YJPSU-58742; No of Pages 5

Journal of Pediatric Surgery xxx (2018) xxx–xxx

Contents lists available at ScienceDirect

Journal of Pediatric Surgery

journal homepage: www.elsevier.com/locate/jpedsurg

Surgical interventions and anesthesia in the 1st year of life for lower
urinary tract obstruction☆,☆☆,★
Kathleen T. Puttmann a,⁎, Jeffrey T. White a, Gene O. Huang a, Kunj Sheth a, Rodolfo Elizondo a, Huirong Zhu b,
Michael C. Braun c, David G. Mann d, Olutoyin A. Olutoye d, Duong D. Tu a, Rodrigo Ruano e, Michael Belfort f,
Mary L. Brandt g, David R. Roth a, Chester J. Koh a
a
Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, and Scott Department of Urology, Baylor College of Medicine, Houston, TX
b
Outcomes & Impact Services, Texas Children's Hospital, Houston, TX
c
Renal Section, Department of Pediatrics, Texas Children's Hospital, Houston, TX
d
Department of Anesthesiology, Texas Children's Hospital, Houston, TX
e
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN
f
Department of Women Services, Texas Children's Hospital, Houston, TX
g
Division of General Surgery, Department of Surgery, Texas Children's Hospital, Houston, TX

a r t i c l e i n f o a b s t r a c t

Article history: Background: Patients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal
Received 20 March 2018 interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract
Received in revised form 14 June 2018 obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of
Accepted 26 June 2018 anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the
Available online xxxx
number of anesthesia events for prenatally diagnosed LUTO patients.
Methods: We retrospectively reviewed the prenatal and postnatal clinical records for patients with prenatally di-
Key words:
Lower urinary tract obstruction
agnosed LUTO from 2012 to 2015. Patients were stratified by prenatal VAS status and by LUTO disease severity
Fetal surgery according to Ruano et al. (Ultrasound Obstet Gynecol. 2016).
Anesthesia encounter Results: 31 patients were identified with a prenatal LUTO diagnosis, and postnatal records were available for 21
patients (seven patients in each stage). When combining prenatal and postnatal anesthesia, there was a signifi-
cant difference in the number of anesthesia encounters by stage (1.6, 3.7, and 6.7 for Stage I, II, and III respectively,
p = .034).
Upon univariate analysis, higher gestational age (GA) at birth was associated with a decreased number of anes-
thesia events in the first year (p = .031).
Conclusions: The majority of infants with prenatally diagnosed LUTO will undergo postnatal procedures with gen-
eral anesthesia exposure in the first year of life. Patients with higher prenatal LUTO severity experienced a higher
number of both prenatal and postnatal anesthesia encounters. In addition, higher GA at birth was associated with
fewer anesthesia encounters in the first year.
Level of evidence: This is a prognostic study with Level IV evidence.
© 2018 Elsevier Inc. All rights reserved.

Lower urinary tract obstruction (LUTO) is a rare disease seen in ap-

Abbreviations: LUTO, lower urinary tract obstruction; VAS, vesicoamniotic shunting; FDA,
Food & Drug Administration; GA, gestational age; PUV, posterior urethral valves; PLUTO
trial, percutaneous shunting in LUTO trial; G-tube, gastrostomy tube.
☆ FINANCIAL DISCLOSURE: The authors have no financial relationships relevant to this
article to disclose.
☆☆ CONFLICT OF INTEREST: The authors have no conflicts of interest to disclose.
★ FUNDING: This research received support from the Department of Surgery, Texas
Children's Hospital.
⁎ Corresponding author at: Texas Children's Hospital and Baylor College of Medicine,
MWT Suite 620, 6701 Fannin Street, Houston, Texas 77030. Tel.: +1 513 403 5272;
fax: +1 832 825 3159.
E-mail address: kxp103@gmail.com (K.T. Puttmann).
proximately 2.2–3.4 of 10,000 live births [1, 2]. Patients with a prenatal
diagnosis of LUTO may undergo both prenatal and postnatal therapeutic
interventions. Prenatal interventions, such as vesicoamniotic shunt
(VAS) placement, can provide a temporary solution for relieving urinary
tract obstruction. Although some studies have shown a survival benefit
after VAS, little is known regarding the influence of prenatal interven-
tions on the subsequent frequency of postnatal procedures [3, 4]. The
Food & Drug Administration (FDA) recently released a communication
on the potential neurocognitive adverse effects associated with re-
peated or lengthy anesthetic exposure in children less than three
years old and fetuses in the third trimester of gestation [5]. Concern

https://doi.org/10.1016/j.jpedsurg.2018.06.033
0022-3468/© 2018 Elsevier Inc. All rights reserved.

