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Methods We performed a single-center, retrospective review of 20 neonates (aged ≤ 35 days) hospitalized with BJIs between 2017 and 2025. Data on demographics, clinical presentation, laboratory and imaging findings, treatment, and outcomes were collected and analyzed. Results The mean age was 21.2 days, and 65% of the neonates were male. Pseudoparalysis was the most common presenting symptom (observed in 95% of cases). Pathogens were identified in 14 of the 20 cases (70%), with Staphylococcus aureus being the most prevalent (identified in 11 patients, 55%). Concurrent bone and joint infections were observed in 65% of the patients. Ultrasound demonstrated a high detection rate (95%). Surgical drainage was performed in 12 patients (60%), who presented with significantly higher C-reactive protein levels and a higher culture-positive rate than did the nonsurgical group. With one patient lost to follow-up, data were available for 19 patients, of whom five (26.3%) experienced complications. Conclusions Neonatal BJIs often present with nonspecific signs, among which pseudoparalysis is a key indicator. Ultrasound is a sensitive, first-line imaging tool. Early surgical intervention should be considered for patients with concurrent arthritis and significantly elevated inflammatory markers, as it aids in pathogen identification and infection control. neonate osteomyelitis septic arthritis pseudoparalysis surgical drainage outcome INTRODUCTION Bone and joint infections (BJIs) are rare in the neonates. Despite significant advancements in neonatal care, the reported incidence remains relatively high in high-risk populations, such as 1–3 cases per 1,000 neonatal intensive care unit (NICU) admissions.(1,2) Diagnosis in this age group is challenging and carries a risk of long-term orthopedic complications and dysfunction.(3) Staphylococcus aureus is the most common pathogen in newborns and young infants underlying BJIs.(4,5) The clinical manifestations of neonatal BJIs are often subtle and nonspecific; in the early stages, the only sign may be reduced limb movement.(6,7) Delay in diagnosis and treatment can lead to serious sequelae, such as limb length discrepancy and joint dysfunction.(8) Previous studies have indicated that most BJIs can be successfully treated with antibiotics,(9) while surgical intervention is recommended for complex infections or cases showing an inadequate response to intravenous therapy.(10–12) To date, only a limited number of studies have focused specifically on neonatal BJIs. This study reviewed 20 clinical cases to analyze the clinical characteristics, management, and outcomes of neonatal BJIs, comparing our findings with those reported in the literature. Our aim is to assist clinicians in the early recognition and management of this condition, thereby helping to improve patient prognosis. METHODS We retrospectively reviewed the cases of 20 neonates hospitalized with BJIs at the Children’s Hospital, Zhejiang University, School of Medicine, between 2017 and 2025. The inclusion criteria were as follows: 1) aged 35 days and younger; and 2) diagnosed by radiographic changes.(13) Exclusion criteria included neonates with chronic osteomyelitis, congenital abnormalities or metabolic diseases. Data on demographics, clinical presentation, laboratory and imaging findings, treatment, and outcomes were retrospectively collected from electronic medical records. All patients were followed up until July 31, 2025. All the statistical analyses were conducted via SPSS version 27.0 (SPSS Inc., Chicago, IL) for Windows. Continuous data are presented as the means and standard deviations. Categorical variables were assessed via the chi-square (χ²) test. Comparisons between the surgical and nonsurgical groups were performed via Student’s t -test for normally distributed data and the Mann–Whitney U test for non-normally distributed variables. A P -value < 0.05 was considered statistically significant. RESULTS Patient characteristics We outlined patient characteristics in Table 1. A total of 20 neonates with bone and joint infections (BJIs) were included in this study. All patients were aged 35 days or younger, including 4 patients older than 28 days. On the basis of clinical symptoms, the onset of infection was estimated to have occurred approximately 7 days prior to admission. The mean age was 21.2 ± 8.82 days, and 65% of the patients were male. The mean birth weight was 2913 ± 648.18 g, and the mean gestational age was 37.45 ± 2.48 weeks. Six infants were preterm. Nine neonates were delivered vaginally, and 11 were delivered via cesarean section. The mean duration of symptoms at presentation was 5.3 ± 3.63 days. Pseudoparalysis was the most common symptom (19 patients), followed by localized swelling (16 patients) and fever (15 patients). Concurrent bone and joint infections were observed in 65% (13/20) of the neonates. Septic arthritis involved 17 joints, most commonly the hip (41.18%, 7/17) and knee (29.41%, 5/17), followed by the shoulder (11.76%, 2/17), temporomandibular, elbow, and interphalangeal joints. Osteomyelitis affected 21 sites, with 3 patients presenting with multifocal involvement (affecting two bones each). The femur was the most frequently involved bone (42.9%, 9/21), followed by the tibia (19.1%, 4/21), ulna (9.5%, 2/21), and humerus (9.5%, 2/21). Bacterial cultures were obtained from blood samples or drainage fluid from infected sites. Pathogens were identified in 14 of the 20 cases (70%). Among these 14 culture-positive cases, joint fluid cultures were positive in 12 cases (85.7%) and blood cultures in 2 (14.3%). Staphylococcus aureus was the most common pathogen, detected in 11 patients (55%), including 3 patients with methicillin-resistant S. aureus (MRSA). Other pathogens included Escherichia coli (3 patients), Staphylococcus epidermidis (2 patients), Enterococcus avium (1 patient), and Staphylococcus warneri (1 patient). Treatment, imaging and follow-up The treatment, imaging, and follow-up outcomes are summarized in Table 2. Accordingly, all 20 neonates underwent initial ultrasound evaluation; findings consistent with osteomyelitis or septic arthritis were observed in 19 cases (95%). Typical sonographic features included cortical disruption, subperiosteal fluid collection, and joint effusion. Radiographs were obtained for 19 infants and were abnormal in 13 (68.4%). One patient underwent CT imaging, which revealed no definitive abnormalities. MRI was performed in 18 patients, all of whom presented pathological findings (sensitivity 100%). Empirical intravenous antibiotic therapy was initiated in all patients and subsequently adjusted according to the culture results. Linezolid and vancomycin were the most frequently administered agents. Except for one patient who experienced relapse and one who was lost to follow-up, all patients were discharged after clinical recovery. Among the 19 patients with follow-up data, five (26.3%) experienced complications, including leg length discrepancy, joint dislocation, and limited range of motion. Comparative analysis of surgical and nonsurgical groups As detailed in Table 3, surgical drainage was performed in 12 neonates (60%). Compared with the nonsurgical cohort, the surgical cohort presented significantly greater C-reactive protein concentrations at admission (55.79 ± 23.56 mg/L vs 24.61 ± 14.05 mg/L, P = 0.004) and a higher percentage of positive cultures (91.67% vs 37.5%, P = 0.018). Concurrent bone and joint infection was more frequent in the surgical group ( P = 0.004). No significant differences were observed between the two groups with respect to age, sex, birth weight, gestational age, white blood cell count, predisposing factors, time to diagnosis, or length of hospital stay. Comparative Analysis of Published Literatures To further analyze the clinical characteristics and management of bone and joint infections (BJIs) in neonates, we compared recent studies in Table 4. Owing to regional differences, variability in study design, and a lack of uniform case inclusion criteria, some conclusions differ significantly across studies. Overall, we found that the male-to-female ratio was approximately 2:1 in these studies; pathogen cultures predominantly identified Staphylococcus aureus , and antibiotic regimens primarily included linezolid and vancomycin. Ultrasound, X-ray, and MRI are commonly used in the diagnosis of BJIs. Among these, MRI serves as the gold standard, with a sensitivity of 100%, while the use of other imaging modalities varies by research center. The infection sites were mainly in the lower limbs, with long bones frequently involving the femur and tibia. In our study, joint infections primarily affected the hip and knee. In addition to early antibiotic treatment, some patients also underwent surgical intervention. With the exception of the study by Zhan et al ., which did not report sequelae, all other centers documented the occurrence of complications. Discussion Neonatal bone and joint infections (BJIs) refer to an inflammatory condition of the osseous structures and joints resulting from pathogenic microorganisms. This condition occurs following pathogen invasion and proliferation within the bone's cellular components and extracellular matrix, triggering a host inflammatory response. Pathogens can reach the bone through the bloodstream (hematogenous spread), direct inoculation (e.g., traumatic or iatrogenic), or extension from a contiguous site of infection, such as infected soft tissue or joint fluid.(14,15) During the neonatal period, the metaphysis of certain long bones are partially situated within the joint capsule. This unique anatomical relationship facilitates the spread of infection from the metaphyseal region into the articular cavity.(16) Furthermore, transphyseal vascular channels persist in neonates, and communications exist between the metaphyseal and epiphyseal circulations.¹⁶ These factors collectively predispose neonates with hematogenous osteomyelitis to develop concomitant septic arthritis.(17,18) In our study, concurrent bone and joint infection was observed in 65% of cases, whereas rates of 58%(19) and 40.9%(4) have been reported in older infants. The most frequently involved joint was the hip, and the femur was the most commonly affected long bone. The reported incidence of severe sequelae in neonatal BJIs varies across cohorts, ranging from 3% to 30%.(20) During our follow-up, complications occurred in five cases, nearly all of which involved combined bone and joint infection. Differences in sequelae rates compared with other studies may be attributable to variations in the diagnostic criteria for sequelae. Early diagnosis of neonatal BJIs is critical for treatment and improving prognosis.(21) However, the clinical manifestations are often nonspecific, leading to diagnostic delays.(22) In our cohort, five infants presented without fever, and only one lacked restricted limb movement. This underscores the importance of maintaining a high index of suspicion for BJIs in neonates with impaired limb mobility, even in the absence of fever. Ultrasonography and radiography are first-line imaging modalities widely used for the early diagnosis of BJIs. In our study, all infants underwent ultrasonography, which yielded a positivity rate of 85%, compared with 73.68% for radiography. This discrepancy may be explained by the relatively short median diagnostic interval of 5.3 days in our cohort, whereas cortical erosions typically become visible on radiographs only after day 7. (23,24) Therefore, given its low cost and wide availability, ultrasonography should be prioritized in the diagnostic workup of BJIs to facilitate early diagnosis. Close follow-up is recommended even if initial radiographs show no abnormalities suggestive of BJIs. Magnetic resonance imaging (MRI) is the most valuable modality for diagnosing BJIs, offering high sensitivity for the early detection of bone marrow edema and soft-tissue abscesses and allowing precise assessment of lesion extent. However, its application in neonates is limited by long acquisition times, the frequent need for sedation or anesthesia, and high cost.