Clinical and Experimental Pediatrics

Correspondence and Reply

Endocrinology

Authors’ reply to a commentary on “Testosterone therapy in boys with constitutional delay of growth and puberty: a PubMed-based systematic review and exploratory meta-analysis”

Ashraf T. Soliman, Fawzia Alyafei, Nada Alaaraj, Noor Hamed, Shayma Ahmed, Khaled A. Siddiq, Mohammed Qusad, Mohamed AlKhalaf

Clin Exp Pediatr. 2026;69(10):823-824. Published online September 28, 2026

DOI: https://doi.org/10.3345/cep.2026.02285

Correspondence

Endocrinology

A commentary on “Testosterone therapy in boys with constitutional delay of growth and puberty: a PubMed-based systematic review and exploratory meta-analysis”

Muqaddas Boltaboeva, Abdulhamid Haydarov, Lola Rakhmanova

Clin Exp Pediatr. 2026;69(10):820-822. Published online September 17, 2026

Crossref 1

Current evidence suggests that testosterone therapy is effective in boys with constitutional delay of growth and puberty; however, important knowledge gaps persist regarding genetic predisposition, nutritional and clinical factors, baseline endocrine assessments, and long-term outcomes. Addressing these factors may improve patient selection, optimize treatment strategies, and facilitate more individualized clinical decision-making.

DOI: https://doi.org/10.3345/cep.2026.02159

Clinical Note

Gastroenterology

Achalasia, alacrimia, and normal adrenal function in a toddler: GDP-mannose pyrophosphorylase A-congenital disorder of glycosylation mimicking Allgrove syndrome

Prounika Koppula, Siva Satya Prasun Korrapati, Vybhav Venkatesh

Clin Exp Pediatr. 2026;69(10):817-819. Published online August 19, 2026

DOI: https://doi.org/10.3345/cep.2026.01529

Original Article

Neonatology (Perinatology)

Maternal metformin protects developing auditory brainstem function after neonatal hypoxia-ischemia in a neonatal rat model

Sei Eun Kim, Joo Young Kweon, Yong Joo Ahn, Jun Hee Kim

Clin Exp Pediatr. 2026;69(10):806-816. Published online September 17, 2026

Question: Does maternal metformin administration during pregnancy protect offspring auditory brainstem function after neonatal hypoxia-ischemia (HI)?
Finding: Maternal metformin prevented HI-induced hearing threshold elevation, preserved auditory brainstem response amplitudes, and partially rescued neuronal and oligodendrocyte lineage cells in the medial nucleus of the trapezoid body.
Meaning: Maternal metformin during gestation may serve as a prenatal neuroprotective strategy against neonatal hypoxic-ischemic brain injury.

DOI: https://doi.org/10.3345/cep.2026.01368

Endocrinology

Gut microbiota profiles in Korean children with growth hormone deficiency: a case-control study

So Yoon Choi, Seom Gim Kong, Gyu Min Yeon, Yoo Rha Hong, Minyoung Jung, Jung Hyun Lee

Clin Exp Pediatr. 2026;69(10):797-805. Published online August 19, 2026

Question: Is gut microbiota composition altered in children with growth hormone deficiency (GHD)?
Finding: Children with GHD exhibited altered gut microbiota composition and predicted microbial functional pathways despite similar overall microbial diversity.
Meaning: These preliminary findings suggest a potential association between gut microbiota and pediatric GHD and warrant validation in larger prospective studies.

DOI: https://doi.org/10.3345/cep.2026.00493

Gastroenterology

Impact of bacterial infection on native liver survival in children with cirrhosis due to biliary atresia

Varissara Kaewchaivijit, Pornthep Tanpowpong, Songpon Getsuwan, Sophida Boonsathorn, Chatmanee Lertudomphonwanit, Suporn Treepongkaruna

Clin Exp Pediatr. 2026;69(10):788-796. Published online July 24, 2026

Question: Are bacterial infections associated with lower native liver survival in children with biliary atresia (BA)?
Finding: Children with BA and proven/suspected bacterial infections, including cholangitis, had significantly lower native liver survival and higher rates of liver transplantation or death.
Meaning: Early recognition, appropriate management, and prevention of bacterial infections may improve native liver survival in children with BA-related cirrhosis.

DOI: https://doi.org/10.3345/cep.2026.00388

Editorial

Neonatology (Perinatology)

Antenatal strategies for prevention of neonatal hypoxic-ischemic encephalopathy: potential role of metformin

Won-Ho Hahn

Clin Exp Pediatr. 2026;69(10):785-787. Published online September 28, 2026

Neonatal hypoxic-ischemic encephalopathy remains a major cause of death and lifelong disability despite therapeutic hypothermia. Antenatal maternal neuroprotective strategies remain underexplored; however, recent preclinical findings suggest that metformin may be a low-cost and mechanistically distinct approach. Further studies are warranted to define its optimal timing, efficacy, and maternal-fetal safety.

