1. No category

A National Profile of Childhood Epilepsy and Seizure Disorder
Shirley A. Russ, Kandyce Larson and Neal Halfon
Pediatrics 2012;129;256; originally published online January 23, 2012;
DOI: 10.1542/peds.2010-1371
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/129/2/256.full.html
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 © 2012 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
A National Profile of Childhood Epilepsy and Seizure
Disorder
WHAT’S KNOWN ON THIS SUBJECT: Epilepsy/seizure disorder is
known to be associated with a range of mental health and
neurodevelopmental comorbidities, based on clinical studies, and
on population studies largely conducted outside the United States.
WHAT THIS STUDY ADDS: In a nationally representative sample of
US children, estimated prevalence of reported lifetime epilepsy/
seizure disorder was 1%, and of current epilepsy/seizure disorder
was 6.3/1000. Developmental, mental health, and physical
comorbidities are common, warranting enhanced surveillance,
and an integrated service approach.
abstract
OBJECTIVE: To determine sociodemographics, patterns of comorbidity,
and function of US children with reported epilepsy/seizure disorder.
METHODS: Bivariate and multivariable cross-sectional analysis of data
from the National Survey of Children’s Health (2007) on 91 605 children
ages birth to 17 years, including 977 children reported by their
parents to have been diagnosed with epilepsy/seizure disorder.
RESULTS: Estimated lifetime prevalence of epilepsy/seizure disorder
was 10.2/1000 (95% confidence interval [CI]: 8.7–11.8) or 1%, and of
current reported epilepsy/seizure disorder was 6.3/1000 (95% CI: 4.9–
7.8). Epilepsy/seizure disorder prevalence was higher in lower-income
families and in older, male children. Children with current reported
epilepsy/seizure disorder were significantly more likely than those
never diagnosed to experience depression (8% vs 2%), anxiety (17%
vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), conduct
problems (16% vs 3%), developmental delay (51% vs 3%), autism/
autism spectrum disorder (16% vs 1%), and headaches (14% vs
5%) (all P , .05). They had greater risk of limitation in ability to
do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school
grade (relative risk: 2.59; CI: 1.52–4.40), poorer social competence and
greater parent aggravation, and were at increased risk of having
unmet medical and mental health needs. Children with prior but
not current seizures largely had intermediate risk.
AUTHORS: Shirley A. Russ, MD, MPH,a,b
Kandyce Larson, PhD,b,c and Neal Halfon, MD, MPHb,c,d
aDepartment of Academic Primary Care Pediatrics, Cedars-Sinai
Medical Center, Los Angeles, California; bUniversity of California
Los Angeles Center for Healthier Children, Families, and
Communities, Los Angeles, California; and cDepartment of
Pediatrics, David Geffen School of Medicine, and dDepartment of
Health Services, School of Public Health, and Department of
Public Policy, School of Public Affairs, University of California Los
Angeles, Los Angeles, California
KEY WORDS
epilepsy, seizure disorder, children
ABBREVIATIONS
ADHD—attention-deficit/hyperactivity disorder
ASD—autism spectrum disorder
CI—confidence interval
MADDSP—Metropolitan Atlanta Developmental Disabilities Surveillance Program
NSCH—National Survey of Children’s Health
RR—relative risk
www.pediatrics.org/cgi/doi/10.1542/peds.2010-1371
doi:10.1542/peds.2010-1371
Accepted for publication Oct 13, 2011
Address correspondence to Shirley A. Russ, MD, MPH, University
of California Los Angeles Center for Healthier Children, Families,
and Communities, 10990 Wilshire Blvd, Suite 900, Los Angeles, CA
90024. E-mail: shirlyruss@aol.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2012 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
CONCLUSIONS: In a nationally representative sample, children with seizures were at increased risk for mental health, developmental, and physical comorbidities, increasing needs for care coordination and specialized
services. Children with reported prior but not current seizures need further study to establish reasons for their higher than expected levels of
reported functional limitations. Pediatrics 2012;129:256–264
256
RUSS et al
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
ARTICLE
Epilepsy/seizure disorder is the most
common childhood neurologic condition,1 and a major public health
concern.2 Children diagnosed with
epilepsy face considerable challenges. The seizures themselves, especially when poorly controlled, may
be disabling and interfere with the
child’s ability to learn, whereas secondary influences, such as stigma
and lack of knowledge about the
condition can negatively affect social
and psychological function.3–5 In addition, children with epilepsy frequently
exhibit comorbidities that affect developmental progress and emotional
health, including attention-deficit/
hyperactivity disorder (ADHD),6–8 learning disabilities,9–11 depression, and
anxiety.1,12–16 Knowledge of the epidemiology of childhood epilepsy and of
current functioning of children with
this condition will help inform the
development of systems of care that
move beyond a narrow focus on seizure
control to address implications of the
condition for the child’s social, emotional, and developmental well-being.3
Most studies of childhood epilepsy in
the United States have been conducted
on subjects recruited from general and
specialist medical settings, so may be
biased toward inclusion of children
with the most complex clinical pictures.17 Population-based studies, with
subjects recruited from nonmedical
community-based settings have generally been based on local samples,2
with limited ability to examine a wide
range of potential comorbidities and
functional attributes, or have been
conducted outside the United States.18
Identifying and characterizing the full
range of comorbidities in people with
epilepsy has been identified as a National Institute of Neurologic Disorders
and Stroke Epilepsy Research Benchmark.19 To address this gap in knowledge, we used data from the 2007
National Survey of Children’s Health
(NSCH) to estimate the prevalence of
reported epilepsy/seizure disorder for
US children, and to examine comorbid mental health/developmental disorders, physical health conditions, and
child and family functioning. To our
knowledge, this is the first national
study to estimate prevalence of reported epilepsy/seizure disorder in US
children and to examine patterns of
reported comorbidity.
METHODS
Sample
The 2007 NSCH was conducted as
a module of the State and Local Area
Integrated Telephone Survey by the
National Center for Health Statistics.
