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52 Prenatal Diagnosis
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Figure 4.7 Vesicoamniotic shunt. (a) A double pigtail shunt diverts urine from the fetal bladder into
the amniotic cavity. (b) Postnatal image showing the extra-abdominal portion of the shunt with
associated prolapsed, hypertrophic bladder tissue.
Table 4.1 Threshold values of fetal urine
parameters that predict good renal function
Good prognosis
Sodium <100 mEq/L
Chloride <90 mEq/L
Calcium <4 mEq/L
Osmolality <210 mOsm/L
-microglobulin <10 mg/L
β
2
Total protein <20 mg/dl
and/or echogenic kidneys with cortical cysts is a
contraindication to shunting.
Although vesicoamniotic shunting appears
to have the potential to improve pulmonary outcomes, the benets (if any) for renal and bladder
function remain unproven. e incidence of complications is high (45%) – including premature
labor, shunt migration, shunt blockage, and chorioamnionitis. Further shunting procedures are
oen required, with an average of 2.5 shunt placements per pregnancy. e percutaneous shunting
in lower urinary tract obstruction (PLUTO ) trial
was a randomized-controlled study to evaluate
the ecacy and safety of vesicoamniotic shunting. Analysis of the initial results indicated that
survival rates were improved by shunting but the
prognosis for renal function remained poor. e
trial was terminated prematurely because of difculties in recruiting sucient patient numbers.
Myelomeningocele closure
e traditional surgical management of myelomeningocele consists of surgical closure in the
early neonatal period. In utero surgical closure
was proposed in the hope of improving neurologic
outcomes. e rst case was reported in 1997 and
the results of an initial comparative outcome trial
(management of myelomeningocele study [MOMS]
were published in 2003. ese demonstrated that in
utero closure of the myelomeningocele was associated with a reduced requirement for ventriculoperitoneal shunting and improved early outcomes
for cognitive and motor function. However, it did
not lead to any improvement in bladder function.
Complications of intrauterine closure of myelomeningocele include increased rates of premature
birth and uterine dehiscence. Fetoscopic techniques have been developed as an alternative to
open fetal surgery, with initial data suggesting they
carry a lower risk of maternal complications.
Amnioinfusion
Amnioinfusion is a technique in which saline
is infused into the amniotic cavity with the
Prenatal counseling 53
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intention of alleviating the eects of oligohydramnios on pulmonary development. ere
have been recent case reports that the use of
amnioinfusion in cases of bilateral renal agenesis
permitted sucient pulmonary development for
postnatal survival followed by postnatal dialysis
as a bridge to renal transplant. is is still considered an experimental intervention and should
not be routinely oered.
Termination of pregnancy
(therapeutic abortion)
Although this remains a controversial issue,
termination of pregnancy for severe or lethal
congenital abnormalities has long been legally
permissible (subject to certain criteria) in many
countries. e combination of prenatal diagnosis
and termination of pregnancy may explain why
the last two to three decades have seen declining numbers of referrals for severe but nonlethal
urologic malformations such as prune-belly syndrome and cloacal and classic bladder exstrophy.
and signicant coexisting nonurologic condition)
counseling will involve input from specialists in
the relevant disciplines to ensure parents are fully
informed on the implications for their child and
the family. ese discussions may include, for
example the probable requirement for intermittent catheterization for children with neurogenic
bladder and dialysis and future kidney transplant in urologic conditions posing a risk of renal
insuciency and chronic kidney disease. Broader
issues relating to changes in lifestyle and nancial
implications of caring for a child with a long-term
chronic condition will also need to be raised with
the parents.
ese are uncomfortable issues to discuss,
but a full discussion is necessary to ensure that
parents have all the information they need when
making life-changing decisions.
Following the prenatal diagnosis of severe
anomalies, parents must be reassured that whatever course of action they choose (aggressive
medical intervention, limited medical intervention, comfort care, and termination of pregnancy) is valid, and that their medical team will
support them in their decision.
PRENATAL COUNSELING
When counseling expecting parents, clinicians
should explain the dierential diagnosis, the
likely perinatal course (including required investigations,) and provide an overview of the longer
term prognosis.
