Frontiers

Frontiers in Pediatrics

Published by Frontiers

Online ISSN: 2296-2360

Disciplines: Pediatrics

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Top-read articles

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(A) This is a case of phimosis, characterized by a narrowed preputial opening that restricts the full retraction of the foreskin, resulting in the inability to expose the glans penis. (B) Smegma detected during surgery, which is a white lumps formed by sloughed epithelial cells under the foreskin, located around the corona. It may lead to complications such as local infection, adhesions, balanitis, and Balanitis xerotica obliterans (BXO). (C) BXO is an acquired, non-contagious, chronic inflammatory skin disease that typically affects the foreskin, glans penis, and prepuce, resulting in sclerotic scarring, secondary phimosis, urinary difficulties, sexual dysfunction, and even potentially malignant transformations. (D) The most common symptoms of BXO are foreskin scars and sclerosis, there may also be evidence of pallor and similar thickening of the glans surface.
(A) The Chinese Shang Ring, comprising an inner ring and an outer ring, is applied by inserting the inner ring into the inner aspect of the foreskin and advancing it to the coronal sulcus. After adjusting the position of the foreskin, the outer ring is assembled and the two locking teeth are secured, thereby completing the surgical procedure. (B) Postoperative status of the Shang Ring: Following surgery, the inner and outer rings of the Shang Ring are securely in place, with redundant foreskin trimmed and the glans penis exposed. (C) “Protective shorts”: These are designed specifically for postoperative protection of the pediatric perineal region, aiming to prevent accidental contact or injury to the surgical site during movement or unforeseen situations.
Postoperative pain scores in two groups (x ± s). The horizontal axis represents the postoperative follow-up time. The vertical axis represents the degree of postoperative pain evaluated using Visual Analog Scale (VAS), with a score range of 0–10 points. At 0 points, it indicates complete pain, while at 10 points, it indicates complete intolerance of pain. There was no significant difference (P > 0.05) in the comparison of data between the two groups at two hours, 1 day, 3 days, and 7 days after surgery.
Optimizing treatment strategies for pediatric phimosis and redundant prepuce: a comparative study of traditional circumcision and disposable circumcision stapler

July 2024

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3,452 Reads

Guoyan Zhang

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Yongliang Luo

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Shangchao Cheng

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[...]

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Xiyuan Chen
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Aims and scope


Frontiers in Pediatrics is a multidisciplinary journal publishing research that addresses challenges in pediatric patient care and child health.

Led by Field Chief Editor Dr Andrew S. Day (University of Otago, New Zealand), Frontiers in Pediatrics publishes both basic and clinical research related to all aspects of pediatrics.

Topics include, but are not limited to:

  • Children and Health
  • General Pediatrics and Pediatric Emergency Care
  • Genetics of Common and Rare Diseases
  • Neonatology
  • Obstetric and Pediatric Pharmacology
  • Pediatric Cardiology
  • Pediatric Critical Care
  • Pediatric Endocrinology
  • Pediatric Gastroenterology, Hepatology and Nutrition
  • Pediatric Hematology and Hematological Malignancies
  • Pediatric Immunology
  • Pediatric Infectious Diseases
  • Pediatric Nephrology
  • Pediatric Neurology
  • Pediatric Obesity
  • Pediatric Oncology
  • Pediatric Orthopedics
  • Pediatric Otolaryngology
  • Pediatric Pulmonology
  • Pediatric Rheumatology
  • Pediatric Surgery
  • Pediatric Urology.

In particular, the journal welcomes submissions which support and advance the UN’s Sustainable Development Goal (SDG), notably SDG#3: Ensure healthy lives and promote well-being for all at all ages.

Frontiers in Pediatrics is committed to advancing developments in the field of pediatrics by allowing unrestricted access to articles, and communicating scientific knowledge to researchers and the public alike, to enable the scientific breakthroughs of the future.

Recent articles


The impact of prebiotics, probiotics and synbiotics on the prevention and treatment of atopic dermatitis in children: an umbrella meta-analysis
  • Article
  • Full-text available

March 2025

Lifeng Wang

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Lijuan Xu

Background Studies have suggested that the administration of prebiotics, probiotics and synbiotics (pre-, pro-, and synbiotics) may potentially decrease the incidence of atopic dermatitis (AD) and alleviate its severity in children; however, recent studies have yielded inconclusive findings. Objective This umbrella meta-analysis aimed to comprehensively assess the effect of pre-, pro-, and synbiotics on AD among children. Methods A systematic search was carried out in the PubMed and Scopus databases up to April 2024 to identify relevant meta-analyses. Relative risks (RR) and weighted mean differences (WMD) along with their 95% confidence intervals (CI) were pooled using a random effects model to evaluate the impacts on both the incidence of AD and its severity, as assessed by the Scoring Atopic Dermatitis (SCORAD) index. Results This umbrella meta-analysis included 38 meta-analyses, with 127,150 participants. The analysis suggested that intervention with pre-, pro-, and synbiotics significantly reduced the incidence of AD (RR = 0.74, 95% CI: 0.70–0.79), which was confirmed by subgroup analyses. The treatment significantly reduced SCORAD score (WMD = −3.75, 95% CI: −5.08 to −2.42). In subgroup analysis, multi-strain probiotics, Lactobacillus , synbiotics, and pre-, pro-, and synbiotics mixtures were found to significantly decrease the SCORAD score, while, Bifidobacterium and prebiotics alone did not show a significant effect on the SCORAD score. The treatment resulted in a significant decrease in SCORAD score among children with moderate to severe AD, but not in subjects with mild AD. Conclusions Probiotics and synbiotics could be promising interventions to reduce the risk of developing AD and alleviate its severity in children.


