Zhang et al. BMC Pediatrics(2024) 24:583
https://doi.org/10.1186/s12887-024-05011-7

BMC Pediatrics

RESEARCH

Open Access

Promoting medication compliance in epileptic
children: a cross sectional survey
Lijuan Zhang1†, Ping Li2†, Junping He1, Jing Qian1 and Yiming Liu1*
Abstract
Background Compliance with medication is crucial for the favorable prognosis of children with epilepsy. The
objective of this study was to assess the determinants of medication compliance and to construct a predictive modelfor the risk of non-compliance among pediatric epilepsy patients.
Methods The study included children diagnosed with epilepsy and treated at our hospital between February 1 and
September 30, 2023. We evaluated the demographic characteristics and medication compliance profiles of thesepatients. The predictive model’s performance was assessed using the receiver operating characteristic (ROC) curve todetermine its sensitivity and specificity.
Results A total of 168 children with epilepsy were analyzed. The rate of non-compliance with medication was foundto be 32.74% (55 out of 168). Logistic regression identified the educational level of parents (OR = 2.844, 95% CI: 2.182–
3.214), monthly household income (OR = 1.945, 95% CI: 1.203–2.422), the number of medications taken (OR = 1.883,
95% CI: 1.314–2.201), and the level of epilepsy knowledge received (OR = 2.517, 95% CI: 1.852–3.009) as significant
factors influencing non-compliance (all p < 0.05). A total score threshold of 6 was set for the predictive model. The area
under the ROC curve was 0.713 (95% CI: 0.686–0.751), indicating the model’s discriminative ability.
Conclusions The compliance to medication regimens among children with epilepsy is suboptimal and influenced
by a multitude of factors. This study has developed a predictive model for medication compliance, which could serve
as a valuable tool for clinical assessment and intervention planning regarding medication compliance in pediatricepilepsy patients.
Keywords Compliance, Children, Epilepsy, Treatment, Care, Nursing†

Lijuan Zhang and Ping Li contributed equally to this work.

*Correspondence:
Yiming Liu
rjnj28@sina.com
1
Department of Neurosurgery, Children’s Hospital of Nanjing Medical
University, Nanjing, Jiangsu province, China
2
Department of Outpatient, Children’s Hospital of Nanjing Medical
University, Nanjing, China

Introduction
Epilepsy is a neurological disorder caused by abnormal
discharge of neurons in the brain. Globally, it is estimatedthat approximately 70 million individuals are living withepilepsy, with China alone accounting for a significant
proportion of this population, harboring at least 9 million affected individuals. Notably, a substantial majority of these cases, nearly two-thirds, are concentrated
among the pediatric population, specifically those under
the age of 18 years [1, 2]. The total prevalence rate of epilepsy in children is about 151/ 100,000, which is morethan 4 times that of adults [3]. The first-line treatment of© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

Zhang et al. BMC Pediatrics(2024) 24:583

epilepsy is long-term oral antiepileptic drugs, which caneffectively control 70% of the incidence of epilepsy [4].
30–40% of patients need other treatment measures, suchas ketogenic diet, vagal nerve stimulation surgery, etc.,
but they still need to take antiepileptic drugs for a longtime [5, 6]. Therefore, improving the medication compliance of patients with epilepsy is of great significance tothe prognosis of patients.
Antiepileptic drug therapy is the most important andcommonly used means for the treatment of epilepsy [7].
If the family members of the children can carry out standard treatment for the children, about 80% of the children can be completely controlled by drugs. It is reported
that 70 to 80% of children with epilepsy in China can betreated with systematic regular antiepileptic drugs, but
about 20% of children’s epilepsy cannot be controlled[8, 9]. Epilepsy is a neurological disorder influenced bya multitude of factors, predominantly stemming from alack of parental awareness regarding the diagnosis andtreatment protocols. This condition is further complicated by the unique challenges associated with pediatricepilepsy management. The condition not only significantly impairs the physical and psychological well-beingof the affected children and their caregivers but also
imposes a substantial economic burden on the family
unit. Consequently, this can impede the enhancementof the children’s overall quality of life [10, 11]. Consequently, compliance to prescribed antiepileptic medications is pivotal in the chronic management of epilepsy[12]. It has been reported by many studies [13–15] that
there are about 29% of patients with poor compliancein the treatment of epilepsy, among which the treatment non-compliance rate of children with epilepsy is
between 25% and 50%. At present, the body of researchconcerning medication compliance among children withepilepsy is notably limited, with the determinants of thiscompliance still not well elucidated. There is a substantial
need to delve into the patterns of medication compliancein this vulnerable demographic, dissect the underlying causes of potential non-adherence, and enhance thestrategies for compliance management. Such an investigation holds profound implications for optimizing treatment outcomes and improving the health and well-beingof children with epilepsy [16]. Therefore, the objectiveof this study is to systematically assess the determinants
influencing medication compliance in pediatric epilepsy
patients, to develop a predictive model that can predicatecompliance behaviors in this patient group, to offer valuable insights into the clinical management and nursing
practices for children with epilepsy.

