The phoenix sepsis score for high mortality risk identification and prognostic predict in pediatric liver transplant recipients

Abstract

To evaluate the performance of Phoenix Sepsis Score (PSS) in pediatric liver transplant (LT) recipients admitted to PICU with suspected or proven infection, and to explore the association between PSS and PICU mortality for risk stratification. We retrospectively enrolled pediatric LT recipients admitted to PICU. PSS threshold of ≥ 2 was applied to assess early identification of patients at high mortality risk compared with the International Pediatric Sepsis Consensus Conference (IPSCC) criteria, while PSS was further evaluated in relation to PICU mortality. Among 132 pediatric liver transplant recipients, 117 (88.6%) developed sepsis. Compared with non-sepsis patients, those with sepsis were younger, had lower body weight, and were admitted to PICU earlier after transplantation. Organ dysfunction was more frequent in sepsis group, whereas the incidence of acute kidney injury did not differ. Overall mortality was 28.8% (38/132) exclusively in patients with sepsis. Using PICU mortality as the reference outcome, PSS-based sepsis and septic shock demonstrated higher sensitivity (100.0%, 95% CI 90.82–100.00; 76.32%, 95% CI 60.79–87.01) and positive predictive value (32.48%, 95% CI 24.67–41.40; 54.72%, 95% CI 41.45–67.34) than IPSCC criteria. PSS showed superior discrimination, with the highest area under the receiver operating characteristic curve (AUROC 0.868; 95% CI 0.802–0.934) and precision–recall curve (AUPRC 0.784; 95% CI 0.656–0.880), outperforming the conventional scores. PICU mortality increased stepwise across higher PSS categories.

Conclusion: The Phoenix Sepsis criteria achieves superior mortality risk identification over IPSCC criteria and score outperforms conventional scoring systems in predicting PICU mortality, supporting its risk stratification in pediatric liver transplant recipients.

What is Known: • Immunocompromised pediatric liver transplant recipients have higher PICU mortality after sepsis. While the Phoenix Sepsis Criteria has been validated to outperform conventional IPSCC criteria in general critically ill children, its prognostic predictive performance remains unassessed in this high-risk transplant population.

What is New: • This study demonstrates that among pediatric liver transplant recipients, an immunocompromised high-risk cohort, the Phoenix Sepsis Criteria is superior to the IPSCC Criteria in identifying PICU mortality risk, and this scoring system exhibits better prognostic predictive performance than conventional scoring tools. • The findings provide evidence to support clinical adoption of the Phoenix Sepsis Score for optimized risk stratification in post-transplant children.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00431-026-07294-7.

Introduction

Liver transplantation (LT) is the definitive curative treatment for children with acute or chronic end-stage liver disease, specific hepatic malignancies, and inherited metabolic disorders [1–3]. Advances in surgical techniques and perioperative care have markedly improved survival outcomes in pediatric LT recipients. A large retrospective cohort study from Japan reported 1-, 10-, 20-, and 30-year survival rates of 88.9%, 82.2%, 77.1%, and 75.4%, respectively, underscoring the favorable long-term prognosis of pediatric LT [4].

Despite these encouraging outcomes, postoperative management in this population remains highly challenging. Infection is the most common complication following pediatric LT, with an incidence of 26.8%, and represents the leading cause of mortality [5]. Owing to immunosuppression, surgical stress, and frequent exposure to invasive procedures, pediatric LT recipients are particularly vulnerable to severe infections.

In 2024, the Society of Critical Care Medicine (SCCM) released updated diagnostic criteria for pediatric sepsis and simultaneously introduced the Phoenix Sepsis Score (PSS), a novel organ dysfunction–based scoring system specifically developed for children under 18 years of age [6]. The Phoenix Sepsis Criteria were designed to improve identification of pediatric patients with infection-associated organ dysfunction. Recent studies have demonstrated that the Phoenix Sepsis Criteria and PSS exhibit satisfactory diagnostic performance in the general pediatric population, particularly in the pediatric intensive care unit (PICU) setting [7].

However, accumulating evidence suggested that the performance of the Phoenix Sepsis Criteria may vary substantially across specific pediatric subgroups [8–10]. Pediatric LT recipients constitute a unique and particularly vulnerable subgroup, in whom infection-related organ dysfunction may be influenced by immunosuppression, altered inflammatory responses, and postoperative physiological changes. To date, no studies have specifically evaluated the applicability or clinical performance of the Phoenix Sepsis Criteria or the PSS in children with suspected or confirmed infection following LT.

