Clinical Characteristics and Risk Factors for Symptomatic Pediatric Gallbladder Disease
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ARTICLE
Clinical Characteristics and Risk Factors for
Symptomatic Pediatric Gallbladder Disease
AUTHORS: Seema Mehta, MD,a Monica E. Lopez, MD,b WHAT’S KNOWN ON THIS SUBJECT: Gallbladder disease in
Bruno P. Chumpitazi, MD,a Mark V. Mazziotti, MD,b children is an evolving entity and studies suggest an increasing
Mary L. Brandt, MD,b and Douglas S. Fishman, MDa frequency of symptomatic pediatric gallbladder disease and
aDepartment of Pediatrics, Baylor College of Medicine, Section of resultant cholecystectomies.
Gastroenterology, Hepatology, and Nutrition, Texas Children’s
Hospital, Houston, Texas; bMichael E. DeBakey Department of WHAT THIS STUDY ADDS: Hispanic ethnicity and obesity are
Surgery, Baylor College of Medicine; Division of Pediatric Surgery,
Texas Children’s Hospital, Houston, Texas
epidemiologically significant risk factors for symptomatic
gallbladder disease in the pediatric population.
KEY WORDS
children, cholecystectomy, gallbladder, Hispanic, obesity
ABBREVIATIONS
ERCP—endoscopic retrograde cholangiopancreatography
HIDA—hepatobiliary iminodiacetic acid
IOC—intraoperative cholangiogram
TCH—Texas Children’s Hospital
abstract
OBJECTIVE: Our center previously reported its experience with pedi-
All authors contributed extensively to this study. Drs Mehta,
Lopez, Brandt, and Fishman conceived and designed the study. atric gallbladder disease and cholecystectomies from 1980 to 1996. We
Drs Mehta, Lopez, and Fishman acquired the data. Drs Mehta, aimed to determine the current clinical characteristics and risk fac-
Chumpitazi, and Fishman analyzed and interpreted the data. Drs tors for symptomatic pediatric gallbladder disease and cholecystecto-
Mehta, Brandt, and Fishman drafted the manuscript. All authors
contributed to critical revisions of the manuscript and gave final mies and compare these findings with our historical series.
approval of the version to be published. STUDY DESIGN: Retrospective, cross-sectional study of children, 0 to 18
www.pediatrics.org/cgi/doi/10.1542/peds.2011-0579 years of age, who underwent a cholecystectomy from January 2005 to
doi:10.1542/peds.2011-0579 October 2008.
Accepted for publication Sep 9, 2011 RESULTS: We evaluated 404 patients: 73% girls; 39% Hispanic and 35%
Address correspondence to Seema Mehta, MD, 6621 Fannin white. The mean age was 13.10 6 0.91 years. The primary indications
Street, CC1010.02, Houston, TX 77030. E-mail: seemam@bcm.edu
for surgery in patients 3 years or older were symptomatic cholelithi-
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). asis (53%), obstructive disease (28%), and biliary dyskinesia (16%).
Copyright © 2012 by the American Academy of Pediatrics The median BMI percentile was 89%; 39% were classified as obese. Of
FINANCIAL DISCLOSURE: The authors have indicated they have the patients with nonhemolytic gallstone disease, 35% were obese and
no financial relationships relevant to this article to disclose.
18% were severely obese; BMI percentile was 99% or higher. Gallstone
disease was associated with hemolytic disease in 23% (73/324) of patients
and with obesity in 39% (126/324). Logistic regression demonstrated older
age (P = .019) and Hispanic ethnicity (P , .0001) as independent risk
factors for nonhemolytic gallstone disease. Compared with our historical
series, children undergoing cholecystectomy are more likely to be
Hispanic (P = .003) and severely obese (P , .0279).