Page 2 of 8

Methods
Ethical issue

This study was a cross-sectional survey design. The study
had been obtained the ethical approval from the ethical committee of children’s hospital of Nanjing medical
university (approval number: 202401015-1). The written
informed consents had been obtained from all the guardian of included children.
Sample size calculation

Drawing from established methodological report [17],the optimal sample size for a questionnaire-based study
was typically recommended to be at least tenfold thenumber of variables under examination. In the context
of this investigation, which utilized a scale encompassing 11 distinct variables, the requisite sample size wasmeticulously calculated. Accounting for a projected 10%
attrition rate during the distribution and collection of thesurvey instruments, as well as the need to ensure statistical robustness, the calculated sample size necessitateda minimum of (11*10*(1 + 10%)=121) participants. Consequently, the study design mandated the inclusion of atleast 121 children diagnosed with epilepsy to meet themethodological standards and achieve a reliable and valid
analysis.
Study population

The study populations of this study were children withepilepsy who were treated in our hospital from February
1 to September 30, 2023. The diagnosis of epilepsy wasin accordance with the classification and diagnostic criteria of epilepsy issued by the international league against
epilepsy (ILAE) [18, 19]: (1) epilepsy has a tendency tocontinue to attack again, and electroencephalography(EEG) examination shows typical epileptiform discharge;(2) recurrent seizures, two or more times, EEG examination shows abnormal epileptiform discharge. (3) recurrent attacks in a short time, frequency ≥ 1/day, normal
EEG but abnormal imaging examination, and recurrent
attacks induced by fixed fever and typical epileptiformdischarge. The inclusion criteria of children in this study
were follows: the age of children was less than 18 years
old; the diagnosis of epilepsy was in accordance with thediagnostic criteria of epilepsy established by the ILAE;
the history of diagnosis and treatment of epilepsy was
more than 1 year. The children and guardians informed
consent and volunteered to participate in this study. The
children with mental illness were excluded.
Survey tool
General information questionnaire

In order to understand the possible factors, this study
designed a basic information questionnaire, which
includes two parts: The general data of the guardians

Zhang et al. BMC Pediatrics(2024) 24:583

included gender, age, marital status, religious belief,
education level, family monthly income, whether theyreceived education on the knowledge of epilepsy. The
general data of the children included gender, age, bodymass index (BMI), whether the child was the only child offamily, payment of medical expenditure, number of drugs
taken, number of convulsions in recent 6 months. Under
the guidance of the questionnaire collectors, the information was filled in by the guardians of the children according to the actual situation.
Treatment compliance questionnaire

In this investigation, a rigorously validated questionnaire [20] was employed to assess medication adherence.
This instrument was noted for its simplicity and expedience, along with its demonstrated reliability and validity.
Upon evaluation, the questionnaire exhibited an impressive overall Cronbach’s α coefficient of 0.906, indicative of strong internal consistency. Furthermore, theCronbach’s α coefficients for the individual dimensions
ranged from 0.82 to 0.94, reinforcing the scale’s reliability and validity [21, 22]. The questionnaire included thefollowing four questions: (1) do you sometimes not pay
attention to taking medicine to your child? (2) have you
forgotten to give your child medication? (3) have you everstopped taking medication when your child’s symptoms
are worse? (4) have you ever stopped taking medication
when your child’s symptoms have improved? According
to the family members’ answers to the four questions, thetreatment compliance was evaluated, the answers to all
the four questions were “no”, that is, the family members
had good compliance with drug treatment, and as long as
the answer to more than one of the four questions was“yes”, it was considered that the family members had poor
compliance with drug treatment.
Data collection