Please cite this article as: Puttmann KT, et al, Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction, J
Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.06.033
2 K.T. Puttmann et al. / Journal of Pediatric Surgery xxx (2018) xxx–xxx

from parents and providers makes it prudent to evaluate the anesthetic
encounters associated with the postnatal treatment of LUTO.
Ruano et al. recently proposed a staging system to grade prenatal
LUTO severity. The system was developed to help assess the severity
of disease and predict outcomes from in utero interventions [6]. We
reviewed the postnatal anesthesia encounters in the first year of life in
patients with prenatally diagnosed LUTO and stratified these events ac-
cording to LUTO stage and VAS status. The primary objective of this
study was to investigate the number of surgical interventions and re-
lated anesthesia encounters for patients with prenatally diagnosed
LUTO. Our secondary objective was to evaluate whether the prenatal
LUTO staging system by Ruano et al. was predictive of the number of an-
esthesia encounters for prenatally diagnosed LUTO patients.
1. Patients & methods
After obtaining IRB approval, we retrospectively reviewed the pre-
and postnatal records for patients with prenatally diagnosed LUTO
from 2012 to 2015. This included the number of prenatal and postnatal
anesthesia encounters defined as patient exposure to general anesthe-
sia in the first year of life and fetal exposure in utero. The types of pro-
cedures performed were recorded and categorized by organ system.
Prenatal anesthesia was defined as direct anesthesia to the fetus, i.e. in-
tramuscular (IM) injection. Although mothers received epidurals for
prenatal procedures, these are low-risk exposures for the fetuses and
were not included in analysis. Patients were stratified by prenatal VAS
status and by LUTO disease severity according to the staging by Ruano
et al. [6]. The staging system categorizes patients as I, II, or III based on
increasing severity of obstruction. Stage I is mild obstruction as defined
by absence of oligohydramnios with bilateral hydroureteronephrosis.
Both stages II and III are described as severe obstruction owing to the
presence of oligohydramnios with bilateral hydroureteronephrosis but
can be differentiated with stage III also including permanent renal in-
jury with visual evidence of dysplasia on the ultrasound and abnormal
fetal urine chemistry. Two independent reviewers assessed the ultra-
sound and fetal urine chemistries of the cohort (JW and KP) without
knowledge of the patient outcomes or VAS status. Some patients did
not have fetal urine chemistries, so the analysis was based upon ultra-
sound alone. As described by Ruano et al., renal dysplasia was consid-
ered a severe finding on ultrasound, and these patients were classified
as stage 3. A subset analysis was performed on the number of additional
anesthesia encounters in the first three years of life for patients who had
reached three years of age.
Demographic data were also recorded for the patients including
gestational age (GA) at delivery, GA at VAS placement, birth weight,
creatinine at 6 months and 1 year, and prenatal interventions (e.g.
vesicoamniotic shunting). Negative binomial modeling, the Fisher
exact test and Mann–Whitney test were used to assess relationship of
gestational age, birth weight, VAS, and LUTO stage with the rate of
anesthesia encounters.
2. Results
2.1. Demographics
During the study period, 31 patients were identified with a prenatal
LUTO diagnosis, and postnatal records were available for 21 patients,
seven in each stage. Only patients who survived past the first 24 h of
life were included. Of the five patients who died in-utero or within
24 h of life, two received shunts. The remaining five patients were lost
to follow-up with their mothers delivering at another hospital, and
three had received VAS. When comparing the three grades of LUTO se-
verity, there were no significant differences in maternal age, birth
weight, or gestational age at first shunt placement (Table 1). Maternal
age ranged from 16 to 38 years. The average gestational age at birth
was 35.9 ± 3.6 weeks. Average birth weight was 2.893 ± 0.830 kg.
Twelve of the 21 LUTO patients received at least one shunt (Table 1).
The average number of shunt placement procedures was 1.9 (1–5).
One stage II patient received fetal cystoscopy with fetal IM anesthesia.
2.2. Outcomes
The average number of postnatal anesthesia encounters in the first
year increased with increasing prenatal LUTO disease severity; 1.4, 2.3,
and 5.1, respectively (p = .10). (Table 2) The median number of anes-
thesia encounters was 1.0, 2.0, and 3.0 for stages I, II and III, respectively.
To discuss the total anesthesia encounters including the prenatal period
and the first twelve months after birth, we introduced the term infant
anesthesia encounters. There was a significant difference (p = 0.03)
in the number of infant anesthesia encounters when classified by
LUTO stage with an average of 1.6, 3.7, and 6.7 for stages I, II, and III, re-
spectively. The rate of infant anesthesia encounters for stage II and III
patients was 3.3 times higher than for stage I. Regarding the effect of
prenatal interventions on anesthesia events after birth, patients with
VAS underwent a mean of 2.8 postnatal anesthesia events versus 3.2
events in those without VAS. This difference did not reach statistical sig-
nificance (p = .97). All patients except one received fetal IM anesthesia
during VAS placement. For the exception, fetal anesthesia was not given
owing to early gestational age. Removal of VAS postnatally was com-
bined with other procedures or completed without anesthesia in all pa-
tients in this cohort. When looking at infant anesthesia encounters, the
average number of anesthesia encounters for patients receiving VAS
was 4.7 versus 3.2 for those without VAS (p = .28).
Serum creatinine was used as a surrogate for renal function. At one
year of life, average creatinine for stage I patients was 0.73 versus 1.62
and 1.64 for stage II and stage III patients respectively, although these
differences did not reach statistical significance.
Both GA and birth weight had significant effects on infant anesthesia
encounters. As GA increased by one week, the rate of anesthesia en-
counters decreased 13.2% (p = .005), with an estimated model of log
(μi) = 6.3 − 0.14*(gestational age), (p = .25). As birth weight in-
creased by .50 kg, the rate of prenatal and first year of life anesthesia