FIGURE 1
Caregiver and child characteristics.
Caregiver and provider perspectives on developmental services for children with sickle cell disease: a mixed methods analysis

Mollie Tamboli

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Erin MacArthur

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Natalie Collins

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[...]

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Andrew M. Heitzer

Introduction Sickle cell disease (SCD) is a monogenic blood disorder characterized by neurodevelopmental delays. Most children with SCD do not receive developmental services due in part to disparities in care access. To inform the design of a developmental intervention for children with SCD, we evaluated factors that influence access to developmental services. Methods Interview data were collected from educational and medical providers ( n = 15) and caregivers ( n = 15) of children aged 4–6 years with SCD at a single center and the surrounding area. Caregivers completed questionnaires about their child's background/medical history, caregiver depression (PROMIS SF v1.0-8a), and caregiver knowledge of early development (Knowledge of Infant Development Inventory). A convergent design was used to integrate the qualitative and quantitative data. Results We identified three themes as factors that influence caregivers' access to developmental services: quality of medical and educational experiences, caregiver knowledge and beliefs about SCD and development, and caregiver preferences for developmental services. Most caregivers denied barriers to obtaining developmental services for their child, whereas providers acknowledged numerous barriers for families. Caregivers and providers shared that a positive caregiver-provider relationship facilitates access. Caregivers reported that there was limited attention to SCD within the hospital system and broader society. Caregivers displayed limited knowledge of early development, and providers identified these knowledge gaps as a barrier to utilizing developmental services. Caregivers expressed a strong interest in SCD education and community building. Conclusions Our mixed method analysis identified barriers and facilitators to developmental services for children with SCD.



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Relationship between patent ductus arteriosus and platelet indices in newborn: a systematic review and meta-analysis

March 2025

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1 Read

Yanbing An

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Gaowa Arigong

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Wuyun Zhao

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[...]

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Xiaoyun Wang

Background The role of platelet indices in the early hours of life and their potential association with patent ductus arteriosus (PDA) have been subjects of investigation in recent studies. This study aimed to investigate the relationship between PAD and platelet indices in newborn. Methods A systematic review and meta-analysis and were preformed based on Chinese databases CNKI and Wanfang database, as well as the international databases PubMed, Web of Science, Cochrane Library, and Embase from their inception to January 31, 2024. Results This study included 32 literatures, with 20 of English and 12 of Chinese ones. The meta regression analysis showed that neonates with PDA tend to exhibit lower platelet count (PLT) and plateletcrit (PCT), as well as higher platelet large cell ratio (P-LCR) (all P < 0.05), while platelet mass, platelet distribution width (PDW), and mean platelet volume (MPV) remain comparable (all P > 0.05). Conclusion PDA neonates might have decreased PLT and PCT, while increased P-LCR. These dynamic shifts in platelet indices provide fresh insights into the pathophysiology of PDA and have potential to serve as important indicators for early identification, disease assessment, and personalized treatment decisions in clinical practice.


FIGURE 1 Echocardiographic characteristics before and after KTx among the non-LVH and LVH groups. (A) LVMI, LVEF, LV-GLS, and LAEF. (B) LASr, LAScd, and LASct. (C) DEI, PEI, and AEI. *P < 0.05 (before vs. after KTx), **P < 0.01 (before vs. after KTx), ***P < 0.001 (before vs. after KTx), and #P < 0.05 (LVH group vs. non-LVH group after KTx). KTx, kidney transplantation; LVH, left ventricular hypertrophy; LVMI, left ventricular mass index; LV, left ventricle; EF, ejection fraction; LV-GLS, global longitudinal peak systolic left ventricular strain; LA, left atrium; LASr, LAScd, and LASct, left atrial reservoir, conduit, and contraction strain; LAVI, left atrial volume index; DEI, diastolic emptying index; PEI, passive emptying index; AEI, active emptying index.
FIGURE 2
Changes in echocardiographic and clinical characteristics before and after KTx according to left ventricular mass index categories before KTx.
The logistics regression model analysis of the association between changes in clinical and echocardiographic parameters and a lack of a Hb increase.
Left heart function and strain for predicting change in hemoglobin levels in pediatric kidney transplantation recipients

Shufan Yue

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Fei Xiao

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Rui Fan

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[...]

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Cuiling Li

Introduction Anemia is prevalent after kidney transplantation (KTx) and is associated with reduced graft survival. The associations between temporal changes in hemoglobin (Hb) level in the early posttransplant period with left ventricular (LV) and atrial (LA) function and strain are unknown. Methods The study cohort included 71 successful pediatric KTx recipients between January 2021 and September 2022. Echocardiography was used to evaluate the cardiac structure, function, and strain both before and after KTx. Temporal changes in Hb values within 6 months after KTx were evaluated. According to the LV mass index (LVMI), recipients were divided into a left ventricular hypertrophy (LVH) group and a non-LVH group. Results Before KTx, the LVH group had a lower level of Hb and a higher incidence of anemia than the non-LVH group. However, this difference between the groups disappeared after KTx. Changes in Hb were faster in the LVH group than in the non-LVH group. There was a negative association between the absence of an Hb increase and diastolic blood pressure, the LVMI, early diastolic mitral annulus velocity to early diastolic filling wave ratio (E/E’), and the left atrial emptying volume index (LAEVI), while there was a positive association between LV ejection fraction (LVEF), LV global longitudinal strain, and LA strain. The LVMI and changes in LVEF showed a negative correlation, whereas changes in the LAEVI showed a positive correlation with the absence of Hb increase during the early period after KTx. Conclusion Children with LVH have a lower level of Hb before KTx and a higher level of Hb increase in the early postoperative period following KTx. LVMI and changes in LVEF and LAEVI have predictive value in absence of Hb increase in pediatric KTx recipients.


