Journal of Pediatric Surgery 50 (2015) 12451250

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Journal of Pediatric Surgery

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Original Articles

VACTERL associations in children undergoing surgery for esophageal

atresia and anorectal malformations: Implications for
pediatric surgeons,
Timothy B. Lautz a,, Ankur Mandelia a, Jayant Radhakrishnan b
a
Division of Pediatric Surgery, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA
b
University of Illinois College of Medicine, Chicago, IL USA

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

Article history: Purpose: The aim of this study was to compare the frequency and nature of VACTERL associations between
Received 6 August 2014 children who underwent surgery for esophageal atresia/tracheoesophageal stula (EA/TEF) and anorectal
Received in revised form 8 February 2015 malformation (ARM).
Accepted 14 February 2015 Methods: We identied all children who underwent surgery for EA/TEF and/or ARM at hospitals participating in
the Pediatric Health Information System (PHIS) database between 2004 and 2012. PHIS is an administrative
Key words:
database of free-standing children's hospitals managed by the Child Health Corporation of America (Overland
Trachea-esophageal stula
Esophageal atresia
Park, KS) that contains patient-level care data from 43 hospitals. The complete records of patients in this cohort
Anorectal malformation were cross-referenced for diagnoses of vertebral, cardiac, renal and limb anomalies.
VACTERL Results: 2689 children underwent repair of esophageal atresia. Mean gestational age was 36.5 3.2 weeks and
mean birth weight was 2536.0 758.7 g. Associated VACTERL diagnoses included vertebral anomaly in 686
(25.5%), ARM in 312 (11.6%), congenital heart disease in 1588 (59.1%), renal disease in 587 (21.8%) and limb de-
fect in 192 (7.1%). 899 (33.4%) had 3 or more anomalies and met criteria for a VACTERL diagnosis. 4962 children
underwent repair of ARM. Mean gestational age was 37.4 2.7 weeks and mean birth weight was 2895.2
765.1 g. Associated VACTERL diagnoses included vertebral anomaly in 1562 (31.5%), congenital heart disease
in 2007 (40.4%), EA/TEF in 348 (7.0%), renal disease in 1723 (34.7%) and limb defect in 359 (7.2%). 1795
(36.2%) had 3 or more anomalies and met criteria for a VACTERL diagnosis.
Conclusion: VACTERL associations are relatively common in children with EA/TEF and ARM and occur in specic
clusters, with cardiac disease more common in EA/TEF and spinal and renal/urinary anomalies more common
in ARM.
2015 Elsevier Inc. All rights reserved.

Anomalies of the spine or vertebrae (V), anorectal malformations (A),
congenital cardiac anomalies (C), esophageal atresia/tracheoesophageal
stula (TE), renal and urinary abnormalities (R), and limb lesions
(L) frequently occur together and are referred to as VACTERL anomalies.
This association was rst described by Quan and Smith in 1972 and 1973
[1,2], while the cardiac component was incorporated by Temtamy and
Miller in 1974. In more recent years, a number of publications from
single centers and birth defect registries have further delineated the pat-
terns and frequency of these associations [312]. However, the diagnostic
Funding source: There are no sources of funding to report for this study.
Financial disclosure: The authors have no nancial relationships relevant to this article
to disclose.
Corresponding author at: Division of Pediatric Surgery, Ann & Robert H. Lurie
Children's Hospital of Chicago, 225 E. Chicago Ave, Box 63, Chicago, IL 60611. Tel.: +1
312 227 4210.
E-mail address: tlautz@luriechildrens.org (T.B. Lautz).
criteria for VACTERL, the list of specic diagnoses included within this
spectrum, and the optimal evaluation of children born with one or more
apparent components remain debated [1315].
In the eld of pediatric surgery, VACTERL associations are encountered
most frequently in patients who require an operation for esophageal
atresia/tracheoesophageal stula (EA/TEF) or anorectal malformation
(ARM). Pediatric surgeons play an important role in counseling parents
of children with EA/TEF and ARM in the prenatal and early postnatal
periods. A prenatal diagnosis of EA/TEF can now be established in approxi-
mately 25% of cases [16]. Prenatal diagnosis of ARM, though still rare, is in-
creasingly possible, especially in high risk patients [17]. Comprehensive,
modern, multiinstitutional data on the frequency and signicance of
VACTERL associations in these patients can better inform these conversa-
tions and guide the patients' diagnostic evaluations. To this end, this
study was designed to compare the frequency of VACTERL anomalies
between patients with EA/TEF and ARM using a national database of
large children's hospitals and to determine predictors of mortality.

