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Most-cited articles are from the articles published during the last two years (2024 ~ ).

Editorial
Neonatology (Perinatology)
The predetermined future: tackling South Korea’s total fertility rate crisis
Jin Kyu Kim
Clin Exp Pediatr. 2025;68(3):225-227.   Published online November 6, 2024
· South Korea faces a severe demographic crisis with the lowest global fertility rate. Despite significant investments, the total fertility rate continues to decline.
· It is necessary to fully mobilize national capabilities and execute comprehensive strategies that focus on both intangible and tangible values.
· Immediate and decisive action is essential to addressing these challenges effectively.
Review Article
Endocrinology
Hidden link between endocrine-disrupting chemicals and pediatric obesity
Min Won Shin, Shin-Hye Kim
Clin Exp Pediatr. 2025;68(3):199-222.   Published online November 28, 2024
Studies indicate potential connections between exposure to endocrine-disrupting chemicals (EDCs) and childhood obesity. Variations in the impact of EDCs in epidemiological studies may result from differences in exposure concentrations and timing, measurement methods, and interactive effects of multiple EDCs. Longitudinal studies on exposure to multiple EDCs are crucial to elucidating their contribution to pediatric obesity and minimize the adverse health consequences of EDC exposure.
Original Article
Critical Care Medicine
Cytokine profile of Post–cardiopulmonary bypass in children
Kantara Saelim, Kanokpan Ruangnapa, Jirayut Jarutach, Pongsanae Duangpakdee, Smonrapat Surasombatpattana, Pharsai prasertsan
Clin Exp Pediatr. 2025;68(12):1015-1022.   Published online September 19, 2025
Question: Can cytokine levels predict low cardiac output syndrome (LCOS) in children post–cardiopulmonary bypass?
Finding: Elevated interleukin (IL)-6, IL-8, and tumor necrosis factor-α levels were associated with LCOS, with an increase in IL-8 of >56 pg/mL from baseline to immediately postoperative being the strongest predictor.
Meaning: Monitoring immediately postoperative IL-8 levels may help identify pediatric patients at risk of LCOS, enabling timely interventions to improve outcomes.
Endocrinology
Long-term epidemiological insights into rickets: a nationwide population-based retrospective study
Chun-Hao Chu, Ying-Chuan Chen, Pei-Yao Liu, Chun-Chieh Hu, Yu-Lung Lin, Feng-Chih Kuo, Chieh-Hua Lu, Tzu-Ju Hsu, Yu-Tung Hung, Fuu-Jen Tsai, Chien-Ming Lin
Clin Exp Pediatr. 2025;68(11):879-891.   Published online August 20, 2025
Question: What are the nationwide trends and mortality risk factors of nutritional versus hereditary rickets among children in Asia?
Finding: In 2012–2018, the incidence of rickets steadily increased, whereas mortality rates declined. Mortality is associated with a low household income, anemia, chronic kidney disease, secondary hyperparathyroidism, and a prolonged hospital stay.
Meaning: Early diagnosis and targeted interventions addressing social and medical vulnerabilities are critical to reducing ricket-related mortality.
Review Article
Other
Acetaminophen causes neurodevelopmental injury in susceptible babies and children: no valid rationale for controversy
Lisa Zhao, John P. Jones, Lauren G. Anderson, Zacharoula Konsoula, Cynthia D. Nevison, Kathryn J. Reissner, William Parker
Clin Exp Pediatr. 2024;67(3):126-139.   Published online June 14, 2023
Despite worldwide acceptance of acetaminophen (paracetamol) in pediatric medicine, careful examination reveals no valid objections to the conclusion that early exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and children. Nevertheless, debate that early exposure to acetaminophen causes neurodevelopmental injury has centered around the prenatal period, evidence of which is relatively limited compared to that in the postnatal period, which is the time of greatest absolute and relative risk.
Original Article
General Pediatrics
Nonpharmacological interventions for managing postoperative pain and anxiety in children: a randomized controlled trial
Edlin Glane Mathias, Mamatha Shivananda Pai, Vijay Kumar, Dinesh Narayanakurup, Malavika Kulkarni, Vasudeva Guddattu, Ann-Cathrine Bramhagen, Baby S Nayak, Anice George
Clin Exp Pediatr. 2024;67(12):677-685.   Published online October 31, 2024
Question: What is the effect of nonpharmacological interventions on postoperative pain and anxiety among children.
Finding: Nurse-provided distraction interventions reduce pain and anxiety among pediatric surgical patients.
Meaning: The findings suggest that nonpharmacological interventions provided postoperatively to children reduce their pain and anxiety levels.
