. Geburtshilfe Frauenheilkd 1989;49(8):705-10. 8. Sagi J, Vagman I, David MP, Van Dongen LG, Goudie E, Butterworth A, et al. Fetal kidney size related to gestational age. Gynecol Obstet Invest 1987;23(1):1-4. 9. Scott JE, Wright B, Wilson G, Pearson IA, Matthews JN, Rose PG. Measuring the fetal kidney with ultrasonography. Br J Urol 1995;76(6):769-74. 10. Bertagnoli L, Lalatta F, Gallicchio R, Fantuzzi M, Rusca M, Zorzoli A, et al. Quantitative characterization of the growth of the fetal kidney. J Clin Ultrasound 1983;11(7):349-56. 11. Bernaschek G, Kratochwil A. [Ultra-sound study on the growth of the fetal kidney in the second half of pregnancy (author's transl)]. Geburtshilfe Frauenheilkd 1980;40(12):1059-64. 12. Jeanty P, Dramaix-Wilmet M, Elkhazen N, Hubinont C, van Regemorter N. Measurements of fetal kidney growth on ultrasound. Radiology 1982;144(1):159-62. 13. Chiara A, Chirico G, Barbarini M, De Vecchi E, Rondini G. Ultrasonic evaluation of kidney length in term and preterm infants. Eur J Pediatr 1989;149(2):94-5. 14. Gonzales J. [Anatomical measurements during fetal growth of the kidney. Its value for the ultrasonographer and the anatomo-pathologist (author's transl)]. J Gynecol Obstet Biol Reprod (Paris) 1981;10(2):113-7. 15. Vries de L, Levene MI. Measurement of renal size in preterm and term infants by real-time ultrasound. Arch Dis Child 1983;58(2):145-7. 16. Goldstein H. Multilevel statistical models. 2nd ed. London: University of London. ed; 1995. 17. Chitty LS, Altman DG. Charts of fetal size: kidney and renal pelvis measurements. Prenat Diagn 2003;23(11):891-7. 18. Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal adrenal gland in utero: clinical application. Gynecol Obstet Invest 1988;25(1):16-22. 19. Jeanty P, Chervenak F, Grannum P, Hobbins JC. Normal ultrasonic size and characteristics of the fetal adrenal glands. Prenat Diagn 1984;4(1):21-8.

Summary, discussion and conclusion 129 20. Lewis E, Kurtz AB, Dubbins PA, Wapner RJ, Goldberg BB. Real-time ultrasonographic evaluation of normal fetal adrenal glands. J Ultrasound Med 1982;1(7):265-70. 21. Altman DG, Chitty LS. Design and analysis of studies to derive charts of fetal size. Ultrasound Obstet Gynecol 1993;3(6):378-84. 22. Altman DG, Chitty LS. Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994;101(1):29-34. 23. Royston P, Altman DG. Design and analysis of longitudinal studies of fetal size. Ultrasound Obstet Gynecol 1995;6(5):307-12. 24. Royston P, Wright EM. How to construct 'normal ranges' for fetal variables. Ultrasound Obstet Gynecol 1998;11(1):30-8. 25. Cuckow PM, Nyirady P, Winyard PJ. Normal and abnormal development of the urogenital tract. Prenat Diagn 2001;21(11):908-16. 26. Aubertin G, Cripps S, Coleman G, McGillivray B, Yong SL, Van Allen M, et al. Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management. Prenat Diagn 2002;22(5):388-94. 27. Al-Khaldi N, Watson AR, Zuccollo J, Twining P, Rose DH. Outcome of antenatally detected cystic dysplastic kidney disease. Arch Dis Child 1994;70(6):520-2. 28. Wacksman J, Phipps L. Report of the Multicystic Kidney Registry: preliminary findings. J Urol 1993;150(6):1870-2. 29. Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities in multicystic-dysplastic kidney disease. J Pediatr 1992;121(1):65-7. 30. Eijk van L, Cohen-Overbeek TE, den Hollander NS, Nijman JM, Wladimiroff JW. Unilateral multicystic dysplastic kidney: a combined pre- and postnatal assessment. Ultrasound Obstet Gynecol 2002;19(2):180-3. 31. Rudnik-Schoneborn S, John U, Deget F, Ehrich JH, Misselwitz J, Zerres K. Clinical features of unilateral multicystic renal dysplasia in children. Eur J Pediatr 1998;157(8):666-72. 32. Elder JS, Hladky D, Selzman AA. Outpatient nephrectomy for nonfunctioning kidneys. J Urol 1995;154(2 Pt 2):712-4; discussion 714-5. 33. LaSalle MD, Stock JA, Hanna MK. Insurability of children with congenital urological anomalies. J Urol 1997;158(3 Pt 2):1312-5. 34. Webb NJ, Lewis MA, Bruce J, Gough DC, Ladusans EJ, Thomson AP, et al. Unilateral multicystic dysplastic kidney: the case for nephrectomy. Arch Dis Child 1997;76(1):31-4. 35. Lazebnik N, Bellinger MF, Ferguson JE, 2nd, Hogge JS, Hogge WA. Insights into the pathogenesis and natural history of fetuses with multicystic dysplastic kidney disease. Prenat Diagn 1999;19(5):418-23. 36. Kent A, Cox D, Downey P, James SL. A study of mild fetal pyelectasia - outcome and proposed strategy of management. Prenat Diagn 2000;20(3):206-9. 37. Langer B, Simeoni U, Montoya Y, Casanova R, Schlaeder G. Antenatal diagnosis of upper urinary tract dilation by ultrasonography. Fetal Diagn Ther 1996;11(3):191-8. 38. Persutte WH, Koyle M, Lenke RR, Klas J, Ryan C, Hobbins JC. Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically significant. Ultrasound Obstet Gynecol 1997;10(1):12-8.