Blood pressure measurement practices in children and adolescents within primary care setting

Kamilė Čeponytė

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Karolis Ažukaitis

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Augustina Jankauskienė

Objective Poor compliance to the technical aspects of blood pressure (BP) measurement procedure may lead to inaccurate estimation of BP and misclassification of patients. However, the latter have not been explored systematically. We aimed to assess real-life BP measurement practices in Lithuanian children and adolescents at the primary care setting, and their compliance with current European Society of Hypertension (ESH) guidelines. Methods Two cross-sectional surveys were conducted in Lithuania. The study population included parents, who have children aged 0–17 years, and was further enriched by adolescents aged 14–17 years. Original questionnaires were developed and used to survey the participants. Results Study included 1,504 parents and 448 adolescents. Median age of the surveyed parents' children and adolescents was 6 years and 50.2 percent were female. Overall, among all children aged 3 years or older only 55% of respondents reported BP measurements at least once. The rates of BP measurements increased with age and exceeded 80 percent from 14 years. Only 3.3 percent of respondents reported no issues with BP measurement procedure. The most common errors included single measurements of BP (81.4%), lack of feedback (60.2%), incorrect positioning (40.7%), miscuffing (39.2%) and lack of rest period (27.9%). Conclusions Our study reveals not only insufficient BP screening rates within Lithuanian primary care setting, but also high rates of technical errors during BP measurement procedure. Collectively, these issues likely contribute to misdiagnosing of arterial hypertension and suboptimal care of children who are at risk of inaccurate and imprecise BP results.


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Comparison of prenatal and neonatal characteristics and perinatal interventions in MPH, non-MPH, MPH mortality, and non-MPH mortality groups.
A decision tree analysis to predict massive pulmonary hemorrhage in extremely low birth weight infants: a nationwide large cohort database

March 2025

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1 Read

Kyu Hee Park

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Eun Yeob Kim

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Hye Won Cho

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[...]

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Byung Min Choi

Objective To develop a decision tree model using clinical risk factors to predict massive pulmonary hemorrhage (MPH) and MPH-related mortality in extremely low birth weight infants (ELBWIs). Method We retrospectively analyzed data from a national multicenter prospective web-based registry using machine learning algorithms with the C5.0 decision tree model to develop a clinical prediction rule for MPH and MPH-related mortality in ELBWIs admitted to participating neonatal intensive care units (NICUs) from January 2013 to December 2020. This C5.0 model was developed through data preprocessing, attribute selection based on splitting criteria, and pruning techniques to minimize overfitting. Results A total of 5,752 infants were included. Of them, MPH occurred in 664 (11.5%) infants. Among infants with MPH, 136 (20.5%) infants died due to MPH. The decision tree model for MPH identified “gestational age (GA) ≤ 25 ⁺² ” as the first discriminator, followed by “APGAR score at 5 min ≤ 7” and “multiple gestation”. The decision tree model for MPH-related mortality identified “GA ≤ 25 ⁺² ” as the first discriminator, followed by “APGAR score at 5 min ≤2”. The predictive accuracy of the C5.0 MPH model achieved an area under the ROC curve (AUC) of 88.2% on the training set and 89.0% on the test set, while the MPH-related mortality model attained an AUC of 97.7% on the training set and an AUC of 97.4% on the test set. Conclusions We developed a C5.0 decision tree model using clinical risk factors to predict MPH and MPH-related mortality in ELBWIs, enabling early identification of high-risk infants and facilitating timely interventions to improve neonatal outcomes. This decision-based risk stratification tool requires additional verification using larger multicenter cohorts to evaluate its practical applicability and clinical effectiveness before routine clinical implementation in NICUs.


FIGURE 1
Demographic characteristics of the participants (n = 892).
Test-retest reliability for the open-ended version of the MBQ-C.
Validity and reliability of the movement behaviour questionnaire child in Chinese preschoolers

March 2025

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8 Reads

Background The Movement Behaviour Questionnaire Child (MBQ-C) was developed to measure physical activity, screen time, and sleep in preschool children, but the Chinese version lacked validation. Methods This cross-sectional study aimed to assess the validity and reliability of the open-ended version of the MBQ-C among Chinese preschoolers. Data were collected from 892 parents of children aged 0–5 years across 10 provinces via an online questionnaire. The MBQ-C includes items on physical activity, screen time, and sleep, and was validated against device-measured physical activity using accelerometers. Results Internal consistency was high, with Cronbach's alpha values ranging from 0.80 to 0.88 for different sections. Test-retest reliability showed moderate intraclass correlation coefficients (ICCs) between 0.52 and 0.72. Confirmatory factor analysis indicated good construct validity (CFI = 0.95). Moderate significant correlations were found between MBQ-C reported physical activity and device-measured moderate-to-vigorous physical activity ( R = 0.35, p < 0.001). Conclusion The open-ended version of the MBQ-C demonstrates good validity and reliability in assessing movement behaviours among Chinese preschoolers. This tool is effective for proxy-reported measurements and can contribute to understanding and promoting healthy movement behaviours in early childhood.


FIGURE 1 (A) The numbers of prevalence, (B) age-standardized prevalence rate, (C) numbers of deaths, (D) age-standardized death rate, (E) numbers of DALYs, and (F) numbers of DALYs are illustrated for orofacial clefts at the global and regional levels from 1990 through 2021. DALYs, Disability-Adjusted Life Years. SDI, Sociodemographic index.
TABLE 1 Continued
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Burden of orofacial clefts from 1990–2021 at global, regional, and national levels

March 2025

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18 Reads

Qinqin Ma

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Jie Wei

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Bo Peng

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[...]