Neonatology (Perinatology)
Mortality of very low birth weight infants by neonatal intensive care unit workload and regional group status
Sung-Hoon Chung, Chae Young Kim, Yong-Sung Choi, Myung Hee Lee, Jae Woo Lim, Byong Sop Lee, Ki-Soo Kim; the Korean Neonatal Network
Clin Exp Pediatr. 2024;67(11):619-627.   Published online September 12, 2024
Question: How do structural and staffing characteristics of neonatal intensive care units (NICUs) influence the mortality rates of very low birth weight infants (VLBWIs)?
Findings: NICUs with higher staffing levels, particularly with more neonatologists, and those offering advanced care levels were associated with lower mortality rates. Additionally, regional disparities were observed, with some areas demon-strating significantly higher survival rates.
Meaning: Adequate staffing and equitable regional distribution of medical resources are crucial for improving survival outcomes in VLBWIs. Efforts to enhance NICU staffing and address regional healthcare disparities are essential for optimizing care quality and reducing mortality in this vulnerable population.
Review Article
Endocrinology
Growth plate closure and therapeutic interventions
Ja Hyang Cho, Hae Woon Jung, Kye Shik Shim
Clin Exp Pediatr. 2024;67(11):553-559.   Published online October 28, 2024
Height gains result from longitudinal bone growth. Upon adequate growth, growth plate closure limits longitudinal bone growth. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure and increase human height. The development of more effective therapeutic modalities for short stature, precocious puberty, and skeletal dysplasia is anticipated.
Original Article
Critical Care Medicine
High-dose methylprednisolone and tocilizumab improve survival of patients with high-risk pediatric acute necrotizing encephalopathy
Chaonan Fan, Fei Li, Kechun Li, Zheng Li, Yiyang Mao, Lijuan Wang, Gang Liu, Yingchao Liu, Quan Wang, Suyun Qian
Clin Exp Pediatr. 2026;69(1):56-64.   Published online October 22, 2025
Question: Which immunomodulatory strategies can reduce mortality in children with acute necrotizing encephalopathy (ANE)?
Finding: High-dose methylprednisolone (30 mg/kg/day) significantly improved the survival of high-risk patients, particularly when combined with tocilizumab.
Meaning: These findings support the use of a severity-based immunotherapy approach to optimize the outcomes of pediatric ANE.
Editorial
General Pediatrics
Artificial intelligence in pediatric healthcare: bridging potential, clinical practice, and ethical considerations
Yoon Lee, Seohyun Hong, Dong Keon Yon
Clin Exp Pediatr. 2025;68(9):652-655.   Published online August 28, 2025
· Artificial intelligence (AI) holds transformative potential for pediatric healthcare, with applications spanning prevention, diagnosis, treatment, and follow-up across diverse subspecialties; however, ethical concerns, scarcity of pediatric- specific data, and limited funding remain significant challenges.
· International consensus on pediatric AI guidelines, expanding child-specific datasets, and incorporating explainable AI are essential to ensure safety and trust.
· Multicenter collaboration and increased investment can address these gaps, enabling equitable, reliable, and pediatric- centered AI solutions.
Original Article
Pulmonology
Nonlinear association between neutrophil-to-lymphocyte ratio and asthma in children and adolescents in the United States: a cross-sectional study
Chuhan Cheng, Liyan Zhang
Clin Exp Pediatr. 2025;68(7):489-496.   Published online March 11, 2025
Question: Is there a nonlinear relationship between neutrophil-to-lymphocyte ratio (NLR) and asthma in children and adolescents?
Finding: NLR showed a nonlinear association with asthma, with an NLR threshold of 2.23 identifying individuals at higher risk.
Meaning: An NLR<2.23 may serve as a potential biomarker for asthma risk assessment and management in pediatric populations, thereby offering a simple tool for the early identification of at-risk individuals.
Review Article
Immunology
NLRP3 inflammasome: a key player in neonatal brain injury
Cagla Kiser, Ilkcan Ercan, Defne Engur, Sermin Genc
Clin Exp Pediatr. 2025;68(7):475-485.   Published online April 1, 2025
Hypoxic-ischemic encephalopathy is the major cause of neonatal brain injury. NOD-like receptor family pyrin domain containing 3 inflammasome activation leads to neuroinflammation, which significantly affects newborn mortality. The establishment of preventive and therapeutic strategies against brain damage requires a thorough understanding of the mechanisms underlying neuroinflammation and inflammasome activation in the neonatal brain.
