Seizure: European Journal of Epilepsy 61 (2018) 149–152

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Seizure: European Journal of Epilepsy

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National survey of factors associated with repeated admissions due to febrile T

seizure
⁎
Yusuke Okuboa,b, , Atsuhiko Handac, Hiroki Nariaid
a
Department of Epidemiology, UCLA Fielding School of Public Health, LA, CA, USA
b
Department of Social Medicine, National Research Institute for Child Health and Development, Tokyo, Japan
c
Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
d
Division of Pediatric Neurology, Department of Pediatrics, UCLA Medical Center, LA, CA, USA

A R T I C LE I N FO A B S T R A C T

Keywords: Purpose: Several studies reported recent trends in febrile seizure (FS) in terms of prevalence, incidence, and
Febrile seizure hospitalization rates at a national level in the USA. However, no studies have revealed risk factors for repeated
Repeated admission admissions due to FS.
Risk factor Method: We extracted discharge records of patients with FS aged < 6 years for the years 2010–14 using the
Nationwide readmission database
Nationwide Readmission. Data were weighted to estimate the readmission rates and ascertain the factors as-
sociated with readmission due to FS, using multivariable negative binomial regression and Cox proportional
hazard models.
Results: The readmission rate of FS is approximately 3.45 cases per 1000 person-months after hospital discharge.
Children aged 1–3 years had elevated rate of FS readmission with a peak age of 2 (adjusted IRR, 5.09; 95%CI,
2.25–11.5). Boys had 1.75 times higher rates of FS readmission than girls (95%CI, 1.13–2.70). Children with
very-low income levels were more likely to be readmitted, compared to those with very-high income levels
(adjusted IRR, 2.57; 95%CI, 1.39–4.76).
Conclusions: We provided novel insights into the current epidemiology of children with FS and risk factors
associated with FS readmissions.

1. Introduction rates at a national level have been uncertain.

Febrile seizure (FS) is the most common seizure observed in chil-
dren. FS is characterized by episodes of convulsions that occur in as-
sociation with fever in children aged between 3 months and 5 years in
the absence of a central nervous system (CNS) infections or electrolyte
imbalance [1–5]. FS is believed to be a benign seizure syndrome dis-
tinct from other neurologic disorders [4].
Several studies have investigated the epidemiology and risk factors
of FS. The incidence of FS peaks at the age of 18 months, and is 2%–5%
among all children [1–5]. Risk factors for developing FS are male
gender, children living in Asian and Pacific Island countries, high fever,
infections to human herpesvirus 6 and 7, influenza, iron deficiency
anemia, allergic rhinitis, family history of FS, and prenatal exposure to
cigarettes. However, the potential association between these factors
and repeated admissions remain unclear. Furthermore, no studies have
revealed risk factors for readmission to the hospitals and readmission
To address the gaps in knowledge, this study investigated risk fac-
tors for readmission due to febrile seizure using US national re-
presentative readmission database.
2. Methods
2.1. Study population and participation
We conducted retrospective observational study using the National
Readmission Database (NRD) for the year 2010–2014. The detailed
explanation of NRD can be found elsewhere [6]. Briefly, the NRD is a
unique database constructed from 21 State Inpatient Databases (SID) to
estimate national readmission rates for all payers and the uninsured. It
consists of reliable, verified patient linkage numbers in the SID that can
be used to track patients across hospitals within a state while adhering
to strict privacy guidelines. The NRD includes approximately 14million

⁎
Corresponding author at: UCLA Fielding School of Public Health, 650 Charles E. Young Dr. South, 16-035 Center for Health Sciences, Los Angeles, CA 99095,
USA.
E-mail address: sunning_dale@yahoo.co.jp (Y. Okubo).

https://doi.org/10.1016/j.seizure.2018.08.013
Received 6 May 2018; Received in revised form 3 July 2018; Accepted 12 August 2018
1059-1311/ © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Y. Okubo et al. Seizure: European Journal of Epilepsy 61 (2018) 149–152