130 Chapter 9

39. Scott JE, Renwick M. Antenatal renal pelvic measurements: what do they mean? BJU Int 2001;87(4):376-80. 40. Gool van JD, Hjalmas K, Tamminen-Mobius T, Olbing H. Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children. J Urol 1992;148(5 Pt 2):1699-702. 41. Dremsek PA, Gindl K, Voitl P, Strobl R, Hafner E, Geissler W, et al. Renal Pyelectasis in fetuses and neonates: Diagnostic value of renal pelvis diameter in pre and postnatal sonographic screening. AJR Am J Roentgenol 1997(Apr;168(4)):1017-9. 42. Harding LJ, Malone PS, Wellesley DG. Antenatal minimal hydronephrosis: is its follow-up an unnecessary cause of concern? Prenat Diagn 1999;19(8):701-5. 43. Kort de LM, Verhulst JA, Engelbert RH, Uiterwaal CS, de Jong TP. Lower urinary tract dysfunction in children with generalized hypermobility of joints. J Urol 2003;170(5):1971-4. 44. Dudley JA, Haworth JM, McGraw ME, Frank JD, Tizard EJ. Clinical relevance and implications of antenatal hydronephrosis. Arch Dis Child Fetal Neonatal Ed 1997;76(1):F31-4. 45. Petrikovsky BM, Cuomo MI, Schneider EP, Wyse LJ, Cohen HL, Lesser M. Isolated fetal hydronephrosis: beware the effect of bladder filling. Prenat Diagn 1995;15(9):827-9. 46. Persutte WH, Hussey M, Chyu J, Hobbins JC. Striking findings concerning the variability in the measurement of the fetal renal collecting system. Ultrasound Obstet Gynecol 2000;15(3):186-90. 47. Visser GH, Goodman JD, Levine DH, Dawes GS. Micturition and the heart period cycle in the human fetus. Br J Obstet Gynaecol 1981;88(8):803-5. 48. Stigter RH, Mulder EJ, Visser GH. Hourly fetal urine production rate in the near-term fetus: is it really increased during fetal quiet sleep? Early Hum Dev 1998;50(3):263-72.

Nederlandse samenvatting 131

NEDERLANDSE SAMENVATTING

Sinds in 1950 Ian Donald e.a. voor het eerst ultrageluid toepasten voor onderzoek

van de ongeborene, heeft deze techniek een enorme invloed gehad op de dagelijkse

praktijk in de verloskunde. Tot dan toe was uitwendig onderzoek van de zwangere

buik de enige manier om foetale groei te bepalen. Informatie over de foetale conditie

werd verkregen door het voelen van kindsbewegingen door de zwangere en het

beluisteren van de foetale harttonen met behulp van een houten stethoscoop.

Aanvankelijk werd echoscopie alleen gebruikt om de zwangerschapsduur vast te

stellen, de ligging van het kind en de placenta te bepalen, of om een

tweelingzwangerschap vast te stellen.

Door het voortdurend verbeteren van de apparatuur werden het oplossend vermogen

en de beeldkwaliteit steeds beter. Hierdoor nam de kennis over ontwikkeling en groei

van foetale organen snel toe en werden toenemend foetale afwijkingen ontdekt.

Heden ten dage is het opsporen van aangeboren afwijkingen een van de meest

belangrijke redenen voor echoscopisch onderzoek in de zwangerschap.