Table 1
Demographics.

Stage I Stage II Stage III P value

(n = 6) (n = 5) (n = 10)

Gestational Age at Birth (weeks) 38.0 + 1.4 33.9 + 3.3 35.7 + 4.5 .06
Birth Weight (kg) 3.329 + 5.3 2.493 + 9.4 2.859 + 8.6 .31
Maternal Age (years) 27.4 + 8.3 25.6 + 4.4 25.1 + 4.8 .87
Patients Receiving Shunts n=1 n=6 n=5 P value
Average Gestational Age at First Vesicoamniotic Shunt Placement (weeks) 19* 24.1 25.7 .70
Vesicoamniotic Shunt Without Shunt Placement P value
(n = 12) (n = 9)

Gestational Age at Birth (weeks) 34.3 (26.6–39.0) 37.9 (30.1–39.4) .24

Birth Weight (kg) 2.7 (1.3–3.7) 3.2 (1.7–4.2) .12
Maternal Age (years) 25.3 ± 4.6 27.0 ± 7.3 .91

Please cite this article as: Puttmann KT, et al, Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction, J
Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.06.033
 K.T. Puttmann et al. / Journal of Pediatric Surgery xxx (2018) xxx–xxx
Table 2
Average number of events or procedures occurring during the first year of life by LUTO stage. LUTO = Lower Urinary Tract Obstruction.
LUTO Stage Genitourinary Dialysis-related
(p = 1.0) (p = .38)
Stage I
Mild 1.1 0.3
n=6
Stage II
Severe 1.2 0.0
n=5
Stage III
Severe 2.6 2.3
n = 10
encounters decreased 10% (p = .04), log(μi) = 2.71 − 0.0005 ∗ weight.
Shunt placement did not have significant effects based on univariate
analysis.
Upon univariate analysis, LUTO stage demonstrated a significant
correlation with the number of anesthetic events postnatally while
gestational age at birth showed a statistically significant inverse rela-
tionship. The rate of postnatal anesthesia encounters for stage I is de-
creased 72% compared to stage III (p = .01). Gestational age was
associated with a decreased number of postnatal anesthesia events
(p = .03). As the gestational age increased by one week, the rate of post-
natal anesthesia encounters decreased by 12%. The estimated model
was log(μi) = 5.41 − 0.12*(gestational age) and was a good fit for the
data (p = .33).
2.3. Procedure breakdown
Sixty-two postnatal anesthesia events occurred for the entire cohort
in the first year of life. Nearly one quarter of these events included com-
bined operations for more than one organ system or indication. To ana-
lyze the distribution, procedures were classified into genitourinary,
gastrointestinal (GI), dialysis-related (including both hemodialysis and
peritoneal dialysis), abdominal wall hernia repair, and miscellaneous
categories. The most common type was genitourinary with 36 proce-
dures (58%). There were 20 for dialysis-related procedures, 8 GI, 9 her-
nia, and 6 miscellaneous (Fig. 1). Nineteen patients received cystoscopic
procedures (90.5%); 11 were transurethral posterior urethral valve
(PUV) ablations. For 8 patients (38%), the transurethral procedure was
their only anesthesia encounter in the first year. Five of these patients
received VAS prenatally. Concerning VAS removal, six patients had
shunt removal combined with another anesthesia event, two shunts
fell out before delivery, and two shunts were removed at the bedside
Fig. 1. Anesthesia events classified by type of procedure. Misc. =Miscellaneous.
Please cite this article as: Puttmann KT, et al, Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction, J
Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.06.033
3
Hernia Repair Gastrointestinal Miscellaneous
(p = .20) (p = .36) (p = .91)
0.0 0.1 0.1
0.2 0.0 0.7
1.0 0.9 0.1
without anesthesia. GI interventions were performed for feeding and
elimination difficulties (gastrostomy tube placement, anoscopy, and
proctoscopy). One patient in each LUTO stage cohort received a
gastrostomy tube except stage III; three stage III patients received a
gastrostomy tube. The miscellaneous procedures included PICC line, ar-
terial line, MRI imaging, liver biopsy, and bronchoscopy. Hernia repairs
were performed in 43% of stage III patients, 29% of stage II, and 0% of
stage I (p = .14). There were four umbilical repairs, four inguinal hernia
repairs, and one incisional hernia repair. When analyzed by stage, there
was a trend for more genitourinary, hemodialysis, and abdominal wall
hernia procedures seen in the stage III patients (p = .20).
Ten patients (48% of the cohort) were greater than three years old at
the time of the analysis. There were two stage I, four stage II, and four
stage III LUTO patients. Of these patients, five (50%) had no additional
anesthesia encounter after the first year. Three patients (33%) had