The study used a stratified randomdigit-dial sampling design to achieve
a nationally representative sample of
91 642 parents of children 0 to 17 years
of age. One child was randomly selected from each household and interviews were conducted with the parent
or guardian who knew most about the
child’s health and health care. Interviews lasting ∼30 minutes were conducted in English and Spanish. The
overall weighted response rate was
51.2% (American Association of Public
Opinion Rate 4).
The sample for this study included 91
605 children ages birth to 17 with
nonmissing data on the question
about lifetime epilepsy/seizure disorder. There is some variability in the
final study sample for each different
comorbid condition/functioning indicator owing to missing data, and
because certain measures were not
relevant and/or not asked for infants
or very young children. Questions
about learning disability were asked
only of children ages 3 to 17 years,
questions about severe headaches
were asked only of children ages 6 to
17 years, and questions about oral
health problems were asked only of
children ages 1 to 17 years. Height/
weight data were restricted to children ages 10 and older because of
concerns about the validity of parent report for younger ages.20 School
functioning and social competence
were measured only for children ages
6 to 17. Questions about mental health
treatment were asked only of children
older than 24 months, and special education services only of children aged 6
to 17 years.
To produce population-based estimates,
data records for each interview were
assigned a sampling weight. NSCH
sampling weights adjust for stratification by geographic area and various forms of nonresponse, including
poststratification to match population
control totals on key demographic
variables obtained from Census Bureau data. Further details on the design and operationof NSCH are reported
elsewhere.20 This study was granted
exempt status by the University of
California Los Angeles Institutional Review Board.
Measures
Lifetime Epilepsy or Seizure Disorder
Parents were asked if a doctor or
health care provider ever told them
that their child had epilepsy or seizure
disorder, and if so, if their child currently had epilepsy or seizure disorder. Children were categorized as
never diagnosed with epilepsy/
seizure disorder, currently diagnosed,
or previously but not currently
diagnosed.
Mental Health and Developmental
Indicators
Children were identified as having
comorbid mental health/developmental
disorders if the parent reported that the
child currently had depression, anxiety,
attention-deficit disorder/ADHD, conduct problems, learning disability, developmental delay, or autism/autism
spectrum disorder (ASD).
PEDIATRICS Volume 129, Number 2, February 2012
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
257
Physical Health Indicators
Measures of physical health included
parent report of a child currently having a hearing or vision problem and
currently having asthma. Additional
measures included a health care provider telling the parent the child had
migraine headaches in the past year;
hay fever/respiratory allergy, food/
digestive allergy, or eczema/skin allergy; and 3 or more ear infections.
Obesity was defined as a BMI in the 95th
percentile and above according to
Centers for Disease Control and Prevention growth charts.20 Oral health
problems were assessed by parent
report of whether the child had
decayed teeth or cavities, broken
teeth, or bleeding gums in the past 6
months.
Functional Health Indicators
Parents reported an activity restriction
(yes/no) if the child was “limited or
prevented in any way in his/her ability
to do the things most children of the
same age can do.” School functioning
was assessed by parent report of
whether the child had ever repeated
a grade, and contact in the past year by
the school about problems. Social
competence was measured by parent
ratings of how often the child shows
respect for teachers and neighbors;
gets along well with other children;
tries to understand others’ feelings;
and tries to resolve conflicts with
classmates, family, and friends. Items
were summed to create a composite
following criteria established by previous research21; scores ,12 on the
16-point scale identified children with
low social competence. The Aggravation in Parenting scale22 measures
stress in parenting through 3 items
where parents rate how often the child
was much harder to care for than
other children; does things that really
bothers them; and how often they felt
angry with him or her. Items were
summed to create a scale ranging from
258
0 to 12, and scores above 6 (corresponding with an answer of “sometimes” for each item) identified parents
with high aggravation.
Service Use and Access Indicators
Parents reported whether their child
received preventive medical care at
least 1 time in the past 12 months, and
mental health treatment or counseling.
Children ages 6 to 17 years were
coded as receiving special education if
parents reported an Individualized Educational Program (IEP). Children were
coded as having an unmet health need if
their parent reported that during the
past 12 months, the child needed health
care but care was delayed or not received. The medical home variable was
constructed by researchers at the Child
and Adolescent Health Measurement
Initiative.23 The following criteria must
be met for presence of a medical home:
(1) having a personal doctor or nurse,
(2) having a usual place for sick/well
care, (3) presence of family-centered
care, (4) no trouble obtaining needed
referrals, and (5) receipt of needed
care coordination.
Study Covariates
Study covariates included household
income in relation to the federal poverty
level, family structure, race/ethnicity,
highest parent education, child age in
years, and child gender. Missing data on
household income were imputed following routines from National Center
for Health Statistics.20
Analysis
All statistical analyses were performed using Stata (version 11.0; Stata
Corp, College Station, TX). Survey estimation procedures were applied and
the Taylor-series linearization method
adjusted the standard errors for the
complex survey design. We present
prevalence estimates for comorbid
conditions, functioning, and service
use by epilepsy/seizure disorder status (never diagnosed, current epilepsy/
seizure disorder, previously diagnosed).
Bivariate associations were examined
using x 2 tests with post hoc pairwise
comparisons between selected categories. Regression models added controls
for sociodemographics. Relative risks
were estimated using generalized linear
models with a Poisson distribution and
log link.24
RESULTS
Prevalence and
Sociodemographics of Epilepsy/
Seizure Disorder
The estimated lifetime prevalence of
epilepsy/seizure disorder was 10.2 per
1000 (95% confidence interval [CI]: 8.7–
11.8), or 1%, and current epilepsy/
seizure disorder was 6.3 per 1000
(95% CI: 4.9–7.8), or 0.6%. After adjustment for sociodemographics, lifetime epilepsy/seizure disorder was
more common in children from families with income ,100% federal poverty level (relative risk [RR]: 1.95; CI:
1.16–3.27) (Table 1). There was no relationship between childhood epilepsy
and family structure, race/ethnicity, or
parent educational level. Prevalence of
lifetime epilepsy/seizure disorder (and
also current epilepsy, data not shown)
increased with age. Epilepsy/seizure
disorder was more common in boys
(RR: 1.38; CI: 1.03–1.84).