Therefore, the present study aimed to evaluate the performance of the Phoenix Sepsis Criteria in identifying children at high mortality risk with suspected or proven infection after LT. In addition, we sought to examine the prognostic predictive performance of the PSS in relation to PICU mortality comparing with that of existing sepsis scoring systems and risk stratification.

Methods

Study design

We conducted a retrospective cohort study to evaluate the performance of PSS in pediatric LT recipients admitted to the PICU of Shanghai Children’s Medical Center with suspected or confirmed infection between January 2020 and December 2023.

The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Shanghai Children's Medical Center (Approval No. SCMCIRB-K2025010-1) prior to the initiation of data collection. Written informed consent was obtained from the parents or legal guardians of all enrolled patients after a detailed explanation of the study purpose, procedures, potential risks, and benefits. Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Population

Eligible patients were consecutively enrolled if they met the following inclusion criteria: (1) age < 18 years at the time of PICU admission; (2) history of LT, regardless of the time elapsed since transplantation; (3) suspected or confirmed infection within 24 h of PICU admission. Suspected infection was comprehensively determined based on combined clinical manifestations, inflammatory laboratory markers, and pathogen culture results, with consensus review completed by two specialized intensivists. Patients were excluded if they met any of the following criteria: (1) withdrawal of life-sustaining treatment during hospitalization due to personal or family decisions; or (2) incomplete or missing key clinical data required for analysis.

Group setting

Based on Phoenix Sepsis criteria, the enrolled subjects were divided into two groups: the sepsis group and the non-sepsis group. Sepsis was defined accordance with the new criteria established by the Pediatric Sepsis Definition Task Force of the SCCM [6]. The PSS was used to identify sepsis, with a score ≥ 2 points in children with suspected or confirmed infection; Septic shock was defined as sepsis accompanied by cardiovascular dysfunction, with the cardiovascular system component of the PSS scored at least 1 point, which included: (1) Age-appropriate severe hypotension (defined as systolic blood pressure below the 5th percentile for age); (2) Blood lactate level > 5 mmol/L; (3) Requirement for vasoactive agents. The PSS was calculated using the worst values of relevant indicators recorded within 24 h after the patient's admission to the PICU.

Outcomes

The primary outcome was PICU mortality. Secondary outcomes included duration of mechanical ventilation (MV), length of stay (LOS) in the PICU, 28-day ventilator-free days (VFDs, defined as the number of days within 28 days after PICU admission during which the patient was alive and did not require mechanical ventilation), and 28-day PICU-free days (PFDs, defined as the number of days within 28 days after PICU admission during which the patient was alive and not in the PICU).

Data collection

Demographic and clinical data were retrospectively extracted from the electronic medical record system. Collected demographic variables included age, sex, and body weight. Clinical characteristics comprised the interval between LT and PICU admission, indications for LT, post-transplant complications, and relevant medical treatments during hospitalization. Based on clinical and laboratory data obtained within 24 h after PICU admission, patients were classified according to the Phoenix Sepsis Criteria and the International Pediatric Sepsis Consensus Conference (IPSCC) criteria [11]. In addition, severity scores including the PSS, pediatric Sequential Organ Failure Assessment (pSOFA) [12], and Pediatric Risk of Mortality Ⅲ (PRISM Ⅲ) [13] were calculated for each patient.

Statistical analysis

All baseline variables were screened for missing data; Only reason for LT contained 2 missing records, detailed in Supplementary Table 1. Complete-case analysis was limited to etiology comparison, no imputation was applied. Normally distributed data were expressed as mean ± standard deviation (SD), whereas non-normally distributed data were presented as median with interquartile range (IQR). Comparisons between two groups were conducted using the independent samples T test for normally distributed variables or the Mann–Whitney U test for non-normally distributed variables. Categorical variables were summarized as counts and percentages and compared using the Pearson chi-square test or Fisher’s exact test, as appropriate. Given the binary nature of these diagnostic classifications, sensitivity and positive predictive value (PPV) were calculated to assess the ability for early identification of patients at high mortality risk. The area under the receiver operating characteristic curve (AUROC) and precision–recall curve (AUPRC) were used to predicting PICU mortality. All statistical analyses were performed using R software (version 4.5.2; R Foundation for Statistical Computing, Vienna, Austria). A two-sided P value < 0.05 was considered statistically significant.