more anesthesia events in the second and third years of life when com-
pared to the first year of life, and two patients (20%) had fewer anesthe-
sia events after the first year of life (Fig. 2).
3. Discussion
3.1. Staging system
Studies of prenatal interventions for LUTO have seen a greater bene-
fit in patients with a poorer initial prognosis [3]. This finding encour-
aged the idea that, if properly stratified at the time of diagnosis,
physicians can determine which LUTO patients will benefit from an in-
tervention. The prenatal LUTO staging system combines ultrasound and
fetal urine chemistry to give a more accurate picture of disease severity
[6]. In our cohort, we showed that disease severity based on this staging
4 K.T. Puttmann et al. / Journal of Pediatric Surgery xxx (2018) xxx–xxx
Fig. 2. Anesthesia events in patients 3 years of age. Each column represents an individual patient.
system predicts the number of infant anesthesia events. LUTO severity
correlated directly with the number of procedures.
3.2. Anesthesia exposure
Fetuses with LUTO are exposed to intravenous and IM anesthetic
agents, which are implicated in the recent FDA anesthesia safety warn-
ing. This public service announcement was based on the possibility that
anesthesia exposure to the developing brain causes neuroapoptosis [7].
The editorial review by Patel suggested that after reaching a threshold
level of neuroapoptosis, behavioral changes can be seen despite causa-
tion not being demonstrated [8]. In a population-based cohort, one an-
esthesia encounter in the first year of life did not create appreciable risk
but after two or more encounters, the risk of learning disability in-
creased proportional to the exposure [9]. We sought to develop a clear
picture of the procedure requirements and anesthesia encounters in
this population. Based on the results of our study, expectant parents
with a prenatal LUTO diagnosis should be counseled on the likely med-
ical and surgical course of their child's condition, in light of the potential
risks of multiple anesthesia encounters. Furthermore, the effect of these
anesthetic agents on the fetal brain is unknown.
3.3. Prenatal interventions
A 2003 meta-analysis of LUTO studies concluded there was insuffi-
cient evidence to draw a definitive conclusion about the benefit of pre-
natal interventions [10]. However, more recent trials have described the
benefits of antenatal bladder drainage [11]. The 2013 percutaneous
shunting in LUTO (PLUTO) randomized controlled trial showed an 86%
probability that VAS improved survival at 28 days [11]. This is likely
owing to a decrease in pulmonary hypoplasia, the greatest cause of mor-
tality in LUTO patients [11,12]. This benefit must be balanced against the
possible need for multiple prenatal interventions and associated risks.
According to our findings, there is a trend toward decreased number
of postnatal interventions in shunted patients, which is balanced by an
increased amount of infant anesthesia encounters. Shunt placement re-
quires careful counseling as to possible risks and benefits.
3.4. Renal disease
The relevance of renal and urologic effects becomes more apparent
when studying LUTO patients who survive. Renal disease burden is sec-
ond only to pulmonary disease, with 28%–36% of patients with PUV re-
quiring dialysis during their lifetime and an additional 21% developing
renal insufficiency [13,14]. Despite the survival benefit of antenatal
Please cite this article as: Puttmann KT, et al, Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction, J
Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.06.033
bladder drainage, there remains a high risk of renal disease in the sur-
viving population. Furthermore, diversion does not necessarily abrogate
this risk from developmental dysplasia [3,15]. Looking at the histopa-
thology of the LUTO kidneys, a reduction in glomerular density and a de-
crease in cortical thickness were consistently seen [16]. Fetal urine
chemistries have often been used to evaluate renal function in utero
[3,17] by performing vesicocentesis to obtain two to three urine sam-
ples separated by several days [17].
Renal ultrasound is another tool to identify renal damage in prenatal
and neonatal patients. The microscopic changes of irreversible renal
damage correlate closely with renal hyperechogenicity in 95% of pa-
tients. Renal hyperechogenicity has a positive correlation with intersti-
