Introduction

Cardiovascular disease (CVD) remains one of the leading causes of death and a major source of healthcare burden globally [1]. Beyond its direct impact, CVD is closely associated with the onset and progression of numerous other diseases, further compounding its health and economic challenges [2–5]. While CVD is often diagnosed in adulthood, the risk factors contributing to its development often begin in childhood and adolescence. The accumulation of cardiovascular risk factors in early life, such as obesity, dyslipidemia, hypertension, congenital heart defects and coronary artery abnormalities, strongly influences long-term cardiovascular health. These conditions exert both immediate effects and lasting biological impacts. Evidence from cohort studies shows that children carrying multiple risk factors can develop early atherosclerotic changes and vascular dysfunction by adolescence. This progression underscores the growing recognition that early identification of risk is essential. As a result, early intervention has become a central strategy to slow the development of cardiovascular disease and reduce its long-term burden [6–10]. Among these early risk factors, obesity is both common and modifiable. However, not all children with obesity share the same future risk. Differences in biological markers, behavior, and family environment may lead to distinct health outcomes. Understanding this variation is essential for identifying which children require more intensive monitoring or intervention.

Early intervention targeting multiple cardiovascular risk factors requires comprehensive prevention strategies. A variety of evidence-based approaches have been investigated, including dietary modifications [11], structured physical activity programs, promotion of healthier lifestyles, innovative approaches like cell-based therapy for cardiovascular repair [12], and minimizing exposure to environmental risk factors such as tobacco smoke [6]. Dietary interventions that focus on reducing caloric intake and improving nutritional quality have been shown to improve weight management and metabolic health [13–16], while physical activity initiatives incorporating both aerobic and resistance training have shown effectiveness in reducing cardiometabolic risk factors [17,18]. Public health efforts also emphasize the importance of creating a supportive environment for children to adopt sustainable healthy behaviors [19]. Although these interventions perform well in controlled settings, their real-world effectiveness remains limited, especially in fast-changing urban environments such as Shenzhen.

Recent evidence shows that childhood cardiovascular risk does not follow a single pathway but emerges through different developmental patterns. This shift has moved research away from uniform approaches toward precision strategies that reflect individual differences in genetics, environment, and lifestyle. This paradigm shift has led to the recognition that cardiovascular risk develops through multiple pathways, requiring targeted intervention approaches [20]. Recent multi-omics approaches have enhanced our understanding of cardiometabolic disorders, revealing distinct molecular signatures and pathways that contribute to cardiovascular disease risk through various mechanisms [21]. These insights point to the importance of integrating biological measures with family-level factors when developing early risk identification strategies for children with obesity.

Several notable cohort studies worldwide have investigated cardiovascular risk factors in children and adolescents. The Bogalusa Heart Study pioneered the understanding of cardiovascular risk factor trajectories from childhood to adulthood, demonstrating that atherosclerotic changes begin in youth [22,23]. The Young Finns Study established the relationship between childhood lifestyle factors and adult cardiovascular outcomes, following over 3,500 children [24]. More recently, the Generation R Study (Netherlands) [25] and the QUebec Adipose and Lifestyle Investigation in Youth (QUALITY) (Canada) [26] have focused on genetic and environmental determinants of cardiovascular health in contemporary youth populations. In Asia, the Hong Kong Children of May 1997 Birth Cohort [27] showed unique patterns of cardiovascular risk factor clustering in Chinese children. Within mainland China, existing cohorts include the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study [28], which followed 19,593 children since 2004. However, the Chinese cohort primarily concentrated on metabolic syndrome or obesity in isolation, rather than comprehensive cardiovascular risk assessment. Moreover, none have specifically addressed the unique characteristics of rapid urbanization zones like Shenzhen, where lifestyle transitions occur at unprecedented rates [29]. The existing cohorts also predate significant technological and social changes that have dramatically altered children’s living environments in Chinese mega-cities over the past decade.