discharges per year in the community, specialty, and federal hospitals Table 1
from 21 states (West: CA, HI, NM, NV, UT, WA; Midwest: IA, MO, NE, Baseline patient characteristics.
SD, WI; South: AR, FL, GA, LA, SC, TN, VA; Northeast: NY, RI, VT) N or Mean (% or SD)
accounting for 49.1% of US hospitalizations (36million when
weighted). Total population 40,956 (100)
Age 1.45 (0.03)
We extracted data on patients hospitalized with FS aged under 6
Male 22,847 (55.8)
years. Hospitalizations with FS were identified using the International Income level
Classification of Diseases, Ninth Revision, Clinical Modification (ICD- Very low 15,640 (38.2)
9CM) code (780.31: febrile convulsions (simple), unspecified, and Low 10,120 (24.7)
780.32: complex febrile convulsions) in the primary or secondary di- High 8352 (20.4)
Very high 6843 (16.7)
agnosis fields, as we did in the previous study [1]. The data were
Primary payer
weighted with discharge weight (DISCWT) variables to calculate the Public 26,229 (64.0)
estimated number of hospitalizations in the entire United States. Private 12,239 (29.9)
Other 2488 (6.08)
County of residence
Central area 21,265 (51.9)
2.2. Measurements of variables Medium or small area 12,589 (30.7)
Other area 7102 (17.3)
Patient characteristics included age, sex (male or female), the type Weekend admission 11,454 (28.0)
of admission (weekend/weekday), utilization of emergency department Utilization of emergency services 30,615 (74.7)
LOS in index admission, days 1.98 (0.03)
services (no/yes), primary payer information (private, Medicare/
Season
Medicaid, other types [self-pay, no insurance, or no information]), Spring 10,996 (26.8)
median household income quartiles for counties of residence (very-low, Summer 9806 (23.9)
low, high, very-high), patient county location (central counties [metro Fall 8660 (21.1)
and fringe areas of > = 1 million population], medium or small Winter 11,495 (28.1)
Presence of chronic disorder 3083 (7.53)
counties [metro areas of 50,000–999,999 population], and other
counties [micropolitan or other]). *
LOS, length of hospital stay.
We also identified patient chronic medical conditions (congenital
heart, kidney, pulmonary, endocrine, hematologic, gastrointestinal, and 3. Results
neurologic diseases; cancer or leukemia; and autoimmune disease).
Pediatric chronic medical conditions were determined using pediatric Table 1 shows the baseline characteristics of children with FS from
complex chronic conditions classification system version 2 developed NRD, 2010-2014. The mean age for hospitalized children with FS was
by Feudtner and colleagues to investigate the role of chronic conditions 145 years. Majority of children were covered by public insurance
among children [10]. coverage (64%), resided in central area (51.9%). Most patients were
Hospital characteristics included ownership (government, not-for- hospitalized during weekday (72%), utilized emergency department
profit or private hospital), bed size (small, medium, or large), and services (75%), and stayed at hospital for approximately 2 days. The
teaching status (teaching or non-teaching) of the hospital. proportions of admission season were higher in spring and winter than
in summer and fall. About 7.53% of patients had at least one of chronic
disorders, including neuromuscular (2.8%), cardiovascular (1.3%), re-
2.3. Outcomes spiratory (0.4%), renal (0.4%), hemato-immunologic (1.2%), metabolic
(0.7%), malignancy (0.2%), and neonatal (0.3%) disorders defined by
Outcomes of interest are incidence rates (IR) of readmissions over pediatric complex chronic conditions classification system version 2
the study. IRs were calculated based on the number of readmissions as developed by Feudtner et al. [10]. FS children were more likely to be
the numerator and the total person-months as the denominator. As admitted to the hospitals with the large bed size (64.3%), having
unique patient identifiers in the NRD cannot be tracked across data teaching purpose (71.6%), and private for-profit hospitals (75.2%) as
years, we considered all patients were censored on December. their primary resource for healthcare (Table 2).
Table 3 demonstrates the risk factors associated with repeated ad-
missions using negative binomial regression model. Children aged 1–3
2.4. Statistical analysis years had significantly higher rates of readmissions than children aged
4 years or older. The highest rate was observed among children aged 2
We presented descriptive statistics of patient and hospital char- years (IRR, 5.09; 95%CI 2.25–11.5). Male had 1.75 times higher rates of
acteristics using frequencies and proportions for categorical variables, readmission than females did (95%CI, 1.13–2.70). The rate of read-
and mean and standard deviation (SD) for continuous variables. mission among children with very-low income levels was 2.57 times
Multivariable negative binomial regression was conducted to in-
vestigate the factors associated with repeated admissions. We used
negative binomial regression model to account for over-dispersion of Table 2
the data and to calculate valid incidence rate ratio (IRR) using log- Hospital characteristics.
transformed person-months as an offset. Furthermore, to check the N (%)
robustness of our results, Cox proportional hazard model was con-
Bed size
structed to ascertain the factors associated with readmissions. For the
Large 26,332 (64.3)
Cox proportional hazard model, we excluded data on patients who were Medium 10,700 (26.1)
readmitted > 2 times. The results for the regression models were ad- Small 3924 (9.6)
justed for patient and hospital characteristics as well as years of ad- Teaching hospital 29,322 (71.6)
missions, and were reported with 95% confidence intervals. All tests Hospital type
Government 6417 (15.7)
were two-sided, and P < .05 was considered statistically significant.
Private, non-profit 30,805 (75.2)
All data were analyzed using STATA software version 14.2 (StataCorp Private, investor owned 3734 (9.1)
LP, Texas, USA).