DOI: https://doi.org/10.3345/cep.2026.02306

Review Article

Developmental and Behavioral Medicine

Electronic media exposure and neurodevelopment in children under 5 years of age: an updated evidence-based narrative review

Soumi Kundu, Sudip Bhattacharya, Rajan Kumar, Kusum Kumari, Chandrima Biswas, Asha Premlata Omega Oraon, Abhimanyu Ganguly

Clin Exp Pediatr. 2026;69(10):773-784. Published online September 8, 2026

Excessive digital media exposure before 5 years is consistently associated with poorer language development, attention, executive functioning, sleep quality, and socioemotional development. The adverse effects are particularly evident when screen exposure replaces caregiver-child interaction and active play. High-quality educational content combined with caregiver coviewing may mitigate some of these risks. Pediatric counseling should emphasize age-appropriate media use, family media plans, and balanced daily routines.

DOI: https://doi.org/10.3345/cep.2026.01417

Immunology

Current review of pediatric Fas-associated death domain protein deficiency: expanding clinical and therapeutic perspectives

Chuin-Hen Liew, Kah Kee Tan, Jelitha Ramachanderam, Sin Yee Teo, Khuen Foong Ng

Clin Exp Pediatr. 2026;69(10):762-772. Published online September 4, 2026

Fas-associated death domain protein deficiency expands beyond a severe infantile immunodeficiency to a broader clinical spectrum in children involving autoimmunity, autoinflammation, and susceptibility to bacterial and viral infections. This review highlights recurrent febrile encephalopathy, invasive pneumococcal disease, and liver dysfunction as key features and identifies later-onset and self-limiting phenotypes.

DOI: https://doi.org/10.3345/cep.2026.01291

Gastroenterology

Patient-derived intestinal organoids in pediatric inflammatory bowel disease: applications in disease modeling and therapeutic response prediction

Ky Young Cho

Clin Exp Pediatr. 2026;69(10):753-761. Published online September 1, 2026

· Patient-derived intestinal organoids provide a human-relevant platform for studying disease mechanisms and evaluating therapeutic responses in pediatric inflammatory bowel disease (PIBD).
· By preserving patient-specific epithelial characteristics, these models enable the functional assessment of disease heterogeneity and drug responsiveness.
· Although technical and biological limitations remain, ongoing advances in immune-inclusive and microphysiological systems are expected to enhance their translational value and support personalized treatment strategies for PIBD.

DOI: https://doi.org/10.3345/cep.2026.00913

Letter to the Editor

Pulmonology

Telomere biology disorders in childhood interstitial lung disease: from genetic diagnosis to bedside suspicion – A commentary on “Telomere biology disorders associated with childhood interstitial lung disease”

Weerapong Lilitwat

Clin Exp Pediatr. 2026;69(9):751-752. Published online August 19, 2026

DOI: https://doi.org/10.3345/cep.2026.01760

Clinical Note

Nephrology (Genitourinary)

Marifat Ganieva, Muqaddas Boltaboeva, Umida Ganiyeva, Oksana Efimenko, Abdulhamid Haydarov, Sherzod Toshboev

Clin Exp Pediatr. 2026;69(9):748-750. Published online July 20, 2026

Crossref 1

DOI: https://doi.org/10.3345/cep.2026.00563

Neurology

Anti-GD1b-positive sensory ataxic Guillain-Barré syndrome with bulbar involvement and Bickerstaff brainstem encephalitis-like features in an adolescent: a case report

Hamza Reaz Aziz, Kirsh Kumar, Nabiha Naveed, Saira Awan

Clin Exp Pediatr. 2026;69(9):743-747. Published online August 27, 2026

DOI: https://doi.org/10.3345/cep.2026.00717

Original Article

Endocrinology

Rising incidence of central precocious puberty in Thailand: a nationwide population-based study before, during, and after the COVID-19 pandemic (2018–2024)

Pattara Wiromrat, Preamrudee Poomthavorn, Ratikorn Chaisiwamongkol, Chaiyawat Suppasilp, Ouyporn Panamonta, Ratchaneewan Sinitkul

Clin Exp Pediatr. 2026;69(9):733-742. Published online August 19, 2026

Web of Science 1 Crossref 1

Question: Did the incidence of central precocious puberty (CPP) and premature thelarche (PT) among Thai children change during 2018–2024?
Finding: CPP incidence in girls more than doubled during the COVID-19 pandemic and remained elevated thereafter, primarily at age 8 to <9 years. PT incidence increased progressively, particularly in girls aged 7 to <8 years.
Meaning: In peripubertal age groups, CPP and PT incidence increases may reflect pandemic-related factors, obesity, awareness, or earlier pubertal onset.