The investigators all received unified training in advance.
First of all, they strictly abided by the principles of voluntariness, equality and confidentiality, before collecting
the questionnaire, under the introduction of the doctor
in charge of diagnosis and treatment, they explained theimportance and significance of the study to the children
and guardian in detail, and to obtain the consent andcooperation of the family members. In the course of thesurvey, unified professional guidance terms were used
to give appropriate explanations to the items and questions that guardian did not understand one by one. The
completion time of each questionnaire was not less than
10 min. After the questionnaire was completed, the questionnaire would be collected on the spot and the integrityof the questionnaire would be tested. If any omissions
or deficiencies were found, the family members wereencouraged to make up the missing items on the basis ofPage 3 of 8

not violating the voluntary principle. After the questionnaire survey, two different personnel input the data at thesame time to ensure the authenticity of the data.
Statistical analysis

All the data were processed and analyzed with SPSS
24.0 software. Measurement data with normal distribution were expressed by mean ± standard deviation, two
independent sample t test was used for group analysis. Measurement data without normal distribution was
expressed by median and interquartile range, non-parametric test was used for the group comparison. The countdata were expressed by frequency and percentage, Chisquare test or Fisher’s exact probability test were used
for data comparison. First of all, univariate analysis was
carried out, and the statistically significant risk factors in
the results were included in logistic regression analysis toscreen out the independent influencing factors. Pearson
correlation analysis was conducted to evaluate the correlation of medication compliance and characteristics ofincluded children with epilepsy. This survey developed arisk prediction model for medication non-compliance inchildren with epilepsy. The Hosmer-Lemeshow test was
performed to evaluate the conformity of the model; thesensitivity and specificity of the developed model were
evaluated based on the area under the receiver operating
characteristic (ROC) curve. There was significant difference between the two groups when p < 0.05.

Results
A total of 168 children with epilepsy were included inthis survey. The incidence of medication non-compliancein children with epilepsy was 32.74% (55/168). As presented in Table 1, there were statistical differences in the
education level of parents, monthly household income,number of drugs taken, number of convulsions in recent
6 months and received education on the knowledge of
epilepsy between compliance and non-compliance group(all p < 0.05). There were no statistical differences in theage, gender, BMI, only child of family, place of residence,
payment of medical expenditure between complianceand non-compliance group (all p > 0.05).
As indicated in Table 2, results of correlation analysis showed that the education level of parents(r = 0.556),
monthly household income(r = 0.549), number of drugs
taken(r = 0.602), and received education on the knowledge of epilepsy(r = 0.610) were associated with the medication compliance of included children with epilepsy (allp < 0.05).
As indicated in Table 3, the logistic regression
analysis results showed that the education level ofparents(OR = 2.844, 95%CI: 2.182 ~ 3.214), monthly
household income(OR = 1.945, 95%CI: 1.203 ~ 2.422),
number of drugs taken(OR = 1.883, 95%CI: 1.314 ~ 2.201),

Zhang et al. BMC Pediatrics(2024) 24:583

Page 4 of 8

Table 1 Characteristics of included children with epilepsy (n = 168)
Variables
Age(y)
Male/female
BMI (kg/m2)
Only child of family
Yes
No
Place of residence
Rural area
City
Education level of parents
Junior high school
Senior high school
CollegeMonthly household income< 5000 Yuan
5000 ~ 10,000 Yuan
> 10,000 Yuan
Payment of medical expenditure
Medical insurance
Self-covered
Number of drugs taken
12≥3
Number of convulsions in recent 6 months
≤2
3~4
≥5
Received education on the knowledge of epilepsy
Yes
No

Compliance group(n = 113)
6.05 ± 2.18
69/44
20.89 ± 3.42

Non-compliance group(n = 55)
6.16 ± 2.73
34/21
21.01 ± 3.39

83(73.45%)
30(26.55%)

38(69.09%)
17(30.91%)

36(31.86%)
77(68.14%)

20(36.36%)
35(63.64%)

3(2.65%)56(49.56%)
54(47.79%)

23(41.82%)
20(36.36%)
12(21.82%)

10(8.85%)
45(39.82%)
58(51.33%)

