This study demonstrates the potential effect of KD heterogeneity on cognitive development and parenting stress. Our data revealed that no significant differences in developmental index, cognitive function or parenting stress between KD patients and controls. Both IVIG administration and CAL development were not associated with KD children’s cognitive profiles. In addition, the profiles of parenting stress in caregivers of KD patients were examined in this study. We found that caregivers’ education is associated to parenting stress, and the caregivers of patients who had CAL suffered from greater parenting stress than those of patients without CAL.
In our study sample, 4% never received IVIG, and 88.6% and 7.4% received IVIG treatment, once and twice, respectively. Although IVIG has been established as a standard treatment for KD [8], 4% of patients still never received such intervention, and 7.4% received IVIG treatment twice due to treatment resistance at the first administration. Since the study sample included patients referred from local hospitals of remote areas, some of the patients may have missed the opportunity to be correctly diagnosed and receive IVIG at the critical period. Notably, 10–20% of patients show resistance to IVIG therapy and are at risk for complications [9]. Our KD population consisted of 42% patients who exhibited CAL, a higher proportion of CAL than has been reported in the current literature [10]. Current studies suggest that approximately 20% of KD patients suffer from CAL [45]. This discrepancy may be due to Kaohsiung Chang Gung Memorial Hospital being the main medical center in Southern Taiwan and patients recruited for this study possibly having a higher severity or greater comorbidities than those in general hospitals.
The results of the current study show that KD is not related to cognitive impairment sequelae, which was generally consistent with the previous literature [19–21]. Because IVIG reduces vasculitis that presumably underlies any cognitive impairment, we assumed that KD patients who had a poor response to IVIG or had developed CAL may be related to a higher severity of systemic vasculitis [13, 14]. However, we found that neither IVIG administration nor CAL development was associated with cognitive performance. In our study population, most KD patients (96%) received IVIG treatment. The case numbers of children who didn't receive IVIG (only 4%) and treatment resistance (7.4%) were too small and it is difficult to make a sufficient comparison. Therefore, a future study with larger sample size is required to verify whether IVIG administration is associated with cognitive outcomes or not. Notably, a nationwide survey in Taiwan previously demonstrated that epilepsy and developmental delay were factors associated with cognitive impairments [21]. Whether physical comorbidities other than KD have a greater influence on cognitive function than KD itself or the disease characteristics of KD warrants further research.
We provide more scientific evidence related to parental stress or mental health of caregivers of KD patients and keeping in mind that situation implies more health service. It is noteworthy that patients’ caregivers were not assessed during patients’ acute phase of KD. The clinical meaning of our findings is that parenting stress of caregivers in KD children during follow-up was comparable those of control children. Nevertheless, our data revealed that caregivers of patients who had CAL suffered from greater parenting stress than the caregivers of patients who did not have CAL. A previous study from Canada revealed a similar finding with ours. The parents of children with coronary artery complications may suffered from a greater anxiety level [25]. The psychological distress is associated with family characteristics, such as family income and maternal education [26]. Children with persistent CAL may develop complications [11], so caregivers may worry, feel stressed, and experience helplessness with regard to facing the uncertainty of their children’s risk of myocardial infarction and the possibility of sudden death. This finding suggests that the parental stress or mental health of caregivers of patients with CAL require particular assistance. Furthermore, caregivers with an education level of a master’s degree or above showed lower parenting stress than those who had education levels of college or lower. This finding may imply that caregivers with high education levels had greater internal or external resources to handle the patients’ physical illness [26]. Alternatively, caregivers with lower education levels may require support or help to fulfill their parenting roles.
This study has certain limitations. First, due to small case numbers of KD patient without IVIG or treatment resistance, it is difficult to make a strong conclusion about cognitive impairment. Second, this is a cross-sectional study, with a mean interval between KD onset and assessment for cognition and parenting stress of 40.5 months (ranged from 1 to 159 months). Therefore, the measurement for parenting stress was highly dependent on parental recall. The parenting stress reported herein did not necessarily represent the state of patients’ caregivers who take care of patients during the acute onset of KD. Third, CAL was only recorded as a categorical variable (with or without), but the influence of CAL severity on cognition or parenting stress was not assessed in this study. Moreover, we did not record any physical comorbidity besides KD. Whether other comorbidities (i.e., developmental delay or epilepsy) actually influence or moderate children’s cognitive development warrants further investigation. Fourth, the KD group and control group were not perfectly matched in age and caregivers’ characteristics, and those differences may have influenced the results of this study. Finally, all participants were recruited from a single site, whether this finding can be generalized into other patient populations warrants further investigation.