Epilepsy/Seizure Disorder
Comorbidity
Compared with children never diagnosed, children with current
epilepsy/seizure disorder were more
likely to experience mental health and
developmental comorbidities (Table 2).
Depression (8% vs 2%), anxiety (17% vs
3%), ADHD (23% vs 6%), conduct problems (16% vs 3%), learning disability
(56% vs 7%), developmental delay (51%
vs 3%), and autism/ASD (16% vs 1%)
were all significantly more likely in
RUSS et al
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
ARTICLE
TABLE 1 Sociodemographic Correlates of Lifetime Epilepsy /Seizure Disorder
Child Ever Diagnosed with Epilepsy/Seizure Disorder
Total
Former diagnosis
Current diagnosis
Household income
,100% FPL
100% –199% FPL
200% –299% FPL
300% –399% FPL
400% FPL or greater
Family structure
Two biological/ adoptive parents
Single mother
Other
Race/Ethnicity
White
African American
Hispanic
Multiracial/Other
Highest parent education
HS diploma
More than HS
Child age, y
0–5
6–11
12–17
Child gender
Male
Female
No. in Sample
(Unweighted)
No. Ever Diagnosed
(Unweighted)
Weighted Prevalence per 1000
95% CI per 1000
Adjusted
RR
95% CI
91 605
977
451
526
10.2
3.9
6.3
8.7–11.8
3.3–4.6
4.9–7.8
10 956
15 575
16 531
14 215
34 328
170
226
183
111
287
12.8
12.5
12.4
5.9
7.7
9.6–17.1
9.8–15.9
7.6–20.2
4.3–8.1
6.0–10.0
1.95
1.79
1.51
0.78
base
1.16–3.27
1.20–2.65
0.80–2.85
0.51–1.17
70 595
14 722
5741
669
217
86
9.1
13.6
13.6
7.4–11.2
10.7–17.2
9.8–18.7
base
1.22
1.20
0.86–1.73
0.80–1.80
61 352
8869
11 520
8320
633
108
121
95
10.9
10.6
8.9
8.2
8.8–13.5
7.8–14.3
6.2–12.9
4.9–13.4
base
0.72
0.68
0.75
0.51–1.03
0.43–1.06
0.44–1.27
20 811
69 703
309
658
11.7
9.5
9.6–14.1
7.7–11.8
1.03
base
27 555
27 781
36 269
204
303
470
6.3
10.3
14.0
4.9–8.3
8.2–12.8
10.8–18.2
base
1.62
2.26
47 513
43 983
508
469
11.8
8.6
9.4–14.9
7.2–10.3
1.38
base
0.73–1.45
1.13–2.31
1.54–3.33
1.03–1.84
FPL, federal poverty level.
children with current epilepsy (P ,
.05). Each of these conditions was also
reported more frequently in children
with previously but not currently diagnosed epilepsy/seizure disorder (eg,
depression [7% vs 2%], developmental
delay [17% vs 3%], autism/ASD [7% vs
1%]).
Compared with children never diagnosed, children with current epilepsy/
seizure disorder were more likely to
experience a range of physical health
comorbidities including hearing or vision problems (22% vs 2%), asthma
(18% vs 9%), headaches (14% vs 5%),
allergies (43% vs 26%), ear infections
(11% vs 6%), and poor oral health
(Table 3). Children with a former
epilepsy/seizure disorder diagnosis also
had elevated risks. Epilepsy/seizure disorder status was not associated with
obesity.
Epilepsy/Seizure Disorder and
Function
Epilepsy/Seizure Disorder and
Service Use and Access
Compared with children never diagnosed, children with current epilepsy/
seizure disorder were more likely to
have limited activity (RR: 9.22; CI: 7.56–
11.24), grade repetition (RR: 2.59; CI:
1.52–4.42), school problems (RR: 1.63;
CI: 1.26–2.10), low social competence
(RR: 2.16; CI: 1.61–2.90), and high levels
of parent aggravation (RR: 2.46; CI:
1.54–3.93) after adjustment for sociodemographics (Table 4). Children previously but not currently diagnosed
with epilepsy/seizure disorder also
had greater risks of poorer function
across all domains, in each case with
an intermediate level of risk (eg, activity limitation [RR: 2.92; CI: 2.14–4.00],
grade repetition [RR: 1.55; CI: 1.05–
2.27], high parent aggravation [RR:
2.19; CI: 1.44–3.32]).
Compared with children never diagnosed,
children with current epilepsy/seizure
disorder were more likely to access
mentalhealthtreatment(RR:3.07;CI:2.25–
4.20) and special education services (RR:
6.39; CI: 5.44–7.50) (Table 5). They were
reported to be as likely to attend preventive health visits as children never
diagnosed, less likely to report receiving
care in a medical home (RR 0.72; CI: 0.54–
0.96), and more likely to report unmet
needs for care coordination, medical
care, and mental health services. Children with a former epilepsy/seizure disorder diagnosis also had elevated unmet
care coordination needs.
