Breastfeeding and Risk of

Kawasaki Disease: A Nationwide

Longitudinal Survey in Japan
Takashi Yorifuji, MD, PhD,a Hirokazu Tsukahara, MD, PhD,b Hiroyuki Doi, MD, PhDc

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is the most common cause of childhood- abstract
acquired heart disease in developed countries. However, the etiology of KD is not known.
Aberrant immune responses are considered to play key roles in disease initiation and
breastfeeding can mature immune system in infants. We thus examined the association
between breastfeeding and the development of KD.
METHODS: We used a nationwide population-based longitudinal survey ongoing since 2010
and restricted participants to a total of 37630 children who had data on their feeding
during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses
to questions about hospital admission for KD during the period from 6 to 30 months of age
were used as outcome. We conducted logistic regression analyses controlling for child and
maternal factors with formula feeding without colostrum as our reference group.
RESULTS: A total of 232 hospital admissions were observed. Children who were breastfed
exclusively or partially were less likely to be hospitalized for KD compared with those
who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95%
confidence interval: 0.120.55) for exclusive breastfeeding and 0.27 (95% confidence
interval: 0.130.55) for partial breastfeeding. Although the risk reduction was not
statistically significant, feeding colostrum only also provided a protective effect.
CONCLUSIONS: We observed protective effects of breastfeeding on the development of
KD during the period from 6 to 30 months of age in a nationwide, population-based,
longitudinal survey in Japan, the country in which KD is most common.

aDepartment of Human Ecology, Okayama University Graduate School of Environmental and Life Science,
WHATS KNOWN ON THIS SUBJECT: Kawasaki
Okayama, Japan; and Departments of bPediatrics, and cEpidemiology, Okayama University Graduate School of disease (KD), an acute self-limiting systemic
Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan vasculitis, is the most common cause of childhood-
acquired heart disease in developed countries, but
Dr Yorifuji contributed to obtaining the data, the study design, data analysis and interpretation,
the etiology of the disease is unknown. Aberrant
and writing and revision of the manuscript; Dr Tsukahara contributed to the study design, data
immune responses are considered to play key roles
interpretation, and revision of the manuscript; Dr Doi contributed to the negotiation with the
Ministry of Health to obtain the data, interpreting the data, revision of the manuscript, and study in disease initiation.
supervision; and all authors approved the nal manuscript as submitted. WHAT THIS STUDY ADDS: We observed protective
DOI: 10.1542/peds.2015-3919 effects of breastfeeding on the development of KD
Accepted for publication Mar 8, 2016 during the period from 6 to 30 months of age in
Japan, the country in which KD is most common.
Address for correspondence to Takashi Yorifuji, MD, PhD, Department of Human Ecology, Okayama
University Graduate School of Environmental and Life Science, 3-1-1 Tsushima-naka, Kita-ku,
Okayama 700-8530, Japan. E-mail: yorichan@md.okayama-u.ac.jp
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
To cite: Yorifuji T, Tsukahara H, Doi H. Breastfeeding and
Copyright 2016 by the American Academy of Pediatrics Risk of Kawasaki Disease: A Nationwide Longitudinal
Survey in Japan. Pediatrics. 2016;137(6):e20153919

