Pediatric Surgery International

https://doi.org/10.1007/s00383-018-4363-9

ORIGINAL ARTICLE

Epidemiology of Hirschsprung disease in California from 1995 to 2013

Jamie E. Anderson1 · Melissa A. Vanover1 · Payam Saadai1 · Rebecca A. Stark1 · Jacob T. Stephenson1 ·
Shinjiro Hirose1

Accepted: 9 October 2018

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
Purpose  This study seeks to update current epidemiology of Hirschsprung disease (HD) in California.
Methods  Using data from the California Office of Statewide Health Planning and Development Linked Birth (1995–2012)
and Patient Discharge Databases (1995–2013), patients from either dataset with an ICD-9 diagnosis code of HD (751.3) or
procedure code of Soave (48.41), Duhamel (48.65), or Swenson/other pull-through (48.49) were included. Patients > age 18
during their first admission were excluded.
Results  Of 9.3 million births, 2,464 patients were identified. Incidence was 2.2 cases/10,000 live births, with rates peak-
ing at 2.9/10,000 births in 2002. Incidence was highest among African American (4.1/10,000) and Asian/Pacific Islander
(2.5/10,000) births. Most were male (n = 1652, 67.1%). Sixty patients (2.4%) had Down syndrome. The median gestational
age at birth was 38 weeks 6 days (interquartile range [IQR] 37 weeks 1 day–40 weeks 1 day). Mortality during the first year
of life was 1.7%. Median age at death was 14.5 days (IQR 0–113 days).
Conclusion  This is one of the largest population-based studies of HD. In California, the incidence of HD is stable, risk is
highest among African American children, and the mortality rate is < 2%.

Keywords  Hirschsprung disease · Incidence · Epidemiology · California

Background studies report incidence rates from the 1960s–1990s, with

The incidence of Hirschsprung disease (HD) is typically
reported between 1 and 2 cases per 10,000 live births world-
wide (Table 1) [1–14]. However, few studies have examined
the epidemiology of HD in the US [1–3]. Furthermore, most
only a few examining data after the year 2000 [3, 4, 6–9,
11, 13].
Using a population database in California, one of the larg-
est and most diverse states in the US, this study seeks to
update current epidemiology of HD in this population.

* Jamie E. Anderson Methods

jeanderson@ucdavis.edu
Melissa A. Vanover This is a retrospective observational population analy-
mvanover@ucdavis.edu sis using data from the California Office of Statewide
Payam Saadai Health Planning and Development Linked Birth (Janu-
psaadai@ucdavis.edu ary 1995–December 2012) and Patient Discharge Data-
Rebecca A. Stark bases (January 1995–December 2013). The Linked Birth
rstark@ucdavis.edu database includes information on all births in California,
Jacob T. Stephenson including infant birth records and readmissions within
jstephenson@ucdavis.edu 1 year, as well as maternal antepartum and postpartum
Shinjiro Hirose hospital records. It links information from the following
shirose@ucdavis.edu datasets: California Patient Discharge Data, Vital Statistics
1
Division of Pediatric General, Thoracic, and Fetal Surgery,
Birth/Death Certificate Data, Vital Statistics Fetal Death
University of California, Davis Medical Center, 2215 Data, and Vital Statistics Birth Cohort File. The Patient
Stockton Boulevard, OP512, Sacramento, CA 95817, USA

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Table 1  Incidence of Hirschsprung disease as published in the literature

Geography Years Incidence per 10,000 live births Cases References

California 1983–1992 1.4 (White: 1.4; Hispanic: 1.0; Black 314 [1]
2.0; Asian 2.8)
Baltimore County, Maryland 1969–1977 1.9 33 [2]
Utah 1970–2011 2.3 404 [3]
Federated States of Micronesia 1994–2002 3.1 9 [4]
British Columbia 1964–1982 2.3 156 [5]
Ontario 1991–2013 2.1 679 [6]
Europe 1980–2009 1.1 1322 [7]
UK/Ireland Oct 2010–Sep 2012 1.8 305 [8]
North of England, UK 1990–2008 1.6 105 [9]
Denmark 1960–1980 1.4 207 [10]
Japan 1978–1982; 1988–1992; 1.8–2.1 4939 [11]
1998–2002; 2008–2012
Japan 1978–1982 2.1 1628 [12]
Taiwan 1998–2010 2.2 629 [13]
Oman 1989–1994 3.3 85 [14]