Bij 1 tot 2% van alle foetussen kan met behulp van echoscopie een ernstige of

minder ernstige afwijking worden vastgesteld. Hiervan hebben 15 tot 20% betrekking

op de urinewegen. In het begin van de jaren tachtig werd ongeveer 15% van alle

nierafwijkingen tijdens de zwangerschap opgespoord, momenteel is dit ruim 90%. Dit

percentage is zo hoog, omdat afwijkingen aan de urinewegen veelal gepaard gaan

met vochtophoping in de nieren en vocht is met echoscopie goed te zien. Hierdoor

kunnen afwijkingen, die meestal symptoomloos zijn in de zwangerschap, worden

ontdekt zodat een behandelbeleid voor na de geboorte tijdig kan worden vastgesteld

en nierschade zo veel mogelijk kan worden voorkomen. Bovendien hebben de

ouders, in voorkomende gevallen, de mogelijkheid om de zwangerschap te laten

afbreken, indien een niet met het leven verenigbare afwijking is aangetoond of

afwijkingen die zo ernstig zijn dat zij de kwaliteit van leven ernstig aantasten. Hierbij

moet men bijvoorbeeld denken aan het beiderzijds ontbreken van de nieren of aan

beiderzijds multicysteuze nieren waarbij door een zeer vroege afsluiting een

vochtophoping in beide nieren ontstaat waardoor het aanvankelijk gezonde

nierweefsel te gronde gaat.

132 Chapter 9

In de voorbije decennia zijn vele onderzoeken verschenen over nierafwijkingen bij

ongeborenen. Studies waarin langdurige vervolgonderzoek van deze kinderen

worden beschreven zijn echter schaars. Hierdoor is het moeilijk om de ouders juist

voor te lichten over wat er met hun kind aan de hand is en over de eventuele

gevolgen met betrekking tot het verdere leven. Ook advisering omtrent de juiste

behandeling na de geboorte wordt hierdoor bemoeilijkt. In het kader van dit

proefschrift werden daarom de volgende studies gedaan:

1 – Het vaststellen van grootte en groei van de foetale nier, het nierbekken en de

bijnier in het verloop van de zwangerschap.

2 – Het verzamelen van de lange termijn follow-up gegevens van een grote groep

kinderen bij wie vóór de geboorte nierafwijkingen waren vastgesteld.

3 – Onderzoek naar bijkomende afwijkingen bij kinderen bij wie vóór de geboorte

een enkelzijdige multicysteuze nier is vastgesteld.

4 – Het beantwoorden van de vraag of kinderen bij wie rond 20 weken

zwangerschapsduur met echoscopie een lichte verwijding van het nierbekken (tussen

de 5 en 10 mm) werd gezien, meer kans hebben op problemen aan de urinewegen

op de kinderleeftijd, dan kinderen bij wie dit niet was waargenomen.

5 – Het bestuderen van de relatie tussen de mate van verwijding van het nierbekken

en de vulling van de foetale blaas.

groeicurven van foetale nier, nierbekken en bijnier

Groeicurven van foetale organen zijn van belang als een afwijking wordt vermoed.

Eerdere groeicurven van foetale nieren vertoonden veelal beperkingen zoals: het niet

nauwkeurig bepalen van de duur van de zwangerschap met een vroege echoscopie,

alleen curven voor het tweede en derde trimester van de zwangerschap, bepaling

van uitsluitend de lengte van de nier, of ontwikkeling van de groeicurven op basis

van metingen gedaan bij te vroeg geboren kinderen of met de nieren van overleden

kinderen.

In hoofdstuk 2 wordt een zogeheten intra- en interobserver variantie analyse

beschreven, die is uitgevoerd om vast te stellen of herhaalde metingen gedaan door

één persoon tot dezelfde resultaten leiden èn of er een goede overeenkomst is

tussen de metingen gedaan door twee echoscopisten. De afmetingen van nier en


bijnier blijken door één persoon consistent gemeten te worden en de overeenkomst

tussen de metingen van twee onderzoekers was groot.

Hoofdstuk 3 en 4 beschrijven de longitudinale onderzoeken waarbij de grootte en

groei van lengte, voorachterwaartse diameter en dwarse diameter van de foetale nier

en van de voorachterwaartse en dwarse diameter van het nierbekken en de lengte

van de bijnier zijn bepaald. Bij 111 zwangeren werden deze afmetingen iedere vier

weken gemeten waarbij alle metingen drie maal achterelkaar werden gedaan. Bij de

ene helft van de zwangeren startte dit onderzoek bij 16 weken en bij de andere helft

bij 18 weken zwangerschapsduur.

Omdat de verzamelde gegevens een groot aantal foetussen betreffen, die

herhaaldelijk in de zwangerschap werden gemeten, kunnen de verkregen curven

gebruikt worden om de groei van de organen te meten maar ook om tijdens de

zwangerschap te beoordelen of de grootte overeenkomt met de zwangerschapsduur.

De statische berekeningen werden gedaan met behulp van de ‘multilevel analysis’.

Dit is een recent ontwikkelde methode die corrigeert voor ontbrekende data èn

berekeningen kan doen met gegevens die van elkaar afhankelijk zijn. De curven voor

linker en rechter nier, linker en rechter nierbekken en linker en rechter bijnier bleken

nagenoeg identiek. De uiteindelijke curven werden dan ook gemaakt op basis van de

gemiddelde gegevens van links en rechts.