(25) Computed tomography (CT) has limited diagnostic value and involves considerable radiation exposure; thus, it is not recommended for routine use.(26) In our study, one infant underwent CT to differentiate BJIs from lymphangiomas. Bone scintigraphy may serve as an adjunctive tool for detecting bone and joint infections, although its clinical utility in neonates requires further validation.(27) Antibiotic management of neonatal osteomyelitis follows the principles of early, aggressive, and often prolonged therapy to prevent severe skeletal sequelae and sepsis. Initial empirical regimens typically consist of combination intravenous antibiotics aimed at covering the most common pathogens, particularly Staphylococcus aureus and gram-negative bacteria.(28) Common regimens include a glycopeptide (e.g., vancomycin) or an antistaphylococcal penicillin (e.g., oxacillin) combined with an aminoglycoside (e.g., gentamicin) or a third-generation cephalosporin (e.g., ceftriaxone). Carbapenems (e.g., meropenem) may be used in settings with resistant organisms or in critically ill infants. Therapy should be adjusted on the basis of microbiological results once available (8) A significant challenge is the high rate (17.6%–68.2%) of culture-negative cases, (9) which limits guidance for targeted therapy and decisions regarding treatment conversion To improve pathogen yield, recent guidelines strongly recommend invasive diagnostic procedures (e.g., bone aspiration or abscess drainage) for culture.(29) Previous studies suggest that 90% of cases of acute hematogenous osteomyelitis (AHO) can be cured with appropriate antibiotic therapy.(30) However, recent studies also recommend surgical intervention for AHO, particularly for septic arthritis (SA).(12) Surgical intervention can significantly improve the microbiological yield,(26) facilitate pus drainage and compartment decompression, and may reduce the risk of epiphyseal injury and joint deformity. It is especially indicated for patients with abscess formation or those refractory to conservative management. (31,32) In our study, the majority (60%) of infants underwent surgery; nearly all had osteomyelitis accompanied by arthritis, particularly those with significantly elevated C-reactive protein (CRP) levels, suggesting more severe disease. Rubin et al . (17) reported that septic hip arthritis is common in neonates with concomitant bone infection and often requires urgent surgical drainage to reduce intra-articular pressure and prevent avascular necrosis of the femoral head. This view is supported by the 2017 guidelines from the European Society for Pediatric Infectious Diseases (ESPID), which recommend surgical drainage for septic arthritis (especially of the hip) to reduce the risk of permanent functional impairment. (26) Moreover, the diagnostic yield of cultures was significantly greater in the surgical group (p = 0.018), providing a basis for the use of sensitive antibiotics. Although our study did not demonstrate that early surgical intervention shortened hospital stay, it is still recommended for patients with abscess formation, joint involvement, or inadequate response to medical therapy. Conclusions Neonatal bone and joint infections often present with atypical clinical symptoms in the early stages, posing a diagnostic challenge. Ultrasonography, due to its sensitivity in detecting joint effusion and early soft-tissue changes, should be considered a first-line imaging modality to facilitate early diagnosis. In addition to initiating empirical antibiotic therapy promptly, surgical intervention should be actively considered for patients with osteomyelitis complicated by arthritis and markedly elevated C-reactive protein (CRP) levels. Early surgical drainage can help control infection, reduce complications, and improve long-term outcomes. This study has several inherent limitations. Its single-center, retrospective design, small sample size, and lack of standardized treatment and follow-up protocols limit the generalizability and comparability of the findings. Future multicenter, large-sample, prospective studies are warranted to validate these observations and optimize diagnostic and therapeutic strategies for neonatal osteomyelitis. Abbreviations BJIs, bone and joint infections; MRSA, methicillin-resistant S. aureus; AHO, acute hematogenous osteomyelitis; SA, septic arthritis. Declarations Ethics approval and consent to participate This study was approved by the Ethical Committee of Children's Hospital of Zhejiang University School of Medicine (Approval No. 2025-IRB-0538-P-01). The study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Due to the retrospective nature of the study and the use of anonymized patient data, the requirement for informed consent was waived by the aforementioned Ethical Committee. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are not publicly available due to patient privacy and confidentiality regulations but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study did not receive any specific funding. Authors’ contributions Chaojin Qin: Conceptualization, Data curation, Formal analysis, Writing – original draft. Shi Gao: Data curation, Investigation, Methodology. Li Li: Investigation, Resources. Haiqiong Chen: Validation, Visualization. Yijie Chi: Project administration, Supervision. Guoqiang Zhao: Conceptualization, supervision, writing – review & editing. All the authors reviewed and approved the final manuscript. Acknowledgements Not applicable. References Berberian G, Firpo V, Soto A, Mañan JL, Torroija C, Castro G, et al. Osteoarthritis in the neonate: risk factors and outcome. Braz J Infect Dis. 2010;14(4):413–8. Boeck HD. Osteomyelitis and septic arthritis in children. Acta Orthop Belg. 2005;71(5):505–15. Vorhies JS, Lindsay EA, Tareen NG, Kellum RJ, Jo CH, Copley LA. Severity Adjusted Risk of Long-term Adverse Sequelae Among Children With Osteomyelitis. Pediatr Infect Dis J. 2019;38(1):26–31. Mediamolle N, Mallet C, Aupiais C, Doit C, Ntika S, Vialle R, et al. Bone and joint infections in infants under three months of age. Acta Paediatr. 2019;108(5):933–9. Gottlieb M, Holladay D, Rice M. Current Approach to the Evaluation and Management of Septic Arthritis. Pediatr Emerg Care. 2019;35(7):509–13. Roversi M, Chiappini E, Toniolo RM, Cirillo M, Natale F, Deriu D, et al. 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Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Published Journal Publication published 20 Apr, 2026 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 12 Feb, 2026 Reviews received at journal 12 Feb, 2026 Reviewers agreed at journal 12 Feb, 2026 Reviews received at journal 03 Feb, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor assigned by journal 13 Jan, 2026 Editor invited by journal 09 Jan, 2026 Submission checks completed at journal 09 Jan, 2026 First submitted to journal 09 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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and joint infections (BJIs) are rare in the neonates. Despite significant advancements in neonatal care, the reported incidence remains relatively high in high-risk populations, such as 1\u0026ndash;3 cases per 1,000 neonatal intensive care unit (NICU) admissions.(1,2) Diagnosis in this age group is challenging and carries a risk of long-term orthopedic complications and dysfunction.(3) \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is the most common pathogen in newborns and young infants underlying BJIs.(4,5) The clinical manifestations of neonatal BJIs are often subtle and nonspecific; in the early stages, the only sign may be reduced limb movement.(6,7) Delay in diagnosis and treatment can lead to serious sequelae, such as limb length discrepancy and joint dysfunction.(8) Previous studies have indicated that most BJIs can be successfully treated with antibiotics,(9) while surgical intervention is recommended for complex infections or cases showing an inadequate response to intravenous therapy.(10\u0026ndash;12)\u003c/p\u003e \u003cp\u003eTo date, only a limited number of studies have focused specifically on neonatal BJIs. This study reviewed 20 clinical cases to analyze the clinical characteristics, management, and outcomes of neonatal BJIs, comparing our findings with those reported in the literature. Our aim is to assist clinicians in the early recognition and management of this condition, thereby helping to improve patient prognosis.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eWe retrospectively reviewed the cases of 20 neonates hospitalized with BJIs at the Children\u0026rsquo;s Hospital, Zhejiang University, School of Medicine, between 2017 and 2025. The inclusion criteria were as follows: 1) aged 35 days and younger; and 2) diagnosed by radiographic changes.(13) Exclusion criteria included neonates with chronic osteomyelitis, congenital abnormalities or metabolic diseases. Data on demographics, clinical presentation, laboratory and imaging findings, treatment, and outcomes were retrospectively collected from electronic medical records. All patients were followed up until July 31, 2025.\u003c/p\u003e \u003cp\u003eAll the statistical analyses were conducted via SPSS version 27.0 (SPSS Inc., Chicago, IL) for Windows. Continuous data are presented as the means and standard deviations. Categorical variables were assessed via the chi-square (χ\u0026sup2;) test. Comparisons between the surgical and nonsurgical groups were performed via Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test for normally distributed data and the Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test for non-normally distributed variables. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eWe outlined patient characteristics in Table\u0026nbsp;1. A total of 20 neonates with bone and joint infections (BJIs) were included in this study. All patients were aged 35 days or younger, including 4 patients older than 28 days. On the basis of clinical symptoms, the onset of infection was estimated to have occurred approximately 7 days prior to admission. The mean age was 21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.82 days, and 65% of the patients were male. The mean birth weight was 2913\u0026thinsp;\u0026plusmn;\u0026thinsp;648.18 g, and the mean gestational age was 37.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48 weeks. Six infants were preterm. Nine neonates were delivered vaginally, and 11 were delivered via cesarean section. The mean duration of symptoms at presentation was 5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63 days. Pseudoparalysis was the most common symptom (19 patients), followed by localized swelling (16 patients) and fever (15 patients).\u003c/p\u003e \u003cp\u003eConcurrent bone and joint infections were observed in 65% (13/20) of the neonates. Septic arthritis involved 17 joints, most commonly the hip (41.18%, 7/17) and knee (29.41%, 5/17), followed by the shoulder (11.76%, 2/17), temporomandibular, elbow, and interphalangeal joints. Osteomyelitis affected 21 sites, with 3 patients presenting with multifocal involvement (affecting two bones each). The femur was the most frequently involved bone (42.9%, 9/21), followed by the tibia (19.1%, 4/21), ulna (9.5%, 2/21), and humerus (9.5%, 2/21).