23(41.82%)
21(38.18%)
11(20.00%)

101(89.38%)
12(10.62%)

39(70.91%)
16(29.09%)

59(52.21%)
35(30.97%)
19(16.81%)

12(21.82%)
25(45.45%)
18(32.73%)

77(68.14%)
31(27.43%)5(4.42%)18(32.73%)
32(58.18%)5(9.09%)89(78.76%)
24(21.24%)

34(61.82%)
21(38.18%)

t/χ2
2.045
1.988
3.066
1.985

p
0.071
0.104
0.078
0.112

1.813

0.202

1.296

0.017

1.118

0.013

1.633

0.052

1.851

0.009

1.986

0.046

1.477

0.039

Table 2 Correlation analysis of medication compliance andcharacteristics of included children with epilepsy

Table 4 The scoring criteria of the predicating model for the riskof medication non-compliance in children with epilepsy

Variables
Age(y)
Gender
BMI (kg/m2)
Only child of family
Education level of parents
Monthly household income
Payment of medical expenditure
Number of drugs taken
Number of convulsions in recent 6 months
Received education on the knowledge of epilepsy

Variables
Low education level of parents
Monthly household income < 5000 Yuan
Number of drugs taken ≥ 3
Did not receive education on the knowledge of epilepsy

r
0.212
0.115
0.101
0.212
0.556
0.549
0.133
0.602
0.158
0.610

p
0.097
0.103
0.064
0.085
0.028
0.015
0.092
0.004
0.067
0.012

scores3223

and received education on the knowledge of
epilepsy(OR = 2.517, 95%CI: 1.852 ~ 3.009) were the influencing factors of medication non-compliance in children
with epilepsy(all p < 0.05).
As shown in Table 4, this study developed the scoring criteria for the predictive model of medication

Table 3 Logistic regression analysis on the influencing factors of medication non-compliance in children with epilepsy
Variables
Education level of parents
Monthly household income
Number of drugs taken
Received education on the knowledge of epilepsy

β
0.103
0.126
0.143
0.117

Wald
0.115
0.192
0.125
0.205

OR
2.844
1.945
1.883
2.517

95%CI
2.182 ~ 3.214
1.203 ~ 2.422
1.314 ~ 2.201
1.852 ~ 3.009

p
0.019
0.034
0.027
0.040

Zhang et al. BMC Pediatrics(2024) 24:583

Page 5 of 8

non-compliance in children with epilepsy. Based on the
ROC curve (Fig. 1) and scoring critieria of the prediction model, the sensitivity and specificity of the developed model under different scores were analyzed, andthe corresponding Youden index (sensitivity + specificity− 1) was calculated. As presented in Table 5, the Youden
index of this model was higher between the total score of
5.5 ~ 6.5. Thus the total score = 6 was adopted as the cuff
value of the developed model. At this time, the sensitivity
and specificity of the prediction model were both high.
The area under the ROC curve (AUC) was 0.713 withand 95% CI: 0.686 ~ 0.751, indicating that the developedmodel had good discriminative level to predict the medication non-compliance in children with epilepsy.

Discussion
Epilepsy has an important impact on the physical andmental health of individuals and families, it can bringheavy economic burden and reduce the quality of life[23]. Moreover, the characteristics of its chronic diseases
also determine that its treatment cannot be achieved
overnight, but need to adhere to long-term medication,and need to maintain a stable drug blood concentration,
which requires patients must have good compliance [24,25]. The results of previous investigations [26, 27] showthat the main reason for the failure in the treatment of
epilepsy is that the patients do not take the medicine
according to the doctor’s advice, that is, the patients do
not comply with the treatment. The patient with epilepsy
may stop the drug, change the drug or secretly increaseor decrease the drug dose due to various factors during
the medication period [28, 29]. These behaviors will to alarge extent lead to the increase or decrease of the concentration of antiepileptic drugs in the blood of patients,
resulting in a series of side effects and adverse reactions[30]. The patient’s low compliance with clinical treatment
will lead to the deterioration of the disease [31]. Related
studies [32, 33] have proven that patients with poor treatment compliance often have recurrent seizures, whichbrings a greater economic burden to the health care system. It can be seen that more in-depth researches areneeded to take positive measures to improve the clinical medication compliance of patients with epilepsy [34].
The results of this survey have found that the incidenceof medication non-compliance in children with epilepsy
is 32.74%, and the education level of parents, monthly
household income, number of drugs taken, and received
education on the knowledge of epilepsy are the influencing factors of medication compliance in children withepilepsy. Besides, this research has crafted a predictivemodel specifically designed to assess the potential risks
associated with non-compliance to medication regimens
among pediatric epilepsy patients. This model stands asa valuable tool in the clinical sphere, offering healthcare