Het vergelijken van onze niercurven met eerdere studies was moeilijk vanwege de

genoemde gebreken in de opzet van die studies. Daar waar vergeleken kon worden

bleken onze curven een aanzienlijk geringere spreiding te hebben ten opzichte van

de 50ste percentiel-lijn. De reden hiervan is vermoedelijk het grote aantal door ons

geïncludeerde foetussen en het feit dat wij gemiddelde waarden gebruikten van drie

achtereenvolgende metingen.

Voor de bijniercurve was er geen mogelijkheid om deze te vergelijken met eerdere

studies. Er werd een lineair verband gevonden tussen de lengte van de bijnier en de

nier met een verhouding van 2 tot 7. Deze bevinding kan gebruikt worden bij het

vermoeden op vergrote nieren ten gevolge van een afwijking, of bij aandoeningen

waarbij de bijnier te groot of te klein is.

134 Chapter 9

afwijkingen aan urinewegen

In hoofdstuk 5 beschrijven we de bevindingen en follow-up van 402 foetussen bij wie

prenataal afwijkingen aan de urinewegen waren vastgesteld. Er werd gebruik

gemaakt van de database van de afdeling obstetrische echoscopie van het

Universitair Medisch Centrum in Utrecht. Tijdens het na-onderzoek was de

gemiddelde leeftijd van deze kinderen bijna 8 jaar (spreiding 3 tot 17 jaar). Er werd

onderscheid gemaakt tussen structurele afwijkingen en afwijkingen tengevolge van

uitzetting van de nieren en urinewegen omdat deze afwijkingen een verschillende

ontstaanswijze kennen. De bedoeling was om inzicht te krijgen in de prognose voor

en de uiteindelijke uitkomst van deze kinderen.

Van de 402 foetussen hadden 151 een structurele afwijking, 247 een uitzetting van

nieren en/ of urinewegen en 4 een afwijking zonder invloed op de functie van de nier.

In totaal overleden ruim 25% van de foetussen als gevolg van de afwijking aan de

urinewegen.

Van de overlevende kinderen met een structurele afwijking had ongeveer 80% een

enkelzijdige multicysteuze nier, waarvan een kwart een bijkomende afwijking had

aan de andere nier. De Nederlandse kinderurologen adviseren de aangedane nier te

verwijderen. Dit betreft een relatief kleine ingreep die meestal verricht wordt rondom

de leeftijd van 6 maanden en veelal slechts één dag opname vereist. Tot verwijdering

van de nier wordt overgegaan nadat met een renogram is aangetoond dat er

inderdaad geen functie meer is in de aangedane nier. Een renogram is een

functieonderzoek van de nieren met radioactieve isotopen waarbij door de

uitscheiding van deze isotopen de functie van de nier kan worden bepaald. Het

voordeel van een dergelijke ingreep is dat geen levenslange follow-up meer

noodzakelijk is om de bloeddruk te meten vanwege een kans op verhoogde

bloeddruk en om het nierrestant te onderzoeken op een mogelijke eventuele

kwaadaardige ontwikkeling.

Tot de onderzoekspopulatie met een structurele afwijking behoorden verder twee

kinderen, die beiderzijds dysplastische nieren hadden. Dysplasie is een

ontwikkelingsstoornis van het nierweefsel waardoor dit slecht functioneert. Het ene

kind krijgt buikdialyse en het andere heeft een gestoorde nierfunctie.

Bij de kinderen met een verwijding van de nieren en urineleiders kwam deze

afwijking ongeveer even vaak een- als tweezijdig voor. Ruim de helft van de kinderen


had een enkel- of dubbelzijdige verwijding van het nierbekken terwijl de overigen ook

afwijkingen hadden aan de urineleiders en/ of blaas. Bijna de helft van de kinderen

(n=107) werd geopereerd en bij hen werden in totaal 315 ingrepen verricht. Alle

kinderen met afsluitende kleppen in de plasbuis werden geopereerd evenals 87%

van de kinderen met reflux (terugstroom van urine vanuit de blaas naar het

nierbekken tijdens het plassen).

Bij 21 kinderen werd de bevalling vóór 37 weken zwangerschapsduur ingeleid, omdat

er naast een toenemende uitzetting van het nierbekken een sterke afname van de

hoeveelheid vruchtwater plaatsvond. Afname van de hoeveelheid vruchtwater bij

deze kinderen wijst meestal op afname van de foetale mictie (hoeveelheid urine in

het vruchtwater geloosd) en daarmee op een afname van de nierfunctie. Al deze

kinderen werden binnen enkele dagen na de geboorte geopereerd. Zes van hen

hebben een verminderde nierfunctie en één kind heeft een hoge bloeddruk.