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Y. Okubo et al. Seizure: European Journal of Epilepsy 61 (2018) 149–152

Table 3
Risk factors for repeated admissions using negative binomial regression.
Case N Person Month IR Adjusted IRR (95%CI) P-value

Total 950 40,956 275126.5 3.45 – –

Age
0 113 8830 58591.96 1.94 1.10 (0.40, 3.02) 0.86
1 449 17541 118812.9 3.78 3.26 (1.51, 7.02) 0.003
2 266 7610 51154.64 5.20 5.09 (2.25, 11.5) < 0.001
3 81 3487 23022.39 3.53 3.17 (1.13, 8.95) 0.029
4 or older 40 3487 23544.61 1.70 Reference –
Gender
Male 627 22847 151463.4 4.14 1.75 (1.13, 2.70) 0.012
Female 324 18109 123663.1 2.62 Reference –
Income
Very Low 404 15640 104946.9 3.85 2.57 (1.39, 4.76) 0.003
Low 224 10120 68419.26 3.28 1.53 (0.81, 2.90) 0.191
High 204 8352 56555.98 3.60 1.99 (0.93, 4.29) 0.078
Very High 119 6843 45204.33 2.63 Reference –
Insurance 950 40,956 275126.5
Public 602 26,228 176048.2 3.42 Reference –
Private 306 12,239 82387.66 3.72 1.42 (0.90, 2.25) 0.13
Other 42 2489 16690.64 2.52 0.73 (0.27, 1.94) 0.53
Residential area
Central 508 21265 140882.3 3.60 Reference –
Medium or small 285 12589 85679.59 3.32 1.79 (0.99, 3.24) 0.053
Other 158 7102 48564.61 3.25 1.43 (0.73, 2.81) 0.29
Admission
Weekend 257 11454 197715.6 1.30 0.96 (0.61, 1.53) 0.87
Weekday 693 29502 77410.88 8.96 Reference –
ED use
use 655 30615 206699.8 3.17 0.63 (0.38, 1.04) 0.07
no use 295 10341 68426.69 4.32 Reference –
Chronic disease
Presence 95 3083 20658.39 4.61 1.38 (0.70, 2.73) 0.36
Absence 855 37873 254468.1 3.36 Reference –

IR, incidence rate (cases per 1000 person-months); IRR, incidence rate ratio; 95%CI, 95% confidence interval.