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PEDIATRICS Volume 137, number 6, June 2016:e20153919 ARTICLE
Kawasaki disease (KD), an acute
self-limiting systemic vasculitis of
childhood, is the most common cause
of childhood-acquired heart disease
in most developed countries.15 KD
mainly occurs in young children5;
88% of cases occurred under 5
years of age during the 2-year period
of 2011 through 2012 in Japan.6,7 The
highest incidence of KD is reported in
Japan.8 Although the etiology of the
disease is unknown,1 KD may occur
in genetically susceptible individuals
with an aberrant immune response
to some environmental trigger.3,4,9
Breastfeeding, a normative standard
for infant feeding and nutrition, is
considered to provide protection
against infections and contain
numerous factors that modulate
and promote development of the
immune system during infancy.10
Immune maturation may relate to
lifelong immunologic disorders11;
thus, breastfeeding may be important
to the development of the diseases
in which the immune system plays
a role in disease initiation, including
KD. However, as far as we know,
no studies have examined the
association between breastfeeding
and the development of KD.
In the current study, we therefore
examined the association in
children between breastfeeding
and the development of KD from
6 to 30 months of age, using data
from a nationwide, population-
based, longitudinal survey in Japan,
the country in which KD is most
common.8
METHODS
Study Participants
Since 2010, the Japanese Ministry
of Health, Labor, and Welfare
has conducted an annual survey
among newborn infants and their
parents, known as the Longitudinal
Survey of Babies in the 21st
Century. Questionnaires were sent
to all families in Japan who had
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2 YORIFUJI et al
FIGURE 1
Participant owchart.
had an infant (or infants) born
between May 10 and 24, 2010, to
collect information of infants at 6
months of age. Among the 43767
questionnaires mailed, 38554
were completed and returned
(response rate of 88.1%). Follow-up
questionnaires were sent to
participating families each year (at
age 18 months, 30 months). Data
from 20102012 (ie, the third survey
at age 30 months) are currently
available from the Ministry of Health,
Labor, and Welfare. Birth records
from the Japanese vital statistics
system are also linked to each child
surveyed. Birth record data include
birth length; birth weight; gestational
age; singleton, twin, or other multiple
birth; gender; parity; and parental
age at delivery.
In the current study, we used data
from the first (age 6 months), second
(age 18 months), and third surveys
(age 30 months) because information
on feeding practices during infancy
was queried only in the first survey,
and hospital admission for KD during
the previous year was queried in
the second and third surveys (ie,
hospitalizations between the ages
of 6 and 18 months and between
18 and 30 months). Children with
information missing about feeding
practices during infancy (n = 924)
were excluded, leaving a total of
37630 participants for the analysis
(Fig 1). We then excluded 3702
participants who lacked information
from the second and third surveys
on hospital admission owing to
KD. Among the remaining 33928
participants, 27735 had information
on hospital admission for KD from
both surveys: 31355 participants
only at the second survey, and 30308
only at the third survey.
Infant Feeding Practices
The first survey at 6 months of age
included questions on breastfeeding
practices (infant was breastfed, only
fed colostrum, or never breastfed)
and formula feeding practices
(infant was fed formula or never
fed formula). Using information
on both breastfeeding and formula
feeding practices, we established
the categories of formula feeding
without colostrum (and never
breastfed), formula feeding
(only) with colostrum, partial
breastfeeding, and exclusive
breastfeeding. We used category as a
main exposure of interest.
Additionally, the duration (months)
of breastfeeding and formula
feeding was queried. We divided the
category of partial breastfeeding
based on breastfeeding duration
(breastfeeding for 12 months,
35 months, or 67 months) in an
additional analysis. Although the first
survey was conducted at 6 months
of age, children breastfed up to age 7
months were included owing to the
timing of the survey.
Hospital Admission for KD
Hospital admission for KD during
the previous 1 year was queried at
the second and third surveys (ie,
hospitalizations between the ages
of 6 and 18 months and between 18
and 30 months). We used hospital
admission at least once from age 6 to
30 months as the outcome of interest.
We targeted KD incidence between
age 6 and 30 months, owing to a high
incidence of the disease during this
period7 and the availability of data.
The diagnostic criteria for KD has not
changed in Japan since 2002.12,13
Statistical Analyses
To evaluate the impact of loss to
follow-up (Fig 1), we first compared
baseline characteristics between
children with information on
breastfeeding (eligible children),
children who were included in the
analysis, and children who lacked
information on hospital admission
owing to KD at both surveys. We then
compared baseline characteristics
between the participants who were
admitted for KD and those who were
not.
We conducted logistic regression
analyses to evaluate the relationships
among the 4 infant feeding practice
categories (formula feeding without
colostrum, formula feeding with
colostrum, partial breastfeeding, and
exclusive breastfeeding) and hospital
admission from age 6 to 30 months.
We first estimated a crude odds ratio
(OR) and a 95% confidence interval
(CI) for the main outcome (model
PEDIATRICS Volume 137, number 6, June 2016
1). We then examined the OR and
95% CI after controlling for child
factors (model 2) and both child
and maternal factors, in addition to
residential information (model 3).
Throughout the analyses, we used the
formula feeding without colostrum
category as our reference group.
Child factors included gender
(dichotomous), singleton birth or not
(dichotomous), term or preterm birth
(<37 weeks gestation; dichotomous),
parity (0 and >1 birth; dichotomous).
Maternal factors included maternal
age at delivery (<30, 3034, 35
years; categorical), maternal smoking
habits (dichotomous), and maternal
educational level (categorical).
Residential information included
the residential area where the
participant was born (ward, city, and
town or village; categorical). The
childs gender, singleton birth or not,
gestational age, parity, and maternal
age at delivery were listed in the
birth record. Maternal smoking status
was ascertained at the first survey.
Maternal educational level was used
an indicator of socioeconomic status
and obtained from the second survey
(age 18 months). We reclassified
the original 8 education categories
into 3, as follows: university (4
years) or higher, junior college (2
years) or vocational school, and
