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Funded articles
Original Article
Infection
Clinical, biochemical, and genetic study of TACE/TNF-α/ACE signaling pathway in pediatric COVID-19 infection
Ahmed El-Abd Ahmed, Sawsan M.A. Abuhamdah, Mohammed H. Hassan, Nagwan I. Rashwan, Eman A. Abd-Elmawgood, Haggagy Mansour, Hoda S. Sherkawy, Shymaa G. Rizk
Clin Exp Pediatr. 2024;67(12):704-717.   Published online November 27, 2024
Question: Is the tumor necrosis factor (TNF) signaling pathway (TNF-α-converting enzyme [TACE]/TNF-α/angiotensin converting enzyme [ACE]) involved in pediatric coronavirus disease 2019 (COVID-19) infection?
Finding: Significantly increased circulating TACE/TNF-α and decreased ACE2 levels were noted. TNF-α-308G/A plays a significant role in susceptibility to COVID-19 infection among children. The ACE (I/D) (rs4646994) and ACE2 (rs2285666) single nucleotide polymorphisms lack significant associations with pediatric COVID-19 infection.
Meaning: The TNF signaling pathway participates in pediatric COVID-19 infection.
General Pediatrics
Role of proper postnatal care in continued exclusive breastfeeding among young Indonesian mothers
Wahyu Triadmajani, Shinta Prawitasari, Abdul Wahab
Clin Exp Pediatr. 2024;67(12):686-693.   Published online September 12, 2024
Question: Is proper postnatal care (PNC) associated with exclusive breastfeeding (EBF) practice among young Indonesian mothers?
Finding: Proper PNC elevates the likelihood of EBF among Indonesian adolescent mothers aged 15–19 years.
Meaning: Breastfeeding services should be provided during the early postnatal period to support EBF practice among adolescent mothers. High-quality PNC is a tailored intervention for vulnerable populations.
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.
Editorial
Allergy
Advancements in food allergen immunotherapy: improving quality of life and reducing risks
Jihyun Kim
Clin Exp Pediatr. 2024;67(12):672-674.   Published online July 31, 2024
· Pediatric food allergies considerably impair patient and family quality of life, particularly those with persistent allergies to common food allergens.
· Recent research has focused on developing diverse approaches to food allergen immunotherapy, showing promising outcomes of oral, sublingual, and epicutaneous immuno therapies.
· Critical considerations in immunotherapy candidate selection underscore the need for personalized approaches and reliable biomarkers in future studies to improve treatment outcomes.
Review Article
Developmental and Behavioral Medicine
Screen time among preschoolers: exploring individual, familial, and environmental factors
Sangha Lee, Donghee Kim, Yunmi Shin
Clin Exp Pediatr. 2024;67(12):641-650.   Published online September 12, 2024
This systematic review examined the correlation between screen time and various factors in preschoolers. Findings suggest that media parenting, including setting appropriate media limits, is crucial in protecting against excessive screen exposure. However, limited research has been done on the impact of family and personal factors, particularly with the increasing use of portable devices among young children.
Rheumatology
Double-negative T cells in pediatric rheumatic diseases
Dimitri Poddighe, Tilektes Maulenkul, Kuanysh Dossybayeva, Gulsamal Zhubanova, Zaure Mukusheva, Lyudmila Akhmaltdinova
Clin Exp Pediatr. 2024;67(12):632-640.   Published online September 12, 2024
Double-negative T (DNT) cells appear to be increased in several pediatric rheumatic diseases and this finding may be correlated with disease activity to some extent. However, due to significant heterogeneity in several methodological aspects, further investigations in rheumatic children are needed to assess the potential relevance of DNT cells as biomarkers and clarify their immunopathological role.
Original Article
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.
Pulmonology
Efficacies of different treatment strategies for infants hospitalized with acute bronchiolitis
Hyeri Jeong, Dawon Park, Eun Kyo Ha, Ju Hee Kim, Jeewon Shin, Hey-Sung Baek, Hyunsoo Hwang, Youn Ho Shin, Hye Mi Jee, Man Yong Han
Clin Exp Pediatr. 2024;67(11):608-618.   Published online October 28, 2024
· This study analyzed 45 randomized controlled trials (5,061 participants, 13 interventions) of the comparative efficacies of treatments for acute bronchiolitis in infants.