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Shuixue Mo

Objectives We aimed to study and comprehensively evaluate the burden of OFCs at global, regional, and national levels. Methods Based on data from the Global Burden of Disease database for 2021, we analysed the prevalence, mortality, and disability-adjusted life years (DALYs) of orofacial clefts (OFCs) from 1990–2021, categorised by sex, regions, and sociodemographic index (SDI). Numbers and age-standardised rates (ASRs) of the aforementioned indices were estimated through a systematic analysis of modelled data from the GBD 2021 study. Finally, the relationship between SDI and the epidemiological parameters of OFCs was evaluated. Results In 2021, the global prevalence of OFCs included 4,124,007 cases, resulting in 1,719 deaths and 408,775 DALYs. From 1990–2021, prevalence cases decreased by 40.38%, while mortality rates, and DALYs decreased by 86.08%, and 68.33%, respectively. Moreover, the ASRs for prevalence, mortality, and DALYs demonstrated a decreasing trend during the period. In 2021, the highest age-standardised prevalence rates (ASPRs) of OFCs were recorded in South Asia, North Africa, the Middle East, and Central Asia. Nationally, Palestine, Qatar, and Bangladesh reported the three highest ASPRs in 2021. A nonlinear association was observed between the ASRs of OFCs and the SDI at regional and national levels. Conclusions The global burden of OFCs decreased from 1990–2021. However, there is a disparity in disease burden across different regions, over 80% of the burden is borne by patients in low- and middle-income countries, the burden of OFCs remains a major public health challenge globally. Our findings will help to formulate appropriate policies to reduce the OFCs burden.


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Last follow-up characteristics in 45 children at median time of 8.7 (serology-based group) and 10 years (biopsy-based group) on gluten- free diet.
Impact of ESPGHAN no-biopsy strategy on the outcome of celiac disease treatment in children

Aim The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) allows a no-biopsy diagnostic of celiac disease under certain conditions. We assessed the impact of the diagnostic algorithm on the patient's long-term outcome by comparing the serology-based diagnosed patients to biopsy-proven ones. Methods We reviewed the charts of children presenting with antitransglutaminase IgA titers above ten times upper limit of normal and consecutively diagnosed with celiac disease between 2010 and 2014, a time-period overlapping with ESPGHAN diagnostic guideline change in 2012. Outcome measures for no-biopsy vs. biopsy-proven diagnosed patients were clinical and laboratory findings, compliance to gluten-free diet and to regular visits after one, two and 8–10 years of follow-up. Results Clinical and laboratory, i.e., serum chemistry and autoantibody outcome measures on gluten-free diet clearly showed worse patient healing in the 33 serology-based diagnosed children compared to the 30 biopsy-proven ones. The attendance of the follow-up visits was also higher in the biopsy group. Conclusions Our results indicate that dietary transgressions are common in childhood celiac disease resulting in slow healing. Therefore, there is a need of improvement of the management, with special attention regarding the ESPGHAN no-biopsy criteria diagnosed patients. Our study also indicates that novel treatments adjunctive to diet are warranted in children.


Consistency of NIPS scores between the two evaluators.
Demographic information (N = 198).
Univariate linear regression analysis of contextual factors and neonatal pain scores.
Multiple linear regression analysis of neonatal pain response variables.
Contextual factors associated with neonatal pain responses: clinical observational study

March 2025

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1 Read

Xinling Zhan

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Nanxi Zhu

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Bingjie Long

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[...]

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Renli Deng

Objectives This study aimed to identify the contextual factors of neonatal pain responses and provide clinical medical staff with evidence regarding effective means of evaluating neonatal pain and strengthen clinical pain management. Methods Two trained nurses independently used the Neonatal Infant Pain Scale (NIPS) to assess the pain scores of 198 neonates after they underwent painful medical procedures. Univariate linear regression analysis was performed to analyze the correlation between contextual factors and NIPS scores. Variables with statistically significant differences ( p < 0.2) after univariate linear regression analysis were selected as independent variables, and the NIPS score was used as the dependent variable. Multiple linear regression was used to determine the salient factors associated with neonatal pain responses. This study was registered at the Chinese Clinical Trial Registry (ChiCTR2300074086). Results Univariate linear regression analysis showed that the NIPS scores were associated with days after birth, types of painful procedures, Apgar scores at 1 min after birth, and gestational age (GA) ( p < 0.2). Multiple regression analysis showed that Apgar score at 1 min after birth ( β = 0.272, p < 0.001) and GA ( β = 0.503, p < 0.001) were independent associated factors of neonatal pain responses. Neonates with low Apgar scores at 1 min after birth and younger GA had less pronounced pain responses. Conclusions The Apgar score at 1 min after birth and GA affected the neonatal pain responses. In this regard, the current clinical method of pain assessment solely through observation of neonatal pain responses is occasionally inaccurate. The Apgar score at 1 min after birth and GA should be considered in determining the neonatal pain status and hence enhance the quality of neonatal pain management.


Distribution of regions, physical activity (PA) and socioeconomic status (SES) of adolescents in China.
Interaction of gender and SES on MVPA.
Physical activity in adolescents of different family socioeconomic status: the moderating role of gender

Ting Zhang

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Ming Li

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Feng Zhang

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[...]