DOI: https://doi.org/10.3345/cep.2026.00983

Basic Research

Longitudinal changes in serum soluble C5b-9 levels following immunomodulatory therapy for multisystem inflammatory syndrome in children

Amrita Pattanaik, Prasad Varamballi, Srilatha Marate, Sushma Bhandarkar B., Shrikiran Aroor, Somashekar A.R., Suchetha S. Rao, Chiranjay Mukhopadhyay

Clin Exp Pediatr. 2026;69(9):726-732. Published online August 19, 2026

Question: Do serum soluble C5b-9 (sC5b-9) levels change following immunomodulatory therapy in children with multisystem inflammatory syndrome in children (MIS- C)?
Finding: In this longitudinal multicentric study of 100 children with MIS-C, serum sC5b-9 concentrations significantly decreased following treatment, although some patients showed persistently elevated levels at discharge.
Meaning: Serial sC5b-9 measurements may indicate treatment-associated immune activity and recovery in MIS-C.

DOI: https://doi.org/10.3345/cep.2026.01179

Oncology

Pediatric patients with cancer exhibit increased neutrophil extracellular traps and reduced active deoxyribonuclease I: diagnostic, prognostic, and therapeutic opportunities

Nuria Benavent, Julia Oto, Patricia Verger, Alejandro Herreros-Pomares, Raquel Herranz, Bienvenida Argilés, Julia Balaguer, Antonio Juan-Ribelles, Santiago Bonanad, Pilar Medina, Adela Cañete

Clin Exp Pediatr. 2026;69(9):713-725. Published online August 19, 2026

· Circulating neutrophil extracellular trap (NET) markers are increased in pediatric cancer and correlate with disease risk and outcomes.
· Cell-free DNA and calprotectin levels show diagnostic and prognostic value, whereas impaired deoxyribonuclease I activity identifies a targetable mechanism.
· NETs are promising biomarkers and therapeutic targets for high-risk pediatric tumors.

DOI: https://doi.org/10.3345/cep.2026.01004

Cardiology

Red cell distribution width and reticulocyte hemoglobin content as predictors of iron depletion in children with cyanotic congenital heart disease

Hanyudh Prichayudh, Kanhatai Chiengthong, Khwaunrat Whaidee, Navaporn Phiphattanatikanunt, Vidhavas La-orkhun, Pornthep Lertsapcharoen

Clin Exp Pediatr. 2026;69(9):706-712. Published online July 29, 2026

Question: Are red cell distribution width (RDW) and reticulocyte hemoglobin content (CHr) reliable alternative markers for detecting iron depletion in children with cyanotic congenital heart disease, whose status is often masked by compensatory polycythemia?
Finding: Multivariate analysis demonstrated that RDW (≥18.8%) and CHr (<28 pg) are strong independent predictors of iron depletion in this vulnerable population.
Meaning: Combined use of these accessible markers facilitates earlier diagnosis and improves clinical management in resource-limited healthcare facilities.

DOI: https://doi.org/10.3345/cep.2026.00241

Editorial

Endocrinology

A commentary on “Rising incidence of central precocious puberty in Thailand: a nationwide population-based study before, during, and after the COVID-19 pandemic (2018–2024)”

Won Kyoung Cho

Clin Exp Pediatr. 2026;69(9):704-705. Published online August 27, 2026

Nationwide Thai data showed that central precocious puberty (CPP) incidence rose sharply during the COVID-19 pandemic and plateaued, whereas premature thelarche (PT) continued to increase postpandemic, particularly among girls aged 7-8 years. Because progression from PT to CPP cannot always be predicted at presentation, longitudinal follow up is preferable to reassurance after a single visit. Childhood obesity may further complicate diagnosis by blunting gonadotropin responses, warranting cautious interpretation of stimulation testing.

DOI: https://doi.org/10.3345/cep.2026.02348

Review Article

Emergency Medicine

Reconciling conflicting evidence on stress ulcer prophylaxis in critically ill children: a systematic review and meta-analysis

Hiroyuki Oikawa, Shotaro Nozaki, Munehiro Furuichi

Clin Exp Pediatr. 2026;69(9):694-703. Published online August 24, 2026

By appraising all nonrandomized studies using the ROBINS-I V2 (Risk Of Bias In Non-randomized Studies of Interventions, version 2) and finding them at critical risk of confounding, we restricted the synthesis to randomized trials. Stress ulcer prophylaxis (SUP) showed no demonstrated benefit; the previously reported mortality signal was not reproduced, and an exploratory signal of increased central line-associated bloodstream infection could not be excluded. With very low overall certainty, current evidence is insufficient to support routine SUP.