CONCLUSION: Obesity and Hispanic ethnicity are strongly correlated
with symptomatic pediatric gallbladder disease. In comparison with
our historical series, hemolytic disease is no longer the predominant
risk factor for symptomatic gallstone disease in children. Pediatrics
2012;129:1–7
PEDIATRICS Volume 129, Number 1, January 2012 1
Downloaded from by guest on November 4, 2015Gallbladder disease in children is We hypothesize that the epidemiologic Nutrition and Research Center com-
evolving and studies suggest an ever- risk factors for pediatric gallbladder puterized calculator, which is based
increasing frequency of gallbladder disease now resemble those seen in on the Centers for Disease Control
disease and resultant cholecystecto- adults (eg, female gender, race, and and Prevention’s standardized charts
mies in children.1–8 In 1959, the pre- obesity).19,25–28 In this retrospective (http://www.bcm.edu/cnrc/bodycomp/
valence of cholelithiasis in children series of consecutive children under- bmiz2.html). BMI percentiles were cat-
younger than 16 years was noted to be going cholecystectomy, we aimed to egorized as follows: lower than 85%,
0.15%.9 Since that time, the prevalence identify the clinical characteristics and normal weight; 85% to 94.9%, over-
has increased with estimates ranging risk factors for pediatric gallbladder weight; 95% to 98.9%, obese; and 99%
from 1.9% to 4.0%.3–6 The number of disease resulting in cholecystectomy or higher, severely obese.
cholecystectomies has increased ac- and to compare current demographics SPSS 17.0 (Chicago, IL) was used for all
cordingly. At our own institution, 36 cho- and indications for surgery with our statistical analyses. Comparison of
lecystectomies were performed from historical series.1 categorical values between groups was
1960 to 1980, and 128 were performed done via x 2 analyses. Comparison of
over the next 17 years (1980–1997).1,10 METHODS continuous variables between groups
Cholelithiasis in infancy is typically re- The Texas Children’s Hospital (TCH) pa- was completed with Mann-Whitney
lated to prematurity, total parenteral thology database was used to identify U analysis. Binary multivariate logistic
nutrition use, abdominal surgery, or all patients, 0 to 18 years of age, who regression analysis with presence or
sepsis.2,11–13 During adolescence, pre- underwent a cholecystectomy from absence of gallstone disease as the
vious reports identified hemolytic dis- January 2005 through October 2008. All dependent variable was completed. A
ease as the most common associated patients who underwent an incidental P value # .05 was used to indicate
comorbidity. More recent data sug- cholecystectomy secondary to liver statistical significance. Z-scores were
gest that gallbladder disease related transplantation or hepatobiliary sur- used for all statistical analyses of BMI.
to nonhemolytic risk factors, including gery (eg, Kasai portoenterostomy) were BMI was not calculated for patients
pregnancy, oral contraceptive use, and excluded. younger than 3 years because only a
obesity, is on the rise.1,2,14–16 length was available for these patients,
The medical records of study patients
not a height; therefore, these patients
The change in etiology of gallbladder were examined for demographics (age,
were excluded from BMI analyses.29
disease is temporally related to the gender, race/ethnicity), anthropomor-
well-documented rise in childhood phic measurements (weight, height), Hemolytic disease is a well-described,
obesity. The NHANES data from 2003 to comorbidities, primary and secondary strong independent risk factor for
2004 revealed the prevalence of child- indications for cholecystectomy, find- cholelithiasis; therefore, patients with
hood obesity in the United States to be ings on imaging studies (hepatobiliary hemolytic disease (sickle cell anemia,
17.1%, compared with 13.9% from 1999 iminodiacetic acid [HIDA] scan, abdo- hereditary spherocytosis, hemoglobin
to 2000.17 In addition, the prevalence of minal ultrasound, magnetic resonance H disease, autoimmune hemolytic ane-
severe obesity, BMI percentile of 99% cholangiopancreatography) and/or mia, congenital dyserythropoietic ane-
or higher, increased by more than endoscopic retrograde cholangio- mia) were excluded when assessing the
300%: 0.8% from 1976 to 2000 to 3.8% pancreatography (ERCP), and histo- impact of other potential risk factors,
from 1999 to 2004.18 Severe obesity was pathology. Patients were identified as age, gender, BMI, and race, on gallstone