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Yaru Guo

Background To investigate the association between family socioeconomic status (SES) and the physical activity (PA) levels of adolescents, as well as the moderating effect of gender on this relationship. Methods A total of 10,327 Chinese adolescents aged 12–17 were recruited to complete questionnaires regarding their SES and PA levels. “Physical Activity Questionnaire for Children and Adolescents Aged 7–18 Years” was utilized to examine the specific items, intensity, duration, and frequency of PA. The Kruskal–Wallis test and the Mann–Whitney U test were employed to compare PA time among adolescents across different groups. To analyze the interaction effect between gender and SES, the Scheirer-Ray-Hare test was conducted using R software. Additionally, SPSSAU was utilized to examine the moderating effect of gender and SES on PA. Result (1) Different intensities of PA: Overall, the times for LPA, MPA, VPA, MVPA, and TPA in the low SES group were 190 (100, 400) minutes, 190 (80, 400) minutes, 60 (0, 160) minutes, 290 (150, 570) minutes, and 580 (345, 925) minutes, respectively.The duration of PA at each intensity level in the low SES group was significantly lower compared to that in the middle and high SES groups (all P -values < 0.05). (2) Different PA types: The low SES group exhibited the shortest durations for both transportation PA (260 min) and exercise PA (155 min), while household PA was the longest (15 min)(all P -values < 0.05). (3) Moderating effect test: After controlling for relevant variables, the interaction term coefficient between gender and SES was statistically significant (B = −19.141, t = −2.059, P < 0.05). Conclusion Adolescents from low SES backgrounds exhibited the lowest levels of MVPA and TPA, which were mainly manifested in transportation PA and exercise PA. Gender moderates the relationship between SES and MVPA, with different SES levels having a more pronounced effect on PA in boys than in girls.


Relapse-multivariate analyses.
Overall survival before and after 365 days-multivariate analysis.
Clinical outcomes and relapse patterns in pediatric acute leukemia patients undergoing hematopoietic cell transplantation: a multicenter Brazilian experience

Polliany Roberta Dorini Pelegrina

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Rita de Cassia Barbosa Tavares

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Adriana Mello Rodrigues

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[...]

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Carmem Bonfim

Background Hematopoietic cell transplantation (HCT) represents a well-established therapeutic strategy for high-risk leukemia, though post-transplant relapse remains a significant challenge, particularly in resource-limited settings Procedure In this retrospective study, we analyzed medical records of 310 pediatric patients (age < 18 years) who underwent HCT for acute leukemias at four Brazilian institutions between 2010 and 2019. Results The cohort included patients with acute lymphoblastic leukemia (ALL; 74.2%) and acute myeloid leukemia (AML; 25.8%). The median age was 9.52 years (range: 0.25–17.97), with male predominance (68.3%). Total body irradiation (TBI)-based conditioning was utilized in 72.6% of cases, and bone marrow served as the predominant graft source (74.5%). Prior to transplantation, 46.5% of patients were in first complete remission. Post-transplant relapse occurred in 36.7% of patients at a median of 245 days (range: 38–2,505). With a median follow-up of 2,019 days (5.5 years), overall survival was 69.3% at one year, declining to 62.4% at two years. The cumulative incidence of relapse was 12.6%, 28.8%, and 33.4% at 100 days, one year, and two years post-HCT, respectively. Adjusted analysis revealed increased relapse risk in patients with mixed donor chimerism, positive minimal residual disease (MRD) status before HCT, and disease status beyond first complete remission (including CR2, advanced disease, and refractory disease). Conclusion(s) These findings underscore the elevated relapse risk associated with advanced disease status, positive pre-HCT MRD, and mixed donor chimerism post-transplant. Future interventions should prioritize improving diagnostic capabilities, expanding access to modern treatment protocols, and facilitating early referral to transplant centers, particularly for aggressive disease presentations.


Economic evaluations of human milk for very preterm infants: a systematic review

March 2025

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1 Read

Anfeng Lu

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Peilu Huang

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Xin Guo

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[...]

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Guosheng Huang

Background Very preterm infants are highly vulnerable to complications, imposing a significant economic burden on healthcare systems. Human milk has protective effects on these infants, but there is no systematic review on its economic impact. Objective We conducted a comprehensive review of studies assessing the economic evaluations of human milk for very preterm infants. Methods Our literature search covered PubMed, Embase, the Cochrane Library, and Web of Science. Two reviewers independently extracted data on economic evaluations and assessed study quality using the Pediatric Quality Appraisal Questionnaire (PQAQ). Results Fourteen studies of moderate quality, conducted in the United States, Germany, and Canada, met the inclusion criteria. However, the studies analyzed had notable variations and shortcomings. The majority of these studies ( n = 11) performed economic evaluations from a healthcare system perspective, utilizing cost-consequence analysis ( n = 6) up to the point of neonatal discharge ( n = 11). All human milk interventions indicated cost-effective or cost saving results; only a minority included discounting ( n = 2). Conclusion This systematic review suggests that economic evaluation of human milk for very preterm infants is an expanding area of research. Human milk for very preterm infants offers substantial economic advantages during neonatal intensive care unit hospitalization. Standardized and high-quality studies are needed to determine the cost-effectiveness of human milk for very preterm infants in the future. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO , identifier (CRD42024539574).


FIGURE 1
FIGURE 2 Prevalent, death, and disability-adjusted life-years (DALYs) cases of congenital heart disease in 204 countries and territories. (A) Prevalent cases. (B) Death cases. (C) DALYs cases.
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Prevalence of congenital heart disease in infants Between 1990 and 2021 at the global and regional level.
Evaluating the global, regional, and national burden of congenital heart disease in infants younger than 1 year: a 1990–2021 systematic analysis for the GBD study 2021