high school or less. Residential
information was obtained from
the national census conducted in
2010. We selected these potential
confounders based on previous
studies or previous knowledge of the
association between breastfeeding
and some allergic diseases.1416 We
excluded cases with missing data
and conducted our analyses with
complete cases.
In further analyses, we divided the
category partial breastfeeding
based on breastfeeding duration
(breastfeeding for 12 months,
35 months, or 67 months) and
used the following categories:
formula feeding without colostrum,
formula feeding with colostrum,
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partial breastfeeding for 1 to 2
months, partial breastfeeding for 3
to 5 months, partial breastfeeding
for 6 to 7 months, and exclusive
breastfeeding to 6 to 7 months of age.
We then examined the association
between infant feeding practices and
hospital admission for KD.
Because of small numbers in the
categories formula feeding without
colostrum and formula feeding with
colostrum, we also combined these
categories into 1 category designated
formula feeding and repeated the
analyses.
Furthermore, we stratified by
gender and examined the association
between infant feeding practices and
hospital admission from age 6 to 30
months.
In the sensitivity analyses, we
further adjusted for the following
variables in addition to the same set
of covariates as in model 3 because
of possible potential confounding17:
paternal annual income during the
year the child was born as another
indicator of socioeconomic status,
obtained at the second survey (as a
continuous variable), and day-care
attendance. Persons who took care of
the children during the daytime were
queried at the first survey; children
cared for by preschool teachers were
classified as attending day care.
Furthermore, most participants were
considered to be of Japanese origin.
We restricted participants to those
whose father and mother are both
Japanese and repeated the analyses
because of high occurrence of KD
among children of Japanese origin.18
In the additional analysis, to explore
the possible mechanism between
breastfeeding and the development
of KD, we conducted logistic
regression analyses to evaluate the
relationships between breastfeeding
and hospital admission for any cause
excluding injuries, burn injuries, and
fractures from 6 to 30 months of
age. We adjusted for the same set of
potential confounders.
3
All CIs were calculated at the 95% TABLE 1 Demographic Characteristics of Eligible Children With or Without KD Hospital Admission
level. Stata statistical software Data (n = 37 630)
Release 13 (StataCorp LP, College Eligible Included in Without Pa
Station, TX) was used for all Children the Analyses Information in
analyses. This study was approved Both Periods
by the Institutional Review Board (n = 37 630) (N = 33 928) (n = 3702)
at Okayama University Graduate Characteristics of children
School of Medicine, Dentistry, Gender, n (%)b
and Pharmaceutical Sciences (No. Male 19 346 (51.4) 17 442 (51.4) 1904 (51.4) .98
Female 18 284 (48.6) 16 486 (48.6) 1798 (48.6)
1506-073).
Singleton or multiple birth, n (%)b
Singleton birth 36 918 (98.1) 33 307 (98.2) 3611 (97.5) .008
Multiple birth 712 (1.9) 621 (1.8) 91 (2.5)
RESULTS Term or preterm birth, n (%)b
Term birth 35 593 (94.6) 32 136 (94.7) 3457 (93.4) .001
Among eligible children, >34% Preterm birth 2037 (5.4) 1792 (5.3) 245 (6.6)
were in the category of exclusive Parity, n (%)b
breastfeeding (Table 1). Children 0 17 682 (47.0) 15 895 (46.9) 1787 (48.3) .10
who lacked information on hospital 1 19 948 (53.0) 18 033 (53.2) 1915 (51.7)
admission for KD at the second and Breastfeeding statusc
Formula feeding without colostrum 406 (1.1) 341 (1.0) 65 (1.8) <.001
third surveys were more likely to Formula feeding with colostrum 939 (2.5) 789 (2.3) 150 (4.1)
be multiple births, preterm births, Partial breastfeeding 23 399 (62.2) 21 003 (61.9) 2396 (64.7)
formula fed, and to have young Exclusive breastfeeding to 67 mo 12 886 (34.2) 11 795 (34.8) 1091 (29.5)
mothers, mothers who smoked, of age
Maternal characteristics
mothers with lower educational level,
Maternal age at delivery, yb
and mothers who lived in rural areas <30 14 275 (37.9) 12 302 (36.3) 1973 (53.3) <.001
(towns or villages) compared with 3035 13 892 (36.9) 12 848 (37.9) 1044 (28.2)
children included in the analyses. 35 9463 (25.2) 8778 (25.9) 685 (18.5)
Maternal smoking status, n (%)c
We show the baseline characteristics Nonsmoker 34 896 (93.0) 31 801 (94.0) 3095 (84.0) <.001
between the participants who were Smoker 2634 (7.0) 2045 (6.0) 589 (16.0)
admitted for KD during the period Maternal educational attainment, n
of 6 to 30 months of age and those (%)d
University or higher 8635 (26.5) 8581 (26.7) 54 (15.6) <.001
who were not in Table 2. Among Junior college 13 386 (41.1) 13 271 (41.2) 115 (33.2)
27735 participants, a total of 232 Less than or equal to high school 10 524 (32.3) 10 347 (32.1) 177 (51.2)
admissions for KD were observed, Residential area, n (%)
that is, the incidence proportion of Wards 10 739 (28.5) 9774 (28.8) 965 (26.1) <.001
0.84% for 2 years. The participants Cities 23 829 (63.3) 21 445 (63.2) 2384 (64.4)
Towns or villages 3062 (8.1) 2709 (8.0) 353 (9.5)
who were admitted tended to have
a The differences in the proportions of the group included in the analyses and the group without information in both
more siblings, been formula fed, and
periods were tested by using the 2 test.
older mothers compared with those b Obtained from the birth record.
c Obtained from the rst survey (at age 6 mo).
who were not admitted. The same
d Obtained from the second survey (at age 18 mo).
information among participants with
information on hospital admission
either at the second or third survey partial breastfeeding. Although not without colostrum and formula
is shown in Supplemental Tables 5 statistically significant, a protective feeding with colostrum into 1
and 6. association was observed even for category of formula feeding, we
the category of formula feeding with obtained similar findings. Protective
Children who were breastfed were colostrum: OR 0.39 (95% CI: 0.14 associations remained for exclusive
less likely to be hospitalized for KD 1.09). When we divided the category and partial breastfeeding (Table 4).
from 6 to 30 months of age (Table 3). of partial breastfeeding based on
Even after adjusting for all covariates breastfeeding duration, the ORs
(model 3), protective associations When stratified by sex, protective
reached a plateau at a point estimate
remained for exclusive and partial associations between breastfeeding
of around 0.26 for the category of
breastfeeding; ORs for hospitalization and the development of KD did not
breastfeeding for 3 to 5 months.
were 0.26 (95% CI: 0.120.55) change substantially between male
for exclusive breastfeeding and Even after we combined the and female participants; however,
0.27 (95% CI: 0.130.55) for categories of formula feeding exclusive breastfeeding was more