noted to be the highest among African having a primary indication of compli- formation.30–33
American and Hispanic individuals.18 cated obstructive disease if they were
RESULTS
The relationship between obesity and diagnosed with gallstone pancreatitis,
gallbladder disease is well recognized in jaundice, choledocholithiasis, or found Patient Population
the adult population.19,20 Obesity has to have dilation of the common bile duct A total of 455 cholecystectomies were
previously been described as a rare risk on an imaging study. This study was completed at TCH from January 2005 to
factor for gallbladder disease in chil- conducted after approval from the October 2008. Of these, 404 patients met
dren; however, as a result of the obesity Baylor College of Medicine Institutional inclusion criteria (Fig 1). Demographic
epidemic, obesity-related comorbidities, Review Board. data for these patients are shown in
including gallbladder disease, are in- BMI (kg/m2), Z-scores, and BMI per- Table 1. The BMI distribution of all
creasingly affecting the pediatric pop- centiles were calculated using the patients $3 years of age was as follows:
ulation.1,2,13,14,21–24 Baylor College of Medicine Children’s 45% (n = 174) were considered to be
2 MEHTA et al
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TABLE 2 Primary Comorbidities
Hemolytic disease 76 (19%)
Obesity 18 (4%)
Post partum 14 (3%)
Malignancy 9 (2%)
Polycystic ovary syndrome 6 (2%)
Thyroid disease 5 (2%)
Cardiac disease 7 (1.5%)
Diabetes 5 (1%)
Prematurity 4 (1%)
Hyperlipidemia 4 (1%)
Cystic fibrosis 2 (0.5%)
FIGURE 1 Gilbert disease 1 (0.2%)
Excluded patients. Others 38 (9%)
None 216
TABLE 1 Demographics (n = 2). A primary indication was not
Age, y identified for one patient. For those 3 to 7 years old, and 3% (n = 7) were
Range 0.6–18.0 patients younger than 3 years, symp- younger than 3 years. Most of the
Mean 13
Median 14
tomatic cholelithiasis (n = 5, 71%) and patients (76%, n = 190) were girls.
Age categories, n (%) complicated obstructive disease (n = 2, For patients $3 years old with non-
13–18 y 271 (67) 29%) were the primary indications for hemolytic gallstone disease (n = 244),
8–12 y 88 (22)
surgery. Gallstones were identified on the BMI percentile distribution was as
3–7 y 38 (9)
Younger than 3 y 7 (2) gross pathology or imaging in 80% follows: 31% (n = 74) were considered
Gender (324/404) of patients. None of the pa- to be a normal weight, 16% (n = 37)
Males, n (%) 111 (27) tients with biliary dyskinesia (n = 64)
Females, n (%) 293 (73) were overweight, 35% (n = 82) were
Male:Female 1.0:2.6 or gallbladder polyps (n = 3) had evi- obese, and 18% (n = 44) were severely
Race/Ethnicity, n (%) dence of gallstones. obese. As such, ∼69% (n = 163/237) of
Hispanic 144 (39)
White 126 (35)
Patients with complicated obstructive patients with gallstone disease were
African American 90 (25) disease (n = 112) presented with one or overweight or obese. The median BMI
Other 5 (1) a combination of the following: chol- percentile for these patients was 95%
Unknown 39 (10)
edocholithiasis (n = 43), gallstone pan- and the mean BMI percentile was 81%. A
creatitis (n = 42), jaundice (n = 16), and height or weight was absent for 7 pa-
a normal weight, 16% (n = 63) were dilation of the common bile duct (n = 64). tients with gallstone disease; therefore,
overweight, 24% (n = 94) were obese, More than one-third of patients with these patients were excluded from all
and 15% (n = 57) were severely obese. complicated obstructive disease (n = 42; BMI analyses.
The median BMI percentile was 89%. 38%) presented with a combination of Logistic regression was used to predict
Of the patients with a BMI percentile obstructive findings. the impact of gender, age, BMI, and
$95%, 52% (n = 79) were Hispanic. A Associated comorbidities were identi- Hispanic ethnicity on the incidence of
height or weight was unavailable for fied for 189 (47%) of 404 patients. These nonhemolytic gallstone disease. Older
9 patients; therefore, these patients are listed in Table 2. A positive family age (P = .019) and Hispanic ethnicity
were excluded from all BMI analyses. history of cholelithiasis was reported (P , .0001) were independent risk
for only 9 patients. factors for nonhemolytic gallstone dis-
Indications ease. Gender and BMI percentile were
The primary indications for cholecys- Gallstone Disease: Risk Factors not independent risk factors.