March 2025

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5 Reads

Lili Deng

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Qinhong Li

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Zugen Cheng

Background Previous estimates of congenital heart disease (CHD) have been constrained by limited data sources, narrow geographic focus, and a lack of specific assessment of infants younger than 1 year. As part of the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2021, this research provides comprehensive estimates of mortality, prevalence, and disability attributable to CHD in infants under 1 year. The study encompasses data from 204 countries and territories, covering the period from 1990 to 2021. Methods This cross-sectional analysis utilized data from the 2021 GBD study, encompassing 204 countries and territories. The study focused on infants under 1 year of age with CHD. The GBD dataset was accessed on June 10, 2024. Main outcome measures The primary outcomes included prevalence, all-cause, and cause-specific mortality, disability-adjusted life years (DALYs), and the corresponding estimated annual percentage changes (EAPCs). Trends were stratified by region, country, age, and Sociodemographic Index (SDI). Results In 2021, CHD resulted in 250,811.32 deaths globally [95% uncertainty interval (UI), 207,821.56–304,084.49], representing a 52.58% decrease from 1990. Among these, 167,985.02 deaths (95% UI, 138,221.77–208,321.59) occurred in infants younger than 1 year. In infants under 1 year old, the 1990 mortality rate for CHD ranked behind neonatal encephalopathy due to birth asphyxia and trauma, diarrheal diseases, neonatal preterm birth, and lower respiratory infections. By 2021, its mortality rates had decreased to the eighth leading cause of death. Interpretation CHD remains a significant and rapidly escalating global challenge in child health. While it is difficult to significantly reduce the prevalence of CHD, especially in complex cases, advances in prenatal diagnosis and the availability of medical termination of pregnancy in certain regions have led to demographic changes. Additionally, birth rates, typically lower in high-SDI countries, also influence the prevalence of CHD. Given these factors, the focus should be on improving survival outcomes and quality of life for affected infants. Our findings reveal substantial global disparities in prevalence among infants under 1 year, emphasizing the need for policy reforms that address screening, treatment, and data collection to mitigate these disparities.


FIGURE 1
Baseline characteristics.
Single-center analysis of servo-controlled cooling during the transport of neonates with perinatal asphyxia

March 2025

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4 Reads

Lingzhu Huang

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Qiru Su

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Weimin Huang

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[...]

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Jingbo Jiang

Objective To investigate the safety and efficacy of servo-controlled cooling during the transport of neonates with perinatal asphyxia. Methods We conducted a retrospective non-randomized case-control study at a single-center,which included 65 neonates diagnosed with Hypoxic-Ischemic Encephalopathy (HIE). These neonates were referred by the Shenzhen Children's Hospital medical transport team between January 2020 and June 2024. All subjects received 72 h of mild hypothermia treatment upon admission. Participants were categorized into an active group and a control group based on the use of servo-controlled cooling during transport. To evaluate differences in clinical characteristics, transport variables, and hospitalization outcomes between the two groups, we employed independent samples t -tests, Mann–Whitney U tests, and χ ² tests for inter-group comparison. Results Among the 65 subjects, there were 42 males and 23 females. The active group comprised 17 patients, while the control group included 48. No statistically significant differences were observed in sex, gestational age, birth weight, or HIE grade between the two groups ( P > 0.05). In comparison to the control group, the active group experienced a shorter duration from leaving the referral center to reaching the target temperature (1 h vs. 2.67 h, Z = −4.513, P < 0.05), arrived at the treatment center at a lower temperature (34.03°C vs. 35.6°C, t = −4.991, P < 0.05), and demonstrated a higher proportion of patients within the target temperature range upon arrival [88.2% (15/17) vs. 16.7% (8/48), χ ² = −0.774, P < 0.05]. Additionally, the length of hospitalization was shorter for the active group (15 days vs. 19 days, Z = −2.835, P < 0.05). The proportion of patients in the severe range on the aEEG recorded on the third day of cooling was higher in the control group [45.8% (22/48) vs. 11.8% (2/17), Z = −2.042, P < 0.05]. Conclusion Active therapeutic hypothermia during transport is both safe and feasible.It enables a more rapid and stable achievement of the target temperature, enhances short-term EEG outcomes, and may serve as the preferred method for transporting neonates with hypoxic-ischemic encephalopathy(HIE).


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Characterization and categorization variables by BMI of the sample.
Differences in mood between BMI rating groups.
Differences in mood between genders and PA practice.
Physical activity as a protective factor in the mood of children and adolescents: association with overweight and obesity

March 2025

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3 Reads

Introduction Sedentary children and adolescents are more susceptible to developing diseases, obesity and psychological disorders, but little is known about the relationship between physical activity (PA), body mass index (BMI) and mood state in this population. Methods This is a cross—sectional study with the participation of 2,757 students, aged between 10 and 19 years. The Brunel Mood Scale—BRUMS was used to assess the dimensions of tension, depression, anger, vigor, fatigue and mental confusion, and the PA questionnaire for children and adolescents was used to assess the practice of PA. Results There was a significant difference between the eutrophic and overweight BMI groups for the mood states of depression ( p = 0.004) and vigor ( p = 0.047). On the other hand, the overweight (4.06 ± 4.3) and obese (3.85 ± 4.0) groups had the highest rates of depression. It was observed that a higher BMI was associated with depression, anger and fatigue in children and adolescents and that PA can explain 39% of vigor in this population (F = 103.062, p = 0.000; R ² = 0.039). Active children and adolescents had twice as much vigor as inactive ones. There were differences between males and females, and between active and inactive individuals, in depression, anger, vigor, fatigue and confusion. There was a tendency for overweight and obese children and adolescents to have higher rates of depression when compared to underweight or normal-weight individuals. Conclusion The practice of physical activity (PA) was shown to have a positive effect on mood, with active children and adolescents reporting lower levels of depression, anger, fatigue, and confusion, and higher levels of vigor. These findings underscore the importance of PA as a protective factor against mood disturbances in this population, highlighting its potential role in improving emotional well-being.