· Inhalation therapy with epinephrine and hypertonic saline significantly reduced the length of hospital stay compared with normal saline.
· Hypertonic saline had the greatest ability to improve the clinical severity score of bronchiolitis in infants younger than 2 years of age.
Review Article
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
Nutrition
Energy drink consumption among Korean adolescents: prevalence and associated factors
Jee-Seon Shim, Jeong Mi Lee
Clin Exp Pediatr. 2024;67(10):531-539.   Published online September 24, 2024
Question: How prevalent is energy drink consumption among Korean adolescents and what are the associated factors?
Findings: The prevalence of energy drink consumption among Korean adolescents increased from 3.2% in 2014 to 12.2% in 2019. Energy drink consumption varies according to sociode-mographic and individual factors.
Meaning: Policies and educational strategies are needed to reduce energy drink consumption in adolescents.
Review Article
Developmental and Behavioral Medicine
Effect of pesticide exposure on stunting incidence: a systematic review and meta-analysis
Sani Rachman Soleman, Yaltafit Abror Jeem, Muhammad Fathi Banna Al Faruqi, Mahdea Kasyiva, Vita Widyasari, Kuswati Kuswati, Nur Aini Djunet, Muflihah Rizkawati, Ety Sari Handayani
Clin Exp Pediatr. 2024;67(10):510-518.   Published online September 24, 2024
This review aimed to determine whether pesticide exposure is associated with stunting in children. The 13 included studies agree that pesticide exposure is not correlated with stunting incidence regardless of substance type (organophosphate and pyrethroid). Heterogeneity appeared with age covariate as potential confounding. The evidence of this study is challeng-ing, as the adverse effects of pesticides grossly occurred. The protection of children is warranted for preventing future neurodevelopment issues.
Neonatology (Perinatology)
Demographic transition in South Korea: implications of falling birth rates
Chae Young Kim, Sung-Hoon Chung
Clin Exp Pediatr. 2024;67(10):498-509.   Published online June 27, 2024
· Since 1960, South Korea's TFR decreased from 6.33 to 0.78 in 2022, below the 2.1 replacement level since 1983, with women's average age at first marriage rising to 31.3 in 2022.
· Policies needed: financial incentives, longer parental leave, better childcare.
· The U.S. (15.3% immigrants) and Germany (18.8%) use immigration to maintain demographic stability, a strategy South Korea is considering.
Allergy
Skin and oral intervention for food allergy prevention based on dual allergen exposure hypothesis
Kiwako Yamamoto-Hanada, Yukihiro Ohya
Clin Exp Pediatr. 2024;67(10):477-485.   Published online June 14, 2023
To prevent food allergy in infants, based on the dual allergen exposure hypothesis, we recommend a personalized approach consisting of both skin intervention (eczema treatment to achieve early remission and well-controlled skin without eczema to prevent percutaneous immunoglobulin E sensitization) and oral intervention (early allergenic food introduction).
Original Article
Developmental and Behavioral Medicine
Neonatal risk factors associated with autism spectrum disorders: an umbrella review
Amir Mohammad Salehi, Erfan Ayubi, Salman Khazaei, Ensiyeh Jenabi, Saeid Bashirian, Zohreh Salimi
Clin Exp Pediatr. 2024;67(9):459-464.   Published online July 19, 2024
Question: What are the neonatal risk factors for autism spectrum disorder (ASD)?
Findings: Significant effect sizes were observed for congenital heart disease (odds ratio [OR], 1.35), macrosomia (OR, 1.11), low birth weight (OR, 1.63), very low birth weight (OR, 2.25), small for gestational age (OR, 1.17), jaundice (OR, 1.74), male sex (OR, 1.47), and Apgar score (OR, 1.40).
Meaning: These factors were identified as risk factors for ASD.
Infection
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.