tectomy in patients $3 years of age Of the 76 children with hemolytic dis-
were symptomatic cholelithiasis (n = ease, 73 (96%) were diagnosed with Complicated Obstructive Disease
211; 53%), complicated obstructive gallstone disease. Nonhemolytic gall- Complicated obstructive disease was
disease (n = 112; 28%), and biliary stone disease occurred in 77% (251/ the primary indication for a cholecys-
dyskinesia (n = 64; 16%). Other indi- 324) of patients. The age distribution tectomy in 112 patients $3 years of age.
cations included acalculous cholecys- of patients with nonhemolytic gallstone Of these, 61 had a BMI percentile $85%
titis (n = 4), gallbladder polyps (n = 3), disease was as follows: 76% (n = 192) (P = .496). Univariate analysis identified
and persistent right upper quadrant were 13 to 18 years old, 16% (n = 39) a significant association between the
abdominal pain of unknown etiology were 8 to 12 years old, 5% (n = 13) were risk for gallstone pancreatitis and a BMI
PEDIATRICS Volume 129, Number 1, January 2012 3
Downloaded from by guest on November 4, 2015percentile $85% (P = .003); however, children with hemolytic disease. The complications were postoperative fever
this association was not found for overall percentage of patients with and pancreatitis/pseudocyst formation
jaundice (P = not significant). Hispanic hemolytic disease as an indication for (Table 4). Of the obese patients, 15% (n =
patients (n = 55, 65%) were more likely cholecystectomy has decreased sig- 23) had a minor or major postoperative
than non-Hispanic patients (n = 29, nificantly (41% vs 18%, P , .0001). complication (P = .4). No deaths oc-
35%) to have obstructive disease (P = Additionally, no cholecystectomies were curred as a result of a cholecystectomy
.005). Of the 112 patients with compli- previously performed for biliary dyski- in our current series. In our previous
cated obstructive disease, 56% (n = 63) nesia, whereas now it is the third lead- series, 3 children with congenital heart
underwent the following additional ing indication (0% vs 16%, P , .0001). disease who required emergent chole-
procedures: ERCP (n = 21), intraop- Another significant change has been in cystectomy died after surgery.1
erative cholangiogram (IOC) (n = 28), the approach to surgery. In our current
or ERCP and IOC (n = 14). series, 97% of cholecystectomies were DISCUSSION
performed laparoscopically versus 15% We have found that cholecystectomies
Biliary Dyskinesia in our previous series. The major com- for gallbladder disease are performed
Biliary dyskinesia, by definition, is a plication rate remains similar (9% vs more often in children and the risk
gallbladder ejection fraction of ,35% 9%) (Table 3). The most common major factors for cholecystectomies have
with a cholecystokinin analog infusion
on HIDA scan.34–37 Biliary dyskinesia was
TABLE 3 Texas Children’s Hospital Historical Comparison1
the third leading indication for a cho-
1980–1996 2005–2008 P Value
lecystectomy in our patient cohort.
Total no. of patients 128 404
Females comprised 78% of these Age, y
patients, and 18% were of Hispanic eth- Mean 10 13.00 6 0.19
nicity. Fifty-one percent of patients were Gender
Males 59 (46%) 111 (27%) .0001
overweight and, of these, 30% were
Females 69 (54%) 293 (73%) .0001
severely obese. HIDA scans completed Male:Female 0.8:1 1:2.6
on all 64 patients revealed an ejection Race/Ethnicity
fraction of less than 35% (median of Hispanic 28 (22%) 144 (36%) .003
White 57 (45%) 126 (31%) NS
10%; range 0%–34%). Histologic fea- African American 39 (30%) 90 (22%) NS
tures of chronic cholecystitis were Other 4 (3%) 5 (1%) NS
identified in 80% (n = 51) of patients BMI
Severely obese 8 (6%) 57 (15%) .013
with a preoperative diagnosis of biliary Comorbidities
dyskinesia. Hemolytic disease 52 (41%) 76 (19%) ,.0001
Biliary dyskinesia 0 64 (16%) ,.0001
Surgery
Comparison With Historical Control Laparoscopic 19 (15%) 379 (96%) ,.0001
Miltenburg et al published data on pe- Open 109 (85%) 17 (4%) ,.0001
Major complication 11 (9%) 38 (9%) NS
diatric cholecystectomies at TCH from
NS, not significant.
1980 to 1996.1 We compared our data
with this historical cohort (Table 3).