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Mean and SD of the demographic and anthropometric characteristics of the participants.
Comparison of the predictive models.
Predictive analysis of dominant hand grip strength among young children aged 6–15 years using machine learning techniques: a decision tree and regression analysis

March 2025

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8 Reads

Background This study aimed to investigate and understand predictor variables and isolate the exact roles of anthropometric and demographic variables in the hand grip strength of young children. Material and methods In total, 315 male and female children participated in the study and 11 participants were excluded, therefore, 304 participants completed the assessments. Anthropometric measurements were collected at the time of study, along with age, height, weight, circumference of the hand, hand span, hand length, palm length, and hand grip strength (HGS) was measured. Both decision tree and regression machine learning analyses were used to isolate the relative contribution of independent features in predicting the targeted grip strength of children. Results Two predictive models were developed to understand the role of predictor variables in dominant hand HGS for both boys and girls. For boys, the decision tree was found to be the best model with the lowest error in predicting HGS. The respondents’ age, hand span, and weight were the most significant contributors to male hand grip strength. For the boys under 9.5 years of age, based on the decision tree analysis, weight (split at 27.5 kg) was found to be the most significant predictor. Furthermore, for the boys under 14.5 years of age, weight (split at 46.7 kg) remained the most important predictor. For boys 14.5 years and older, hand span was important in predicting handgrip strength. Backward regression was found to be the best model for predicting female hand grip strength. The R ² value for the model was 0.6646 and the significant variables were body mass index (BMI), hand length, hand span, and palm length, showing significance at a p -value of ≤0.05. This model predicted 66.46% of the variance in handgrip strength among the girls. Conclusion Anthropometric factors played a significant role in hand grip strength. Age, weight, and a larger hand span were found to be significant in impacting male HGS, while BMI, hand length, and palm length contributed to higher grip strength among the girls.


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IL-36RN gene: key insights into its role in pediatric pustular psoriasis pathogenesis and treatment

March 2025

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2 Reads

Pediatric pustular psoriasis (PPP) is an autoimmune skin disease that seriously affects the physical and mental health of children. The IL-36RN (Interleukin-36 Receptor Antagonist) gene plays a key role in the pathogenesis of PPP. This review comprehensively elaborates on the research progress of IL-36RN in the context of the pathogenesis and treatment of PPP, covering the basic structure, function, mutation sites and types, and inheritance patterns of the gene and its role in the pathogenesis of PPP. In addition, we discussed the frequency of IL-36RN mutations in patients with different types of PPP and the treatment methods for these patients, aiming to provide a valuable reference for further research and treatment of this disease.


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Beyond the present: current and future perspectives on the role of infections in pediatric PCD

March 2025

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17 Reads

Introduction Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder affecting motile cilia, leading to impaired mucociliary clearance and increased susceptibility to respiratory infections. These infections contribute to long-term complications such as bronchiectasis and lung function decline. Objectives This review explores both the acute and long-term impact of respiratory infections in children with PCD, while highlighting the multiple contributors to infection susceptibility. The review also evaluates emerging personalized approaches such as gene and mRNA therapy that hold promise for restoring ciliary function and reducing the burden of acute infections in pediatric PCD. Key findings and conclusions Acute respiratory infections have a significant impact on morbidity in pediatric PCD, driving progressive airway remodeling. While current treatment strategies focus on managing infections directly, emerging therapies targeting inflammation and genetic causes hold promise for reducing infection burden and improving long-term outcomes. Future advances in personalized medicine could further enhance therapeutic approaches in this population.


Efficacy and safety of extracorporeal membrane oxygenation combined with continuous renal replacement therapy in the management of pediatric acute respiratory distress syndrome

March 2025

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2 Reads

Background The efficacy and safety of combining extracorporeal membrane oxygenation with continuous renal replacement therapy remain controversial. This study aimed to evaluate the efficacy and safety of extracorporeal membrane oxygenation combined with continuous renal replacement therapy in the treatment of pediatric acute respiratory distress syndrome. Methods This retrospective study, conducted at Hunan Children's Hospital between January 2019 and December 2023, included 30 pediatric patients with acute respiratory distress syndrome who underwent extracorporeal membrane oxygenation treatment. The patients were divided into two groups based on whether continuous renal replacement therapy was used during treatment: 21 in the extracorporeal membrane oxygenation with continuous renal replacement therapy group and nine in the extracorporeal membrane oxygenation-only group. The groups were compared using t -test or Wilcoxon rank-sum test. Results This study included 19 (63.3%) male and 11 (36.7%) female patients (mean age: 63.33 ± 54.41 months). The ratios of arterial partial pressure of oxygen to fraction of inspired oxygen before and at withdrawal of extracorporeal membrane oxygenation were 58.50 (40.75–70.31) and 257.00 (113.25–358.33) mmHg, respectively ( P < 0.05). In the extracorporeal membrane oxygenation with continuous renal replacement therapy group, 21 patients (70.0%) underwent continuous renal replacement therapy, including those with acute renal injury ( n = 5), fluid overload ( n = 13), hyperkalemia ( n = 3), and removal of inflammatory mediators ( n = 3), and improvement was observed. Conclusions The combination of extracorporeal membrane oxygenation and continuous renal replacement therapy provides safe and effective respiratory support for pediatric patients with severe acute respiratory distress syndrome and enables effective fluid-balance management, removal of inflammatory factors, and maintenance of electrolyte equilibrium.


Analytical sensitivity in crude blood extract samples.
Details of the laboratory-created CMV-positive DBS samples.
Characteristics of infants with and without cCMV.
Dried blood spots and dried saliva spots taken from infants confirmed to have cCMV.
A high-sensitivity, high-throughput newborn screening assay for congenital cytomegalovirus—is it time for universal screening in the United Kingdom?

