Breastfeeding reduce the risk of Kawasaki disease in a Chinese population based case-control study

Backgroud: Kawasaki disease (KD) is the leading cause of acquired heart disease in the pediatric age group in developed countries. But its etiology is unknown. We assessed whether brestfeeding time can influence risk of KD. Methods: We collected feeding, clinical and laboratory details from 200 KD patients and 100 controls. Then we use SPSS to assess the comparison of the general characteristics of KD patients and control patients, and the Correlation of BF time with clinical and laboratory of KD patients. Results: The haemoglobin level was significantly lower in Kawasaki disease patients compared with controls (p<0.05). There were no significant differences between group of KD with coronary artery lesions (CALs) and group of KD without CALs in age, sex, WBC, platelet, HB, CRP . However, there were significantly decreased frequencies for the longer beestfeeding time in KD patients without CALs when compared with KD patients with CALs (OR=668, 95%CI=0.454-0.984 ， p=0.041). Moreover, HB level were positively correlated with brestfeeding time in patients with KD (r=0.163, p=0.028) Conclusion: W e have shown that breast-feeding is associated with KD and the CALs. Brestfeeding may reduce the risk or KD with CALs. Brestfeeding may reduce the risk of KD with CALs.

CRP . However, there were significantly decreased frequencies for the longer beestfeeding time in KD patients without CALs when compared with KD patients with CALs (OR=668, 95%CI=0.454-0.984，p=0.041).
Moreover, HB level were positively correlated with brestfeeding time in patients with KD (r=0.163, p=0.028)

Conclusion:
We have shown that breast-feeding is associated with KD and the CALs. Brestfeeding may reduce the risk or KD with CALs.
Brestfeeding may reduce the risk of KD with CALs.

Background
Kawasaki disease (KD) is a vasculitis of unknown etiology, which mainly occurs in infants and young children. The most severe complications that KD patients experience are coronary artery lesions (CALs), leading to myocardial ischemia, infarction and sudden death. At present, KD is the leading cause of acquired heart disease in the pediatric age group in developed countries [1].
Cause and pathogenesis of KD are unclear. Therefore literature is replete with multiple factors considered as associations of KD [2]. KD may occur with an aberrant immune response to some environmental trigger [3]. Recently researchers found that nutrition during critical windows in early life can influence and program later cardiometabolic health [4]. Brestfeeding is the best source of nutrition for infants to optimize growth and development. The World Health Organization(WHO) recommends exclusive breastfeeding for the first 6 months of life, introduction of complementary foods at 6 months of age, and continued breastfeeding up to 2 years of age and beyond [5].
A Japanese study and a German study already have indicated a potential protective effect of brestfeeding in KD [6,7]. This suggested that brestfeeding potentially play a role in the pathogenesis of KD. But there are few study about the specific association between the brestfeeding and KD. Therefore, in a retrospective case-control study we investigated the association and impact of breastfeeding practices and on Laboratory indexes of KD.

Methods
This investigation was a retrospective analysis. All cases were performed at a single institution. The study was approved by the Ethics We collected 200 KD patients, as controls, 100 healthy children were selected.
We collected feeding, clinical and laboratory details from each KD case. All enrolled patients met the criteria proposed by the Japanese Kawasaki Disease Research Committee [8]. Patients with KD were divided into 2 groups according to the presence of CAL: patients with CALs and patients without CALs. CALs were defined as a z score 2.5 in the right coronary artery or the left anterior descending coronary artery or the presence of ectasia or aneurysms. Coronary arterial lesion severity assessment was visualised using echocardiography or coronary artery angiography along with dilatation and/or evidence of ectasia and aneurysms. Collection of clinical data were approved by the Chengdu Women's and Children Central Hospital.

Statistical analyses
Statistical analysis was performed using SPSS version 20 software (SPSS Inc., Chicago, IL, USA). We presented the data as mean ± standard deviation (SD) for all values. Statistical significance of the differences between the continuous variables was evaluated by One-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA and Mann-Whitney U tests. A Pearson ' s test was used to measure associations between sequential parameters. The association between brestfeeding time and Kawasaki disease risk was estimated by computing odds ratios and 95% confidence intervals from a multivariate logistic regression analysis. A p value of ＜ 0.05 was considered to be statistically significant. Table 1, platelet count, white blood cell counts, C-reactive protein were higher in Kawasaki disease patients compared with controls (p<0.001), whereas haemoglobin level was significantly lower in Kawasaki disease patients compared with controls (p<0.05).

As shown in
There were no significant differences between group of KD with CALs and group of KD without CALs in age, sex, WBC, platelet, HB, CRP (Table 2). However, there were significantly decreased frequencies for the longer beestfeeding time in KD patients without CALs when compared with KD patients with CALs (OR=668, 955CI=0.454-0.984， p=0.041. Table2). Moreover, as shown in Table 3, HB level were positively correlated with brestfeeding time in patients with KD (r=0.163, p=0.028) ( Table 3).

Discussion
It is widely accepted that breast-feeding has numerous health benefits for both the infant and mother [9] . Increasing evidence suggests that breast-feeding is associated with lower cardiovascular disease (CVD) risk factors [10 ].It is reported to be the most frequent pediatric systemic vasculitis globally, and the most important cause of acquired heart disease among children. There were only few studies about the association between brest-feeding and Kawasaki disease. Up to now, we are the first to report the relationship between brestfeeding and the KD laboratory index.
In addition to standard diagnostic criteria, KD patients may experience a variety of nonspecific clinical features, such as anemia [11].
Anemia is the most common clinical feature in KD patients and is thought to have a more prolonged duration of active inflammation [12].
Studies found that hemoglobin is a useful early differentiating feature between KD shock syndrome from toxic shock syndrome in a pediatric intensive care unit [13].
In this study, we showed that the HB level was significantly lower in Among other advantages, breastfeeding seems to protect against a variety of infectious diseases [14] and non-breastfed children have a higher risk of developing allergies and bronchial asthma later in life [15].
During the perinatal and infancy periods, these and other factors potentially play a role in the pathogenesis of KD.
The WHO recommends that infants should be fed breast milk exclusively for the first six months of life. Our study provide further evidence for the promotion of breast-feeding. A large study from Japan has indicated that breastfeeding may be protective for KD [16], our data reinforce the findings.
Our study has limitations. The cross-sectional analysis cannot determine causality. Further, we were not able to adjust for unmeasured potential confounders, such as infant feeding patterns or early introduction of complementary foods. Another major limitation of this study was its relatively small sample size.

Conclusions
In summary, we have shown that breast-feeding is associated with KD and the CALs. The results from the present study add to the literature supporting a beneficial effect of breastfeeding on health-related parameters.
Acknowledgements The authors would like to thank Muchen Li for the idea of the research, Yiling Liu and Lingxia Fan who were involved in data collection.
Contributors Feifei Si conceptualised and designed the study, drafted the initial manuscript. Yanfeng Yang conducted analyses and reviewed and revised the manuscript for important intellectual content. Qian Duan contributed to interpretation of data and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding No funding was used for the creation of this manuscript.

Disclaimer
The study sponsors had no role in study design; the collection, analysis and interpretation of data; the writing of the report or the decision to submit the manuscript for publication.

Competing interests None declared.
Patient consent for publication Not required.

Ethics approval No approval was required by the institutional review board at
Chengdu Women's and Children Central Hospital.
Availability of data and materials Please contact authors for data requests.