Results

Comparison of demographic and clinical variables by sepsis status

A total of 132 pediatric liver transplant recipients were included in this study, among whom 67 (50.8%) were female with the median age of 10 months. Of all patients, 117 (88.6%) met the diagnostic criteria for sepsis, while 15 (11.4%) were classified as non-sepsis Fig. 1. Compared with non-sepsis patients, those with sepsis were younger (10 [7–18] vs. 24 [11.5–56.5] months; P = 0.003), had lower body weight (8 [6–10] vs. 12 [8–15.5] kg; P = 0.013), and were admitted to the PICU earlier after LT (15 [3.0–81.0] vs. 120 [66.5–540.0] days; P < 0.001). The incidence of major clinical complications was significantly higher in the sepsis group, including respiratory failure (86.3% vs. 20.0%, P < 0.001), coagulation disorders (94.0% vs. 46.7%, P < 0.001), and multiple organ dysfunction syndrome (MODS) (63.2% vs. 13.3%, P < 0.001). Although acute kidney injury (AKI) was more frequent in the sepsis group, the difference did not reach statistical significance (27.4% vs. 6.7%, P = 0.114). The use of continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) was comparable between the two groups (22.2% vs. 6.7%, P = 0.305; 6.0% vs. 0.0%, P = 1.000, respectively). No patient in either group received extracorporeal membrane oxygenation (ECMO). Patients with sepsis had higher pSOFA and PRISM III scores than those without sepsis (6 [3–11] vs. 1 [0–2.5]; 9 [4–15] vs. 0 [0–5.5], both P < 0.001). Details are shown in Table 1.

Fig. 1.

Flow chart of patients enrollment

Table 1.

Baseline characteristics of LT recipients by sepsis status

	All patients (n = 132)	Sepsis (n = 117)	Non-sepsis (n = 15)	P value
Age, months	10 (7–21.5)	10 (7–18)	24 (11.5–56.5)	0.003*
Female, n (%)	67 (50.8)	61 (52.1)	6 (40.0)	0.541
Weight (kg), median (IQR)	8 (6–11)	8 (6–10)	12 (8–15.5)	0.013*
Days post LT, median (IQR)	17 (4.5–110)	15 (3.0–81.0)	120(66.5–540.0)	< 0.001*
Reason for LT, n (%)				0.290
- Congenital biliary atresia	99 (75.0)	89 (76.1)	10 (66.7)
- Congenital metabolic diseases	7 (5.3)	5 (4.3)	2 (13.3)
- Others	24 (18.2)	22 (18.8)	2 (13.3)
Clinical complications, n (%)
- Respiratory failure	104 (78.8)	101 (86.3)	3 (20.0)	< 0.001*
- Coagulation disorder	117 (88.6)	110 (94.0)	7 (46.7)	< 0.001*
- AKI	33 (25.0)	32 (27.4)	1 (6.7)	0.114
- MODS	76 (57.6)	74 (63.2)	2 (13.3)	< 0.001*
Supportive therapies, n (%)
- CRRT	27 (20.5)	26 (22.2)	1 (6.7)	0.305
- TPE	7 (5.3)	7 (6.0)	0 (0.0)	1.000
- ECMO	0 (0.0)	0 (0.0)	0 (0.0)	—
Clinical scores
- pSOFA, median (IQR)	6 (2–9.25)	6 (3–11)	1 (0–2.5)	< 0.001*
- PRISM III, median (IQR)	8 (3–13)	9 (4–15)	0 (0–5.5)	< 0.001*

AKI acute kidney injury, CRRT continuous renal replacement therapy, ECMO extracorporeal membrane oxygenation, IQR interquartile range, LT liver transplantation, MODS multiple organ dysfunction syndrome, PRISM III pediatric risk of mortality ill. TPE therapeutic plasma exchange, pSOFA pediatric sequential organ failure assessment; *P < 0.05 was considered statistically significant

Primary and secondary outcomes by sepsis status

Overall PICU mortality was 28.8% (38/132) and occurred exclusively in patients with sepsis (32.5% vs. 0%; P = 0.006). Compared with non-sepsis patients, those with sepsis had a longer PICU LOS (15.5 [8–26.3] vs. 7.5 [3.5–13.5] days; P = 0.006), longer duration of MV (9 [2.5–15.5] vs. 7.5 [0–14] days; P < 0.001), and fewer 28-day PDFs (2 [0–13] vs. 21 [12.5–24.5] days; P = 0.001). 28-day VFDs did not differ significantly between groups. Details are shown in Table 2.