http://dx.doi.org/10.1016/j.jpedsurg.2015.02.049
0022-3468/ 2015 Elsevier Inc. All rights reserved.
1246 T.B. Lautz et al. / Journal of Pediatric Surgery 50 (2015) 12451250

1. Methods
We performed a retrospective cohort study to identify all patients
who underwent surgery for EA/TEF or ARM at hospitals participating
in the Pediatric Health Information System (PHIS) database between
2004 and 2012. PHIS is an administrative database of free-standing
children's hospitals managed by the Child Health Corporation of
America (Overland Park, KS) that contains patient-level care data. The
PHIS hospitals are 43 of the largest children's hospitals in America. The
participating hospitals are located in noncompeting markets in 27 states
and the District of Columbia. Participating hospitals provide patient-
level data including demographics, diagnoses, and procedures, as well
as billing data which includes all medication, diagnostic imaging, labo-
ratory, and supply charges. Data in PHIS are deidentied, but contain
an encrypted medical record number that allows tracking of individual
patients across multiple inpatient and outpatient encounters. In accor-
dance with PHIS policies, analysis was blinded to the identity of the hos-
pitals. The application of the PHIS database to important issues in the
eld of pediatric surgery has considerable precedent [18,19].
Patients were identied based on International Classication of Diseases
9th Revision (ICD-9) diagnosis codes for the various VACTERL anomalies
shown in Table 1. Inclusion in the study was limited to patients who
also had an ICD-9 procedure code indicative of surgery for EA/TEF
(31.73 or 42.89) or ARM (48.49, 49.79, 46.11, 46.10, 46.03, 46.13). All hos-
pital encounters for these patients were captured, regardless of whether a
VACTERL diagnosis was addressed during that encounter. Data were ag-
gregated across all encounters for a given patient to determine the total
number of visits (inpatient, emergency department, ambulatory surgery
or outpatient) and the range of time (and age) between those visits. Not
all types of encounters were captured for all hospitals in every year.
Table 1
ICD-9 codes used to identify VACTERL associations.
Demographic data and birth information (birth weight and gestational
age) were captured from the patient's earliest encounter. Birth weight
and gestational age were generally only available for patients whose
rst admission was in the neonatal period. The median age at rst
encounter was 0 days (interquartile range 1 day) for those with a
birthweight reported compared to 151 days (interquartile range
454 days) for those whose birth weight was not recorded. Race was sum-
marized as white, black, Asian, and other/unknown. The complete records
of patients in this cohort were searched for ICD-9 diagnosis codes indica-
tive of the other VACTERL anomalies listed in Table 1.
Selection of the exact diagnoses meeting criteria for inclusion as a
VACTERL association was based on review of prior literature. The verte-
bral category was broadened to include both bony vertebral anomalies
and spinal dysraphisms [7,20]. The anorectal malformations category
was limited to atresia of the rectum and not expanded to include other in-
testinal atresias as has been suggested by some [7]. For purposes of com-
paring to other studies, these more proximal gastrointestinal atresias
were reported separately. Cardiac defects included major structural
anomalies of the heart, but not a patent ductus arteriosus or noncardiac
aortic anomalies. The renal anomalies category was broadened to in-
clude all renal and internal urinary anomalies but not external defects
such as hypospadias. Finally the limb anomalies included both upper
and lower extremity reduction deformities, polydactyly and syndactyly.
The study was approved with exempt status by the Institutional Re-
view Board of the Ann & Robert H. Lurie Children's Hospital of Chicago
(#2013-15531). Statistical analysis was performed using IBM SPSS Sta-
tistics v20. Q-Q plots were examined to determine variation from a nor-
mal distribution in this large sample. Variables with a clear nonnormal
distribution were reported as a median (interquartile range [IQR]). Other-
wise, continuous variables were reported as a mean standard devia-
tion. A logistic regression was performed to identify factors associated
with mortality. For all analyses, statistical signicance was set at a two-
tailed p b 0.01 because of the large sample size.