Editorial
General Pediatrics
Global breastfeeding efforts: a long way to go
Hye-Jung Shin
Clin Exp Pediatr. 2025;68(4):300-302.   Published online November 13, 2024
· Despite much effort, breastfeeding practices remain unsatisfactory worldwide.
· Effective breastfeeding-promoting interventions are needed that are appropriate for age, culture, and social environment.
· Interventions can promote breastfeeding, especially in younger populations such as adolescent mothers.
Review Article
Neonatology (Perinatology)
Recent advances in understanding pathophysiology of non-nutritional stunting in very preterm infants
Eduardo Cuestas, Alina Rizzotti
Clin Exp Pediatr. 2025;68(4):287-297.   Published online December 23, 2024
· Previous reviews of extrauterine growth restriction focused mainly on weight growth restriction caused by nutritional factors or pathological conditions.
· This review summarizes recent developments in the pathophysiology of nonnutritional length growth restriction in very preterm infants with focus on the impact of sustained neonatal inflammation on their short- and long-term outcomes.
· Further research is needed to investigate optimal strategies to improve length growth restriction in very preterm infants.
Original Article
Developmental and Behavioral Medicine
Characteristics of temper tantrums in 1–6-year-old children and impact on caregivers
Warangkana Prutipaisan, Issarapa Chunsuwan, Tippawan Hansakunachai, Paskorn Sritipsukho
Clin Exp Pediatr. 2025;68(2):170-177.   Published online November 13, 2024
Question: What are common tantrum behaviors in preschool children, and how frequently are problematic behaviors observed? Do problematic tantrums have a different emotional impact on caregivers compared to typical tantrums?
Finding: Temper tantrums are common in preschool children, and verbal tantrums are the most common type.
Meaning: Problematic tantrums, defined as tantrums exhibiting aggressive physical behavior, long duration (>15 minutes), or frequent occurrence (>3 days/wk), significantly affected caregivers’ emotions.
Review Article
General Pediatrics
Prevalence of childhood overweight and obesity in Malaysia: a systematic review and meta-analysis
Ker Yang Chua, Ker Yung Chua, Karuthan Chinna, Chooi Ling Lim, Maheeka Seneviwickrama
Clin Exp Pediatr. 2025;68(2):115-126.   Published online November 13, 2024
The incidence of childhood obesity is increasing worldwide. National surveys in Malaysia have shown similar trends. This review aimed to increase our understanding of the prevalence and associated factors of childhood overweight, obesity, and excess weight in Malaysia. A systematic review and meta-analysis were conducted of studies reporting the prevalence of overweight and obesity in Malaysian children aged <18 years....
Original Article
Infection
Carbapenem resistance in gram-negative pathogens in an Iranian hospital: high prevalence of OXA-type carbapenemase genes
Setareh Mamishi, Reihaneh Hosseinpour Sadeghi, Sadaf Sajedi Moghaddam, Babak Pourakbari, Shiva Poormohammadi, Maryam Sotoudeh Anvari, Shima Mahmoudi
Clin Exp Pediatr. 2025;68(1):65-72.   Published online October 31, 2024
Question: What is the prevalence of carbapenem resistance in gram-negative bacteria and associated carbapenemase genes?
Findings: This study identified a notable prevalence of carbapenem-resistant gram-negative isolates, with Escherichia coli being the predominant contributor, follow ed by Klebsiella pneumoniae, Acinetobacter baumannii, while bla OXA48 was the most prevalent carbapenemase gene.
Meaning: These findings highlight the urgent need for proactive measures including the rapid detection of carbapenemase- producing isolates and effective infection control.
Construction and validation of predictive models for intravenous immunoglobulin–resistant Kawasaki disease using an interpretable machine learning approach
Linfan Deng, Jian Zhao, Ting Wang, Bin Liu, Jun Jiang, Peng Jia, Dong Liu, Gang Li
Clin Exp Pediatr. 2024;67(8):405-414.   Published online July 23, 2024
Question: Is there a reliable model to predict intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD)?
Finding: We constructed 5 machine learning models to predict IVIG-resistant KD. Extreme gradient boosting (XGBoost) model was superior to logistic, support vector machine, light gradient boosting machine and multiple layers perception models. The SHAP (SHapley Additive exPlanations) value interpreted the contribution of each feature in XGBoost model.
Meaning: XGBoost model showed the excellent performance to predict IVIG-resistant KD with explainable and visualizable machine learning algorithm.
Editorial
Genetics and Metabolism
Advancing orphan drug development for rare diseases
Jung Min Ko
Clin Exp Pediatr. 2024;67(7):356-357.   Published online November 17, 2023
· Rare diseases present unique challenges and unmet needs for which the development of orphan drugs tailored to them offers hope.