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4 YORIFUJI et al
protective among male children TABLE 2 Demographic Characteristics of Eligible Children With Data of KD Hospital Admission From
(Supplemental Table 7). 6 to 30 Months of Age (n = 27 735)
Total No Admission Admission
In the sensitivity analyses, even after Pa
(n = 27 735) (n = 27 503) (n = 232)
further adjusting for paternal income
or day-care attendance, the main Characteristics of children
Gender, n (%)b
findings did not change substantially
Male 14 335 (51.7) 14 204 (51.7) 131 (56.5) .14
(data not shown). Among the Female 13 400 (48.3) 13 299 (48.4) 101 (43.5)
33928 eligible children, the parents Singleton or multiple birth, n (%)b
of 32783 children (96.7%) were Singleton birth 27 234 (98.2) 27 009 (98.2) 225 (97.0) .16
both Japanese. The results did not Multiple birth 501 (1.8) 494 (1.8) 7 (3.0)
Term or preterm birth, n (%)b
change even after restricting the
Term 26 311 (94.9) 26 093 (94.9) 218 (94.0) .53
analysis to these children, and ORs Preterm 1424 (5.1) 1410 (5.1) 14 (6.0)
for hospitalization for KD were 0.27 Parity, n (%)b
(95% CI: 0.120.59) for exclusive 0 12 996 (46.9) 12 905 (46.9) 91 (39.2) .02
breastfeeding and 0.27 (95% CI: 1 14 739 (53.1) 14 598 (53.1) 141 (60.8)
Breastfeeding statusc
0.130.60) for partial breastfeeding, Formula feeding without colostrum 262 (0.9) 254 (0.9) 8 (3.5) .001
compared with the category of Formula feeding with colostrum 583 (2.1) 576 (2.1) 7 (3.0)
formula feeding without colostrum. Partial breastfeeding 17 097 (61.6) 16 958 (61.7) 139 (59.9)
Exclusive breastfeeding to 67 mo
9793 (35.3) 9715 (35.3) 78 (33.6)
When we examined the relationships of age
between breastfeeding and Maternal characteristics
hospital admission for any Maternal age at delivery, yb
<30 9438 (34.0) 9376 (34.1) 62 (26.7) .008
cause in the additional analysis, 3035 10 799 (38.9) 10 711 (38.9) 88 (37.9)
exclusive breastfeeding and partial 35 7498 (27.0) 7416 (27.0) 82 (35.3)
breastfeeding for longer months Maternal smoking status, n (%)c
were protective for the risk of Nonsmoker 26 292 (95.0) 26 080 (95.0) 212 (92.6) .09
hospital admission (Supplemental Smoker 1388 (5.0) 1371 (5.0) 17 (7.4)
Maternal educational attainment, n (%)d
Table 8). University or higher 7735 (27.9) 7662 (27.9) 73 (31.5) .45
Junior college 11 584 (41.8) 11 494 (41.9) 90 (38.8)
Less than or equal to high school 8365 (30.2) 8296 (30.2) 69 (29.7)
DISCUSSION Residential area, n (%)
Wards 7988 (28.8) 7909 (28.8) 79 (34.1) .10
In the current study, we examined Cities 17 548 (63.3) 17 407 (63.3) 141 (60.8)
Towns or villages 2199 (7.9) 2187 (8.0) 12 (5.2)
the association in children between
breastfeeding and the development
a The differences in the proportions of the no admission group and the admission group were tested by using the 2
test.
of KD from 6 to 30 months of age, b Obtained from the birth record.