Spinal and vertebral anomalies 2. Results

Congenital absence of vertebra 756.13
Hemivertebra 756.14 2.1. Esophageal atresia/tracheoesophageal stula
Spina bida 741.X
Tethered cord 742.59
Absent rib 756.3
2689 children underwent repair of EA/TEF. Demographics are shown
Congenital vertebral fusion 756.15 in Table 2. The majority of patients (n = 1429, 53.1%) were admitted to
Other 756.10, 756.19 their respective PHIS hospital on the day of birth, while 708 (26.3%), 113
Anal atresia 751.2 (4.2%), and 48 (1.8%) were admitted/transferred on the 1st, 2nd, and
Cardiac anomalies
3rd days of life, respectively. For the remaining 391 (14.5%) patients,
ASD 745.5
VSD 745.4 the rst admission was at a later age. Mean gestational age was
Tetralogy of Fallot 745.2 36.5 3.2 weeks among the 1649 (61.3%) patients in whom it was
Anomalies of the great veins 747.4X
Transposition of the great vessels 745.1X
Congenital anomalies of the aorta 747.2X Table 2
Truncus arteriosis 745.0 Patient demographics.
Hypoplastic left heart 746.7
EA/TEF ARM
Endocardial cushion defect 745.6X
Common ventricle 745.3 Gender
Other 745.8, 745.9 Male 55.4% 54.0%
Esophageal atresia 750.3 Female 44.6% 46.0%
Renal anomalies Race
Agenesis/dysgenesis 753.0 Caucasian 67.9% 62.5%
Obstructive uropathy 753.2 African-American 9.6% 12.0%
Vesicoureteral reux 593.7X Asian 1.3% 3.8%
Dysplastic kidney 753.15 Other 16.5% 16.5%
Posterior urethral valves 753.6 Unknown 4.6% 5.1%
Other 753.3, 753.4 Ethnicity
Limb deformities Hispanic 15.8% 19.4%
Reduction deformity upper limb 755.2X Not Hispanic 36.0% 28.9%
Reduction deformity lower limb 755.3X Unknown 48.2% 51.6%
Polydactyly 755.0X Birth weight (mean SD) 2536.0 758.7 g 2895.2 765.1 g
Syndactyly 755.1X (n = 2287) (n = 3267)
Other anomalies Gestational age (mean SD) 36.5 3.2 weeks 37.4 2.7 weeks
Trisomy 21 758.0 (n = 1649) (n = 2443)
Single umbilical artery 747.5 Hospital encounters, median 4 (IQR 8) 4 (IQR 7)
Duodenal atresia 751.1 (interquartile range)
 T.B. Lautz et al. / Journal of Pediatric Surgery 50 (2015) 12451250 1247