Table 2.

Clinical outcomes in pediatric LT recipients by sepsis status

Outcomes	All patients (n = 132)	Sepsis (n = 117)	Non-sepsis (n = 15)	P value
Primary outcome
- PICU mortality, n (%)	38 (28.8)	38 (32.5)	0 (0)	0.006*
Secondary outcomes
- PICU LOS days, median (IQR)	15 (7–25)	15.5 (8–26.3)	7.5 (3.5–13.5)	0.006*
- MV duration days, median (IQR)	7 (1–15)	9 (2.5–15.5)	7.5 (0–14)	< 0.001*
- 28-day VFDs, median (IQR)	7 (2–13)	7 (1–13)	8 (3.5–13)	0.505
- 28-day PFDs, median (IQR)	4 (0–15)	2 (0–13)	21 (12.5–24.5)	0.001*

IQR interquartile range, LOS length of stay, LT liver transplantation, MV mechanical ventilation, PFDs PICU-free days, PICU pediatric intensive care unit, VFDs ventilator-free days. *P < 0.05 was considered statistically significant

Comparison of pediatric sepsis and septic shock criteria

The sensitivity and PPV of Phoenix Sepsis criteria were evaluated in relation to PICU mortality and compared with those of IPSCC criteria as shown in Table 3. Full statistical metrics in Supplementary Table 2. Both PSS-based sepsis and septic shock criteria demonstrated consistently higher sensitivity than the corresponding IPSCC criteria. Notably, the PSS sepsis criteria achieved maximal sensitivity (100.0%, 95% CI 90.82–100.00), whereas sensitivity (65.79%, 95% CI 49.89–78.79) was substantially lower for IPSCC-based sepsis or severe sepsis. Although PPV varied across criteria, Phoenix Sepsis criteria also showed more favorable PPV (32.48%,95% CI 24.67–41.40) than IPSCC criteria, with the highest PPV observed for the PSS-based septic shock criteria (54.72%, 95% CI 41.45–67.34).

Table 3.

Performance for identifying PICU mortality of different sepsis criteria

Diagnostic Criteria	PPV (%) (95% CI)	Sensitivity (%) (95% CI)
Phenix Sepsis Criteria	32.48 (24.67–41.40)	100.00 (90.82–100.00)
Phenix Septic Shock Criteria	54.72 (41.45–67.34)	76.32 (60.79–87.01)
IPSCC Sepsis	28.09 (19.81–38.18)	65.79 (49.89–78.79)
IPSCC Severe Sepsis	28.74 (20.29–38.98)	65.79 (49.89–78.79)
IPSCC Septic Shock	44.44 (30.94–58.82)	52.63 (37.26–67.52)

95%CI 95% confidence interval, IPSCC International Pediatric Sepsis Consensus Conference, PICU pediatric intensive care unit, PPV positive predictive value

Performance of PSS, pSOFA, and PRISM III scores

Using PICU mortality as the primary outcome, the performance of PSS, pSOFA, and PRISM III for mortality and risk stratification was compared. PSS demonstrated the highest specificity (0.936, 95% CI 0.883–0.979) and PPV (0.800, 95% CI 0.643–0.935), indicating superior ability to identify patients at high risk of death compared with pSOFA and PRISM III. Overall discrimination was also highest for PSS, with the highest AUROC (0.868, 95% CI 0.802–0.934) and AUPRC (0.784, 95% CI 0.656–0.880), followed by PRISM III (AUROC 0.852, 95% CI 0.780–0.923; AUPRC 0.686, 95% CI 0.525–0.840) and pSOFA (AUROC 0.825, 95% CI 0.748–0.902; AUPRC 0.653, 95% CI 0.485–0.811). Details are shown in Table 4 and Supplementary Fig. 1. Consistent with these findings, PICU mortality increased stepwise across higher PSS score categories, with higher scores corresponding to progressively greater mortality despite fewer patients in the highest score categories Fig. 2.

Table 4.