\u003c/p\u003e \u003cp\u003eBacterial cultures were obtained from blood samples or drainage fluid from infected sites. Pathogens were identified in 14 of the 20 cases (70%). Among these 14 culture-positive cases, joint fluid cultures were positive in 12 cases (85.7%) and blood cultures in 2 (14.3%). \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was the most common pathogen, detected in 11 patients (55%), including 3 patients with methicillin-resistant \u003cem\u003eS. aureus\u003c/em\u003e (MRSA). Other pathogens included \u003cem\u003eEscherichia coli\u003c/em\u003e (3 patients), \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e (2 patients), \u003cem\u003eEnterococcus avium\u003c/em\u003e (1 patient), and \u003cem\u003eStaphylococcus warneri\u003c/em\u003e (1 patient).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTreatment, imaging and follow-up\u003c/h3\u003e\n\u003cp\u003eThe treatment, imaging, and follow-up outcomes are summarized in Table\u0026nbsp;2. Accordingly, all 20 neonates underwent initial ultrasound evaluation; findings consistent with osteomyelitis or septic arthritis were observed in 19 cases (95%). Typical sonographic features included cortical disruption, subperiosteal fluid collection, and joint effusion.\u003c/p\u003e \u003cp\u003eRadiographs were obtained for 19 infants and were abnormal in 13 (68.4%). One patient underwent CT imaging, which revealed no definitive abnormalities. MRI was performed in 18 patients, all of whom presented pathological findings (sensitivity 100%).\u003c/p\u003e \u003cp\u003eEmpirical intravenous antibiotic therapy was initiated in all patients and subsequently adjusted according to the culture results. Linezolid and vancomycin were the most frequently administered agents.\u003c/p\u003e \u003cp\u003eExcept for one patient who experienced relapse and one who was lost to follow-up, all patients were discharged after clinical recovery. Among the 19 patients with follow-up data, five (26.3%) experienced complications, including leg length discrepancy, joint dislocation, and limited range of motion.\u003c/p\u003e\n\u003ch3\u003eComparative analysis of surgical and nonsurgical groups\u003c/h3\u003e\n\u003cp\u003eAs detailed in Table\u0026nbsp;3, surgical drainage was performed in 12 neonates (60%). Compared with the nonsurgical cohort, the surgical cohort presented significantly greater C-reactive protein concentrations at admission (55.79\u0026thinsp;\u0026plusmn;\u0026thinsp;23.56 mg/L vs 24.61\u0026thinsp;\u0026plusmn;\u0026thinsp;14.05 mg/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) and a higher percentage of positive cultures (91.67% vs 37.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018). Concurrent bone and joint infection was more frequent in the surgical group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). No significant differences were observed between the two groups with respect to age, sex, birth weight, gestational age, white blood cell count, predisposing factors, time to diagnosis, or length of hospital stay.\u003c/p\u003e\n\u003ch3\u003eComparative Analysis of Published Literatures\u003c/h3\u003e\n\u003cp\u003eTo further analyze the clinical characteristics and management of bone and joint infections (BJIs) in neonates, we compared recent studies in Table\u0026nbsp;4. Owing to regional differences, variability in study design, and a lack of uniform case inclusion criteria, some conclusions differ significantly across studies. Overall, we found that the male-to-female ratio was approximately 2:1 in these studies; pathogen cultures predominantly identified \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and antibiotic regimens primarily included linezolid and vancomycin. Ultrasound, X-ray, and MRI are commonly used in the diagnosis of BJIs. Among these, MRI serves as the gold standard, with a sensitivity of 100%, while the use of other imaging modalities varies by research center. The infection sites were mainly in the lower limbs, with long bones frequently involving the femur and tibia. In our study, joint infections primarily affected the hip and knee. In addition to early antibiotic treatment, some patients also underwent surgical intervention. With the exception of the study by Zhan \u003cem\u003eet al\u003c/em\u003e., which did not report sequelae, all other centers documented the occurrence of complications.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNeonatal bone and joint infections (BJIs) refer to an inflammatory condition of the osseous structures and joints resulting from pathogenic microorganisms. This condition occurs following pathogen invasion and proliferation within the bone's cellular components and extracellular matrix, triggering a host inflammatory response. Pathogens can reach the bone through the bloodstream (hematogenous spread), direct inoculation (e.g., traumatic or iatrogenic), or extension from a contiguous site of infection, such as infected soft tissue or joint fluid.(14,15) During the neonatal period, the metaphysis of certain long bones are partially situated within the joint capsule. This unique anatomical relationship facilitates the spread of infection from the metaphyseal region into the articular cavity.(16) Furthermore, transphyseal vascular channels persist in neonates, and communications exist between the metaphyseal and epiphyseal circulations.\u0026sup1;⁶ These factors collectively predispose neonates with hematogenous osteomyelitis to develop concomitant septic arthritis.(17,18) In our study, concurrent bone and joint infection was observed in 65% of cases, whereas rates of 58%(19) and 40.9%(4) have been reported in older infants. The most frequently involved joint was the hip, and the femur was the most commonly affected long bone. The reported incidence of severe sequelae in neonatal BJIs varies across cohorts, ranging from 3% to 30%.