reported. Gestational age was between 24 and 29 weeks in 57 (3.5%),
between 30 and 36 weeks in 632 (38.3%), and between 37 and
42 weeks in 960 (58.2%).
Associated VACTERL diagnoses included spinal or vertebral anomaly
in 683 (25.4%), ARM in 312 (11.6%), congenital heart disease in 1588
(59.1%), renal or internal urinary disease in 587 (21.8%) and limb defect
in 171 (6.4%). Details of these associated diagnoses are shown in Table 3.
Associated procedures for these VACTERL diagnoses were performed at
the respective PHIS hospital in 218 (8.1%) patients with ARM and 372
(13.8%) with cardiac disease.
Eight hundred and ninety-two patients (33.2%) had 3 or more
anomalies and met criteria for a VACTERL diagnosis. Overall, 760
(28.3%) had isolated EA/TEF while 1037 (38.6%) had two total anoma-
lies, 528 (19.6%) had three, 235 (8.7%) had four, 102 (3.8%) had ve,
and 27 (1.0%) had all six categories of VACTERL anomalies.
Other conditions included trisomy 21 in 89 (3.3%), single umbilical
artery in 78 (2.9%), and duodenal atresia in 127 (4.7%).
2.2. Anorectal malformation
4962 children underwent repair of ARM. The majority of patients
(n = 1980, 39.9%) were admitted to their respective PHIS hospital on
the day of birth, while 937 (18.9%), 231 (4.7%), and 53 (1.1%) were ad-
mitted/transferred on the 1st, 2nd, and 3rd days of life, respectively. For
the remaining 1761 (35.5%) patients, the rst admission was at an older
age. Mean gestational age was 37.4 2.7 weeks among the 2443
(49.2%) patients in whom it was reported. Gestational age was between
23 and 29 weeks in 45 (1.8%), between 30 and 36 weeks in 653 (26.7%),
and between 37 and 42 weeks in 1745 (71.4%).
Associated VACTERL diagnoses included spinal or vertebral anomaly
in 1558 (31.4%), congenital heart disease in 2007 (40.4%), EA/TEF in 348
(7.0%), renal or internal urinary disease in 1723 (34.7%) and limb defect
in 280 (5.6%). Details of these associated diagnoses are shown in Table 4.
Associated procedures for these VACTERL diagnoses were performed at
the respective PHIS hospital in 218 (4.4%) patients with EA/TEF and 404
(8.1%) with cardiac disease.
1774 (35.8%) had 3 or more anomalies and met criteria for a
VACTERL diagnosis. Overall, 1802 (36.3%) had isolated anal atresia
while 1386 (27.9%) had two total anomalies, 1000 (20.2%) had three,
593 (12.0%) had four, 154 (3.1%) had ve, and 27 (0.5%) had all six cat-
egories of VACTERL anomalies.
Other conditions included trisomy 21 in 245 (4.9%), single umbilical
artery in 100 (2.0%), and duodenal atresia in 176 (3.5%).
2.3. Comparison of EA/TEF and arm cohorts
The frequency of VACTERL associations was compared between the
EA/TEF and ARM groups. Cardiac disease, with or without an association
operation, was more common in the EA/TEF cohort (p b 0.0001 both for
diagnosis and for diagnosis with or without an associated surgery).
Spinal or vertebral anomalies in general, and the specic diagnosis of
tethered cord, spina bida, and absent vertebra were all more common
in the ARM group (p b 0.001). An absent rib was more common in EA/
TEF (p b 0.001). Renal and internal urinary anomalies as a whole, as
well as the specic diagnoses of agenesis/dysgenesis, obstructive
uropathy, VUR, dysplastic kidney, and posterior urethral valve were all
more common in the ARM group (all p b 0.001). Limb anomalies in ge-
neral were equally distributed between the two cohorts (p = 0.20),

Table 4
Table 3 VACTERL associations in patients undergoing repair of anorectal malformation (n = 4962).
VACTERL associations in patients undergoing repair of EA/TEF(n = 2689).
Diagnosis Diagnosis and
Diagnosis Diagnosis and surgerya surgerya