Performance of sepsis score systems in relation to PICU mortality

Diagnostic Performance	PSS	pSOFA	PRIMS III
Sensitivity (95% CI)	0.632 (0.474–0.763)	0.605 (0.447–0.763)	0.868 (0.763–0.974)
Specificity (95% CI)	0.936 (0.883–0.979)	0.894 (0.830–0.947)	0.692 (0.596–0.787)
PPV value (95% CI)	0.800 (0.643–0.935)	0.697 (0.545–0.846)	0.532 (0.410–0.655)
Area under the ROC (95% CI)	0.868 (0.802–0.934)	0.825 (0.748–0.902)	0.852 (0.780–0.923)
Area under the PRC (95% CI)	0.784 (0.656–0.880)	0.653 (0.485–0.811)	0.686 (0.525–0.840)

95%CI 95% confidence interval, PICU pediatric intensive care unit, PPV positive predictive value. PRC precision recall curve, PRISM III pediatric risk of mortality ill, pSOFA pediatric sequential organ failure assessment, PSS phoenix sepsis score, ROC Receiver operating characteristic curve

Fig. 2.

Distribution of patients and PICU mortality across PSS score categories

Discussion

In this retrospective cohort study of 132 pediatric LT recipients with suspected or confirmed infection admitted to the PICU between 2018 and 2020, we evaluated the performance of the Phoenix Sepsis Criteria for early identification of patients at high mortality risk and further assessed the performance of PSS for mortality prediction and risk stratification.

Our findings demonstrated that the Phoenix Sepsis Criteria effectively identifies infected pediatric liver transplant recipients at high mortality risk. Patients classified as having sepsis according to the Phoenix Sepsis criteria exhibited significantly higher PICU mortality and worse outcomes with those without sepsis. Further observations revealed that, using PICU mortality as the primary outcome, compared with the IPSCC Criteria, the Phoenix Sepsis Criteria demonstrated higher sensitivity and PPV for identifying high-risk infected pediatric LT recipients. Only two-thirds of deceased patients in our cohort met the IPSCC criteria, yielding a substantially lower sensitivity than the Phoenix Sepsis Criteria, which enables effective recognition of children at elevated mortality risk and reduces the under recognition of high-risk fatal cases. The IPSCC criteria is derived from the systemic inflammatory response syndrome (SIRS) framework, with systemic inflammation serving as the core diagnostic indicator [14]. However, a considerable proportion of children in our cohort presented with infection-associated organ dysfunction without fulfilling SIRS criteria, representing so-called “SIRS-negative sepsis.” Children undergoing liver transplantation typically suffer from severe preoperative liver failure and chronic immune dysregulation. Although early-stage disease is characterized by overt systemic inflammation, persistent inflammatory stimulation eventually leads to immune cell exhaustion, apoptosis, and excessive activation of regulatory immune cells [15], resulting in immune paralysis and SIRS-negative sepsis. Our findings are consistent with prior adult sepsis studies demonstrating that SIRS-based criteria was associated with significant underdiagnosis SIRS-negative sepsis [16], which is also linked to a high risk of mortality. Consequently, the 2016 adult sepsis definition (Sepsis-3) shifted the diagnostic paradigm from a SIRS-dependent model toward an organ dysfunction–oriented framework, which more accurately reflects disease severity and predicts clinical outcomes. Collectively, organ dysfunction-oriented diagnostic framework is superior for accurately identifying high mortality risk. This characteristic is of particular clinical importance in this vulnerable pediatric liver transplant population.

We also evaluated the prognostic performance of the PSS for PICU mortality prediction and risk stratification in pediatric LT recipients. Our results demonstrated that PSS exhibited superior discriminative ability for PICU mortality compared with conventional scoring systems, with higher AUROC and AUPRC than pSOFA and PRISM III. Moreover, the mortality increased progressively with rising PSS levels, indicating a clear dose–response relationship between PSS and mortality risk. Host organ dysregulation serves as the core pathological mechanism of sepsis progression, involving multiple physiological pathways including neuroendocrine regulation, inflammatory immunity, coagulation and energy metabolism [17]. The heart and lungs are the core organs maintaining systemic oxygen delivery, their impairment directly disturbs whole -body oxygen supply. Coagulopathy synergizes with inflammatory response and endothelial to disrupt oxygen supply homeostasis, ultimately leading to vital organ damage [18]. The PSS incorporates indicators reflecting dysfunction of the respiratory, circulatory, coagulation and nervous systems, which precisely captures the central role of organ failure risk regulation in the onset and progression of sepsis. Moreover, the PSS excludes scoring items for liver and kidney, two major oxygen-consuming organs, rendering it more suitable for liver transplant recipients. Many transplant patients present with severe preoperative hepatic and renal impairment, and such baseline organ dysfunction persists a period time after surgical stress. These abnormalities are not induced by infection and can be rapidly alleviated with standardized perioperative management as the graft regains full function, which would impair the performance of conventional scoring systems in mortality prediction and risk stratification for this population. Taken together, the PSS exhibits superior prognostic predictive performance.