March 2025

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2 Reads

Introduction Congenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment resulting from in utero infection, affecting over a million infants globally each year. Early antiviral treatment can limit sequelae; however, most newborns are diagnosed late—or not at all—due to the lack of universal screening. Ensuring the availability of appropriate screening tools is critical to facilitate accurate and timely cCMV diagnosis. Methods A high-sensitivity, high-throughput commercial CMV PCR kit targeting the RRP30 control gene and a conserved region of CMV DNA was provided by Revvity and tested in three population groups: (1) leftover dried blood spot (DBS) samples from the UK newborn screening programme, (2) DBS samples from children with CMV viraemia unrelated to cCMV, and (3) DBS and dried saliva samples from infants with and without cCMV. Results Of 3,345 anonymised newborn DBS samples analysed, CMV was detected in 22 cases (0.66%), with a mean cycle threshold value of 36.70 (range 31.87–41.68). Assay development demonstrated a sensitivity of 2.04 CMV IU per reaction. This level of sensitivity was replicated using DBS samples prepared from infant/child blood samples with known levels of CMV, suggesting that the sensitivity reflects 2,000–3,000 CMV IU/mL blood. Discussion We demonstrated high analytical sensitivity of the qPCR assay with an optimal extraction protocol, making it an effective strategy for cCMV screening using DBS samples. These data suggest a potential cCMV incidence rate of up to 0.66% in the United Kingdom, equivalent to 3,960 infants per year, 25% of whom may develop long-term sequelae, which could be improved through early diagnosis and treatment.


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Gastric perforation with foreign body granuloma formation caused by a short hair—a case report

March 2025

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38 Reads

Objective This case report presents the diagnosis and treatment process of a rare case of gastric perforation caused by a short hair, leading to the formation of a foreign body granuloma in a child. Case Report The patient was a 3-year-old boy who was admitted to the hospital with persistent abdominal pain and fever for more than 20 days. Ultrasound and CT revealed a foreign body and inflammatory encapsulation in the abdominal cavity. Laparoscopic and open surgeries were performed, revealing a full-thickness gastric wall perforation approximately 2 mm in diameter on the greater curvature side of the stomach, which was in contact with the abscess and contained purulent fluid and short hair approximately 1.5 cm long. The intraoperative diagnosis was hair-induced gastric perforation, leading to intra-abdominal foreign body inflammatory granuloma. Granuloma excision, gastric perforation repair, and partial transverse colon resection were performed. Postoperative pathological results revealed a gastric perforation with surrounding acute and chronic inflammation, and the diagnosis was a reactive fibrous granulomatous lesion. The patient recovered well after surgery, and follow-up for one year revealed no significant abnormalities. Conclusion Hair-induced gastric perforation leading to a foreign body granuloma formation is a rare disease. Imaging examinations play a key role in diagnosis, and surgical resection is the main treatment method.


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Primary outcomes based on index SARS-CoV-2 emergency department index visit test result status.
Pediatric SARS-CoV-2 infection and development of anxiety and depression

March 2025

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8 Reads

Objective It remains unclear whether emerging mental health concerns in children infected with SARS-CoV-2 are a direct result of the infection or due to the indirect effects of the pandemic. Therefore, we sought to assess the frequency of new diagnoses of anxiety and/or depression among children diagnosed with and without SARS-CoV-2 infection who were tested in pediatric emergency departments. Methods A prospective cohort study with 6- and 12-month follow-ups was conducted across 14 Canadian tertiary-care pediatric emergency departments of the Pediatric Emergency Research Canada (PERC) network. The study included children aged <18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. The primary outcome was the diagnosis of anxiety and/or depression reported during follow-up. The surveys incorporated a modified version of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Long-COVID Pediatric Questionnaire. Results Among the participants who were eligible for 6- and 12-month follow-ups, 64.7% (268/414) of SARS-CoV-2-positive and 71.9% (743/1,033) of SARS-CoV-2-negative participants completed follow-up at these time points, respectively. The median age was 7.0 [inter-quartile range (IQR): 5.0–11.0] years, and 54.2% (548/1,011) were male. New diagnoses of anxiety and/or depression reported on either survey did not differ significantly between test-positive (4.1%, 11/268) and test-negative (2.8%; 21/743) participants [difference = 1.3% (95% CI: −1.3 to 4.2)]. There was a higher prevalence of new diagnoses of anxiety and/or depression among SARS-CoV-2-negative participants aged ≥12 years relative to those aged <12 years [8.7% (13/149) vs. 1.3% (8/594); difference = 7.4%; 95% CI of the difference = 3.0–12.5], but not among SARS-CoV-2-positive participants [4.4% (2/45) vs. 4.0% (9/223); difference = 0.4%; 95% CI of the difference = −5.6 to 9.4]. At 6 or 12 months, SARS-CoV-2-positive participants were more likely to experience confusion and/or lack of concentration, abdominal pain, and insomnia. Conclusions Although no association was found between SARS-CoV-2 infection and new diagnoses of anxiety and/or depression, SARS-CoV-2-positive participants were more likely to experience confusion/lack of concentration, abdominal pain, and insomnia. This finding, in the context of an increased prevalence of new diagnoses of anxiety and depression, underscores the impacts of societal changes on the mental health of children. Our finding that some non-specific symptoms were more frequently reported by SARS-CoV-2-positive participants emphasizes the need for further investigation of the underlying pathophysiologic mechanisms.


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Case Report: Delayed recurrence of staphylococcal scalded skin syndrome in an extremely low birth weight infant

March 2025

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1 Read

Preterm infants have well-documented deficiencies in their innate and adaptive immune responses, which are indirectly correlated with their gestational age at birth. They also exhibit low levels of circulating immunoglobulins due to the lack of maternal transplacental IgG transfer during the third trimester of pregnancy. These factors place them at a particularly high risk for infectious diseases after birth. Diagnosing infections that primarily manifest through abnormal skin findings can be challenging, given overlapping characteristics attributed to bacterial and yeast pathogens. The case presented involves an infant born extremely premature with staphylococcal scalded skin syndrome (SSSS), a diagnosis rarely made in neonatal patients. However, he was initially treated for a yeast infection of his neck and skin folds, which is very common. This patient's course was complicated by a family history concerning for an undiagnosed, inherited immune deficiency. This case highlights the clinical findings and management of SSSS in preterm infants. It also details the importance of establishing a specialized multidisciplinary team to coordinate and manage the care of these patients.


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