Counseling for the majority of cases of prenatally detected hydronephrosis should focus on
reassuring parents. Mild hydronephrosis (SFU
Grade I) is oen a transient physiological phenomenon and even when it persists postnatally
is unlikely to be clinically signicant or require
invasive investigation. More signicant prenatally detected conditions such as ureteropelvic
junction, vesico ureteral reux, and unilateral
multicystic dysplastic kidney may resolve without requiring operative intervention. Parents
can also be reassured that even when operative
intervention is required, the majority of children
experience favorable outcomes.
When the prognosis is far less favorable (e.g.
oligohydramnios, bilateral renal abnormalities,
KEY POINTS
●
Most infants with prenatally detected
hydronephrosis will require no
intervention.
●
Abnormalities of the renal parenchyma,
ureter, and/or bladder suggest a
clinically signicant pathology.
●
e urinary tract dilation (UTD) classication is the rst system to unify
descriptions of prenatal and postnatal
hydronephrosis, and to provide
guidance regarding initial management.
●
Routine antibiotic prophylaxis, voiding
cystourethrogram, and renography are
unnecessary for the majority of patients
diagnosed with prenatal hydronephrosis.
●
e benets of fetal intervention are
uncertain, and fetal surgery should not be
pursued outside of high volume centers.
54 Prenatal Diagnosis
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FURTHER READING
Braga Luis H, Farrokhyar Forough, D’Cruz
Jennifer, Pemberton Julia, Lorenzo
Armando J. Risk Factors for Febrile Urinary
Tract Infection in Children with Prenatal
Hydronephrosis: A Prospective Study. J Urol.
2015;193(5S):176 6 –1771.
Capolicchio J-P, Braga LH, Szymanski KM.
Canadian Urological Association/Pediatric
Urologists of Canada guidelines on the
investigation and management of antenatally detected hydronephrosis. CUAJ.
2017;12(4):85–92.
Morris RK, Malin GL, Quinlan-Jones E,
Middleton LJ, Hemming K, Burke D, et al.
Percutaneous vesicoamniotic shunting versus
conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised
trial. Lancet. 2013;382(9903):1496–1506.
Nguyen HT, Benson CB, Bryann B, et al.
Multidisciplinary consensus on the classication of prenatal and postnatal urinary tract
dilation (UTD classication system). J Pediatr
Urol. 2014;10:982–999.
Sairam S, Al-Habib A, Sasson S, Thilaganathan
B. Natural history of fetal hydronephrosis diagnosed on mid-trimester ultrasound. Ultrasound Obstet Gynecol.
20 01;17(3):191–196.
Urinary Tract Infection
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STUART J O’TOOLE
Topics covered
5
Epidemiology of childhood urinary infection
Pathogenesis
Infecting organisms
Host factors
Diagnosis
Specimen collection, urine analysis
Clinical features
INTRODUCTION
Urinary tract infection (UTI) is one of the
commonest disorders of childhood, affecting
an estimated 82 000 children a year in the UK.
A UTI may be the first indication of significant underlying pathology of the urinary tract
which may require treatment to prevent ongoing or future renal damage. Diagnosing UTI
in young infants can be problematic because
the clinical features are often non-specific and
reliable urine samples are difficult to obtain.
Nevertheless, greater awareness of the importance and prevalence of UTI in children coupled with the availability of sensitive dipstick
reagent strips has led to UTIs being detected
on a far greater scale than in the past. In turn
this has led to many more children with mild
or asymptomatic lower tract urinary infections
Age differences
Upper and lower tract infection
Investigation
NICE guidelines
International guidelines
Management
being referred for investigation. Standard protocols for the investigation and management
of childhood UTI often dated from a time
when children referred for investigation were
those with more severe infection. As a consequence, many children with mild, lower tract
UTIs have been subjected to unnecessary (and
costly) invasive investigations. To address these
concerns, healthcare organisations across the
developed world have produced evidencebased guidelines on a selective approach to
diagnostic imaging and recommendations on
management. The published guidelines vary
significantly – ref lecting different healthcare
philosophies. Those published in the UK place
greater emphasis on the benefit to the population and costs to the healthcare system whereas
guidelines published in North America place
greater emphasis on the individual child.