Tijdens de follow-up van alle 402 kinderen met een prenataal gediagnosticeerde

nierafwijking, bleek dat 9 van de 281 levende kinderen een gestoorde nierfunctie

hadden, waaronder één jongen een niertransplantatie heeft ondergaan en één

meisje wordt behandeld met buikdialyse. Drie kinderen hebben een verhoogde

bloeddruk. Geconcludeerd kan worden dat, kinderen met een vóór de geboorte

vastgestelde nierafwijking, 25% kans hebben om voor of na de geboorte te

overlijden. Als aan de overlevende kinderen na de geboorte goede zorg gegeven

wordt is de prognose, ongeacht of een of beide nieren zijn aangedaan en ongeacht

de ernst van de eventuele verwijding van de urinewegen, goed. Uitzondering vormt

de groep met een sterke afname van de hoeveelheid vruchtwater.

In hoofdstuk 6 wordt een groep van 100 kinderen besproken die allen een prenataal

vastgestelde enkelzijdige multicysteuze nier hadden. De gegevens werden verkregen

van de afdeling obstetrische echoscopie en van de afdeling kinderurologie van het

Wilhelmina Kinderziekenhuis te Utrecht. Uit de literatuur is bekend dat deze kinderen

vaak bijkomende afwijkingen hebben aan de overige urinewegen; reden waarom het

gehele kind tijdens het echoscopisch onderzoek goed nagekeken dient te worden als

een multicysteuze nier wordt gediagnostiseerd.

136 Chapter 9

Wij vonden bij 75% van deze kinderen een bijkomende afwijking. Dit is veel hoger

dan de 21 tot 57% die in de literatuur wordt vermeld. Achtenveertig procent had een

afwijking aan de andere nier (literatuur: 13 tot 39%). Aan de primair aangedane nier

werd in 48% van de kinderen nog een bijkomende afwijking gevonden (literatuur: 4

tot 14%) en aan het lagere urogenitale stelsel in 33% van de gevallen (literatuur: 4 tot

6%). Een gedeeltelijke verklaring voor deze door ons gevonden hoge incidenties in

vergelijking met de literatuur, vormt de in ons onderzoek routinematig uitgevoerde

cystoscopie (onderzoek van de blaas en plasbuis) bij alle kinderen en daarnaast nog

een colposcopie (onderzoek van de vagina en baarmoedermond) bij meisjes

voorafgaand aan de operatie waarbij de nier werd verwijderd. Deze onderzoeken zijn

eenvoudig uitvoerbaar en weinig belastend bij het kind dat al onder narcose is. Bij

cystoscopie werden 54 afwijkingen gevonden bij 48 kinderen. Hierbij betrof het

meestal een ectope ureter (een niet in de blaas eindigende urineleider) of een

vernauwing van de plasbuis. Bij de colposcopie bij de meisjes werden 3 afwijkingen

gevonden: eenmaal meerdere afwijkingen aan de inwendige geslachtsorganen

waaronder een afwezige vagina, eenmaal een afgesloten maagdenvlies en eenmaal

een ectope ureter die in de vagina uitmondde waardoor het meisje grote kans had

onophoudelijk ‘nat’ te zijn als deze afwijking niet gevonden was.

pyelectasie = milde verwijding van het nierbekken

In hoofdstuk 7 wordt een onderzoek beschreven naar het voorkomen van

urinewegproblemen op kinderleeftijd bij kinderen, bij wie tijdens een echoscopisch

onderzoek bij ongeveer 20 weken zwangerschapsduur een pyelectasie, een milde

verwijding tussen de 5 en 10 mm, gevonden was van één of beide nierbekkens. Er

werd gebruik gemaakt van de echoscopieverslagen van het Amphia ziekenhuis in

Oosterhout. Aldaar is gebruikelijk om patiënten, bij wie tijdens de 20-weken

echoscopie een pyelectasie wordt gezien, een herhaling van dit onderzoek te

adviseren bij ongeveer 32 weken zwangerschapsduur. Als de verwijding groter is dan

10 mm wordt de zwangere verwezen naar een tertiair centrum voor nader

onderzoek. Aldaar krijgt zij tevens een advies voor onderzoek en/ of behandeling van

het kind na de geboorte. De andere patiënten krijgen het advies geen verder

onderzoek te laten doen in de zwangerschap en na de geboorte, onafhankelijk van

het feit of de pyelectasie bij 32 weken nog wel of niet meer aanwezig was. Hen wordt


uitgelegd dat kinderen bij wie een pyelectasie is gezien mogelijk een hoger risico

hebben op reflux en dat als hun kind lusteloos of koortsig is zonder duidelijk

aanwijsbare reden zij de huisarts moeten vragen de urine na te kijken om een

eventuele urineweginfectie te kunnen behandelen.