that among children with very high-income levels (95%CI, 1.39–2.70). Table 4
No significant difference in readmission rates was observed with respect Risk factors for repeated admissions using Cox proportional hazard model.
to insurance status, residential area, weekday or weekend admission, Hazard Ratio (95%CI) P-value
emergency department utilizations, and presence of chronic disease.
Table 4 shows the risk factors associated with readmissions using Age
Cox proportional hazard model. We observed similar results to those in 0 1.22 (0.53, 2.79) 0.64
1 2.27 (1.30, 3.93) 0.004
negative binomial regression model. Age, male gender, very-low in-
2 3.10 (1.72, 5.59) < 0.001
come levels were statistically significantly associated with read- 3 2.08 (1.02, 4.23) 0.043
missions. 4+ Reference –
Gender
Male 1.50 (1.13, 1.98) 0.005
Female Reference –
4. Discussion Income
Very Low 1.61 (1.05, 2.47) 0.03
The present study demonstrates the most recent national estimates Low 1.32 (0.84, 2.08) 0.22
of readmission due to FS in the USA for the years 2010–2014. Overall, High 1.43 (0.80, 2.55) 0.23
Very High Reference –
the readmission rate of FS is approximately 3.45 cases per 1000 person-
Insurance
months after hospital discharge. Children aged 1–3 years, boys, and Public Reference –
those with very-low income levels were more likely to be readmitted. Private 1.16 (0.82, 1.65) 0.41
To the best of the knowledge, this is the first study that investigated the Other 0.75 (0.41, 1.40) 0.37
readmission of FS at a national level in the US. Residential Area
Large Reference –
Several epidemiological studies demonstrated that the overall re- Medium or small 1.30 (0.85, 1.98) 0.23
currence rate of FS was estimated 30%–50% [7,8]. The observed Other area 1.14 (0.71, 1.83) 0.59
readmission rate (3.45 cases per 1000 person-months) was much Admission
smaller than the recurrence rates, indicating that most children who Weekend 0.97 (0.67, 1.39) 0.85
Weekday Reference –
had recurrence of FS did not need readmissions. These discrepancies are
ED use
reasonable since children who require hospitalizations are limited cases use 0.75 (0.54, 1.06) 0.10
such as status epilepticus, complex febrile seizure, and comorbid in- no use Reference –
fectious disorders (pneumonia, urinary tract infection, etc.) and chronic Chronic disorders
medical conditions. Presence 1.40 (0.90, 2.18) 0.14
Absence Reference –
In previous studies, the recurrence rates varied with age from
50%–65% in children < 2 years to 20% in older children [7,8]. Cor-
respondingly, our study demonstrated children aged 1–3 years were
more likely to be readmitted with the highest risk of 2 years of age. We

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Y. Okubo et al.
believe that the elevated risks of recurrence of FS among these age
groups could be multifactorial such as the increased excitability in the
developing brain secondary to a developmental imbalance between
maturation of excitatory and inhibitory circuits, and higher risks of
febrile disorders. Indeed, previous studies revealed children aged 2
years had highest risks of hospitalizations due to several infectious and
non-infectious disorders [11–15].
Several studies reported that male gender was a risk factor for de-
veloping FS and hospital admissions due to FS. Similarly, our results
showed higher risk of readmissions among boys than girls. These male
predominance of incidences, admissions due to FS could be explained
by a higher susceptibility to infections, genetic predispositions, and
elevated severity of FS among boys [11–17].
Finally, we observed higher risk of readmissions among children
with very-low income levels compared to those with very-high income
levels. This may have reflected several risk factors in this group, such as
elevated risks of infectious diseases, parental smoking status, nutri-
tional status of the children (especially for iron deficiency), and par-
ental anxiety and family dysfunction among children with low socio-
economic status, as indicated by previous studies [1,11–20]. Further
studies are required to address these explanations and improve dis-
parities among children.
There are several limitations to our study. The number of FS-asso-
ciated hospitalization, their rates, and comorbid medical conditions
may have been under-estimated because of possible miscoding or mis-
classification. The detailed clinical presentation (including duration of
seizure), physical examination, laboratory data, and results of the
imaging studies were unavailable in the NRD. The NRD captures only
children hospitalized with FS at a national level; therefore, we cannot
identify the recurrence rate of FS in the entire USA, including children
who were not hospitalized. A unique feature and strength of this study
was the use of the NRD, which is the only national inpatient database
currently available in the US so that our analyses reflected overall US
pediatric population, whereas other database, such as Pediatric Health
Information System or Medicaid database, can capture only a limited
portion of the populations, such as those hospitalized in children’s
hospitals or those covered by Medicaid. Using the NRD, we were able to
calculate robust national estimates of epidemiology of children hospi-
talized with FS in the entire US.
In summary, we provided novel insights into the current epide-
miology of children with FS and risk factors associated with repeated
admissions. Children aged 1–3 years, boys, and children with very-low
income levels were more likely to be readmitted. Therefore, they might
deserve closer follow-up plan at the time of initial discharge. We believe
our investigations could provide useful information for further etiolo-
gical or epidemiological studies of FS.
Financial disclosure
The authors have no financial relationships relevant to this article to
disclose.
152
Seizure: European Journal of Epilepsy 61 (2018) 149–152
Funding source
Yusuke Okubo was supported by grants from the Ministry of Health,
Labor and Welfare, Japan. Hiroki Nariai is supported by Susan Spencer
Clinical Research Training Fellowship in Epilepsy, given by the
American Academy of Neurology with funding from the American
Epilepsy Society, the American Brain Foundation, and the Epilepsy
Foundation. We have no other research or project support, including
internal funding.
Potential conflict of interest
The authors have no conflict of interest relevant to this article to
disclose.
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