using data from a nationwide,
population-based, longitudinal
survey in Japan. We then observed
that children who were breastfed
exclusively or partially were less
likely to be hospitalized for KD
compared with those who were
formula fed. Although the risk
reduction was not statistically
significant, feeding colostrum only
also provided a protective effect.
The protective associations did
not change even after adjusting
for an extensive list of potential
confounders or in the sensitivity
analyses. This is the first study
examining the association between
breastfeeding and development
of KD.
c Obtained from the rst survey (at age 6 mo).
d Obtained from the second survey (at age 18 mo).
We consider there to be at least 2 damage from an uncontrolled
reasons for the protective effects inflammatory response.19 Breast
of breastfeeding on development milk contains numerous factors,
of KD. First, the mother may including allergens, which modulate
provide her own immunologic and promote immune system
memory (ie, antimicrobial factors development.10,11,21 Moreover,
such as secretory immunoglobulin breast milk is considered to mature
A, oligosaccharides, lactoferrin, the immune system through
nucleotides) to her infant via breast the establishment of intestinal
milk,19,20 which may prevent the microbiota.10,11 We observed
infant from contracting infections protective effects of breastfeeding
that trigger abnormal immune on the risk of hospital admission
responses. Second, breastfeeding may excluding injuries, burn injuries,
support the maturation of immune and fractures, which may indicate
system (ie, programming of the that breastfeeding has a generic
system),17 which may limit potential effect rather than a specific effect