(20) During our follow-up, complications occurred in five cases, nearly all of which involved combined bone and joint infection. Differences in sequelae rates compared with other studies may be attributable to variations in the diagnostic criteria for sequelae.\u003c/p\u003e \u003cp\u003eEarly diagnosis of neonatal BJIs is critical for treatment and improving prognosis.(21) However, the clinical manifestations are often nonspecific, leading to diagnostic delays.(22) In our cohort, five infants presented without fever, and only one lacked restricted limb movement. This underscores the importance of maintaining a high index of suspicion for BJIs in neonates with impaired limb mobility, even in the absence of fever.\u003c/p\u003e \u003cp\u003eUltrasonography and radiography are first-line imaging modalities widely used for the early diagnosis of BJIs. In our study, all infants underwent ultrasonography, which yielded a positivity rate of 85%, compared with 73.68% for radiography. This discrepancy may be explained by the relatively short median diagnostic interval of 5.3 days in our cohort, whereas cortical erosions typically become visible on radiographs only after day 7. (23,24) Therefore, given its low cost and wide availability, ultrasonography should be prioritized in the diagnostic workup of BJIs to facilitate early diagnosis. Close follow-up is recommended even if initial radiographs show no abnormalities suggestive of BJIs.\u003c/p\u003e \u003cp\u003eMagnetic resonance imaging (MRI) is the most valuable modality for diagnosing BJIs, offering high sensitivity for the early detection of bone marrow edema and soft-tissue abscesses and allowing precise assessment of lesion extent. However, its application in neonates is limited by long acquisition times, the frequent need for sedation or anesthesia, and high cost.(25) Computed tomography (CT) has limited diagnostic value and involves considerable radiation exposure; thus, it is not recommended for routine use.(26) In our study, one infant underwent CT to differentiate BJIs from lymphangiomas. Bone scintigraphy may serve as an adjunctive tool for detecting bone and joint infections, although its clinical utility in neonates requires further validation.(27)\u003c/p\u003e \u003cp\u003eAntibiotic management of neonatal osteomyelitis follows the principles of early, aggressive, and often prolonged therapy to prevent severe skeletal sequelae and sepsis. Initial empirical regimens typically consist of combination intravenous antibiotics aimed at covering the most common pathogens, particularly \u003cem\u003eStaphylococcus aureus\u003c/em\u003e and gram-negative bacteria.(28) Common regimens include a glycopeptide (e.g., vancomycin) or an antistaphylococcal penicillin (e.g., oxacillin) combined with an aminoglycoside (e.g., gentamicin) or a third-generation cephalosporin (e.g., ceftriaxone). Carbapenems (e.g., meropenem) may be used in settings with resistant organisms or in critically ill infants. Therapy should be adjusted on the basis of microbiological results once available (8) A significant challenge is the high rate (17.6%\u0026ndash;68.2%) of culture-negative cases, (9) which limits guidance for targeted therapy and decisions regarding treatment conversion To improve pathogen yield, recent guidelines strongly recommend invasive diagnostic procedures (e.g., bone aspiration or abscess drainage) for culture.(29)\u003c/p\u003e \u003cp\u003ePrevious studies suggest that 90% of cases of acute hematogenous osteomyelitis (AHO) can be cured with appropriate antibiotic therapy.(30) However, recent studies also recommend surgical intervention for AHO, particularly for septic arthritis (SA).(12) Surgical intervention can significantly improve the microbiological yield,(26) facilitate pus drainage and compartment decompression, and may reduce the risk of epiphyseal injury and joint deformity. It is especially indicated for patients with abscess formation or those refractory to conservative management. (31,32) In our study, the majority (60%) of infants underwent surgery; nearly all had osteomyelitis accompanied by arthritis, particularly those with significantly elevated C-reactive protein (CRP) levels, suggesting more severe disease. Rubin \u003cem\u003eet al\u003c/em\u003e. (17) reported that septic hip arthritis is common in neonates with concomitant bone infection and often requires urgent surgical drainage to reduce intra-articular pressure and prevent avascular necrosis of the femoral head. This view is supported by the 2017 guidelines from the European Society for Pediatric Infectious Diseases (ESPID), which recommend surgical drainage for septic arthritis (especially of the hip) to reduce the risk of permanent functional impairment. (26) Moreover, the diagnostic yield of cultures was significantly greater in the surgical group (p\u0026thinsp;=\u0026thinsp;0.018), providing a basis for the use of sensitive antibiotics. Although our study did not demonstrate that early surgical intervention shortened hospital stay, it is still recommended for patients with abscess formation, joint involvement, or inadequate response to medical therapy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eNeonatal bone and joint infections often present with atypical clinical symptoms in the early stages, posing a diagnostic challenge. Ultrasonography, due to its sensitivity in detecting joint effusion and early soft-tissue changes, should be considered a first-line imaging modality to facilitate early diagnosis. In addition to initiating empirical antibiotic therapy promptly, surgical intervention should be actively considered for patients with osteomyelitis complicated by arthritis and markedly elevated C-reactive protein (CRP) levels. Early surgical drainage can help control infection, reduce complications, and improve long-term outcomes.