Deze studie toonde aan dat 4,6% van de ruim 4500 onderzochte kinderen een enkel-

of dubbelzijdige milde pyelectasie had bij 20 weken zwangerschapsduur (literatuur:

0,6 tot 5,5%). De spreiding in de literatuur is het gevolg van het gebruik van

verschillende definities met betrekking tot verwijding van het nierbekken en van het

meten op verschillende tijdstippen in de zwangerschap. Over de klinische betekenis

van milde pyelectasie heerst nog veel onduidelijkheid. Er is overeenstemming dat

pyelectasie kan verergeren tot obstructie van het nierbekken of een uiting kan zijn

van reflux. Het is echter ook mogelijk dat de pyelectasie restloos verdwijnt. Sommige

onderzoekers adviseren om al deze kinderen na de geboorte laaggedoseerde

antibiotica te geven en hen te onderzoeken met een mictiecystogram (onderzoek met

contrastvloeistof in de blaas onder röntgendoorlichting) om reflux uit te sluiten, terwijl

andere een verwijding tot 10 mm als fysiologisch beschouwen.

Wij vergeleken twee groepen kinderen, één groep van 208 kinderen met een een- of

tweezijdige pyelectasie van 5 tot 10 mm tijdens de echoscopie rondom 20 weken

zwangerschap en een groep van 416 controle kinderen zonder deze afwijking. De

kinderen die werden geselecteerd waren tussen 4 en 9 jaar oud omdat zij zindelijk

moesten zijn om de vragen van de vragenlijsten te kunnen beantwoorden. De ouders

kregen een gestandaardiseerde vragenlijst toegezonden waarin gevraagd werd naar

plasgedrag, urine incontinentie, urineweginfecties, bedplassen en ontlastingspatroon

van het kind. Ruim 70% van de ouders van de kinderen met pyelectasie en 60% van

de controlegroep stuurden de vragenlijsten terug. Het bleek dat jongens significant

vaker vóór de geboorte een pyelectasie hadden dan de meisjes.

Er was geen verschil in de incidentie van urineweginfecties en plasgedrag. Wel werd

in beide groepen een hoger percentage urineweginfecties gevonden dan beschreven

is in de literatuur en in een onderzoek van het RIVM onder huisartsenpraktijken. Dit

hogere percentage is ook gevonden in een andere studie van onze onderzoeksgroep

en wordt mogelijk verklaard door het feit dat de vragenlijsten zeer gedetailleerd naar

plasgedrag en stoelgang vragen. Een andere mogelijkheid is misschien dat

huisartsen in de onderzoeksregio sneller urine onderzoeken op een infectie, omdat

138 Chapter 9

zij daar expliciet om gevraagd worden zulks te doen conform het advies dat aan de

ouders is gegeven en daardoor misschien ook eerder de urine nakijken bij kinderen

vanuit de controle groep als die met onbegrepen klachten op het spreekuur komen..

Ondanks het advies het kind na de geboorte niet te laten onderzoeken werd dit bij

ruim 30% van de kinderen toch gedaan. Meestal betrof het vrouwen die in het

ziekenhuis bevallen waren en waarvan het kind door de kinderarts gecontroleerd was

waarbij melding werd gemaakt van de bevinding van pyelectasie in de

zwangerschap. Van al deze kinderen maakten slechts drie een urineweginfectie

door. Eén kind werd geopereerd op de leeftijd van drie jaar omdat het nierbekken

verder verwijdde en de nierfunctie verslechterde. Slechts één kind vertoonde een

geringe reflux die spontaan verdween.

Op grond van dit onderzoek kan geconcludeerd worden dat als een enkel- of

dubbelzijdige pyelectasie wordt gezien tijdens de echoscopie bij 20 weken

zwangerschapsduur het onderzoek herhaald dient te worden rondom de 32e week.

Alleen als de pyelectasie meer dan 10 mm bedraagt dient de zwangere verwezen te

worden (in dit onderzoek bij 9% van de vrouwen; deze groep maakte overigens geen

deel van het huidige onderzoek uit). De andere ouders dient geadviseerd te worden

dat, indien hun kind hangerig of koortsig is zonder duidelijk aanwijsbare reden, zij de

huisarts moeten vragen urine van het kind na te kijken om een eventuele

urineweginfectie te kunnen diagnosticeren en zonodig te behandelen om nierschade

te voorkomen.

In hoofdstuk 8 werd onderzocht of er een relatie bestond tussen een verwijding van

het nierbekken en de vulling van de blaas. Bij het doen van echoscopisch onderzoek

was het regelmatig opgevallen dat de uitzetting van het nierbekken gedurende het

onderzoek wisselde. Omdat vervolgonderzoek in de zwangerschap of na de

geboorte meestal is gebaseerd op één enkele meting van het nierbekken is het van

belang of deze relatie inderdaad aanwezig is. Achttien zwangeren werden

onderzocht bij wie bij het echoscopisch onderzoek rondom 20 weken

zwangerschapsduur een enkel- of dubbelzijdige foetale pyelectasie werd gezien. Bij

de herhalingsechoscopie bij 32 weken was de verwijding niet tot meer dan 10 mm


toegenomen. Tijdens het onderzoek waren de patiënten 37 à 38 weken zwanger

omdat aan het einde van de zwangerschap foetussen een lange blaasvullings/

ledigingscyclus hebben, die gerelateerd is aan foetale gedragstoestanden.