DOI: https://doi.org/10.3345/cep.2026.01823

Endocrinology

Effect of lifestyle interventions on pediatric obesity: a lifestyle medicine systematic review

Jung Eun Choi, Hee Jeoung Lim, Kyung Hee Kim, Hae Soon Kim

Clin Exp Pediatr. 2026;69(9):686-693. Published online August 27, 2026

Lifestyle interventions effectively improve the anthropometric and cardiometabolic outcomes of children and adolescents with overweight or obesity. Multicomponent approaches integrating diet, physical activity, and behavioral strategies demonstrate the most consistent and comprehensive benefits. These findings strongly support the application of lifestyle medicine principles in pediatric obesity management. Long-term integrated interventions addressing multiple health behaviors are needed to ensure sustainable improvements.

DOI: https://doi.org/10.3345/cep.2026.00927

Perspective

Neonatology (Perinatology)

Neonatal care in a low-birthrate society: insights from population-based observations in Japan

Hirokazu Arai, Hiroshi Miura, Yohei Onodera, Hiroyuki Adachi, Akira Sato, Tomoo Ito, Masaru Mizuno

Clin Exp Pediatr. 2026;69(8):683-685. Published online July 24, 2026

Declining birth rates are reshaping neonatal care. In low-birthrate settings, shifts in the underlying causes of neonatal death, including greater use of perinatal palliative care for trisomy 18 and challenges in maintaining expertise in extremely low-birth-weight infants, may contribute to fluctuations in neonatal mortality. These observations highlight the need for a coordinated system-level support.

DOI: https://doi.org/10.3345/cep.2026.01095

Clinical Note

Neonatology (Perinatology)

Peters anomaly: a rare etiology of corneal clouding in the newborn

Gregory Ison, Srividya Naganathan

Clin Exp Pediatr. 2026;69(8):680-682. Published online July 13, 2026

DOI: https://doi.org/10.3345/cep.2026.00794

Nephrology (Genitourinary)

A rare genetically confirmed case of apparent mineralocorticoid excess syndrome due to a homozygous HSD11B2 variant in a 2-year-old child with severe hypertension: response to targeted therapy

Bashair Alabbasi, Mugahid Elamin, Ghadah Alsallum, Ghada Alzahrany

Clin Exp Pediatr. 2026;69(8):676-679. Published online July 24, 2026

DOI: https://doi.org/10.3345/cep.2026.01473

Original Article

Neurology

Patient-independent automated pediatric seizure monitoring based on expert-labeled electrographic ictal data as core reference knowledge

Yoon Gi Chung, Jaeso Cho, Anna Cho, Hunmin Kim, Byung Chan Lim

Clin Exp Pediatr. 2026;69(8):665-675. Published online July 14, 2026

Question: Can deep learning models trained on expert-verified electroencephalography segments reliably detect seizures and be applied to single-channel wearable monitoring?
Finding: This technique demonstrated 80.1%–100% sensitivity and low false-alarm rates. On 1,604 expert-labeled segments, the model outperformed previous studies in terms of latency and accuracy across unseen datasets.
Meaning: Expert-labeled data are essential for achieving universal seizure detection. This channel-specific approach enabled efficient and continuous monitoring using wearable devices.

DOI: https://doi.org/10.3345/cep.2026.01011

Neonatology (Perinatology)

Efficacy and safety of home-based fiberoptic blanket versus hospital-based light-emitting diode phototherapy for neonatal jaundice: a retrospective cohort study from Thailand

Chayatat Ruangkit, Thanyathorn Thaninjeerawat, Saitarn Klaidangklum, Saowalak Prasopa, Pongsakorn Atiksawedparit, Sasivimon Soonsawad

Clin Exp Pediatr. 2026;69(8):655-664. Published online July 1, 2026

Question: Is a home-based fiberoptic phototherapy blanket as effective and safe as hospital-based overhead light-emitting diode phototherapy for the treatment of neonatal jaundice?
Finding: Home phototherapy (HPT) resulted in a slower bilirubin reduction rate than inpatient phototherapy (IPT); however, both modalities achieved the therapeutic targets without phototherapy-related complications.
Meaning: With careful patient selection, structured monitoring, and reliable follow-up, HPT is a safe and feasible alternative to IPT for neonatal jaundice.