DISCUSSION
The estimated lifetime prevalence
of epilepsy/seizure disorder among
PEDIATRICS Volume 129, Number 2, February 2012
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
259
TABLE 2 Mental Health and Developmental Indicators
Depression
(n = 81 860)
Never diagnosed with
epilepsy/seizure disorder
No. cases
1598
Weighted prevalence
1.9 (1.7–2.2)
(95% CI)
Current epilepsy/seizure
disorder
No. cases
49
Weighted prevalence
8.4 (4.3–15.7)
(95% CI)
Relative risk adjusteda 3.43 (1.96–6.00)
Anxiety
(n = 81 857)
ADHD
(n = 81 664)
Conduct
(n = 81 884)
Learning
Disability
(n = 77 731)
Developmental
Delay
(n = 81 794)
Autism
(n = 81 852)
2519
2.7 (2.5–3.0)
5294
6.2 (5.9–6.7)
2247
3.2 (2.9–3.5)
5417
7.3 (6.9–7.8)
2117
2.8 (2.6–3.1)
830
0.9 (0.8–1.1)
95
17.4 (10.2–28.1)
127
23.1 (15.3–33.3)
90
15.6 (9.6–24.4)
249
50.5 (39.1–61.9)
65
15.5 (8.5–26.4)
5.26 (3.26–8.50)
2.92 (2.01–4.25)
3.83 (2.37–6.20)
6.73 (5.47–8.29)
16.37 (12.77–20.99)
15.55 (8.67–27.90)
49
8.9 (5.8–13.4)
70
15.6 (9.9–23.6)
119
26.2 (20.0–33.5)
77
17.1 (12.1–23.6)
25
6.8 (3.5–12.8)
2.6 (1.69–4.01)
1.57 (1.10–2.24)
3.05 (2.32–4.01)
5.42 (3.84–7.65)
7.02 (3.78–13.06)
286
56 (44.6–66.9)
(95% CI)
Former epilepsy/seizure
disorder
No. cases
35
Weighted prevalence
7.3 (4.3–11.9)
(95% CI)
Relative risk adjusteda 2.93 (1.74–4.93)
41
8 (4.9–12.9)
1.99 (1.23–3.20)
(95% CI)
a
Models include controls for household income, family structure, race/ethnicity, parent education, child age, and gender.
TABLE 3 Physical Health Indicators
Hearing/Vision
(n = 91 410)
Never diagnosed with
epilepsy/seizure disorder
No. cases
2025
Weighted prevalence
2.4 (2.1–2.6)
(95% CI)
Current epilepsy/seizure
disorder
No. cases
102
Weighted prevalence
22.2 (12.0–37.5)
(95% CI)
7.96 (4.52–14.02)
Relative risk adjusteda
Asthma
(n = 91 378)
Headaches
(n = 63 996)
Allergies
(n = 91 341)
Ear Infections
(n = 91 547)
Obesity
(n = 44 083)
Oral Health
Problems
(n = 86 465)
7765
9 (8.5–9.4)
3457
5.2 (4.8–5.6)
25 429
5265
6.2 (5.8–6.6)
5918
16.3 (15.4–17.3)
17 627
22.8 (22.1–23.6)
26.4 (25.7–27.1)
96
18.2 (12.1–26.3)
66
13.9 (8.0–22.8)
197
43.1 (34.0–52.7)
70
10.5 (7.1–15.1)
66
16.3 (10.2–25.0)
151
31.7 (22.6–42.5)
1.8 (1.26–2.57)
2.33 (1.38–3.94)
1.63 (1.32–2.02)
1.99 (1.36–2.89)
0.96 (0.63–1.46)
1.35 (0.98–1.85)
(95% CI)
Former epilepsy/seizure
disorder
No. Cases
Weighted prevalence
(95% CI)
Relative risk adjusteda
45
11 (7.2–16.5)
58
13.6 (9.2–19.6)
51
19.1 (12.1–28.9)
170
38.3 (30.7–46.5)
54
14.8 (9.2–23.0)
52
24.8 (16.4–35.5)
120
25.4 (18.4–33.9)
3.92 (2.50–6.15)
1.35 (0.93–1.98)
2.76 (1.91–3.97)
1.35 (1.11–1.65)
2.08 (1.39–3.11)
1.29 (0.89–1.87)
0.91 (0.68–1.21)
(95% CI)
a
Models include controls for household income, family structure, race/ethnicity, parent education, child age, and gender.
children in the United States in 2007
was 10.2 per 1000 (1%). Prevalence of
current epilepsy/seizure disorder
was 6.3 per 1000, corresponding to
just over 450 000 children ages birth
to 17 years nationwide. Children with
current seizures are at increased risk
for mental health, developmental, and
physical comorbidities, as well as
260
functional disabilities. They are less
likely to receive care in a medical
home, and are at increased risk for
having unmet needs for medical and
mental health services. Children reported to have previous but not current epilepsy/seizure disorder also
had more reported comorbidities and
functional limitations, but at lower
levels than children with active seizure
disorders.
Direct comparison with other prevalence studies is hampered by different
methods of case ascertainment, study
samples (local versus national), case
definitions, and cohort ages. These
estimates are slightly higher than the
6.0 to 7.7 per 1000 lifetime prevalence of
RUSS et al
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
ARTICLE
TABLE 4 Functional Health Indicators
Activity Limitation
(n = 91 492)
Never diagnosed with
epilepsy/seizure disorder
No. cases
Weighted prevalence (95% CI)
Current epilepsy/seizure disorder
No. cases
Weighted prevalence (95% CI)
Relative risk adjusteda (95% CI)
Former epilepsy/seizure disorder
No. cases
Weighted prevalence (95% CI)
Relative risk adjusteda (95% CI)
a
Repeated Grade
(n = 63 944)
School Problems
(n = 62 062)
Low Social Competence
(n = 63 553)
High Parent Aggravation
(n = 91 011)
5386
10.4 (9.8–11.0)
17 840
30.3 (29.4–31.3)
11 606
20.0 (19.2–20.8)
4141
5.9 (5.4–6.3)
309
63.0 (52.5–72.5)
9.22 (7.56–11.24)
93
31.2 (17.9–48.5)
2.59 (1.52–4.42)
224
52.2 (38.2–65.9)
1.63 (1.26–2.10)
179
46.8 (33.3–60.8)
2.16 (1.61–2.90)
99
16.1 (10.1–24.6)
2.46 (1.54–3.93)
100
22.8 (16.2–31.0)
2.92 (2.14–4.00)
61
17.6 (12.1–24.9)
1.55 (1.05–2.27)
155
41.2 (33.1–49.8)
1.26 (1.02–1.57)
113
38.5 (29.8–47.9)
1.67 (1.31–2.13)
49
14.9 (9.7–22.2)
2.19 (1.44–3.32)
4932
5.8 (5.4–6.2)
Models include controls for household income, family structure, race/ethnicity, parent education, child age, and gender.
