Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017
Conditions: Mucocutaneous Lymph Node Syndrome
Sponsor: Children's Hospital of Fudan University

Title: Epidemiologic Features of Kawasaki Disease in 
Shanghai From 2013 Through 2017 
 
Document type: Study Protocol and Statistical Analysis Plan 
 
Date: March 7, 2019 
 
 

Study Protocol  
Data Collection 
This study was conducted based on the former three surveys of KD in Shanghai. A set 
of questionnaires and diagnostic guidelines were sent to 50 hospitals providing 
pediatric medical care in Shanghai. All patients discharged from these hospitals from 
January 1, 2013 through December 31, 2017 with an International Classification of 
Diseases (ICD) code for KD or mucocutaneous lymph node syndrome (ICD9 446.1 and 
ICD10 M30.3) were enrolled in the study. Data were collected by pediatricians, 
including demographic information, clinical manifestations, prognosis, laboratory 
indexes, treatment, and echocardiographic findings. The contents of the questionnaire 
was mildly modified with addition of erythema and induration at Bacillus Calmette-
Guérin (BCG) sites, the date of appearance and disappearance of CAL measured by 
echocardiography, the sites and severity of valvular regurgitation, the presence of 
coronary stenosis and coronary thrombosis, and some new laboratory indexes including 
neutrophil count (NEUT), lymphocyte count (LYM), aspartate transaminase (AST), 
serum sodium (Na), and total bilirubin (TB). 
 
Inclusion and Exclusion Criteria 
After all questionnaires were returned, two senior pediatric cardiologists were 
responsible for further verification. Patients who met the diagnostic criteria for KD 
released by the American Heart Association (AHA)1,12 were included in this study. 
Exclusion criteria were as follows: 1) not meeting the above diagnostic criteria; 2) not 
in acute phase; 3) repeated cases; 4) cases not from 2013 to 2017. All eligible cases 
were entered into to the KD database. 
 
Definitions 
Among patients diagnosed with KD, those with persistent fever and at least 4 of 5 
principal features were classified as complete KD (CKD). The others with persistent 
fever but less than 4 principal features were classified as incomplete KD (IKD). 

 
The first day of illness was defined as the first day of fever. Intravenous 
immunoglobulin (IVIG) resistance was defined as persistent fever (>38°C) after 36 
hours of completion of initial IVIG infusion or recurrent fever requiring another dose 
of IVIG or other adjunctive therapies. 
 
Laboratory indices before initial IVIG infusion were recorded, including the highest 
values of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet 
count (PLT), white blood cell count (WBC), creatine kinase-muscle/brain (CK-MB), 
alanine aminotransferase (ALT), AST, and TB, and the lowest values of hemoglobin 
(HB), serum albumin (ALB), and Na if laboratory tests were performed more than once 
before initial IVIG. NEUT and LYM of the same blood test with highest WBC were 
also recorded. 
 
On two-dimensional echocardiography, a coronary artery was defined as abnormal if 
the luminal diameter was >3.0 mm in children aged younger than 5 years or >4.0 mm 
in those aged 5 years and older, or when the internal diameter of a segment was ≥1.5 
times that of an adjacent segment13. A medium aneurysm was defined as an internal 
luminal diameter from 4 to 8 mm and a giant aneurysm was defined as an internal 
luminal diameter >8 mm. The coronary measurements of the most severe 
echocardiography were recorded if the measurement was performed more than once. 
Coronary stenosis was assessed only by coronary angiography and coronary artery 
thrombosis was assessed by echocardiography or angiography. 
 
Long-term outcomes of CAL were classified into three categories based on the duration 
of the lesions from the appearance of CAL detected by echocardiography, including 
resolution within one month, resolution after one month, and sustained lesions. All 
patients without echocardiography suggesting resolution of CAL during the 5-year 
period were classified as the sustained lesions group, regardless of spans of the follow-
up time. Resolution was defined as regression of CAL to normal. 

Statistical Analysis 
The incidence of KD was calculated by dividing the number of newly diagnosed KD 
patients under 5 years old who inhabited in shanghai by the resident population of the 
corresponding age group in Shanghai. Census data were acquired from Shanghai 
Municipal Center for Disease Control and Prevention. 
 
Data are presented as mean (±standard deviation) or median (interquartile range) for 
continuous variables, and count (percentage) for categorical variables. Continuous 
variables were compared between groups by using unpaired Student’s t tests or Mann-
Whitney U test. Categorical variables were compared by using χ2 test or Fisher exact 
test. 
 
Univariate analysis was performed to explore potential risk factors for CAL using above 
statistical methods, including age of onset, male sex, KD type, fever days before initial 
IVIG, the dose of initial IVIG and all 13 laboratory indexes. Among them, CRP was 
divided into four groups based on quartiles due to the presence of truncated values. 
Multivariate logistic regressions were performed to identify risk factors independently 
associated with CAL. A two-tailed P<0.05 was considered statistically significant. 
Analyses were performed with SPSS 23.0 (IBM, Armonk, NY). 
 
A Kaplan-Meier curve was drawn to describe the resolution time of CAL and the Log-
rank test was performed for comparison between groups. Event was defined as 
regression of CAL to normal. Time was defined as months from the appearance of CAL 
to an event by echocardiography, or to last echocardiography if no event occurred. 
Patients who did not have an event or lost contact during the 5-year period (from 2013 
to 2017) were considered as censored.