A major strength of the present study is that it systematically validates the clinical utility of the Phoenix Sepsis Criteria and the corresponding PSS in the high-risk population of pediatric liver transplant recipients for the first time. Previous studies have largely overlooked this unique and vulnerable subgroup. Accumulated evidence has confirmed that the Phoenix Sepsis criteria outperforms conventional criteria in high-risk identification, and scoring tools for mortality prediction, and risk stratification in general PICU pediatric patients. However, clinical evidence supporting its application in specific high-risk subgroups remains scarce, with existing studies primarily limited to children with malignancies and neonates. By addressing this critical research gap, our findings extend the applicable scope of the Phoenix sepsis to pediatric solid organ transplant recipients.

Several limitations of the present study should be acknowledged. First, this study has potential incorporation bias (circularity), which arises from the pathophysiological overlap between organ dysfunction indicators in the scoring systems and mortality outcomes, and may theoretically overestimate the true prognostic performance of the scoring tools. Despite this limitation, it does not reduce the clinical practical value of this research. This study aims to identify which scoring criterion enables earlier and more accurate mortality risk stratification for post-transplant patients, which can counteract the impact of the above bias to a certain extent and provide a reliable bedside evaluation basis for timely initiation of intensive care interventions in clinical practice. Second, this was a single-center retrospective analysis with a relatively small sample size, and the findings may have been influenced by local clinical practices and management strategies, which could limit the generalizability of our results. Future multicenter, prospective studies across different LT centers and PICU care models are warranted to further validate the diagnostic and prognostic performance of the PSS. Third, a substantial proportion of deaths after LT are attributable to non-infectious complications, including acute or chronic rejection and post-transplant malignancies [5]. These conditions frequently coexist with infection, and the resulting organ dysfunction is not exclusively driven by infectious processes. In addition, immunosuppressive therapy itself represents an independent risk factor for adverse outcomes, and the intensity of immunosuppression varies over time after transplantation. These factors reflect the inherent clinical complexity and may, to some extent, affect the accuracy of the PSS in predicting mortality risk. Future investigations may benefit from incorporating cause-specific mortality analyses to distinguish infection-attributable deaths from all-cause mortality and from exploring whether expanded organ dysfunction models (e.g., PSS-8) could further improve the precision of risk stratification in this population.

Conclusion

The Phoenix Sepsis criteria achieves superior mortality risk identification over IPSCC criteria and score outperforms conventional scoring systems in predicting PICU mortality, supporting its risk stratification in pediatric liver transplant recipients.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Contributors Statement Conceptualization: Teng Teng, Xinhui Wang, Long Xiang; Methodology: Teng Teng, Xinhui Wang, Fang Zhang, Biyuan Xie, Siqi Zhu, Long Xiang; Formal analysis and investigation: Fang Zhang, Biyuan Xie, Siqi Zhu; Writing—original draft preparation: Teng Teng, Xinhui Wang; Writing—review and editing: Teng Teng, Xinhui Wang, Fang Zhang, Biyuan Xie, Siqi Zhu, Long Xiang; Supervision: Long Xiang.

Funding

All phases of this study were supported by Shanghai PuJiang Programme (No.25PJD085.) and The Development Project for Innovative Teams of Clinical Subspecialties,Shanghai Children's Medical Center (SCMC-XEQ-202602).

Data availability

The data that support the findings of this study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author upon reasonable request, with appropriate institutional review board approval.

Declarations

Ethical approval and informed consent

The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Shanghai Children's Medical Center (Approval No. SCMCIRB-K2025010-1) prior to data collection. All clinical procedures and data analyses were performed strictly in accordance with the ethical principles outlined in the Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all enrolled patients following comprehensive explanation of the study’s objectives, research procedures, potential risks and clinical benefits. No patients or members of the public participated in the design, conduct, reporting, or dissemination planning of this research.

Competing interests

The authors declare no competing interests.