\u003c/p\u003e \u003cp\u003eThis study has several inherent limitations. Its single-center, retrospective design, small sample size, and lack of standardized treatment and follow-up protocols limit the generalizability and comparability of the findings. Future multicenter, large-sample, prospective studies are warranted to validate these observations and optimize diagnostic and therapeutic strategies for neonatal osteomyelitis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBJIs, bone and joint infections; MRSA, methicillin-resistant S. aureus; AHO, acute hematogenous osteomyelitis; SA, septic arthritis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethical Committee of Children\u0026apos;s Hospital of Zhejiang University School of Medicine (Approval No. 2025-IRB-0538-P-01). The study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Due to the retrospective nature of the study and the use of anonymized patient data, the requirement for informed consent was waived by the aforementioned Ethical Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are not publicly available due to patient privacy and confidentiality regulations but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChaojin Qin: Conceptualization, Data curation, Formal analysis, Writing \u0026ndash; original draft. Shi Gao: Data curation, Investigation, Methodology. Li Li: Investigation, Resources. Haiqiong Chen: Validation, Visualization. Yijie Chi: Project administration, Supervision. Guoqiang Zhao: Conceptualization, supervision, writing \u0026ndash; review \u0026amp; editing. All the authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBerberian G, Firpo V, Soto A, Ma\u0026ntilde;an JL, Torroija C, Castro G, et al. Osteoarthritis in the neonate: risk factors and outcome. Braz J Infect Dis. 2010;14(4):413\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eBoeck HD. Osteomyelitis and septic arthritis in children. Acta Orthop Belg. 2005;71(5):505\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eVorhies JS, Lindsay EA, Tareen NG, Kellum RJ, Jo CH, Copley LA. Severity Adjusted Risk of Long-term Adverse Sequelae Among Children With Osteomyelitis. Pediatr Infect Dis J. 2019;38(1):26\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eMediamolle N, Mallet C, Aupiais C, Doit C, Ntika S, Vialle R, et al. Bone and joint infections in infants under three months of age. Acta Paediatr. 2019;108(5):933\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eGottlieb M, Holladay D, Rice M. Current Approach to the Evaluation and Management of Septic Arthritis. Pediatr Emerg Care. 2019;35(7):509\u0026ndash;13.\u003c/li\u003e\n\u003cli\u003eRoversi M, Chiappini E, Toniolo RM, Cirillo M, Natale F, Deriu D, et al. Neonatal osteomyelitis: an Italian multicentre report of 22 cases and comparison with the inherent literature. J Perinatol. 2021;41(6):1293\u0026ndash;303.\u003c/li\u003e\n\u003cli\u003eZhan C, Zhou B, Du J, Chen L. Clinical analysis of 17 cases of neonatal osteomyelitis. Medicine. 2019;98(2):e14129.\u003c/li\u003e\n\u003cli\u003ePeltola H, P\u0026auml;\u0026auml;kk\u0026ouml;nen M. Acute Osteomyelitis in Children. N Engl J Med. 2014;370(4):352\u0026ndash;60.\u003c/li\u003e\n\u003cli\u003ePeltola H, P\u0026auml;\u0026auml;kk\u0026ouml;nen M, Kallio P, Kallio MJT, Group OSAS. Short- Versus Long-term Antimicrobial Treatment for Acute Hematogenous Osteomyelitis of Childhood: Prospective, Randomized Trial on 131 Culture-positive Cases. Pediatr Infect Dis J. 2010;29(12):1123\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eBrischetto A, Leung G, Marshall CS, Bowen AC. A Retrospective Case-Series of Children With Bone and Joint Infection From Northern Australia. Medicine. 2016;95(8):e2885.\u003c/li\u003e\n\u003cli\u003eDohin B, Gillet Y, Kohler R, Lina G, Vandenesch F, Vanhems P, et al. Pediatric Bone and Joint Infections Caused by Panton-Valentine Leukocidin-Positive Staphylococcus aureus. Pediatr Infect Dis J. 2007;26(11):1042\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eKim J, Lee MU, Kim TH. Nationwide epidemiologic study for pediatric osteomyelitis and septic arthritis in South Korea: A cross-sectional study of national health insurance review and assessment service. Medicine. 2019;98(17):e15355.\u003c/li\u003e\n\u003cli\u003eLew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004;364(9431):369\u0026ndash;79.\u003c/li\u003e\n\u003cli\u003eWoods CR, Bradley JS, Chatterjee A, Copley LA, Robinson J, Kronman MP, et al. Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics. J Pediatr Infect Dis Soc. 2021;10(8):801\u0026ndash;44.\u003c/li\u003e\n\u003cli\u003eShalabi M, Adel M, Yoon E, Aziz K, Lee S, Shah PS, et al. Risk of Infection Using Peripherally Inserted Central and Umbilical Catheters in Preterm Neonates. Pediatrics. 2015;136(6):1073\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eOgden JA. Pediatric osteomyelitis and septic arthritis: the pathology of neonatal disease. Yale J Biol Med. 1979;52(5):423\u0026ndash;48.\u003c/li\u003e\n\u003cli\u003eRubin LG, Shin J, Kaur I, Scheuerman O, Levy I, Long SS. Frequency of Multifocal Disease and Pyogenic Arthritis of the Hip in Infants with Osteoarticular Infection in Three Neonatal Intensive Care Units. J Pediatr. 2020;227:157\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eWeissberg ED, Smith AL, Smith DH. Clinical Features of Neonatal Osteomyelitis. Pediatrics. 1974;53(4):505\u0026ndash;10.\u003c/li\u003e\n\u003cli\u003eLiu Y, Zhao K, Liu Y, Sun YH, Li MX, Yu M, et al. Bone and joint infection complicated with sepsis in neonates and infants under three months of age. J Pediatr. 2024;100(2):156\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eSukswai P, Kovitvanitcha D, Thumkunanon V, Chotpitayasunondh T, Sangtawesin V, Jeerathanyasakun Y. Acute hematogenous osteomyelitis and septic arthritis in children: clinical characteristics and outcomes study. J Méd Assoc Thail Chotmaihet thangphaet. 