Spinal and vertebral anomalies 683 (25.4%) n/a Spinal and vertebral anomalies 1558 (31.4%) n/a
Congenital absence of vertebra 31 (1.2%) Congenital absence of vertebra 216 (4.4%)
Hemivertebra 139 (5.2%) Hemivertebra 196 (4.0%)
Spina bida 32 (1.2%) Spina bida 211 (4.3%)
Tethered cord 223 (8.3%) Tethered cord 897 (18.1%)
Absent rib 172 (6.4%) Absent rib 192 (3.9%)
Congenital vertebral fusion 26 (1.0%) Congenital vertebral fusion 48 (1.0%)
Other 369 (13.7%) Other 752 (15.2%)
Anorectal malformation 312 (11.6%) 218 (8.1%) Cardiac disease 2007 (40.4%) 404 (8.1%)
Cardiac disease 1588 (59.1%) 372 (13.8%) ASD 1674 (33.7%) 303 (6.1%)
ASD 1252 (46.6%) 267 (9.9%) VSD 675 (13.6%) 248 (5.0%)
VSD 569 (21.2%) 211 (7.8%) Tetralogy of Fallot 148 (3.0%) 111 (2.2%)
Tetralogy of Fallot 164 (6.1%) 119 (4.4%) Anomalies of the great veins 152 (3.1%) 78 (1.6%)
Anomalies of the great veins 124 (4.6%) 59 (2.2%) Transposition of the great vessels 86 (1.7%) 67 (1.4%)
Transposition of the great vessels 86 (3.2%) 70 (2.6%) Congenital anomalies of the aorta 105 (2.1%) 57 (1.1%)
Congenital anomalies of the aorta 151 (5.6%) 59 (2.2%) Truncus arteriosis 28 (0.6%) 23 (0.5%)
Truncus arteriosis 24 (0.9%) 20 (0.7%) Hypoplastic left heart 35 (0.7%) 29 (0.6%)
Hypoplastic left heart 29 (1.1%) 24 (0.9%) Endocardial cushion defect 69 (1.4%) 43 (0.9%)
Endocardial cushion defect 66 (2.5%) 50 (1.9%) Common ventricle 18 (0.4%) 15 (0.3%)
Common ventricle 21 (0.8%) 18 (0.7%) Other 4 (0.1%) n/a
Other 6 (0.2%) 2 (0.1%) Esophageal atresia/tracheoesophageal stula 348 (7.0%) 218 (4.4%)
Renal anomalies 587 (21.8%) n/a Renal anomalies 1723 (34.7%)
Agenesis/dysgenesis 129 (4.8%) Agenesis/dysgenesis 466 (9.4%)
Obstructive uropathy 254 (9.4%) Obstructive uropathy 756 (15.2%)
Vesicoureteral reux 212 (7.9%) Vesicoureteral reux 794 (16.0%) n/a
Dysplastic kidney 65 (2.4%) Dysplastic kidney 229 (4.6%)
Posterior urethral valves 22 (0.8%) Posterior urethral valves 107 (2.2%)
Other 191 (7.1%) Other 496 (10.0%)
Limb deformities 171 (6.4%) n/a Limb deformities 280 (5.6%) n/a
Reduction deformity upper limb 107 (4.0%) Reduction deformity upper limb 115 (2.3%)
Reduction deformity lower limb 15 (0.6%) Reduction deformity lower limb 50 (1.0%)
Polydactyly 43 (1.6%) Polydactyly 107 (2.2%)
Syndactyly 22 (0.8%) Syndactyly 58 (1.2%)
Other anomalies n/a Other anomalies 245 (4.9%) n/a
Trisomy 21 89 (3.3%) Trisomy 21 100 (2.0%)
Single umbilical artery 78 (2.9%) Single umbilical artery 176 (3.5%)
Duodenal atresia 127 (4.7%) Duodenal atresia
a a
Captures surgery at the same institution only. Captures surgery at the same institution only.
1248 T.B. Lautz et al. / Journal of Pediatric Surgery 50 (2015) 12451250