tial fibrosis and decreased glomerular number [16,18]. In addition, a
strong relationship between long-term risk of ESRD in PUV patients
and renal parenchymal area as measured by ultrasound has been de-
scribed [19]. Our findings support the prenatal staging system of urine
chemistries and renal ultrasound as a predictor of renal function.
There is a trend of decreasing renal function with increased LUTO
stage severity, and a larger patient cohort would likely show a greater
difference between stage I patients and stage II & III patients.
3.5. Organ systems
The sequelae of fetal LUTO may affect many organ systems, and our
study considered additional contributing factors including infant gesta-
tional age and birth weight. Premature infants generally have delayed
physiologic and feeding milestones [20,21]. The risk for feeding difficul-
ties increases significantly for GA b 28 weeks [22], though the incidence
of gastrostomy tube (G-tube) placement in LUTO has not been previ-
ously examined. Our cohort saw high rates of feeding interventions
(primarily gastrostomy tubes) that increased with more severe LUTO.
Nearly a quarter of these interventions were combined with other pro-
cedures, which was critical to decreasing the number of anesthesia ex-
posures in this patient population. The complexity of care required
emphasizes the importance of managing these patients in a high acuity
care facility where multiple surgical specialties teams can collaborate on
care plans.
There were a high number of anesthesia events for dialysis-related
procedures in our cohort. Our data corroborated the prior association
of prematurity with renal morbidity: lower gestational age in the
LUTO patients was associated with a higher risk of multiple anesthesia
events for dialysis-related procedures [23].
Previous studies have shown an association with birth weight and
renal function [23]. Nephron number at birth is strongly linked with
low birth weight and prematurity, and can predict renal dysfunction
 K.T. Puttmann et al. / Journal of Pediatric Surgery xxx (2018) xxx–xxx
later in life [16,23,24]. All patients with congenital urinary tract obstruc-
tion have increased risk of renal disease progression after surgical cor-
rection of the obstruction [16]. In addition, previous studies have
demonstrated increased renal disease and healthcare utilization in pre-
term infants [25]. Our data agree: patients with low birth weight had a
significantly higher number of infant anesthetic events.
A closer inspection of the cohort showed an even distribution of gen-
itourinary procedures regardless of stage. Most patients underwent cys-
toscopy, although two patients had no interventions. By comparison,
increase in LUTO severity was associated with an increased number of
GI procedures, which primarily addressed feeding difficulties. Hernia re-
pairs were also more common in the stage III population. This is likely
owing to increased pressure from bladder dilatation weakening the ab-
dominal wall and thereby increasing the incidence of herniae.
There are several weaknesses of this study. Univariate negative bino-
mial modeling was used in this study because of the limited sample size.
Many patients received only one fetal chemistry, rather than the stan-
dard 3 measurements. In addition, we limited our follow-up of postnatal
anesthetic events to the first year of life, since this is the typical period
when LUTO interventions occur postnatally. The analysis was completed
retrospectively and there is the potential for attrition bias owing to mul-
tiple patients who were lost to follow up. Finally, it is beyond the scope
of this manuscript to differentiate the neurodevelopmental effects of
gestational age/prematurity from those of infant anesthesia encounters
secondary to GU pathology. Differentiating these effects would require
school age follow-up of these children and should be the goal of future
studies.
4. Conclusions
Most infants with prenatally diagnosed LUTO will undergo postnatal
procedures with general anesthesia exposure in the first year of life. Pa-
tients with increased LUTO severity experienced higher numbers of an-
esthesia events. Higher gestational age at birth was associated with
fewer anesthesia events in the first year. Increased LUTO disease sever-
ity was associated with an increased number of interventions for feed-
ing difficulties and hernia repairs in the first year of life.
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