Shenzhen, as China’s first special economic zone and one of the fastest-growing metropolitan areas globally, presents both unique challenges and opportunities for studying childhood cardiovascular risk factors. The city’s rapid urbanization has brought significant changes in lifestyle, environmental exposures, and healthcare access that may impact children’s cardiovascular health. However, despite these rapid changes, there is a critical lack of longitudinal data on the prevalence and determinants of cardiovascular risk factors among children in urban Chinese settings like Shenzhen. This knowledge gap limits the understanding of how obesity-related cardiovascular risks develop during childhood, especially in rapidly urbanizing regions of China. To address this, the Shenzhen Children Cohort Study (SCCS) is designed as a longitudinal study focusing on overweight and obese children aged 5–11 years in Shenzhen, Guangdong Province. The study will collect detailed anthropometric, biochemical, behavioral, and family-level information to examine how biological and social factors jointly influence the progression of cardiometabolic risk. By following participants over time, SCCS will provide evidence on how individual and household characteristics shape early cardiovascular health trajectories. The findings are expected to inform risk prediction and stratification models that support personalized prevention in urban pediatric populations.

Materials and methods

Study procedure

This prospective cohort study will recruit children aged 5–11 years through public enrollment coordinated by the Department of Child Health at the Third People’s Hospital of Longgang. Upon obtaining written informed consent, participants will be registered using their unique Shenzhen Child Healthcare Number. All physical examinations, laboratory tests, and imaging assessments will be conducted at the hospital’s Physical Examination Center, following a standardized protocol to ensure consistency across follow-up visits (Fig 1).

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Fig 1. Overview of recruitment, data collection, and follow-up in the SCCS.

Children aged 5–11 years were recruited, screened, and enrolled. Multidimensional risk factor data were collected annually and integrated into the HIS, with follow-up and model.

https://doi.org/10.1371/journal.pone.0340049.g001

Questionnaire-based data collection.

At each baseline visit, guardians complete digital informed consent via electronic signature on a secure WeChat mini-program. They then fill out structured questionnaires covering family health history, lifestyle behaviors, psychosocial factors, and child development. The system includes logic checks and mandatory fields to reduce input errors. Completed responses are encrypted and stored directly in the hospital information system (HIS), allowing linkage with corresponding clinical and laboratory records.

Blood sample collection and biochemical measurements.

During each scheduled health examination, fasting venous blood samples are collected by trained nurses at the Physical Examination Center of the Third People’s Hospital of Longgang. Two tubes are drawn after overnight fasting: one EDTA tube for hematological analysis and one plain tube for biochemical and metabolic testing. All samples are processed immediately in the hospital laboratory according to standardized protocols. After initial analysis, aliquots are prepared, labeled with unique identifiers, and stored at −80°C for future assays. Laboratory results are transmitted directly into the HIS. Participants who miss scheduled blood collections are contacted through the research management system and the WeChat mini‑program to arrange resampling within one month.

Follow-up scheduling and data management.

A unified research management system, based on the hospital intranet and supported by a WeChat mini-program, is used to coordinate all follow-up procedures. Upon enrollment, each participant is assigned a unique research code and linked to the HIS. The system automatically generates individualized follow-up schedules, with reminders sent to guardians through the mini-program. During each visit, research coordinators assist with identity verification, physical examinations, anthropometric measurements, blood sample collection, and questionnaire completion. All data are entered directly into the research platform. Laboratory and examination results are uploaded to both the HIS and the mini-program, allowing guardians to access their child’s health reports securely. The research platform provides built-in logic checks and data validation functions. Abnormal results are flagged and reviewed by designated research physicians. Missed visits trigger automatic alerts within 48 hours, and coordinators follow up by phone to arrange rescheduling. The system supports flexible appointment options within the hospital and its affiliated units to facilitate participant retention.

We maintain continuous communication with caregivers throughout the follow-up period to document interim health events, including hospitalizations, new clinical diagnoses, acute illnesses, medication changes, or other relevant developments reported between scheduled visits. Because a wide range of unforeseen events may arise during childhood, all reported information is recorded in the study management system and reviewed by the research team. Each event is assessed against predefined exclusion criteria and continuation rules to determine whether it introduces a condition that would substantially interfere with cardiometabolic assessments or compromise the interpretability of longitudinal outcomes. When an event meets these predefined thresholds, withdrawal is considered following a standardized decision pathway.