Fig. 1 The ROC curve on the sensitivity and specificity of developed prediction model

Table 5 Sensitivity and specificity of the prediction model under
different cuff values
Total score
-1.0
1.0
1.5
2.5
3.5
4.5
5.5
6.5
7.5
8.5
9.5
10.5
11

Sensitivity
1.000
1.000
0.974
0.920
0.839
0.804
0.788
0.765
0.577
0.426
0.102
0.027
0.000

Specificity
0.000
0.125
0.213
0.395
0.551
0.761
0.805
0.846
0.931
0.946
0.960
1.000
1.000

Yorden Index
0.000
0.125
0.187
0.315
0.390
0.565
0.593
0.611
0.508
0.372
0.062
0.027
0.000

professionals a more nuanced understanding of the factors that may influence medication compliance in thisvulnerable population. By identifying and addressingthese risks proactively, health care providers can enhancetheir ability to support children with epilepsy in maintaining a consistent and effective treatment plan, ultimately improving their quality of life and long-term
health outcomes. The predictive capabilities of this model
not only aid in the initial assessment of medication compliance but also provide ongoing insights that can guideZhang et al. BMC Pediatrics(2024) 24:583

adjustments to treatment strategies as needed, ensuringthat each child’s unique needs are met with precision andcare.
The previous survey [35] has shown that the incidenceof poor medication compliance in children with epilepsy
is 23.08% for caregivers with college education level,
while 78.26% for caregivers with high school educationlevel. Therefore, it can be explained that the higher theeducation level of the caregiver, the more thorough theunderstanding of the basic knowledge of epilepsy, thedeeper the understanding of the treatment of antiepileptic drugs, and the better the compliance of children withmedication. Parents with a high level of education cantimely make a correct and scientific understanding of thedisease of epilepsy in children, fully grasp the best time tosee a doctor, and send them to hospital in time when thechildren have relevant clinical symptoms [36, 37]. And
they be able to receive systematic treatment more rationally. However, those parents with low level of education
cannot correctly understand children’s epilepsy, which
not only delays the best time for children to see a doctor, but also cannot correctly treat and accept systematic
treatment, which eventually leads to recurrent seizures[38, 39]. Therefore, it is of great significance to improvethe educational level of parents of children with epilepsy
to ensure timely medical treatment and improve theircompliance.
Epilepsy is a disease with a long period treatment.
Long-term cure will cause a certain financial burden topoor families, and may stop treatment because they may
not afford the high cost of treatment [40, 41]. It has beenreported that some patients with poor compliance after
taking drugs suddenly stop taking drugs because theycannot afford the cost of treatment [42]. Among them,
the prevalence rate of poor treatment compliance is
16.67% for patients with a monthly income of more than
5000 Yuan, and 53.85% for those with a monthly incomeof less than 3000 Yuan. When some children feel that seizures are not frequent, they stop taking drugs on theirown in order to reduce the financial burden, while somechildren have attacks too frequently to afford such highmedical expenses [43]. Some people even change cheap
drugs without consultation of health care providers to
reduce the medical burden [44]. In view of this problem,
attention has been paid to this problem from the social to
the national level in China. The Chinese government has
increased its investment in medical and health care year
by year, and there are also various special funds for epilepsy, which provide families with poor economic conditions and in urgent need of treatment with the ability tomaintain treatment the reduce the economic burden ofpatients with low incomes [45].
Oral antiepileptic drugs in the treatment of epilepsy
is a long process of medication, regular medication isPage 6 of 8