· Despite the hurdles posed by limited patient populations, orphan drug designations from regulatory agencies provide incentives, such as extended market exclusivity and tax credits, that ignite transformative advances.
· Scientific progress in genomics, personalized medicine, and analytics empowers precise interventions by decoding genetic anomalies and encouraging effective treatments.
Review Article
Neonatology (Perinatology)
Strategies to support language development in neonatal intensive care unit: a narrative review
Ju Sun Heo, Ee-Kyung Kim
Clin Exp Pediatr. 2024;67(12):651-663.   Published online November 6, 2024
· Preterm infants often experience speech and language development delays during early childhood, impacting children's ultimate outcomes.
· Promoting breastfeeding, increasing parent-infant interactions in a single-family room, promoting a nurturing language environment by parental book reading and language interventions, and parent-integrated interventions in the neonatal intensive care unit could potentially enhance children's language development.
· Integrating these strategies through family-centered care is essential.
Endocrinology
Lifelong medical challenges and immunogenetics of Turner syndrome
Won Kyoung Cho
Clin Exp Pediatr. 2024;67(11):560-568.   Published online July 31, 2024
· This summary emphasizes the importance of the early diagnosis of Turner syndrome (TS) and presents a multidisciplinary approach to its prevention and management, high-lighting the need for customized care.
· Advancements in immunogenetic research may improve our understanding of TS and improve its outcomes.
· TS encompasses a wide array of medical challenges, including cardiovascular, endocrine, autoimmune, and mental health issues, as well as a heightened cancer risk.
Original Article
Neonatology (Perinatology)
Protective effect of recombinant interleukin-10 on newborn rat lungs exposed to short-term sublethal hyperoxia
Hyeon-Soo Lee, Young-Joon Ryu, Min-Jae Lee
Clin Exp Pediatr. 2024;67(10):540-549.   Published online September 27, 2024
Lung injury is generated from the early stage of hyperoxia through the biologic effects of cell death and inflammatory response, which eventually leads to evolution of bronchopul-monary dysplasia. Therefore, a protective measure against hyperoxia-induced lung injury is needed. The present study observed that anti-inflammatory cytokine, interleukin-10 had protective effects on newborn rat lungs from injury induced at the early stage of hyperoxia, by preventing cell death and down-regulating inflammatory response.
Nephrology (Genitourinary)
Assessing kidney outcomes in childhood-onset lupus nephritis: role of National Institutes of Health-modified histological indices
Nuanpan Penboon, Pornpimol Rianthavorn
Clin Exp Pediatr. 2026;69(2):130-139.   Published online October 23, 2025
Question: In children with proliferative lupus nephritis, do National Institutes of Health-modified indices and treatment choices predict long-term kidney function?
Finding: Higher chronicity index scores, especially tubular atrophy and interstitial fibrosis, predicted kidney impairment. Additionally, the use of mycophenolate mofetil (MMF) for maintenance therapy was associated with a lower risk of kidney function decline.
Meaning: The early recognition of chronic lesions and MMF-based maintenance therapy may improve kidney outcomes in childhood-onset lupus nephritis.
Allergy
Maternal sleep disorders during pregnancy and subsequent risk of allergic diseases in Japanese children: the TMM BirThree Cohort Study
Ami Uematsu, Masatsugu Orui, Mami Ishikuro, Keiko Murakami, Aoi Noda, Genki Shinoda, Taku Obara, Shinichi Kuriyama
Clin Exp Pediatr. 2026;69(1):36-45.   Published online October 22, 2025
Question: Associations have been made between maternal sleep disorders during pregnancy and allergic diseases including bronchial asthma, atopic dermatitis, food allergy, and allergic conjunctivitis/rhinitis/hay fever in their children.
Finding: In the crude model, sleep disorders during pregnancy were associated with all examined allergic diseases in children. After adjustment, significant associations remained for atopic dermatitis and allergic conjunctivitis/rhinitis/hay fever.
Meaning: The study highlights associations between maternal sleep and child allergic diseases.
Gastroenterology
Gut microbiota and metabolomic alterations in newborns of mothers with gestational diabetes mellitus
Wan-Hsin Su, Yi-Wei Wang, Chien-Chang Chen, Ming-Wei Lai, Hsun-Chin Chao, Ming-Chou Chiang, Ren-Huei Fu, Pai-Jui Yeh
Clin Exp Pediatr. 2026;69(1):26-35.   Published online October 22, 2025
Question: Does maternal gestational diabetes mellitus (GDM) affect newborn gut microbiota and metabolomic profiles?