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PEDIATRICS Volume 137, number 6, June 2016 5
TABLE 3 Breastfeeding and KD Hospital Admission From 6 to 30 Month of Age
KD Hospital % of OR (95% CI)
Admission/Total Hospital
Number Admission Model 1: Crude Model 2a Model 3b

Breastfeeding status
Formula feeding without colostrum 8/262 3.1 1 (reference) 1 (reference) 1 (reference)
Formula feeding with colostrum 7/583 1.2 0.39 (0.141.08) 0.39 (0.141.09) 0.39 (0.141.09)
Partial breastfeeding 139/17 097 0.8 0.26 (0.130.54) 0.27 (0.130.56) 0.27 (0.130.55)
Exclusive breastfeeding to 67 mo of age 78/9793 0.8 0.25 (0.120.53) 0.26 (0.120.54) 0.26 (0.120.55)
Breastfeeding duration
Formula feeding without colostrum 8/262 3.1 1 (reference) 1 (reference) 1 (reference)
Formula feeding with colostrum 7/583 1.2 0.39 (0.141.08) 0.39 (0.141.09) 0.39 (0.141.09)
Partial breastfeeding, breastfeeding duration, mo
12 20/2209 0.9 0.29 (0.130.67) 0.29 (0.130.67) 0.30 (0.130.68)
35 21/2689 0.8 0.25 (0.110.57) 0.25 (0.110.58) 0.26 (0.110.59)
67 98/12 199 0.8 0.26 (0.120.53) 0.27 (0.130.56) 0.26 (0.120.55)
Exclusive breastfeeding to 67 mo of age 78/9793 0.8 0.25 (0.120.53) 0.26 (0.120.54) 0.26 (0.120.55)
aAdjusted for childrens factors (gender, preterm birth, parity, singleton or multiple birth).
bAdjusted for childrens factors (gender, preterm birth, parity, singleton or multiple birth), maternal factors (maternal smoking status, maternal education, and maternal age category),
and residential area.

TABLE 4 Associations Between Breastfeeding Duration and KD Hospital Admission From 7 to 30 Months of Age, Using the Category of Formula Feeding
(Both With and Without Colostrum) as a Reference
KD Hospital % of OR (95% CI)
Admission/Total Hospital Model 1: Crude Model 2a Model 3b
Number Admission
Breastfeeding status
Formula feedingc 15/845 1.8 1 (reference) 1 (reference) 1 (reference)
Partial breastfeeding 139/17097 0.8 0.45 (0.270.78) 0.47 (0.270.80) 0.46 (0.270.79)
Exclusive breastfeeding at 67 mo of age 78/9793 0.8 0.44 (0.250.78) 0.45 (0.250.78) 0.45 (0.250.80)
Breastfeeding duration
Formula feedingc 15/845 1.8 1 (reference) 1 (reference) 1 (reference)
Partial breastfeeding, breastfeeding duration, mo
12 20/2209 0.9 0.51 (0.260.99) 0.51 (0.260.99) 0.51 (0.26 1.00)
35 21/2689 0.8 0.44 (0.220.85) 0.44 (0.220.85) 0.44 (0.230.87)
67 98/12 199 0.8 0.45 (0.260.78) 0.47 (0.270.81) 0.45 (0.260.79)
Exclusive breastfeeding at 67 mo of age 78/9793 0.8 0.44 (0.250.78) 0.45 (0.250.78) 0.45 (0.250.80)
a Adjusted for childrens factors (gender, preterm birth, parity, singleton or not).
b Adjusted for childrens factors (gender, preterm birth, parity, singleton or not), maternal factors (maternal smoking status, maternal education, and maternal age category), and
residential area.
c We combined the categories of formula feeding without colostrum and formula feeding with colostrum into a single category, formula feeding.