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56 Urinary Tract Infection
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Table 5.1 The age-related incidence of urinary
tract infection in boys and girls
Age (years) Boys (%) Girls (%)
<1
<3 2.2 2.1
<7 2.8 8.2
<16 3.6 11.3
Lifetime 13.7 53.1
1.0 0.8
EPIDEMIOLOGY
e true incidence of UTI in children is far
higher than was previously thought. In the 1960s,
this was put at 0.02% for boys and 0.04% for girls,
whereas current estimates have increased 20-fold
(Table 5.1). In the rst 12 months of life urinary
infections occur more commonly in boys but
thereaer (and particularly above 3 years of age)
UTIs aect predominantly girls.
PATHOGENESIS OF URINARY
TRACT INFECTION
UTIs occasionally result from haematogenous
spread or the direct transmission of bacteria from
other organs – e.g. vesico intestinal and genitourinary stulae. However, the overwhelming
majority are “ascending infections” in which bacteria which have colonised the perineum or preputial sac gain access to the lower urinary tract
via the urethra. Whether these bacteria go on to
produce an established infection once they have
entered the lower urinary tract is determined
by the interplay of a number of factors set out in
Figure 5.1. e concept of organisms multiply-
ing within bladder urine is largely inaccurate
and research has shown that bacterial replication
occurs predominantly at an intracellular level,
with organisms being shed into the urine from
infected urothelial cells.
Organisms
Escherichia coli is responsible for around 85% of
UTIs. e mbriated forms of E. coli have the
ability to adhere to receptors on the urothelial
surface and are therefore particularly eective at
colonising the urinary tract. P-mbriated E. coli
are particularly potent pathogens because of their
adherence properties. Other common infecting
organisms, in approximately descending order
of frequency, are Proteus vulgaris, Klebsiella,
Enterobacter and Pseudomonas.
Figure 5.1 Host and pathogen factors involved in the pathogenesis of UTI in children.
Laboratory diagnosis of urinary tract infection / Urine Collection 57
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Urinary Stasis
ere is a substantial body of clinical experience which indicates that the risk of UTI is signicantly increased by factors which impede
the clearance of bacteria from the urinary tract.
ese include; urinary stasis due to obstruction,
vesico ureteric reux (VUR) and incomplete
bladder emptying (due to outow obstruction or
dysfunctional voiding).
Anatomical Abnormalities
Because many more children with mild, lower
tract infections are being referred for investigation than in the past, the relative proportion with
signicant underlying urological abnormalities
has decreased from a historical gure of around
30% to closer to 10%. Even when anomalies are
identied on investigation many are of limited
clinical relevance. Examples include; minor
grades of VUR, incomplete duplication anomalies and anomalies of renal ascent and fusion.
Dysfunctional voiding characterised by infrequent toileting and impaired bladder emptying
(particularly in girls) is a far more common predisposing cause of UTIs than anatomical abnormalities of the urinary tract.
Host Susceptibility
Many host factors can increase a child’s susceptibility to urine infection. Premature infants are
at greater risk (although breast-feeding appears
to confer some protection). Other host factors
linked to susceptibility or resistance to UTI
include immunoglobulin A (IgA) secretion and
blood group secretor status. e presence of a
foreskin is an undoubted risk factor – particularly
in the rst year of life. e incidence of urinary
infection is 10–20 times higher in uncircumcised
boys than their circumcised peers. Although
the increased risk of urinary infection in uncircumcised boys has been cited as one of the justications for routine neonatal circumcision, the
ndings of large population-based studies indicate that over 100 boys would need to be circumcised in order to prevent one boy from developing
urinary infection. Nevertheless, although routine
neonatal circumcision is not a cost-eective measure for preventing UTIs in boys with normal
urinary tracts there is growing evidence that circumcision reduces the risk of UTI in boys with
underlying urological abnormalities such as posterior urethral valves and high grade VUR.
LABORATORY DIAGNOSIS OF
URINARY TRACT INFECTION
Urine Collection
“Clean catch” midstream
urine sample
A midstream urine (MSU) sample yields the most
reliable results. Children who are toilet-trained
can usually cooperate with this method of collection. For infants and children unable to provide
a midstream specimen, the non-invasive alternatives include:
●
Adhesive collection bags attached around
the genitalia. is is the simplest and most
commonly used method of collecting urine
specimens in the very young. However, the
results are only reliable if appropriate precautions have been taken to avoid contamination
and if the voided specimen is sent promptly
for culture.