Discharge Database (PDD) includes information from all Results

patient care episodes at nonfederal California-licensed
hospitals. It includes demographic data, diagnosis and
procedure codes for all inpatient discharges.
Cases were identified as patients (from either dataset)
with an ICD-9 diagnosis code of HD (751.3) or procedure
code of Soave submucosal resection of rectum (48.41),
Duhamel (48.65), or Swenson/other pull-through (48.49).
Patients in the PDD are limited to patients with social
security numbers. Although social security numbers were
not identified in this database, they were used to create
scrambled unique patient identifiers to link hospitalization
encounters over time and ensure patients were uniquely
captured. Patients from the Linked Birth dataset were
matched to their PDD encounters using birth date and zip
code to create a longitudinal dataset of hospitalizations
from each patient’s birth encounter.
Patients over the age of 18  years during their first
admission were excluded.
A subset analysis was performed among patients solely
identified from the Linked Birth dataset, comparing birth
characteristics of patients with HD to patients without HD
(Chi-squared and Student’s t tests).
Statistical analysis was performed using Stata/SE ver-
sion 14.2 (StataCorp, College Station, TX). This study
was approved by the UC Davis Institutional Review Board
and the California Committee for the Protection of Human
Subjects.
From 1995 to 2013, a total of 2464 cases of HD were
identified during inpatient hospitalizations in California.
Of 9.3 million births in California from 1995 to 2012,
2,063 patients with HD were born. The overall incidence
of HD was 2.21 cases per 10,000 live births, with rates
peaking at 2.94/10,000 births in 2002 (Fig. 1).
Incidence varied by race, with the highest rates seen
among black/African American children at 4.05 cases per
10,000 live births, Asian/Pacific Islander children at 2.45
cases per 10,000 live births, and other racial groups at
2.63 cases per 10,000 live births, compared to 1.89 cases
per 10,000 live births among white/Caucasian children
(Fig. 2). By ethnicity, higher rates were found in non-
Hispanic populations (2.42 cases per 10,000 live births)
compared to Hispanic populations (2.03 cases per 10,000
live births).
Over two-thirds of patients with HD were male (n = 1652,
67.1%; Table 2). Sixty patients (2.4%) had Down syndrome.
During the study period, 42 patients died (1.7%). Two of
these patients (4.8%) had Down syndrome. Among patients
with HD, there was no statistically significance in the mor-
tality rate among patients with Down syndrome compared
to those without Down syndrome (3.3% vs. 1.7%, p = 0.324).
Median age at death was 14.5 days (IQR 0–113 days) and all
deaths occurred within the first year of life.

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Pediatric Surgery International

Fig. 1  Incidence of HD in Cali- 4
fornia, 1995–2012
3.5

Cases per 10,000 Births

2.5

1.5

0.5

Year

Fig. 2  Incidence of HD by race 4.5

and ethnicity

3.5
Cases per 10,000 Births

2.5

1.5

1
Caucasian African Asian/Pacific Other Non-Hispanic Hispanic
American Islander

Birth characteristics Discussion

The median gestational age in patients with HD was 38
weeks 6 days (IQR 37 weeks 1 day–40 weeks 1 day). The
mean gestational age was 6 days younger in patients with
HD than those without HD (38 weeks 2 days vs. 39 weeks
1 day, p < 0.001), and a higher proportion of patients with
HD were born pre-term (< 37 weeks; 20.1% vs. 9.2%,
p < 0.001, Table 3). A higher proportion of patients with
HD were low birthweight (< 2500 g) compared to patients
without HD (15.1% vs. 5.5%, p < 0.001). Mothers of patients
with HD were slightly older than mothers of patients without
HD (28.8 years vs. 28.0 years, p < 0.001). Patients with HD
were not more likely to be the first and only child (single
parity) than patients without HD (p = 0.050).
This is one of the largest population-based studies of the
epidemiology of HD in the US. In California from 1995 to
2012, the incidence of HD was 2.2 cases per 10,000 births,
has been relatively stable, and was higher among black/Afri-
can American children and Asian/Pacific Islander children.
Incidence was also higher among non-Hispanic vs. Hispanic
patients.
Our findings of differences in incidence by race are
similar to a previous study in California from 1983 to
1992, which reported an overall incidence of 1.41 cases
per 10,000 births, with incidence rates higher among
black and Asian populations (2.0 and 2.8 cases per 10,000
live births, respectively) compared to white or Hispanic

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Table 2  Patient population similar to the mortality rate published in other studies