There has been a notable increase in TABLE 4 Postoperative Complications From the 2005–2008 Texas Children’s Hospital Cohort
the percentage of Hispanic (22% vs
Major (n) Minor (n)
36%, P = .003) and severely obese (6%
Postoperative fever (8) Abdominal pain (13)
vs 18%, P , .027) patients undergoing Pancreatitis/pseudocyst formation (7) Nausea/Vomiting (nonbilious) (6)
cholecystectomy. Patients in the his- Infection (eg, fungemia, urinary tract infection, Ileus (2)
torical cohort were subjectively cate- wound infection) (5)
Papillary stenosis/stricture (4)
gorized as being morbidly obese. BMI Retained stone (4)
data for this historical cohort of Jaundice (4)
patients was not available for direct Bile leak (2)
comparison. Vascular injury (1)
Hemobilia (1)
In our historical series, 52 (41%) of 128 Small bowel obstruction (1)
cholecystectomies were performed on Prolonged intubation (1)
4 MEHTA et al
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changed. In the initial series from TCH, dyskinesia, 78% were female and 70% not previously been investigated. De-
36 cholecystectomies were performed were $13 years of age. These findings spite 25% of the Hispanic children
in 20 years (1.8 per year), followed by may support the suggestion that the being overweight or obese, we dem-
128 in next 17 years (7.5 per year), and hormonal changes occurring during onstrate that independent of their BMI
now 404 in almost 4 years (101 per puberty may contribute to the impair- percentiles, Hispanic children are at
year).1,10 Previously described risk ment of gallbladder motility in biliary a greater risk for cholecystectomy be-
factors such as prematurity (n = 4, 1%) dyskinesia by altering the lipid com- cause of gallstone disease. This finding
and hemolytic disease (n = 76, 19%) did position of bile, increasing cholesterol supports the possible genetic risk
not account for this dramatic increase. saturation, and promoting gallbladder predisposition for stone formation in
Rather, risk factors responsible for the hypomotility.43,45,46 Hispanic children similar to that seen
development of gallbladder disease in We also demonstrate a strong inde- in Hispanic adults.52 Interestingly, we
adults (female gender, age, obesity, pendent correlation between BMI per- identified only 9 patients, of whom only
and ethnicity) were identified as key centile and the presence of gallstone 5 were Hispanic, with a positive family
contributors to this increase in pedi- disease. Based on their BMI, a remark- history of cholelithiasis. We anticipate
atric gallbladder disease resulting in able 69% of our patients with non- that a positive family history may have
cholecystectomy. hemolytic gallstone disease were been underreported or family mem-
Our study mirrors previous observa- overweight or obese; however, only 6% bers may have asymptomatic choleli-
tions that female children are at higher of our patients had “obesity” docu- thiasis. As such, race/ethnicity may be
risk of gallbladder disease than male mented with an International Classifi- a greater risk factor for gallstone dis-
children.1,2,7 A greater proportion of cation of Diseases, Ninth Revision ease than obesity alone. Further stud-
patients in our series were female code as a comorbidity in their medical ies examining the independent risk of
(73%, n = 293), reflecting the trend to- record, demonstrating a significant race/ethnicity on the development of
ward gender bias. In adults, the high underreporting of this condition. Obe- gallstone disease are needed.
prevalence of cholelithiasis in women sity is a major health care issue and its To our knowledge, this is the largest
has been attributed to pregnancy and contribution to the prevalence of cho- single-center study examining gall-
oral contraceptive use.38–43 We identi- lelithiasis has been well elucidated bladder disease in children who un-
fied 14 women with a documented in the adult population.19,20,27,28 The derwent a cholecystectomy. Bogue et al8
pregnancy; however, our study design pathogenesis of gallstone formation in recently studied 382 patients diag-
precluded the evaluation of patients obese individuals has been described nosed with cholelithiasis based on
taking oral contraceptives. as multifactorial with key factors, in- ultrasonography. In this series, only
We found an increase in the mean age of cluding hepatic hypersecretion of 122 patients underwent a cholecystec-
diagnosis for gallstone disease. The cholesterol with resultant supersatu- tomy. The racial and ethnic distribution
previous mean age for children with ration of bile and altered gallbladder of their study population and its impact
gallstone disease has ranged from 8.4 motility.20,27,47 Our study strongly sug- on the development of cholelithiasis
to 10.0 years; however, our mean age gests the obesity epidemic in children was not described. Obesity was iden-
was notably higher at 13.0 years1,2 has contributed significantly to the tified in a significantly lower percent-
(67% were 13 to 18 years of age). This striking increase in pediatric gallstone age of patients than our study population,
phenomenon has previously been disease. ,1% vs 53%. In addition, we report a
suggested and attributed to biliary Our data suggest that Hispanic ethnic- higher rate of complicated disease in
cholesterol saturation occurring sec- ity is also a significant risk factor for patients requiring surgery, 10% vs 28%;
ondary to hormonal changes during pediatric gallbladder disease resulting however, the definitions for compli-
puberty.43,44 An increase in the mean in cholecystectomy. It has previously cated disease varied between studies.