●
Absorbent urine collection pads placed
inside the nappy. In this method, urine
which has soaked into the pad is aspirated
with a syringe and sent for microscopy
and culture. Cotton wool balls may also be
used but are less reliable. Contamination is
common.
Invasive techniques
●
Suprapubic needle aspiration is the ideal
method of collection in sick infants in whom
an urgent diagnosis is required. e procedure should be performed under ultrasound
58 Urinary Tract Infection
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guidance, once it has been conrmed that
there is urine in the bladder.
●
Urethral catheterisation is distressing and is
rarely appropriate for this purpose.
Although it is always preferable to obtain a urine
sample before commencing treatment, there may
be situations (e.g. a severely ill infant) when it is
justiable to commence antibiotic treatment even
if a urine sample cannot be obtained.
Urine Storage and Transport
Once collected, the specimen should ideally be
cultured within 4 hours to minimise the risk
of contaminating organisms multiplying and
yielding a false-positive result. If this is not feasible (e.g. in children presenting outside working
hours), the sample can be refrigerated for up to
24 hours at +4.0°C or transferred to a vessel containing boric acid preservative.
A positive result for protein does not denote infection. A trace of proteinuria is a common nding
and is not a cause for concern. Heavier proteinuria
may, however, signify renal disease and referral to
a paediatric nephrologist should be considered if
this is conrmed on a further test.
Urine Microscopy
When performed on a fresh uncentrifuged sample
of urine, microscopy can be very useful in facilitating a prompt diagnosis and enabling treatment
to be commenced without awaiting the results of
culture. Results are generally expressed as absolute values or counts per high-powered eld.
Signicant pyuria is dened as >10 WBC/mm3.
e concentration of motile bacteria can also be
quantied, with 107 bacteria per ml being deemed
signicant. is gure corresponds to eight
organisms per high-powered eld. e interpretation of microscopy ndings is summarised in
Tab le 5.2.
Urine Dipsticks
e introduction of urine dipsticks with leucocyte esterase and nitrite reagents has been instrumental in facilitating the earlier diagnosis of
UTI. Guidelines published by the UK’s National
Institute of Clinical Excellence make the following recommendations:
●
Leucocyte esterase and nitrite both
positive = denite evidence of UTI. Antibiotic
treatment should be commenced.
●
Leucocyte esterase negative, nitrite positive =
presumptive evidence of UTI. Antibiotic treat-
ment should be commenced and a urine sample
sent for culture.
●
Leucocyte esterase positive, nitrite
negative – a urine sample should be sent for
microscopy and culture but antibiotic treat-
ment should not be commenced unless there
is good clinical evidence of UTI.
●
Leucocyte esterase negative, nitrite
negative = negative result. Antibiotic treatment
should not be started. Nor is it necessary for
urine to be sent for microscopy and culture.
Urine Culture
Provided the urine sample is uncontaminated,
the criterion for the bacteriological diagnosis of
urinary infection is a pure growth of >105 bacterial
colony-forming units (CFUs) per ml. However, in a
specimen which has been obtained by suprapubic
aspiration, any growth of a Gram-negative organism is signicant, as is a growth of greater than
>500–1000 Gram-positive organisms. Following
Table 5.2 Interpretation of microscopy ndings
Microscopy
results
Bacteriuria
positive
Bacteriuria
negative
Pyuria
positive
The infant or
child should
be regarded
as having UTI
Antibiotic
treatment
should be
started if
clinically UTI
Pyuria
negative
The infant or
child should
be regarded
as having UTI
The infant or
child should
be regarded
as not
having UTI
Clinical presentation and diagnosis / Clinical Features 59
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the introduction of sensitive dipsticks, it has
been questioned whether urine culture is still
routinely necessary in all cases. However, at
a time when multiple antibiotic resistance is
increasing there remains a strong argument for
sending a urine specimen for culture to identify
the causative organism and establish its antibiotic sensitivities.
CLINICAL PRESENTATION
AND DIAGNOSIS
History and Examination
It is important to enquire whether there is any
family history of urological abnormalities, particularly VUR. e antenatal history is also
important, specically whether any abnormality
was detected on antenatal ultrasound. In older,
toilet-trained children, information should be
routinely sought on:
●
Voiding history (volume, frequency, stream,
urgency)
●
Fluid intake (volume, type)
●
Bowel habits
Although physical examination is usually uninformative, it should nevertheless be performed
routinely and should include the abdomen,
genitalia, spine and lower limbs. Blood pressure
should always be measured (although this can
be dicult in small or fractious children). It is
important that the appropriate equipment and
paediatric blood pressure cus are always available in the outpatient clinic.