TABLE 5 Service Use and Access
Preventive
Health Visit
(n = 90 784)
Never diagnosed with
epilepsy/seizure disorder
No. cases
78 749
Weighted prevalence
88.5 (88.0–89.0)
(95% CI)
Current epilepsy/seizure
disorder
No. cases
485
Weighted prevalence
92 (81.9–96.7)
(95% CI)
Relative risk adjusteda 1.06 (0.98–1.15)
Mental Health
Treatment
(n = 81 860)
Special Education
Services
(n = 63 795)
Care in a
Medical Home
(n = 88 034)
Unmet Care
Coordination
Need (n = 91 447)
Unmet Medical
Care Need
(n = 91 487)
Unmet Mental
Health Need
(n = 91 487)
6982
7.9 (7.5–8.4)
6625
10.6 (10.0–11.2)
54 197
57.7 (56.9–58.6)
3792
5.5 (5.1–6.0)
2686
3.5 (3.2–3.9)
751
0.8 (0.7–1.0)
147
27.7 (19.4–38.0)
285
74.8 (65.5–82.3)
181
39.7 (28.1–52.5)
106
18.8 (12.3–27.5)
55
18.2 (8.4–34.9)
23
8.1 (3.1–19.6)
3.07 (2.25–4.20)
6.39 (5.44–7.50)
0.72 (0.54–0.96)
3.34 (2.17–5.14)
4.91 (2.29–10.51)
79
15.2 (10.7–21.2)
124
30.6 (23.3–38.9)
207
40.7 (33.1–48.7)
46
14.3 (9.2–21.6)
27
5 (2.9–8.6)
10
1.5 (0.7–3.2)
1.58 (1.13–2.20)
2.62 (2.04–3.37)
0.78 (0.65–0.93)
2.31 (1.50–3.57)
1.32 (0.75–2.31)
1.33 (0.58–3.03)
7.24 (3.13–16.71)
(95% CI)
Former epilepsy/seizure
disorder
No. cases
403
Weighted prevalence
88.5 (88.0–89.0)
(95% CI)
Relative risk adjusteda 1.04 (0.98–1.10)
(95% CI)
a
Models include controls for household income, family structure, race/ethnicity, parent education, child age, and gender.
childhood epilepsy among 10-year-olds
from the 1995 Metropolitan Atlanta
Developmental Disabilities Surveillance
Program (MADDSP),2 and prevalences
reported from other developed countries, possibly reflecting a broader case
definition.25–32 Consistent with prior
studies, epilepsy was more prevalent in
boys,2 and in lower-income families,33–35
yet there were no differences based
on race/ethnicity or household educational level. The prevalence of current
epilepsy/seizure disorder was higher in
older age cohorts. Lack of data on age of
onset of seizures precluded separation
of incident cases, expected to decrease
with age,36,37 from prevalent cases in
each age group.
Our study reports the most comprehensive analysis to date of comorbidities in a nationally representative
sample of US children with epilepsy.
Compared with MADDSP (1995), which
reported 35% prevalence of any of 4
comorbid developmental disabilities
(mental retardation, cerebral palsy,
visual or hearing impairment) among
children with lifetime epilepsy,2 we
observed a 50% prevalence of developmental delay and 56% prevalence
of learning disabilities among children
with current epilepsy/seizure disorder.
Rates of learning disability among
children with epilepsy have varied in
the literature from 25% to 76%,10,11,38
depending on case definitions and
populations studied. Consistent with
prior studies, we also observed a
strong association between epilepsy
and autism/ASD, and a weaker association with ADHD, suggesting a need
for investigation of potential common
genetic and environmental etiologic
factors.39–41 Observed associations with
depression and anxiety are consistent
PEDIATRICS Volume 129, Number 2, February 2012
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
261
with current literature.1,12–14,16,42 Qualitative studies show parents of children with epilepsy to be largely aware
of their children’s emotional and
behavioral difficulties, but are frustrated with inadequate services5 and
stigma associated with accessing
mental health care, particularly among
minority families.43 Reported unmet
needs, and lack of a medical home
approach, suggest that the existing
system of care is not fully responsive
to these issues.
Physical health associations of epilepsy/
seizure disorder have not been well
studied. Reported associations with
asthma, allergies, and ear infections
could reflect common etiologic factors
(eg, immune-mediated response, environmental triggers, genetic predisposition), but must be interpreted with
caution, as parents may have preferential recall for these conditions, especially
if related to seizure onset or exacerbations, or frequent contact with physicians more likely to assign these
diagnoses. Our study confirmed reported associations with headaches.44–46
Researchers have suggested that migraine and epileptic attacks could represent a clinical continuum resulting
from altered cortical hyperexcitability.47
Children with a prior history of seizures
who have continuing headaches could
be an important population to study in
relation to this hypothesis.
Most prior studies of school performance in childhood epilepsy have relied on subjects recruited from medical
settings, with almost all showing increased likelihood of academic difficulties. 9,38,48,49 High rates of school
problems and grade repetition in our
community-based sample support
calls for further study of possible neuropsychological deficits, including
declines in processing speed50 and
vulnerabilities in working memory in
children with seizures.51 One study
suggests there may be a “window”
262
early after onset of seizures to ameliorate impact on school performance.52
We also need more information on
specific contributors to problems
with social competence, and ways to
compensate for or adapt to these
deficits.
Almost 40% of children in our study
previously diagnosed with epilepsy/
seizure disorder were not reported
by parents to currently have the condition. Although these data could reflect
a true remission of seizure activity, they
could result from an initial “misdiagnosis” of epilepsy/seizure disorder, inclusion of some children with
single febrile seizures, or variation in
interpretations of the terms “current”
versus “ever” having seizures. Other
studies have reported children with
a history of prior epilepsy to have
worse behavior problems, lower social competency, slower processing
speeds, and worse reading and spelling abilities.53,54 It is not possible within
the limitations of the NSCH dataset to
answer the important question of
whether it is only those children who
have additional neurologic conditions
(eg, cerebral palsy), who have increased risks of comorbidities and
functional limitations, even if seizures
are reported to resolve. Our finding of
higher frequency of comorbidities
compared with children never reported to have seizures suggests that
children with a previous history of epilepsy remain a clinically important,
potentially vulnerable group that warrants further longitudinal study.