Table 5 children born with these anomalies, but also for prenatal and postnatal
Predictors of mortality among patients with EA/TEF or ARM. counseling of their parents. It is essential for pediatric surgeons, obste-
Odds ratio (95% condence interval) p tricians and pediatricians to have current data on the frequency and na-
Gender 0.27
ture of these associations, derived from a diverse and generalizable
Male 1.0 patient population, to facilitate optimal management and counseling.
Female 0.87 (0.681.11) We analyzed more than 2500 children with EA/TEF and nearly 5000
Race b0.001 with ARM managed at large children's hospitals across the USA. Based
White 1.0
on weighted estimates from the Kids' Inpatient Database, there were
Black 2.04 (1.462.86)
Asian 1.78 (0.923.47) an estimated 1254 children born with EA/TEF and 1937 with ARM in
Other/unknown 1.24 (0.921.66) the year 2009, which corresponds to approximately 10,000 cases of
Ethnicity EA/TEF and 15,500 cases of ARM over an 8 year period [21]. Therefore,
Hispanic 1.0 the current cohort captured a signicant fracture of children with
Not-Hispanic 0.80 (0.551.16)
these conditions during this period, and these data represent some of
Unknown 1.20 (0.861.68) 0.017
Birthweight b0.001 the most current and comprehensive information on the frequency of
b2.0 kg 3.15 (1.825.48) VACTERL associations.
N2.0 kg 0.89 (0.521.52) Modern descriptions of the frequency of VACTERL associations in
Unknown 1.0
children with EA/TEF and ARM have largely come from single institu-
First admission to PHIS hospital b0.001
30 days of life 4.50 (2.139.51) tional reports with differing criteria, making comparisons difcult
N30 days of life 1.0 [5,7,22,23]. For children with EA/TEF, the frequency of associated anom-
TEFa 1.39 (0.802.42) 0.25 alies identied in the current study was similar to those reported by
ARMa 1.15 (0.662.00) 0.64 Quan and Smith in their initial description, by Keckler et al in a review
Vertebral or spinal anomalyb 0.72 (0.540.95) 0.02
of 112 patients, as well as Brown et al who contacted 579 families of
Cardiac disease b0.001
None 1.0 children with EA/TEF from two support groups (Table 6) [2,7,24]. Re-
Diagnosis without surgery 1.97 (1.462.65) sults are also similar to those reported by Pedersen et al in an analysis
Diagnosis and surgery 5.77 (4.148.03) of a large European birth defects registry [25]. The higher frequency of
Renal/urinary anomalyb 1.12 (0.851.47) 0.42
renal/urinary conditions in the current study is likely related to the
Limb anomalyb 1.53 (1.022.30) 0.04
fact that other analyses did not all include nonrenal internal urinary
a
Diagnosis and procedure. anomalies in their categorization. There is still considerable debate
b
Diagnosis only.
over whether functional conditions such as VUR should be included
although reduction deformity of the upper limb was more common in with structural conditions such as renal agenesis. Likewise, the higher
the EA/TEF group (p b 0.001). Trisomy 21 was more common in the rate of cardiac anomalies in this study may relate to the broad denition
ARM group (p = 0.001). There was no clinical or statistical difference used, the long duration of follow-up available beyond the neonatal
in the frequency of a VACTERL diagnosis between the EA/TEF (33.2%) period for many patients in PHIS, and/or the inclusion of patients with
and ARM (35.8%) groups (p = 0.024). a diagnosis of a small ASD or VSD that didn't require intervention. Simi-
Inpatient mortality during any encounter was 6.1% among patients larly, for those children with ARM, the frequency of associated VACTERL
with EA/TEF and 3.3% among patients with ARM (p b 0.001). Mortality anomalies is comparable to those reported by Quan and Smith, as well
was driven by comorbid conditions, especially congenital heart disease. as Cho et al in an analysis of 103 patients at three medical centers in a
Taken together, mortality was 1.3% with isolated EA/TEF or ARM, 5.3% single city, de Blaauw et al in a registry analysis of 203 ARM patients,
with 2 conditions, 6.0% with 3 conditions, 5.8% with 4 conditions, 6.7% and Rittler et al in a study of 887 children (Table 7) [2,5,8,12]. Diffe-
with 5 conditions and 7.9% with all 6 conditions. Most notably, mortality rences in the rates of renal/urinary and cardiac anomalies again likely
was 3.2% for those who did not undergo cardiac surgery compared to relate to variable inclusion criteria. Internal urinary anomalies were in-
13.5% for those who had a cardiac operation. Predictors of mortality cluded by Rittler but not de Blaauw, while Cho also included external
were assessed in a multivariate logistic regression analysis as shown genitourinary anomalies.
in Table 5. Independent predictors of mortality included black race, Iuchtman et al in 1992 demonstrated that mortality is worse in
birthweight b 2 kg, congenital heart disease (greater for those who re- babies with multiple VACTERL anomalies and often related to their car-
quired cardiac surgery than in those with a diagnosis but no operation). diac condition and very low birth weight [26]. However, at the time of
Patients whose rst encounter at the PHIS hospital was in the rst their study in the late 1980s, the mortality rate for these patients was
month of life also had a higher mortality, likely because those who much higher (24%). Nonetheless, the trends were reproduced in the
were seen at a later age were a self-selected population who came for current study. Mortality was signicantly higher in patients with EA/
an elective operation later in life. TEF compared to ARM, but this was driven by the comorbid conditions,
especially congenital heart disease requiring surgery, but also low birth
3. Discussion weight and black race.
It has been proposed that the VACTERL associations actually occur in
The associations between EA/TEF, ARM and other VACTERL diagno- specic clusters [6,9]. Kallen et al identied upper and lower groups [6].
ses have important implications not only for the management of The upper group includes a cluster of EA/TEF, cardiac defects, upper