Clinical Features
e presentation of UTI can be non-specic and
is inuenced by the nature of the infection and the
age of the child. Table 5.3 summarises the clinical
features of UTI at dierent ages. It is important to
maintain a high degree of suspicion and ensure
that a urine sample is collected and tested for
Table 5.3 Presenting features of UTI in children
at different ages
Infant and
Frequency
Common Fever
Less
common
Uncommon Jaundice
toddler Older child
Frequency
irritability
Vomiting
Lethargy
Offensive
urine
Poor feeding
Failure to
thrive
Failure to
thrive
Haematuria
dysuria
Offensive urine
Incontinence
Abdominal
pain
Fever
Vomiting
Haematuria
Loin tenderness
infection in any child with an unexplained fever
exceeding 38.0°C. In addition to age-related differences, the clinical presentation is determined
by whether the child is suering from lower or
upper UTI (Table 5.4).
Lower tract infection (cystitis)
Cystitis typically gives rise to bladder symptoms,
with dysuria being almost universal. In addition,
urinary frequency is common and oen associated with secondary enuresis. However, suprapubic pain is comparatively rare. ere is no fever
or general malaise; indeed, many older children
are able to continue attending school during the
course of their illness.
Table 5.4 Symptoms of urinary tract infections
Lower urinary tract
(cystitis)
Frequency/nocturia Fever
Dysuria Vomiting
Secondary enuresis General malaise
Suprapubic pain Loin pain
Hesitancy Upper/central
Upper urinary tract
(pyelonephritis)
abdominal pain
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Upper tract infection
(pyelonephritis)
Fever is the most reliable clinical feature of upper
tract UTI and, indeed, it is doubtful whether
pyelonephritis ever occurs without a fever. Any
temperature exceeding 38°C should be regarded
as suspicious, although pyelonephritis is typically accompanied by a higher fever. Information
on the presence or absence of fever is usually less
reliable in children referred by general practitioners than those admitted directly to hospital
from Emergency Departments.
e key diagnostic points can be summarised
as follows:
●
Infants and children who have bacteriuria
and fever of 38°C or higher should be considered to have acute pyelonephritis.
●
Infants and children presenting with fever
lower than 38°C with loin pain/tenderness
and bacteriuria should also be considered to
have acute pyelonephritis.
●
All other infants and children who have bacteriuria but no systemic symptoms or signs
should be considered to have cystitis.
Other presenting features of UTI
e presence of haematuria is not in itself a
guide to the severity or site of the infection.
Haemorrhagic cystitis is the commonest cause.
Urinary tract calculi should be suspected whenever the infecting agent is Proteus and it is
important to be aware that stones may be present in the upper urinary tract without giving
rise to any constitutional symptoms. Some boys
referred with haematuria (with or without documented infection) may, in fact, have postmicturition bleeding due to urethritis rather than
genuine haematuria. Epididymo-orchitis is an
occasional presentation of urinary infection in
boys of all ages and should arouse suspicion of
some predisposing abnormality, such as urethral
obstruction distal to the ejaculatory ducts or a
duplication anomaly with the upper pole ureter
draining ectopically into an ejaculatory duct (see
Chapter 8).
Neonates and infants
UTI typically presents in this age group as a
non-specic febrile illness, usually accompanied
by vomiting (and quite oen by diarrhoea). A
dipstick urine test should always be performed
in any infant with an otherwise unexplained
febrile illness. Whenever possible a urine specimen should also be sent for microscopy and culture but this may not always be feasible because
of diculty obtaining a reliable urine sample in
infants. Less common presentations of urinary
infection in neonates and infants include failure
to thrive (or frank weight loss) and prolonged
jaundice in neonates. UTI may also occasionally
present with haematuria (blood-stained nappy)
or as epididymo-orchitis.