closely related to the prognosis of the disease. Control
and medication time after seizures, and relapse after
withdrawal are the most concerned issues for patientsand their families [46]. Regular medication has a significant effect on the prognosis of children. Related studies
have also confirmed that the prognosis of children who
can take medicine regularly is significantly better thanthat of children who cannot take medicine regularly [47].
In the process of long-term treatment, coupled with thelack of self-control at a young age, it is basically difficult
to take medicine on time without the strict supervisionof parents. For children with poor self-control ability, it isnecessary to give positive guidance and support to educate the harm of epilepsy and matters needing attention
to the corresponding parents, and help them understandthe important role of treatment compliance in controlling epilepsy from all aspects [48].
Many previous studies [49, 50] have found that parents of children are generally lack of knowledge about
epilepsy, so it is particularly important to strengthen
publicity and education. Regular distribution of epilepsy
publicity handbooks, small lectures or webcast classes
are necessary to explain the basic knowledge of epilepsy,
the significance and benefits of good drug compliance,
the harm of poor drug compliance and risk management measures. Wechat communication group can also
be established to follow up the medication complianceof children. It can also be scheduled to organize families
with good drug compliance to share their experiences.
Besides, as a new way to teach epileptic patients andcaregivers, video animation will help to enhance children’s understanding and medication compliance [51].
At the same time, it also calls on all sectors of society
to attach importance to children with epilepsy and do agood job in the education of knowledge about epilepsy,
so as to make more people correctly understand the epilepsy [52].
The present investigation is not without its limitations,which merit careful consideration. Initially, the study is
confined to a single center, which inherently restricts thegeneralizability of the findings due to the modest sample
size. Additionally, the scope of the influencing factors
examined in this research is somewhat narrow, potentially overlooking other significant determinants that
could have been integrated into the analysis. Furthermore, the study’s cross-sectional design precludes theexamination of temporal trends in the treatment compliance among pediatric patients with varying epilepsy trajectories. Future endeavors in this domain would benefit
from an expanded temporal frame and an enhanced sample size, ideally encompassing diverse geographic regions,
to yield more robust and precise outcomes. Finaly, given
the dynamic nature of epilepsy and its treatment, compliance to prescribed medical regimens can fluctuateZhang et al. BMC Pediatrics(2024) 24:583

significantly over time. This variability is influenced by
the progression of the disease, changes in the patients’condition, and the evolving understanding of the disorder among both the children and their caregivers. As thecondition evolves, so too do the challenges and responses
to treatment, necessitating a continuous reassessment ofcompliance strategies. This temporal aspect of compliance underscores the importance of longitudinal studies
in understanding the full spectrum of treatment compliance in epilepsy, from initial diagnosis through various
stages of the disease.

Conclusions
In summary, this survey has found that the incidence of
medication non-compliance in children with epilepsy
is 32.74%, and the education level of parents, monthly
household income, number of drugs taken, and received
education on the knowledge of epilepsy are the influencing factors of medication compliance in children withepilepsy. Furthermore, this research has developed a predictive model that predict the likelihood of medication
non-compliance among children suffering from epilepsy.
This model serves as an instrumental aid in the clinicalassessment process, specifically tailored to evaluate thecompliance to prescribed medication regimens in thisdemographic. By providing a more precise and comprehensive evaluation of the factors influencing medication
compliance, the model equips healthcare providers with
the necessary insights to better support and guide children with epilepsy in adhering to their treatment plans.
In the future research, it is necessary to pay more attention to the epileptic children with poor compliance andconstruct healthy intervention measures to improvemedication compliance and improve the therapeutic
effect.
Abbreviations
ROC	Receiver operating characteristic
ILAE	International league against epilepsy
EEG	Electroencephalography
BMI	Body mass index
Acknowledgements
None.
Author contributions
P L, Y L designed research; P L, L Z, J H, J Q, Y L conducted research; P L, L
Z, J H, J Q, Y L analyzed data; P L wrote the first draft of manuscript; Y L had
primary responsibility for final content. All authors read and approved the final
manuscript.
Funding
This study did not receive any funding in any form.
Data availability
The data associated with the paper are not publicly available but are available
from the corresponding author on reasonable request.

Page 7 of 8

Declarations
Ethics approval and consent to participate
In this study, all methods were performed in accordance with the relevant
guidelines and regulations. The study has been reviewed and approved by
the ethics committee of Children’s Hospital of Nanjing Medical University(approval number: 202401015-1). And written informed consents had beenobtained from all the guardians of included children.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 23 April 2024 / Accepted: 13 August 2024

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