Table 6
Frequency of VACTERL associations in children with TEF.

Quan and Smith [2] Brown et al [22] Keckler et al [7] Brosens et al [11] Pedersen et al [25] Current study
(n = 19) (n = 579) (n = 112) (n = 582) (n = 1222) (n = 2689)

Spinal and vertebral 23% 17% 24% 21% 25%

Anorectal 10% 12% 14% 14% 16% 12%
Cardiac 20% 32% 27% 29% 59%
Renal and internal 16% 17% 16% 16% 22%
urinary
Limb 7% 10% 16% 12% 13% 6%
 T.B. Lautz et al. / Journal of Pediatric Surgery 50 (2015) 12451250
Table 7
Frequency of VACTERL associations in children with ARM.
Quan and Smith [2] (n = 19) Cho et al [5] (n = 103)
Spinal and vertebral 27% 9%
Cardiac 27%
EA/TEF 7% 11%
Renal and internal urinary 49%
Limb 5% 4%
costovertebral defects and upper preaxial limb reduction defects. In
contrast, the lower group includes ARM and kidney malformations, as
well as EA/TEF but not cardiac anomalies or upper limb reduction de-
fects. These groupings were generally supported by our data. Cardiac
conditions were diagnosed in 59.1% of neonates with EA/TEF compared
to 40.4% of those with ARM, and required operation in 13.8% and 8.1%,
respectively. While an echocardiogram is advised for all of these pa-
tients in the neonatal period, parents can be advised that the likelihood
of signicant ndings is higher in the EA/TEF group. Likewise, as de-
scribed above, these cardiac comorbidities drive the higher mortality
in the upper group.
Conversely, renal and internal urinary anomalies occurred in 34.7%
with ARM compared to only 21.8% with EA/TEF. Importantly, among
the ARM group, vesicoureteral reux was the most common renal/urinary
anomaly, occurring in 16.0% compared to obstructive uropathy in 15.2%
and renal agenesis/dysgenesis in 9.4%. Prior reports have demonstrated
previously high frequencies of vesicoureteral reux among children with
ARM. For instance, Nah et al reported a rate of 12% in a cohort of 99 neo-
nates with ARM [20]. While renal ultrasound to screen for structural
anomalies is widely performed as a screening tool in any neonate with a
VACTERL condition, voiding cystourethrogram (VCUG) to assess for reux
is utilized less frequently. Given the frequency of reux in neonates with
ARM, combined with recent data showing that ultrasound is a poor
screening test for this condition [27], VCUG must be considered an impor-
tant screening tool in this population. Recommendations for screening
have been described elsewhere. Based on an analysis of renal and urinary
anomalies in 331 children born with ARM, Goossens et al recommended
performing ultrasonography in all patients but reserving VCUG for
patients with dilated upper urinary tracts, lumbosacral and spinal abnor-
malities or recurrent urinary tract infections [28]. Similarly, in an older
study, Boemers et al recommended reserving VCUG for patients with
hydronephrosis and those without a perineal stula [13].
Tethered cord occurred in 18% of patients in this study with ARM. In
a prior review of 99 patients with ARM, Nah et al found that tethered
cord was the most common spinal anomaly, occurring in 20% of patients
[20]. Tethered cord was seen in patients with all types of ARM. Further-
more, Kim et al found that the rate of tethered cord correlated with the
level of the ARM [29]. The frequency of tethered cord was 9% with per-
ineal stula, 13% with vestibular stula, 25% with rectouretheral stula,
27% with rectovesicular stula, and 47% with cloacal anomaly. In that