Review Article
Nephrology (Genitourinary)
Effects of diethylene glycol contamination of pharmaceutical products on unexplained acute kidney injury in children: a systematic review
Sani Rachman Soleman, Muhammad Luthfi Adnan, Hilmi Ardian Sudiarto, Satria Bintang Mahathma, Alya Ayu Tazkia, Hana Afifah Firdaus, Alfreda Amelia Khotijah, Miranti Dewi Pramaningtyas, Emi Azmi Choironi
Clin Exp Pediatr. 2024;67(8):395-402.   Published online January 4, 2024
A recent unexplained acute kidney injury (AKI) outbreak due to pharmaceutical product contamination with diethylene glycol (DEG) raises public attention. Our study revealed that DEG-contaminated paracetamol causes unexplained AKI in children. However, paracetamol is not the only contaminated drug. Other drugs, such as cough expectorants, antihistamines, and sedatives, can also be affected. Other chemicals, such as ethylene glycol and propylene glycol, can also contribute to poisonings.
Original Article
Nutrition
Parental support and exclusive breastfeeding at 3 months in West Java, Indonesia: a mixed-methods approach
Ratu Ayu Dewi Sartika, Fadila Wirawan, Wawan Gunawan, Primasti Nuryandari Putri, Nurul Husna Mohd Shukri
Clin Exp Pediatr. 2024;67(7):358-367.   Published online June 21, 2024
Question: Does paternal support affect exclusive breastfeeding failure?
Finding: Exclusive breastfeeding failure by 3 months was affected by paternal support.
Meaning: Fathers should be included in breastfeeding education and antenatal care.
Review Article
General Pediatrics
Metabolic complications of obesity in children and adolescents
Hyunjin Park, Jung Eun Choi, Seunghee Jun, Hyelim Lee, Hae Soon Kim, Hye Ah Lee, Hyesook Park
Clin Exp Pediatr. 2024;67(7):347-355.   Published online November 16, 2023
· Pediatric obesity increases the risk of metabolic complications (insulin resistance, dyslipidemia, nonalcoholic fatty liver disease) and long-term cardiovascular diseases.
· A new obesity definition and various indicators (continuous metabolic syndrome score, pediatric simple metabolic syndrome score, fatty liver index) have been proposed to evaluate children’s susceptibility to metabolic disorders.
· Laboratory and body composition tests in pediatric screenings can identify groups at high risk of metabolic complications of obesity.
Original Article
Developmental and Behavioral Medicine
Effectiveness of online responsive teaching in young children with developmental disabilities: a pilot study
Jung Sook Yeom, Jeongmee Kim
Clin Exp Pediatr. 2024;67(6):303-311.   Published online May 21, 2024
Question: Does online responsive teaching (RT) impact children's and parents’ emotions and behaviors, and do parents find it satisfactory?
Finding: Online RT significantly improved children's pivotal and problem behaviors, decreased parenting stress, and enhanced parental interactive styles with high satisfaction.
Meaning: This pilot study's findings suggest that online RT can enhance child outcomes, offering accessible interventions amid challenges such as limited access and pandemics.
Endocrinology
Kisspeptin and DLK1 levels for monitoring treatment of girls with central precocious puberty
Witchuwan Onsoi, Nattakarn Numsriskulrat, Suphab Aroonparkmongkol, Vichit Supornsilchai, Khomsak Srilanchakon
Clin Exp Pediatr. 2024;67(6):296-302.   Published online May 21, 2024
Questions: Can the serum levels of kisspeptin and DLK1 be potential biomarkers for monitoring the treatments for central precocious puberty (CPP)?
Findings: There were no significant differences in the baseline serum kisspeptin and DLK1 levels in CPP girls compared to girls with premature thelarche (PT). After 6 months of GnRH analogue treatment in CPP girls, median serum kisspeptin levels decreased, while median serum DLK1 levels increased compared to baseline.
Meanings: Serum levels of kisspeptin and DLK1 may serve as novel biomarkers for monitoring the efficacy of treatments for CPP.