Total (n = 2464 ) a (2.4% in Japan [11], 3.0% in Sweden [17], 1.2% in Utah
[3]).
Female, n (%) 812 (33.0)
Race, n (%)
 White 1374 (55.6) Limitations
 Black 266 (11.0)
 Asian/Pacific Islander 261 (10.8) The primary limitation is that the California Office of State-
 Other 526 (21.7) wide Health Planning and Development databases use hos-
Hispanic ethnicity, n (%) 994 (41.0) pital discharge data and thus rely on accurate physician chart
Down syndrome, n (%) 60 (2.4) documentation and coding to correctly identify cases of HD
Insurance, n (%) and procedures. Although there is a distinct ICD-9 diagno-
 Government (MediCare, MediCal, etc.) 1069 (67.4) sis code for HD, the ICD-9 procedure codes for HD-related
 Private 500 (31.5) procedures are not always uniquely distinct; for example,
 Self-pay 18 (1.1) pull-through resections of the rectum could be for diseases
Died, n (%) 42 (1.7) other than HD.
a
 Numbers may not total 2464 in cases where there are missing data
In an attempt to identify the most accurate number of
true-positive cases, cases were identified by either a diagno-
sis of HD or one of the three most common HD procedures:
populations (1.4 and 1.0 cases per 10,000 live births) [1]. Soave, Duhamel or Swenson. Due to the ambiguity with
We found an overall higher incidence of HD; while we did coding these procedures, false-positive cases may have been
not find an increase in incidence during our study period, included. Alternatively, cases in which a separate procedure
there may be a gradual increase in incidence over time in was performed and a diagnosis of HD was not in the record
California. may have been missed. Furthermore, the diagnosis of HD
We found that 2.4% of patients with HD had Down syn- does not give any indication as to the length of the agangli-
drome in this study. This percentage is smaller than a simi- onic colon or disease severity. Arguably, patients with short-
lar cohort study in Japan, which reported 8.2% from 1998 segment disease have very different trends in management
to 2002 [15], and a cohort from Ireland, which reported and outcomes compared to longer-segment disease.
15% from 1975 to 2003 [16], but higher than a cohort in Cases diagnosed and operations performed during the
Utah, which reported 1.7% from 1970 to 2011 [3]. first year of life should be fairly accurately captured through
Most patients in California were born at early term the Linked Birth dataset, which includes all births in Califor-
or full term, with median gestational age at birth of 38 nia. However, cases identified after age one may be missed
weeks 6 days, and 20.1% born prior to 37 weeks. Birth in this analysis if the patient does not have a social secu-
weight was lower than average, at 3130 g (versus 3337 g). rity number, which was necessary to create a unique patient
However, gestational age was longer and birth weight was identifier. Patients without social security numbers, such as
higher in this cohort compared to a cohort in Utah, in younger children and non-citizens, are thus at higher risk of
which mean gestational age was 34 weeks and mean birth being missed by this study, and our findings may underesti-
weight was 2196 g [3]. mate the incidence of HD in this population.
The overall mortality rate during the study period life It is possible that cases identified solely in the PDD were
was 1.7%, with the highest risk in neonates. This was not born in California, although we assume these patients

Table 3  Birth characteristics of Patients with HD Patients without HD p value

patients with HD compared to (n = 720) (n = 9,363,381)
patients without HD
Gestational age (days), mean (SD) 268 (19) 274 (13) < 0.001
Pre-term birth (< 37 weeks), n (%) 145 (20.1) 857,750 (9.2) < 0.001
Maternal age (years), mean (SD) 28.8 (6.7) 28.0 (6.3) < 0.001
Maternal age (years) among mothers of babies 28.5 (6.5) 28.0 (6.3) 0.044
without Down syndrome, mean (SD)
Birthweight (g), mean (SD) 3130 (662) 3337 (508) < 0.001
Low birth weight (< 2500 g), n (%) 109 (15.1) 518,174 (5.5) < 0.001
Single parity, n (%) 415 (57.6) 5,730,607 (61.2) 0.050

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were born in California, but diagnosed after age one. If these
patients were not born in California, the reported incidence
rate would have been artificially inflated.
Conclusion
This is one of the largest population-based studies of HD. In
California between 1995 and 2012, the incidence was stable,
risk was highest among African American children, and the
mortality rate was < 2%.
Funding  This study was not funded.
Compliance with ethical standards  Hirschsprung’s disease in the North of England: prevalence, asso-
Conflict of interest  None of the authors have any conflicts of interest
to declare.
Ethical approval  All studies involving human participants were in
accordance with the ethical standards of the institutional and state
research committees (UC Davis Institutional Review Board and the
California Committee for the Protection of Human Subjects) and with
the 1964 Helsinki declaration and its later amendments.
Informed consent  Informed consent was not obtained as this was
a database study and consent was not able to be obtained and data
were deidentified; this was found to be acceptable per the institutional
research committees listed above.
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