study, the frequency of tethered cord correlated with the sacral ratio,
and a cutoff of b 0.6 was an optimal cutoff for predicting the need for
MRI. Lumbar ultrasound is also frequently used as a screening tool for
tethered cord and other occult spinal dysraphisms. While abnormal
ndings on lumbar US have good specicity, the sensitivity of this
study is poor [24]. Because ultrasound is an imperfect screening tool
for tethered cord, MRI screening should be performed liberally in chil-
dren with ARM, especially those with sacral ratio b 0.6 and high imper-
forate anus.
While beneting from the large patient cohort drawn from many in-
stitutions, the current study does have several important limitations.
Because of the large sample size, even small differences between the
EA/TEF and ARM cohorts were statistically signicant. This was partially
addressed by utilizing a stricter denition of statistical signicance
(p b 0.01). Nonetheless, differences between the cohorts should be
1249
Rittler et al [8] (n = 524) de Blaauw et al [12] (n = 203) Current study (n = 4962)
20% 18% spinal 31%
18% vertebral
16% 31% 40%
20% 9% 7%
21% 29% 35%
11% 7% upper 6%
11% lower
considered based on both clinically signicant and statistically signi-
cant differences. Furthermore, our analysis was based on ICD-9 diagno-
sis codes and thus was limited in specicity. For example these codes
could not be used to distinguish the type of stula in neonates with
EA/TEF nor the level of the stula in ARM. It has been demonstrated
that the frequency of associations is different in children with low ver-
sus high lesions and these differences may be further dened in the fu-
ture [5,28]. In addition, we could not distinguish children with VACTERL
association from those with the same anomalies owing to an underlying
genetic disorder such as CHARGE syndrome or Fanconi anemia. This
limitation may have resulted in an overestimation of the frequency of
the VACTERL association in these patients. The analysis was also limited
by the availability of birthweight and gestational ages in the database.
These data were generally only available for those patients whose rst
encounter at a PHIS hospital was in the rst few days of life. Finally,
while PHIS allows for tracking of the cohort of patients across multiple
encounters at the same hospital, it does not capture diagnoses made
or operations performed at other hospitals (including other PHIS hospi-
tals). As such, the frequency of associations, especially those not neces-
sarily made during the index hospitalization (such as vesicoureteral
reux) is expected to be underestimated.
In conclusion, the data reported herein represent a comprehensive
and generalizable description of the frequencies of VACTERL associa-
tions in children with EA/TEF and ARM. They are a valuable resource
for guiding the assessment of children born with one of these conditions
and for performing prenatal and postnatal counseling of parents. At that
present time, comprehensive guidelines for the assessment of children
with suspected VACTERL association are available which include para-
meters for initial evaluation in all cases and selective subsequent inves-
tigation [14]. With further insight into the patterns of the VACTERL
associations, it may be possible to optimize the initial evaluation of
these patients based on the presenting diagnoses.
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