2011;94 Suppl 3:S209-16.\u003c/li\u003e\n\u003cli\u003eRutz E, Spoerri M. Septic arthritis of the paediatric hip - A review of current diagnostic approaches and therapeutic concepts. Acta Orthop Belg. 2013;79(2):123\u0026ndash;34.\u003c/li\u003e\n\u003cli\u003eSun K, Zhang C, Mao Z, Wang C, Zhu H, Sun H, et al. Clinical characteristics of neonatal and infant osteomyelitis and septic arthritis: a multicenter retrospective study. J Pediatr. 2024;100(4):430\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eIndia D of R Military Hospital Jodhpur, Paliwal AK, Sahdev R, India D of R Military Hospital Secundrabad, Deshwal A, India D of O Military Hospital Jodhpur, et al. Role of ultrasound in the diagnosis of paediatric acute osteomyelitis. J Ultrason. 2021;21(84):34\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eFaust SN, Clark J, Pallett A, Clarke NMP. Managing bone and joint infection in children. Arch Dis Child. 2012;97(6):545.\u003c/li\u003e\n\u003cli\u003ePugmire BS, Shailam R, Gee MS. Role of MRI in the diagnosis and treatment of osteomyelitis in pediatric patients. World J Radiol. 2014;6(8):530\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eSaavedra-Lozano J, Falup-Pecurariu O, Faust SN, Girschick H, Hartwig N, Kaplan S, et al. Bone and Joint Infections. Pediatr Infect Dis J. 2017;36(8):788\u0026ndash;99.\u003c/li\u003e\n\u003cli\u003eWyngaert TV den, Strobel K, Kampen WU, Kuwert T, Bruggen W van der, Mohan HK, et al. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016;43(9):1723\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eGrimbly C, Odenbach J, Vandermeer B, Forgie S, Curtis S. Parenteral and oral antibiotic duration for treatment of pediatric osteomyelitis: a systematic review protocol. Syst Rev. 2013;2(1):92\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eKrzysztofiak A, Roversi M, Musolino A, Cirillo M, Toniolo RM, Mazza O, et al. Clinical report and predictors of sequelae of 319 cases of pediatric bacterial osteomyelitis. Sci Rep. 2022;12(1):14846.\u003c/li\u003e\n\u003cli\u003eDodwell ER. Osteomyelitis and septic arthritis in children. Curr Opin Pediatr. 2013;25(1):58\u0026ndash;63.\u003c/li\u003e\n\u003cli\u003eGao Y, Liu R, Rai S, Liang Q, Liu Y, Xiao X, et al. Is Early Surgical Intervention Necessary for Acute Neonatal Humeral Epiphyseal Osteomyelitis: A Retrospective Study of 31 Patients. Children. 2022;9(4):527.\u003c/li\u003e\n\u003cli\u003eChou ACC, Mahadev A. Acute Bacterial Osteomyelitis in Children. J Orthop Surg. 2016;24(2):250\u0026ndash;2.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"neonate, osteomyelitis, septic arthritis, pseudoparalysis, surgical drainage, outcome","lastPublishedDoi":"10.21203/rs.3.rs-8488866/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8488866/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo analyze the clinical characteristics, management, and outcomes of neonates with bone and joint infections (BJIs) to improve early diagnosis and guide clinical decision-making.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a single-center, retrospective review of 20 neonates (aged\u0026thinsp;\u0026le;\u0026thinsp;35 days) hospitalized with BJIs between 2017 and 2025. Data on demographics, clinical presentation, laboratory and imaging findings, treatment, and outcomes were collected and analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean age was 21.2 days, and 65% of the neonates were male. Pseudoparalysis was the most common presenting symptom (observed in 95% of cases). Pathogens were identified in 14 of the 20 cases (70%), with \u003cem\u003eStaphylococcus aureus\u003c/em\u003e being the most prevalent (identified in 11 patients, 55%). Concurrent bone and joint infections were observed in 65% of the patients. Ultrasound demonstrated a high detection rate (95%). Surgical drainage was performed in 12 patients (60%), who presented with significantly higher C-reactive protein levels and a higher culture-positive rate than did the nonsurgical group. With one patient lost to follow-up, data were available for 19 patients, of whom five (26.3%) experienced complications.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNeonatal BJIs often present with nonspecific signs, among which pseudoparalysis is a key indicator. Ultrasound is a sensitive, first-line imaging tool. Early surgical intervention should be considered for patients with concurrent arthritis and significantly elevated inflammatory markers, as it aids in pathogen identification and infection control.\u003c/p\u003e","manuscriptTitle":"Clinical characteristics, pathogenesis, treatment, and prognosis of bone and joint infections in neonates: a single-center report of 20 cases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 14:48:06","doi":"10.21203/rs.3.rs-8488866/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-12T17:46:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-12T17:39:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179176588163553235138715413079478448731","date":"2026-02-12T08:41:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-03T23:46:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235642553042659888611874148584039496496","date":"2026-01-14T15:35:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40503402474915902683712792763628874085","date":"2026-01-13T11:24:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330069484799991312713377685259781431276","date":"2026-01-13T10:20:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-13T09:43:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-13T09:31:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-09T07:23:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-09T06:50:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-09T06:42:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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