DOI: https://doi.org/10.3345/cep.2026.00703

Gastroenterology

Prognosis of pediatric hepatic Wilson disease with ATP7B loss of function variants

Amresh Kumar Mishra, Moinak Sen Sarma, Anchal Dubey, Pratik Gadekar, Amita Moirangthem, Anshu Srivastava, Amrita Mathias

Clin Exp Pediatr. 2026;69(8):646-654. Published online July 13, 2026

Question: Do the loss of function (LOF) of ATP7B mutated variants affect the severity or outcomes of hepatic Wilson disease (WD)?
Finding: LOF is associated with advanced liver disease, portal hypertension, and extrahepatic involvement. LOF did not determine hepatic or overall outcomes. ATP7B: c.813C>A (truncation variant) has an aggressive course with higher predisposition to acute liver failure. Lower serum exchangeable copper levels and higher disappearance of Kayser-Fleischer ring were observed in ATP7B: c.3809A>G (nontruncation variant) suggesting a better effect of chelation and lesser systemic copper.
Meaning: Truncation of the ATP7B protein determines the severity of the phenotype in WD.

DOI: https://doi.org/10.3345/cep.2026.00689

Other

Association between sodium content of intravenous immunoglobulin and electrolyte changes and clinical course of Kawasaki disease

Yoshitaka Watanabe, Naomi Yagi, Toya Hattori, Chisato Oyake, Shota Endo, Maria Yoshimi, Takayoshi Kyoda, Hirokazu Ikeda

Clin Exp Pediatr. 2026;69(8):639-645. Published online July 1, 2026

Web of Science 1

Question: Hyponatremia in Kawasaki disease is associated with inflammation and disease severity. Intravenous immunoglobulin (IVIG) formulations feature various sodium contents. What is the clinical impact of such variations?
Finding: IVIG sodium content was associated with sodium, potassium, and protein level changes.
Meaning: Coronary outcomes were similar but electrolyte changes differed: high-sodium IVIG caused hypokalemia, whereas low-sodium IVIG caused hyponatremia. IVIG preparation requires consideration when interpreting laboratory values.

DOI: https://doi.org/10.3345/cep.2026.00619

Editorial

Neurology

Network-based biomarkers in pediatric drug-resistant epilepsy

Joseph Lim, Jaeso Cho, Hunmin Kim

Clin Exp Pediatr. 2026;69(8):636-638. Published online July 24, 2026

Conventional preoperative evaluation in pediatric drug-resistant epilepsy relies on clinical surrogates that quantify seizure exposure but not its impact on brain networks. A newly developed diffusion-weighted imaging connectome biomarker, anchored to intracranial electroencephalography-confirmed seizure onset zones and resolved across 6 neurocognitive domains, addresses this gap. This individualized approach classifies cognitive impairment with high accuracy and may offer a more precise, clinically interpretable tool to inform surgical timing.

DOI: https://doi.org/10.3345/cep.2026.01774

Review Article

Endocrinology

Linking pediatric obesity to youth-onset type 2 diabetes: integrated longitudinal and cross-sectional evidence from population-based studies worldwide

Ashraf T. Soliman, Fawzia Alyafei, Nada Alaaraj, Noor Hamed, Shayma Mohamed, Ahmed Elawwa

Clin Exp Pediatr. 2026;69(8):622-635. Published online July 20, 2026

Pediatric obesity and youth-onset type 2 diabetes have increased simultaneously across 6 continents over the last 25 years. Approximately 75% of affected youths are obese at diagnosis, beta-cell declines occur rapidly, and microvascular complications occur early. Glucagon-like peptide-1 receptor agonists and bariatric surgery achieve meaningful weight loss and glycemic improvement; however, the primary prevention of childhood obesity remains the most powerful strategy for arresting this epidemic.

DOI: https://doi.org/10.3345/cep.2026.01228

Other

Virtual reality for managing pain and fear and anxiety during pediatric needle procedures: an umbrella review

Thomas Saliba, Guillaume Fahrni

Clin Exp Pediatr. 2026;69(8):609-621. Published online July 14, 2026

Meta-analyses suggest that virtual reality (VR) reduces self-reported pain, fear, and anxiety in children during needle procedures but has high heterogeneity, high overlap between primary studies, and low methodological quality, leading to a "very weak" GRADE (Grading of Recommendations Assessment, Development and Evaluation) classification. Clinicians should view VR as a promising additional distraction tool; however, VR cannot yet replace current analgesic and anxiolytic strategies. Future research should focus on age-stratified analyses, measurement tool standardization, and modern VR technology

DOI: https://doi.org/10.3345/cep.2026.01221

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