Bij eenderde van de onderzochte foetussen werd een relatie gevonden tussen de

mate van verwijding van het nierbekken en de vulling van de blaas. Bij deze

subgroep was het gemiddelde verschil in de verwijding van het nierbekken bij volle

of lege blaas 6,7 mm, en bedroeg het grootste gemeten verschil 14,3 mm.

Uit dit onderzoek concluderen wij dat in geval van foetale milde pyelectasie, niet

volstaan kan worden met één enkel meetmoment, maar dat tijdens het onderzoek

meerdere keren gemeten dient te worden, bij voorkeur binnen een kwartier voor en

na leegplassen. Anderzijds houdt dit onderzoek in dat een eenmalige normale

bevinding een milde pyelectasie (een half uur later) niet uitsluit.

conclusie

Afwijkingen aan de foetale urinewegen kennen een hoge mortaliteit. Overlevende

kinderen hebben echter slechts een geringe kans op blijvende schade indien de

juiste diagnose in de zwangerschap wordt gesteld en indien deze kinderen na de

geboorte goede urologische opvang hebben. Het is van belang dat kinderartsen en

urologen bekend zijn met de adviezen die gegeven worden indien prenataal

afwijkingen aan de urinewegen worden vastgesteld, omdat zij na de geboorte

hieromtrent vaak geconsulteerd zullen worden.

140 Chapter 9 Dankwoord

Ik wil graag al diegenen bedanken zonder wie dit proefschrift niet tot stand was

gekomen. Hun inzet en steun waren van onschatbare waarde.

Allereerst gaat heel veel dank naar alle 1316 zwangeren, bij wie tijdens 3091

consulten 27.546 metingen werden verricht ten behoeve van alle onderzoeken die

beschreven zijn in dit proefschrift. Deze vrouwen deden geheel belangeloos mee,

soms moeizaam liggend, gedurende vaak urenlange onderzoeken maar tegelijkertijd

veel interesse tonend in het onderzoek en blij dat zij mee konden doen ten behoeve

van andere toekomstige moeders en kinderen.

Dr. G. H.A. Visser Gerard, ik ben je onbenoembaar dankbaar dat je mij de

gelegenheid hebt geboden onderzoek te gaan doen. Je zei erbij “Als het een beetje

goed gaat, mag je van mij promoveren.” Ik was perplex. Jouw stimulans,

opbouwende kritiek en waardevolle adviezen hebben me enorm gestimuleerd vooral

als ik het eens niet zag zitten. Je straalde het uit en ging er ook van uit dat ik het een

en ander tot een goed einde zou brengen. En ziedaar het proefschrift is klaar. Dank

voor je vertrouwen in me.

Dr. P.H. Stoutenbeek Philip, jouw database, opgestart in een fase van de IT dat dit

nog niet zo gewoon was, vormt een belangrijk deel van dit proefschrift. Dank dat ik

van al die gegevens gebruik mocht maken. Je kritische beoordeling en suggesties

waren een waardevolle en welkome aanvulling van het manuscript. Ik denk met

plezier terug aan al de jaren dat ik bij jou op de echokamer werkte.

Dr. T.P.V.M. de Jong Tom, jij was degene die de basis hebt gelegd voor wat betreft

mijn kennis van de foetale nieren. Altijd gaf je uitgebreid uitleg en was je behulpzaam

met adviezen als ik weer eens vragen had met betrekking tot patiënten uit

Oosterhout. Onbewust, heb jij daardoor aan het begin van dit proefschrift gestaan.

Tom, jouw aanmoediging, het vaak ‘even’ langs komen, “hoe gaat het ermee?” zijn

voor mij een grote steun en stimulans geweest. Nooit was je iets teveel, je las

manuscripten razendsnel en had altijd opbouwend kritiek hetgeen me grote steun

gaf. Dank je wel.

Dankwoord 141

Dr. R.H. Stigter Rob, veel dank ben ik jou verschuldigd. Allereerst dat je me

uitnodigde op jouw kamer om aan dit proefschrift te gaan werken. Ik heb dat enorm

gewaardeerd. Van jou heb ik geleerd wetenschappelijk te gaan denken, vaak via

‘losse’ opmerkingen van je die me tot denken aanzetten en op het goede spoor

brachten. Maar vooral ben ik je dank verschuldigd door je kritische beoordeling van

de diverse artikelen en natuurlijk je onmisbare hulp bij de correctie tot

wetenschappelijk en leesbaar engels. Met groot genoegen denk ik terug aan onze

gezamenlijke jaren op de echokamer en prenatale ‘prik’spreekuren.

Drs. L.R. Pistorius Lou, sinds een klein jaar zijn we kamergenoten en hebben heel

wat afgekletst. Ik dank je voor deze gezellige tijd. Het was heerlijk een ‘native

speaker’ naast me te hebben voor een lastig engels woord of uitdrukking.