age at diagnosis may also be attribut- been shown that Hispanic adults are at Our definition did not include acute
able to the rising incidence of obesity in increased risk for cholelithiasis.48–51 cholecystitis, whereas Bogue et al8 did
adolescents. Genetic and environmental influences not include jaundice or dilation of the
The hormonal changes associated with have been explored as potential ex- common bile duct.
puberty may also play a role in the planations for this epidemiologic as- Our study’s major strengths are a large
etiology of biliary dyskinesia. Of the sociation.48,49,52,53 The impact of racial sample size and diverse patient pop-
patients who underwent a cholecystec- and ethnic variations on gallbladder ulation. The study is limited by its ret-
tomy for the primary indication of biliary disease in the pediatric population has rospective design. At the time of our
PEDIATRICS Volume 129, Number 1, January 2012 5
Downloaded from by guest on November 4, 2015final analysis, some data, including historical cohort and current patient cholecystectomies to laparoscopic
a height or weight for 9 of 404 patients, population may have been influenced cholecystectomies.
a race or ethnicity for 39 of 404, and an by the changing demographics of
indication for cholecystectomy for 1 Houston and advances in medical care. CONCLUSION
patient, were missing. We believe that The Hispanic population of Houston, Hispanic ethnicity and obesity are
given our large sample size, the miss- Texas, has been steadily increasing epidemiologically significant risk fac-
ing data would not have significantly since 1980.54 This demographic change tors for gallbladder disease in the
altered our results. Additionally, BMI pediatric population. Ethnicity is an
likely contributed to the increase in
data for our historical cohort was not unalterable risk factor, but increased
the proportion of Hispanic children
available for direct comparison. With awareness and early screening by
our stringent search criteria, all patients undergoing cholecystectomies. We also
pediatric health care providers could
who underwent a cholecystectomy surmise that biliary dyskinesia was
potentially limit the occurrence of
during our study period should be identified as the third leading indication
complicated obstructive disease. Ob-
represented; however, patients with for cholecystectomy in our cohort sec- esity is a modifiable risk factor. With
gallbladder disease who did not have ondary to the rising awareness of the the prevalence of childhood obesity on
a cholecystectomy were not included in disease in the pediatric population.55,56 the rise, pediatric health care pro-
our epidemiologic data.30 In addition, the significant difference in viders need to be more aware of
We recognize that some of the notable surgical practice is likely a reflection of obesity-related comorbidities, includ-
differences identified between our the shift in standard of care from open ing gallbladder disease.
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PEDIATRICS Volume 129, Number 1, January 2012 7
Downloaded from by guest on November 4, 2015Clinical Characteristics and Risk Factors for Symptomatic Pediatric Gallbladder
Disease
Seema Mehta, Monica E. Lopez, Bruno P. Chumpitazi, Mark V. Mazziotti, Mary L.
Brandt and Douglas S. Fishman
Pediatrics; originally published online December 12, 2011;
DOI: 10.1542/peds.2011-0579
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
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Downloaded from by guest on November 4, 2015Clinical Characteristics and Risk Factors for Symptomatic Pediatric Gallbladder
Disease
Seema Mehta, Monica E. Lopez, Bruno P. Chumpitazi, Mark V. Mazziotti, Mary L.
Brandt and Douglas S. Fishman
Pediatrics; originally published online December 12, 2011;
DOI: 10.1542/peds.2011-0579
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/early/2011/12/07/peds.2011-0579
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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