Children aged 2 years and older
Children as young as 2 years of age can usually give some account of their symptoms, and
by 4 years, if not earlier, it should be possible to
obtain a reasonably accurate history. e history and clinical features of the illness should
provide a guide to whether the child is suering from an upper or lower UTI. Pyelonephritis
is sometimes accompanied by poorly localised
upper abdominal pain but true loin pain is
rare and, if prolonged, is more likely to signify
obstruction than infection.
Potential pitfalls and sources of diagnostic con-
fusion include:
●
Fever, abdominal/loin pain and dysuria in
an older child. is triad of symptoms associ-
ated with pyelonephritis can also be mimicked
by acute inammation of a retroceacal or
pelvic appendix. In acute appendicitis, pain
which occurs at the time of voiding is more
likely to be localised to the abdomen rather
than the urinary tract. In addition, the pain
is more likely to be provoked or exacerbated
by extension of the hip. e temperature
is usually lower in appendicitis than in
pyelonephritis.
●
Dysuria in the absence of other features of
UTI. Symptoms associated with vulvovagi-
nitis in young girls are oen, incorrectly
Investigation: Diagnostic imaging / Ultrasonography 61
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ascribed to UTI. Although the presence of
white blood cells may be evident on urine
microscopy, urine culture is either negative
or may reveal a mixed growth. From the
history it should be possible to distinguish
between the features of dysuria associated
with vulvovaginitis and dysuria due to a
true UTI.
●
Dysuria associated with balanitis may be
confused with UTI in boys.
Classication of UTI
UTI can be classied according to whether it
aects the lower urinary tract (cystitis), upper
urinary tract UTI (pyelonephritis), whether it
is asymptomatic or symptomatic and whether
it is a single episode or recurrent. Asymptomatic
bacteriuria (ABU) is predominantly a condition
of school age girls who do not complain of symptoms of lower tract UTI despite having signicant
bacterial counts in their urine. ere is some evidence that the bacterial strains found in the urine
of girls with ABU are of lower virulence than
the strains of bacteria responsible for causing
symptomatic UTIs. Studies have demonstrated
that ABU does not pose a risk of renal scarring
in a child with an anatomically normal urinary
tract. However, ABU is not an entirely innocent
condition because there is considerable overlap
between ABU and clinically signicant infection.
Not infrequently, girls with ABU subsequently
experience (or have previously experienced)
symptomatic UTIs.
INVESTIGATION: DIAGNOSTIC
IMAGING
Established protocols and guidelines have been
criticised for leading to over-investigation of
children with lower tract infections and for not
being cost-effective. Despite broad acceptance
of new guidelines it seems likely that most
paediatric clinicians will continue to recommend that all children presenting with proven
urinary infection should undergo some form of
investigation. However, a selective approach is
required to ensure that normal children are not
subjected to unnecessarily invasive investigations at the same time as ensuring that abnormalities which predispose to UTI (notably
VUR) are not being missed.
e technical aspects of these investigations
are considered in Chapter 3.
e dierent imaging modalities are summa-
rized in Table 5.5.
Ultrasonography
Ultrasound is the ideal initial screening investigation because it is non-invasive, relatively
inexpensive and does not entail exposure to
radiation. European and North American guidelines recommend that all children presenting
with a UTI should undergo an ultrasound scan.
Somewhat controversially, however, the NICE
(UK) guidelines state that an ultrasound scan
is not routinely indicated in a child aged over
6 months who has experienced only a single
uncomplicated UTI.
Ultrasonography is a reliable means of detecting obstructive and non-obstructive urinary tract
dilatation, major degrees of renal scarring or dysplasia, most urinary calculi and almost all clinically signicant duplication anomalies. It is also
of value in demonstrating evidence of voiding
dysfunction – which is apparent as a signicant
post void residual volume of urine and, in some
cases, bladder wall thickening.
When an abnormality has been revealed by
ultrasonography, the choice of further imaging
is guided by factors which include the type of
abnormality detected, the severity of infection
(upper or lower tract) and the age of the child.
e most widely used investigations are Tc-99m
DMSA scintigraphy and either micturating cystourethrography (MCUG) or indirect radionuclide cystography (IRC). Suspected upper tract
obstruction is investigated by dynamic renography using Tc-99m (MAG3).
One of the main limitations of ultrasonography is its poor sensitivity for detecting renal
scarring and mild to moderate VUR. For example, ultrasonography has a false-negative rate of
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