Finding: Neonates born to mothers with diet-controlled GDM exhibited reduced gut microbiota α-diversity, altered β-diversity, and metabolic shifts, including changes in fumarate and succinate levels, with peroxisome proliferator-activated receptor and adipocytokine signaling pathway activation.
Meaning: Maternal GDM affects early microbial colonization and metabolism in newborns and may have long-term health implications.
Review Article
Gastroenterology
Ingestion of foreign bodies and caustic substances in children: a narrative review on clinical evaluation and management update
Maria Rogalidou
Clin Exp Pediatr. 2026;69(1):11-21.   Published online December 10, 2025
Foreign body and caustic substance ingestion in children aged 1–5 years can feature to severe and, sometimes life-threatening complications. High-risk items include batteries, magnets, and corrosive chemicals. Severity depends on object type, location, and ingestion timing. Prompt diagnosis and early endoscopic intervention are crucial. Individualized management, high clinical suspicion, and parental education are essential to improving outcomes and preventing immediate and long-term complications affecting a child’s quality of life.
Original Article
Pulmonology
Association of macrophage migration-inhibitory factor gene and growth differentiation factor 15 gene polymorphisms and their circulating levels with respiratory distress syndrome among preterm neonates
Ali Helmi Bakri, Mohammed H. Hassan, Khaled Abdalla Abd-Elbaseer, Mahmoud Abo-Alhassan Sayed, Ahmed Alamir Mahmoud Abdallah, Eman Ahmed Abd-Elmawgood
Clin Exp Pediatr. 2025;68(9):680-689.   Published online April 1, 2025
Question: Do macrophage migration-inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) levels and their gene polymorphisms affect RDS among preterm babies?
Finding: Significantly higher serum MIF and GDF-15 levels were observed in patients with severe respiratory distress syndrome (RDS). The mutant G- and C-alleles of GDF-15 rs4808793 C>G single nucleotide polymorphism (SNP) and MIF rs755622 G>C SNP were present at significantly higher frequencies in preterm neonates with RDS.
Meaning: MIF and GDF-15 play a significant role in neonatal RDS and its severity.
Review Article
Other
Cost-effectiveness of newborn screening for severe combined immunodeficiency: a systematic review
Rezwanul Rana, Syed Afroz Keramat, Moin Ahmed
Clin Exp Pediatr. 2025;68(9):628-640.   Published online April 16, 2025
Universal newborn screening for severe combined immunodeficiency (SCID) demonstrates robust cost-effectiveness across diverse high-income healthcare systems, both from healthcare and societal standpoints. Early detection yields substantial savings. While uncertainties persist, impacting precise cost-effectiveness, the overall finding is positive. Future research must prioritize enhanced data collection and statistical rigor to refine our understanding of SCID's economic impact within the Australian context.
Original Article
Cardiology
Unsustainable and overworked: unpacking the challenges faced by pediatric cardiologists and cardiac surgeons in Korea
Soo In Jeong, GI Beom Kim, Sung Hye Kim, Jae Yoon Na, Hong Ju Shin, Sin Weon Yun, Lucy Youngmin Eun, Sang Yun Lee, Chang-Ha Lee, Kwang Ho Choi, Seul Gi Cha, Mi Young Han
Clin Exp Pediatr. 2025;68(9):732-741.   Published online August 6, 2025
Question: What are the key challenges affecting pediatric cardiologists and cardiac surgeons in Korea?
Finding: Excessive workloads, low procedural volumes, and legal risks contribute to high burnout. Regional disparities limit skill maintenance and threaten workforce sustainability.
Meaning: Targeted policies ensuring fair workloads, legal protections, and regional support are essential to stabilizing the pediatric cardiac workforce and maintaining high-quality care.
Hematology
Hematopoietic stem cell transplantation in pediatric patients with type VI mucopolysaccharidosis
Vedat Uygun, Koray Yalçın, Hayriye Daloğlu, Seda Öztürkmen, Suna Çelen, Suleimen Zhumatayev, Gülsün Karasu, Akif Yeşilipek
Clin Exp Pediatr. 2025;68(8):601-607.   Published online March 11, 2025
Question: Could hematopoietic stem cell transplantation (HSCT) be an alternative to enzyme replacement therapy (ERT) for type VI mucopolysaccharidosis (MPS VI)?
Finding: HSCT is generally not offered due to reports of high toxicity and mortality. However, we detected fewer complications and graft-versus-host disease cases and no deaths with HSCT.
Meaning: HSCT is both less expensive than ERT and permanent; thus, it should be considered an alternative treatment for MPS VI.


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