on KD. The protective effects of
breastfeeding on KD may be related
to broad antiinfective functions of
breast milk. In addition, a previous
US cohort study suggested an
increased risk of hospitalization
for any cause among children
who subsequently developed
KD.9 Although it is impossible to
draw a definite conclusion as to
the underlying mechanism, these
observations may support the
preceding theories.
Interestingly, both exclusive and
partial breastfeeding had beneficial
effects on the development of KD. In
the category of partial breastfeeding
for 3 to 5 months, the magnitude
of these effects reached a plateau,
which means that breastfeeding for
at least 3 to 5 months, even together
with formula feeding, may provide
some benefits. Moreover, although
not statistically significant, feeding
colostrum only also provided a
protective effect. Colostrum, the
mammary secretion during the first
few days postpartum, also contains
immunoglobulins and facilitates
establishment of the intestinal
microbiota,22 which may provide
some benefits in children.
The strength of the current
study is that we had a nationally
representative sample, and roughly
one-twentieth of the children born
in 2010 were included in this survey.
We thus had a relatively large
number of KD cases, which allowed
us to examine the dose-response
relationship between breastfeeding
and development of KD. In addition,
the very high response rate at
baseline (88.1%) strengthens the
validity of our findings. The type and
duration of feeding practices should
be accurate because information
on feeding was collected at the first
survey, when children were 6 to 7
months old. However, we could not
evaluate the effect of breastfeeding

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6 YORIFUJI et al
that continued beyond 6 to 7 months
of age.
We have relatively smaller
participants in the categories of
formula feeding without colostrum
and formula feeding with colostrum
to the breastfed group, which may
explain relatively wide 95% CIs.
However, even after we combined
the categories of formula feeding
without colostrum and formula
feeding with colostrum into 1
category (formula feeding),
we obtained the similar findings
(Table 4).
We cannot exclude the possibility
of misclassification of hospital
admission for KD because of the
subjective nature of the questions
used to assess this outcome. We
could not directly confirm the
admission by direct communication
with the hospitals because the data
set obtained from the Ministry was
anonymized data that cannot be
linked to any individual. However,
the diagnostic criteria for KD
in Japan has not changed since
200212,13; therefore, the diagnostic
method used by physicians would
be similar throughout the country
during the study period. Japan has
a universal health insurance system
that covers all of its citizens, so
most patients with KD would have
seen their physicians and then been
hospitalized. Indeed, the incidence
proportions of hospitalization for
KD from 6 to 18 months (0.51%)
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: Supported in part by a grant for Strategies for Efcient Operation of the University (2007030201).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.
REFERENCES
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PEDIATRICS Volume 137, number 6, June 2016
and from 18 to 30 months (0.37%)
(Supplemental Tables 5 and 6) are
close to or slightly higher than the
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Loss to follow-up might be a concern.
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1), we may be underestimating the
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There is the possibility of a biased
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the present findings. Therefore, it is
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Finally, we only included the
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availability, which may limit the
generalizability of the finding.
However, 50% of the KD cases
occurred during this age-group
during the 2-year period of 2011 to
2012 in Japan.6,7
CONCLUSIONS
We observed protective effects of
breastfeeding on the development
of KD from age 6 to 30 months in
children using data of a nationwide
longitudinal survey in Japan, where
KD is most prevalent. Given the
accumulated evidence on its short-
and long-term protective advantages
for other diseases,25 breastfeeding
should be recommended until such
time as further confirmation on the
association between breastfeeding
and KD is obtained.
ACKNOWLEDGMENT
The authors thank Saori Irie for her
help in data collection.
ABBREVIATIONS
CI:confidence interval
KD:Kawasaki disease
OR:odds ratio
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Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey
in Japan
Takashi Yorifuji, Hirokazu Tsukahara and Hiroyuki Doi
Pediatrics 2016;137;; originally published online May 11, 2016;
DOI: 10.1542/peds.2015-3919
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References This article cites 16 articles, 5 of which can be accessed free
at:
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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 2016 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey
in Japan
Takashi Yorifuji, Hirokazu Tsukahara and Hiroyuki Doi
Pediatrics 2016;137;; originally published online May 11, 2016;
DOI: 10.1542/peds.2015-3919

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/137/6/e20153919.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 2016 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on May 11, 2017