Adults with epilepsy have high reported rates of mental health and developmental comorbidities, including
learning disability,11 anxiety,55,56 depression, and suicidal ideation57,58; and
physical comorbidities including severe headaches, asthma, heart disease,59 and arthritis.60 High rates of
unemployment 61 and lower educational achievement62 are reported
frequently. Pathways to poorer adult
functioning have been attributed to the
effects of recurrent seizures, medications, and social stigma, but altered
neurodevelopment of the brain starting very early in the life course may
play a role.63 More research is needed
to determine whether early intervention to address cumulative comorbidities could disrupt what appear
to be complex and continuing pathways to poorer health outcomes in
adulthood.
Study limitations include reliance on
parent report, susceptible to recall bias
and inaccuracies, for assigning children to diagnostic categories, and the
cross-sectional nature of the data that
preclude any inferences about direction of observed associations. Parent report has been widely used in the
literature to give valid estimates of
childhood neurodevelopmental conditions,64–66 and our estimated prevalences were in the same general range
as those obtained from MADDSP using
different methods of case ascertainment.2 Our study lacked data on different subtypes of epilepsy/seizure
disorder (eg, absence, Lennox Gastaut), etiology, frequency or duration of
seizures, age at onset or remission, use
of medications or other treatment
modalities, or whether children had
seen a neurologist, or were diagnosed
with additional neurologic conditions.
We could not exclude children who had
received a “misdiagnosis” of epilepsy
or seizure disorder; however, the
strengths of this study, including the
large, nationally representative nature
of the study sample, coupled with rich
data on a wide range of potential
comorbid conditions and measures of
child and family function, balance if
not outweigh these potential shortcomings. The findings likely reflect
patterns of morbidity encountered
by community-based pediatricians in
daily practice.
RUSS et al
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
ARTICLE
CONCLUSIONS
The estimated 1% prevalence of lifetime
epilepsy/seizure disorder for the US
child population is slightly higher than
prior estimates. High levels of developmental and mental health comorbidities reported for children with current
epilepsy/seizure disorder underscore
the need for a proactive approach to the
prevention of comorbidities, and a more
structured approach to early detection
and management.67 Further study of the
pathophysiologic processes contributing to the development of comorbid
conditions may provide clues to the etiology of individual epilepsy/seizure disorders. Children with reported previous
but not current epilepsy appear to continue to manifest higher rates of neurodevelopmental comorbidities and as
a clinical populations are in need of
more detailed characterization.
ACKNOWLEDGMENT
Dr Halfon was supported in part by
funding from the Maternal and Child
Health Bureau of the Health Resources and Services Administration for
the University of California Los Angeles
National Center for Education in Maternal and Child Health Alliance for
Information on Maternal and Child
Health Child and Adolescent Policy
Center.
childhood-onset epilepsy. Epilepsy Behav.
2004;5(6):937–944
Caplan R, Siddarth P, Gurbani S, Hanson R,
Sankar R, Shields WD. Depression and
anxiety disorders in pediatric epilepsy.
Epilepsia. 2005;46(5):720–730
Caplan R, Siddarth P, Stahl L, et al. Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities. Epilepsia.
2008;49(11):1838–1846
Franks RP. Psychiatric issues of childhood
seizure disorders. Child Adolesc Psychiatr
Clin N Am. 2003;12(3):551–565
Pellock JM. Defining the problem: psychiatric and behavioral comorbidity in children and adolescents with epilepsy.
Epilepsy Behav. 2004;5(suppl 3):S3–S9
Plioplys S. Depression in children and
adolescents with epilepsy. Epilepsy Behav.
2003;4(suppl 3):S39–S45
Cowan LD, Leviton A, Bodensteiner JB, Doherty
L. Problems in estimating the prevalence of
epilepsy in children: the yield from different sources of information. Paediatr Perinat Epidemiol. 1989;3(4):386–401
Sillanpää M, Helen Cross J. The psychosocial impact of epilepsy in childhood. Epilepsy Behav. 2009;15(suppl 1):S5–S10
National Institute of Neurological Disorders
and Stroke. 2007 epilepsy research
benchmarks. National Institutes of Health;
2007. Updated August 26, 2010. Available at:
www.ninds.nih.gov/research/epilepsyweb/
2007_benchmarks.htm. Accessed January
11, 2011
Blumberg S, Foster E, Frasier A, et al Design
and operation of the National Survey of
Children’s Health, 2007. National Center for
Health Statistics. Hyattsville, MD: Department
of Health and Human Services, Centers for
Disease Control and Prevention, National
Center for Health Statistics; 2009. Available at:
ftp://ftp.cdc.gov/pub/health_statistics/
nchs/slaits/nsch07/2_Methodology_Report/.
Accessed October 22, 2009
Blumberg S, Carle C, O’Connor K, Moore K,
Lippman L. Social competence: development of an indicator for children and
adolescents. Child Ind Res. 2008;1:176–197
Macomber JE, Moore KA. Benchmarking
measures of child and family well-being in
the 1997 NSAF. Washington, DC: Urban Institute; 1999. Report No.: 6. Available at:
www.urban.org/publications/410137.html.
Accessed October 22, 2009
Child and Adolescent Health Measurement
Initiative (CAHMI). National survey of children’s health indicator dataset. 2007. Available at: www.childhealthdata.org. Accessed
May 22, 2011
Zou G. A modified poisson regression
approach to prospective studies with binary data. Am J Epidemiol. 2004;159(7):
702–706
Beilmann A, Napa A, Sööt A, Talvik I, Talvik T.
Prevalence of childhood epilepsy in Estonia.
Epilepsia. 1999;40(7):1011–1019
Eriksson KJ, Koivikko MJ. Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia.
1997;38(12):1275–1282
Fong GC, Mak W, Cheng TS, Chan KH, Fong
JK, Ho SL. A prevalence study of epilepsy in
Hong Kong. Hong Kong Med J. 2003;9(4):
252–257
Kurtz Z, Tookey P, Ross E. Epilepsy in young
people: 23 year follow up of the British
national child development study. BMJ.