Samen hebben we de metingen voor de interobserver variatie in een sneltreinvaart

afgerond. Je deed het naast je ‘normale’ werk en ik kon je altijd bellen als een

zwangere was ‘gestrikt’ om mee te doen aan het onderzoek. Veel dank hiervoor.

Dr. P. Westers Paul, jij was mijn steun en toeverlaat bij de statistische berekeningen.

Voor mij vaak een abracadabra waarmee jij me vertrouwd hebt gemaakt en

geholpen. Je beantwoordde altijd razendsnel per mail de vragen die ik op je

afvuurde, hetgeen bijzonder aangenaam was als ik weer eens vastzat. Je hebt een

humor die de vaak ‘droge’ statistiek verteerbaar maakt. Dank voor alles..

Mevrouw M.J. Korenromp Marijke, ik ben heel blij dat je mijn paranimf wilt zijn. We

kennen elkaar van de opleiding en waren dit jaar 40 jaar vroedvrouw! In al die jaren

hebben we samen veel meegemaakt. Je was altijd een enorme steun voor me in

moeilijke tijden en ik ben blij dat jij mijn vriendin bent.

Drs. P.J. Damen, Pieter Jan, het geeft een bijzonder en trots gevoel dat jij tijdens de

promotie naast me staat. Mijn jongste zoon die ook het medische vak is ingegaan en

mijn paranimf wil zijn. Dank je wel.

142 Chapter 9

Verder dank ik alle familieleden en vrienden voor de interesse die zij getoond hebben

de afgelopen jaren. Sommigen hoofdschuddend: Dat je dat leuk vindt! Waar begin je

aan? Ga met de VUT! Anderen ook met ‘bewondering’: echt iets voor Hen! Maar van

iedereen was er steun en aandacht. Dank jullie wel.

En natuurlijk gaat heel, heel veel dank naar het thuisfront. Naar mijn man, Albert, die

ik dank voor zijn onvoorwaardelijke geduld en steun. Ik kon altijd mijn verhaal kwijt

van dit voor hem vaak onbegrijpelijke onderzoek. Ik hoop dat we nog vele jaren

samen mogen delen.

Veel te danken heb ik aan mijn kinderen, Annette, Albert jr. en Pieter Jan, die indien

nodig altijd klaar staan om te helpen en steunen waar maar nodig is. Ik ben trots op

jullie. En jullie kunnen me niet meer plagen want de enige HBO-er in het gezin

verslaat jullie nu in één klap!

Verder dank ik jullie partners, die wat meer vanaf de zijlijn toezien maar door hun

aandacht en interesse veel steun gaven.

En last but not least mijn twee kleinzonen, Joost en Ties. Oma is blij met jullie en nu

kunnen jullie nog vaker komen logeren.

Curriculum vitae 143

Geboren 27 mei 1941, te Tegelen

HBS-b, 1961, Sint Bonifacius Lyceum, Utrecht

opleiding van Verloskundigen, 1961-1964, Vroedvrouwenschool, Heerlen

Verloskundige, 1964 – 1965, Privé-kliniek: Dr.Bohler te Luxemburg, Luxemburg

Verloskundige, 1965 – 1977, Sint Joseph ziekenhuis, Eindhoven.

Aanvankelijk werkzaam op de verloskamers en polikliniek, later speciaal belast met het maken van een jaarverslag van de afdeling, verloskunde, gynaecologie en fertiliteit.

Verloskundige – echoscopiste, 1980 – 2003, Pasteur Ziekenhuis, Oosterhout N-Br.

Verloskundige – echoscopiste, 1989 – nov. 1999, UMCU, Utrecht

Verloskundige – onderzoeker, nov. 1999 – 2004, UMCU, Utrecht

1985 – 1977, Lid Commissie Ultrageluid, Koninklijke Nederlandse Organisatie van

Verloskundigen (KNOV)

1985 – heden, bestuurslid Werkgroep Foetale Echoscopie van de Nederlandse

Vereniging voor Obstetrie en Gynaecologie

!988 – 1996, lid van het hoofdbestuur van de KNOV

1990 – 1996, voorzitter van de afdeling Noord Brabant van de KNOV

1990 – 1992, gedelegeerde Stuurgroep Toekomst Scenario’s Gezondheidszorg

namens de KNOV

1995 – 2003, lid Subwerkgroep Echoscopisch Onderzoek van het Verloskundig

Overleg bij de Ziekenfondsraad namens de KNOV ten behoeve van het Verloskundig

Vademecum, uitgave 1 en 2

1995 – heden, initiator en cursusmanager van de “Cursus Echoscopie voor

verloskundigen werkzaam in de eerste lijn”.

FETAL RENAL ANOMALIES: diagnosis, management and outcome · Webb NJ, Lewis MA, Bruce J, Gough DC,...

Documents

Transcript of FETAL RENAL ANOMALIES: diagnosis, management and outcome · Webb NJ, Lewis MA, Bruce J, Gough DC,...