Discussion

The long-term consequences of cardiovascular and metabolic risk beginning in childhood are now firmly established in epidemiologic literature [32]. Yet rising rates of pediatric obesity continue to challenge this paradigm, especially in settings where rapid social and environmental transitions outpace the development of monitoring systems. Many children with obesity remain uncharacterized beyond body size, and the lack of longitudinal, multidimensional data limits our ability to distinguish who is at risk, when changes begin, and what signals predict divergence. These gaps are especially pressing in urban regions like Shenzhen, where shifting lifestyles reshape the early-life risk landscape. In this context, the present study offers not only new data, but a structural response to a broader epidemiologic need: to observe, stratify, and eventually intervene before disease becomes entrenched. While landmark cohorts such as the Bogalusa Heart Study [22,23] and the Young Finns Study [24] laid the foundation for linking childhood risk factors with adult cardiovascular outcomes, these studies were conducted in different social, environmental, and technological contexts, limiting their relevance to today’s rapidly urbanizing Chinese settings. In contrast, this study will tries to capture the unique impacts of modern urban environments in China, characterized by rapid lifestyle transitions, dietary changes, and physical activity patterns. Moreover, existing Chinese cohorts, such as BCAMS [28], have provided insights into metabolic risk among youth but have not specifically focused on high-density urban environments. Shenzhen’s rapid economic growth and shifting lifestyle patterns create a unique setting to study how these changes influence early cardiovascular health. In this context, there is a clear need to understand how biological and environmental exposures interact before clinical disease becomes evident. Much of the existing pediatric literature relies on single cross-sectional snapshots, which mask individual variability over time. By contrast, this study collects repeated measures of growth, metabolic function, vascular indicators, and family conditions, enabling the reconstruction of individualized cardiometabolic risk trajectories during a formative developmental stage.

Current pediatric practice continues to rely on BMI as the primary definition of obesity. However, BMI captures only external body size and fails to reflect the internal metabolic or cardiovascular state. Children with similar BMI values may differ markedly in lipid metabolism, insulin sensitivity, systemic inflammation, and vascular function. This mismatch between phenotype and physiology has been observed in both adults and children, often leading to delayed recognition of high-risk individuals. While prior studies have proposed metabolic subtypes of obesity, such classifications typically omit concurrent cardiovascular alterations that may evolve independently or in parallel. Grouping all children above a BMI threshold as biologically equivalent masks important variation and limits the effectiveness of early prevention. To improve precision in pediatric risk prediction, a stratified approach is needed that integrates both metabolic and cardiovascular dimensions within the obese pediatric population.

Several limitations must be acknowledged. Although recruitment focuses on children with local household registration to enhance cohort stability, internal migration may contribute to attrition. Findings may not generalize to rural or less urbanized populations. Some exposure data rely on parental reporting, introducing potential recall bias.

Despite these challenges, this cohort enables a more detailed examination of the early divergence in cardiovascular risk among children with similar body size. Previous studies have described metabolic heterogeneity within childhood obesity, yet most rely on isolated biomarkers or clinical thresholds [33–37]. This study incorporates a broader range of indicators, and these data allow for the identification of distinct developmental patterns that are not captured by BMI alone.

The Shenzhen Children Cohort Study provides a structured framework for advancing pediatric obesity research in China. By following children with obesity through repeated assessments across cardiovascular, metabolic, vascular, behavioral, and family domains, the study can detect early divergence in cardiometabolic risk before clinical symptoms emerge. This longitudinal design enhances comparability across visits and supports models that identify shared developmental pathways and early indicators of elevated risk, rather than relying on single-time-point classifications. Beyond serving as a data platform, SCCS functions as a long-term sentinel for monitoring evolving pediatric health risks in rapidly urbanizing settings. Its modular structure allows new measurements to be added as needed and supports continued follow-up into adolescence and adulthood, forming a long-term system capable of tracking developmental changes with sufficient temporal detail and biological specificity. In the context of rising childhood obesity and fragmented prevention strategies globally, SCCS offers a prototype for multimodal cohort infrastructures that can inform scientific discovery and population-level health planning.