1998;316(7128):339–342
Larsson K, Eeg-Olofsson O. A population
based study of epilepsy in children from
a Swedish county. Eur J Paediatr Neurol.
2006;10(3):107–113
Oka E, Ohtsuka Y, Yoshinaga H, Murakami N,
Kobayashi K, Ogino T. Prevalence of childhood epilepsy and distribution of epileptic
REFERENCES
1. Jones JE, Austin JK, Caplan R, Dunn D,
Plioplys S, Salpekar JA. Psychiatric disorders in children and adolescents who have
epilepsy. Pediatr Rev. 2008;29(2):e9–e14
2. Murphy CC, Trevathan E, Yeargin-Allsopp M.
Prevalence of epilepsy and epileptic seizures
in 10-year-old children: results from the
Metropolitan Atlanta Developmental Disabilities Study. Epilepsia. 1995;36(9):866–872
3. Raspall-Chaure M, Neville BG, Scott RC. The
medical management of the epilepsies in
children: conceptual and practical considerations. Lancet Neurol. 2008;7(1):57–69
4. Baker GA, Hargis E, Hsih MM, et al; International Bureau for Epilepsy. Perceived
impact of epilepsy in teenagers and young
adults: an international survey. Epilepsy
Behav. 2008;12(3):395–401
5. Wu KN, Lieber E, Siddarth P, Smith K, Sankar
R, Caplan R. Dealing with epilepsy: parents
speak up. Epilepsy Behav. 2008;13(1):
131–138
6. Dunn DW, Austin JK, Harezlak J, Ambrosius
WT. ADHD and epilepsy in childhood. Dev
Med Child Neurol. 2003;45(1):50–54
7. Dunn DW, Austin JK, Perkins SM. Prevalence
of psychopathology in childhood epilepsy:
categorical and dimensional measures.
Dev Med Child Neurol. 2009;51(5):364–372
8. Kaufmann R, Goldberg-Stern H, Shuper A.
Attention-deficit disorders and epilepsy in
childhood: incidence, causative relations
and treatment possibilities. J Child Neurol.
2009;24(6):727–733
9. Bailet LL, Turk WR. The impact of childhood
epilepsy on neurocognitive and behavioral
performance: a prospective longitudinal
study. Epilepsia. 2000;41(4):426–431
10. Beghi M, Cornaggia CM, Frigeni B, Beghi E.
Learning disorders in epilepsy. Epilepsia.
2006;47(suppl 2):14–18
11. Sillanpää M. Learning disability: occurrence and long-term consequences in
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
PEDIATRICS Volume 129, Number 2, February 2012
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
263
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
264
syndromes: a population-based survey in
Okayama, Japan. Epilepsia. 2006;47(3):626–630
Sidenvall R, Forsgren L, Heijbel J. Prevalence and characteristics of epilepsy in
children in northern Sweden. Seizure. 1996;
5(2):139–146
Waaler PE, Blom BH, Skeidsvoll H, Mykletun
A. Prevalence, classification, and severity of
epilepsy in children in western Norway.
Epilepsia. 2000;41(7):802–810
Tellez-Zenteno JF, Pondal-Sordo M, Matijevic
S, Wiebe S. National and regional prevalence of self-reported epilepsy in Canada.
Epilepsia. 2004;45(12):1623–1629
Schiariti V, Farrell K, Houbé JS, Lisonkova S.
Period prevalence of epilepsy in children in
BC: a population-based study. Can J Neurol
Sci. 2009;36(1):36–41
Chin RF, Neville BG, Peckham C, Wade A,
Bedford H, Scott RC; NLSTEPSS Collaborative Group. Socioeconomic deprivation
independent of ethnicity increases status
epilepticus risk. Epilepsia. 2009;50(5):1022–
1029
Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984.
Epilepsia. 1993;34(3):453–468
Camfield CS, Camfield PR, Gordon K, Wirrell
E, Dooley JM. Incidence of epilepsy in
childhood and adolescence: a populationbased study in Nova Scotia from 1977 to
1985. Epilepsia. 1996;37(1):19–23
Fastenau PS, Jianzhao Shen , Dunn DW,
Austin JK. Academic underachievement
among children with epilepsy: proportion
exceeding psychometric criteria for learning disability and associated risk factors.
J Learn Disabil. 2008;41(3):195–207
Tuchman R. Autism and epilepsy: what has
regression got to do with it? Epilepsy Curr.
2006;6(4):107–111
Saemundsen E, Ludvigsson P, Rafnsson V.
Autism spectrum disorders in children
with a history of infantile spasms: a population-based study. J Child Neurol. 2007;22
(9):1102–1107
Hesdorffer DC, Ludvigsson P, Olafsson E,
Gudmundsson G, Kjartansson O, Hauser WA.
ADHD as a risk factor for incident unprovoked seizures and epilepsy in children.
Arch Gen Psychiatry. 2004;61(7):731–736
Pellock JM. Understanding co-morbidities
affecting children with epilepsy. Neurology. 2004;62(5 suppl 2):S17–S23
Vona P, Siddarth P, Sankar R, Caplan R.
Obstacles to mental health care in pediatric
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
epilepsy: insight from parents. Epilepsy
Behav. 2009;14(2):360–366
Wirrell EC, Hamiwka LD. Do children with
benign rolandic epilepsy have a higher
prevalence of migraine than those with
other partial epilepsies or nonepilepsy
controls? Epilepsia. 2006;47(10):1674–1681
Cai S, Hamiwka LD, Wirrell EC. Peri-ictal
headache in children: prevalence and
character. Pediatr Neurol. 2008;39(2):91–96
Clarke T, Baskurt Z, Strug LJ, Pal DK. Evidence of shared genetic risk factors for
migraine and rolandic epilepsy. Epilepsia.
2009;50(11):2428–2433
Piccinelli P, Borgatti R, Nicoli F, et al. Relationship between migraine and epilepsy in
pediatric age. Headache. 2006;46(3):413–421
Canavese C, Rigardetto R, Viano V, et al. Are
dyslexia and dyscalculia associated with
Rolandic epilepsy? A short report on ten Italian
patients. Epileptic Disord. 2007;9(4):432–436
Piccinelli P, Borgatti R, Aldini A, et al. Academic performance in children with rolandic epilepsy. Dev Med Child Neurol. 2008;
50(5):353–356
Austin JK, Perkins SM, Johnson CS, et al. Selfesteem and symptoms of depression in children with seizures: relationships with neuropsychological functioning and family variables
over time. Epilepsia. 2010;51(10):2074–2083
Schouten A, Oostrom KJ, Pestman WR,
Peters AC, Jennekens-Schinkel A; Dutch
Study Group of Epilepsy in Childhood.
Learning and memory of school children
with epilepsy: a prospective controlled
longitudinal study. Dev Med Child Neurol.
2002;44(12):803–811
Fastenau PS, Johnson CS, Perkins SM, et al.
Neuropsychological status at seizure onset
in children: risk factors for early cognitive
deficits. Neurology. 2009;73(7):526–534
Berg AT, Langfitt JT, Testa FM, et al. Global
cognitive function in children with epilepsy:
a community-based study. Epilepsia. 2008;
49(4):608–614
Berg AT, Vickrey BG, Testa FM, Levy SR,
Shinnar S, DiMario F. Behavior and social
competency in idiopathic and cryptogenic
childhood epilepsy. Dev Med Child Neurol.
2007;49(7):487–492
Gaitatzis A, Trimble MR, Sander JW. The
psychiatric comorbidity of epilepsy. Acta
Neurol Scand. 2004;110(4):207–220
Gaitatzis A, Carroll K, Majeed A, W Sander J.
The epidemiology of the comorbidity of
epilepsy in the general population. Epilepsia. 2004;45(12):1613–1622
57. Tellez-Zenteno JF, Patten SB, Jetté N, Williams J,
Wiebe S. Psychiatric comorbidity in epilepsy:
a population-based analysis. Epilepsia. 2007;
48(12):2336–2344
58. Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander
JW. Suicide in people with epilepsy: how great
is the risk? Epilepsia. 2009;50(8):1933–1942
59. Strine TW, Kobau R, Chapman DP, Thurman
DJ, Price P, Balluz LS. Psychological distress, comorbidities, and health behaviors
among U.S. adults with seizures: results
from the 2002 National Health Interview
Survey. Epilepsia. 2005;46(7):1133–1139
60. Kobau R, Zahran H, Thurman DJ, et al;
Centers for Disease Control and Prevention
(CDC). Epilepsy surveillance among adults
—19 States, Behavioral Risk Factor Surveillance System, 2005. MMWR Surveill
Summ. 2008;57(6):1–20
61. Kobau R, Zahran H, Grant D, Thurman DJ,
Price PH, Zack MM. Prevalence of active
epilepsy and health-related quality of life
among adults with self-reported epilepsy in
California: California Health Interview Survey, 2003. Epilepsia. 2007;48(10):1904–1913
62. Shackleton DP, Kasteleijn-Nolst Trenité DG,
de Craen AJ, Vandenbroucke JP, Westendorp RG. Living with epilepsy: long-term
prognosis and psychosocial outcomes.
Neurology. 2003;61(1):64–70
63. Hermann B, Seidenberg M, Jones J. The
neurobehavioural comorbidities of epilepsy:
can a natural history be developed? Lancet
Neurol. 2008;7(2):151–160
64. Blanchard LT, Gurka MJ, Blackman JA.
Emotional, developmental, and behavioral
health of American children and their
families: a report from the 2003 National
Survey of Children’s Health. Pediatrics.
2006;117(6). Available at: www.pediatrics.
org/cgi/content/full/117/6/e1202
65. Gurney JG, McPheeters ML, Davis MM. Parental report of health conditions and
health care use among children with and
without autism: National Survey of Children’s Health. Arch Pediatr Adolesc Med.
2006;160(8):825–830
66. Kogan MD, Blumberg SJ, Schieve LA, et al.
Prevalence of parent-reported diagnosis of
autism spectrum disorder among children in
the US, 2007. Pediatrics. 2009;124(5):1395–1403
67. Barry JJ, Ettinger AB, Friel P, et al; Advisory
Group of the Epilepsy Foundation as part of
its Mood Disorder. Consensus statement:
the evaluation and treatment of people
with epilepsy and affective disorders. Epilepsy Behav. 2008;13(suppl 1):S1–S29
RUSS et al
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
A National Profile of Childhood Epilepsy and Seizure Disorder
Shirley A. Russ, Kandyce Larson and Neal Halfon
Pediatrics 2012;129;256; originally published online January 23, 2012;
DOI: 10.1542/peds.2010-1371
Updated Information &
Services
including high resolution figures, can be found at:
http://pediatrics.aappublications.org/content/129/2/256.full.ht
ml
References
This article cites 63 articles, 11 of which can be accessed free
at:
http://pediatrics.aappublications.org/content/129/2/256.full.ht
ml#ref-list-1
Citations
This article has been cited by 7 HighWire-hosted articles:
http://pediatrics.aappublications.org/content/129/2/256.full.ht
ml#related-urls
Subspecialty Collections
This article, along with others on similar topics, appears in
the following collection(s):
Development/Behavioral Issues
http://pediatrics.aappublications.org/cgi/collection/developme
nt:behavioral_issues_sub
Attention-Deficit/Hyperactivity Disorder (ADHD)
http://pediatrics.aappublications.org/cgi/collection/attention-d
eficit:hyperactivity_disorder_adhd_sub
Autism/ASD
http://pediatrics.aappublications.org/cgi/collection/autism:asd
_sub
Permissions & Licensing
Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
http://pediatrics.aappublications.org/site/misc/Permissions.xh
tml
Reprints
Information about ordering reprints can be found online:
http://pediatrics.aappublications.org/site/misc/reprints.xhtml
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 © 2012 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014