Pulmonology
Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia
Jeong Eun Shin, Soon Min Lee, Mi-Jung Lee, Jungho Han, Joohee Lim, Haerin Jang, Ho Seon Eun, Min Soo Park, Soo Yeon Kim, Myung Hyun Sohn, Ji Ye Jung, Kyung Won Kim
Clin Exp Pediatr. 2024;67(5):257-266.   Published online April 16, 2024
Question: Is bronchopulmonary dysplasia (BPD) associated with functional/structural abnormalities later in life?
Finding: School-aged children with severe BPD had abnormalities on pulmonary function tests and lung computed tomography despite no subjective respiratory symptoms; however, only prenatal oligohydramnios and prolonged ventilator use were associated with abnormal lung function.
Meaning: Long-term monitoring of preterm infants’ lung health is essential, especially for those with prenatal oligohydramnios or prolonged ventilator use.
Review Article
Neonatology (Perinatology)
Updates in neonatal resuscitation: routine use of laryngeal masks as an alternative to face masks
Eun Song Song, Ga Won Jeon
Clin Exp Pediatr. 2024;67(5):240-246.   Published online July 11, 2023
In neonatal resuscitation:
· Laryngeal masks are recommended when endotracheal intubation or positive-pressure ventilation fails.
· Laryngeal masks are useful even during chest compressions.
· Laryngeal masks aid neonates >34 weeks’ gestation and/or with a birth weight >2 kg.
· Main usage barriers include limited experience (81%), preference for endotracheal tubes (57%), and lack of awareness (56%).
· Second-generation laryngeal masks have a built-in esophageal drainage tube that prevents regurgitation into the glottis, and an orogastric tube can be inserted within the esophageal drainage tube to protect against gastric inflation.
Influence of infant microbiome on health and development
Noelle Younge
Clin Exp Pediatr. 2024;67(5):224-231.   Published online August 21, 2023
· The infant gut microbiome is highly dynamic and individualized.
· Microbes are vertically transmitted from mother to infant during delivery and throughout infancy.
· Delivery mode, gestational age, diet, and antibiotic use influence infant microbiome composition and function.
· In animal studies, the microbiome played critical roles in the structural and functional development of the infant gastrointestinal and immune systems.
· Microbiome-targeted therapies have great potential to reduce infant morbidity and mortality.
Letter to the Editor
Pulmonology
Metabolic syndrome and pulmonary dysfunction in asthmatic children during the COVID-19 pandemic
Jue Seong Lee, Sang Hyun Park, Yoon Lee, Seunghyun Kim, Wonsuck Yoon, Young Yoo
Clin Exp Pediatr. 2024;67(3):168-170.   Published online February 19, 2024
Review Article
Allergy
Practical issues of oral immunotherapy for egg or milk allergy
Sukyung Kim, Kangmo Ahn, Jihyun Kim
Clin Exp Pediatr. 2024;67(3):140-148.   Published online June 19, 2023
· Oral immunotherapy should be supervised by pediatricians with experience administering oral food challenge tests and managing allergic reactions.
· Food allergen intake is gradually increased and maintained for years.
· Patients may experience allergic reactions and psychological problems.
· Adjunctive therapies (biologics, antihistamines, and leukotriene receptor antagonists) may improve efficacy and safety.
· Contraindications include uncontrolled asthma, malignancy, active autoimmune disorders, and beta-blocker usage.
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.
MicroRNAs as novel biomarkers for the diagnosis and treatment of pediatric diseases
Hwal Rim Jeong, Il Tae Hwang
Clin Exp Pediatr. 2024;67(3):119-125.   Published online May 24, 2023
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post transcriptionally, and MiRNA expression levels vary with developmental stages. MiRNAs play an important role in several biological processes in children, including growth, neuro-development, inflammation, and tumor formation. Research on miRNAs may uncover the molecular mechanisms underlying various pediatric diseases, leading to the development of novel biomarkers that aid in the diagnosis, treatment, and prognosis of these diseases.
Original Article
Other
Virtual, augmented, and mixed reality: potential clinical and training applications in pediatrics
Suyoung Yoo, Meong Hi Son
Clin Exp Pediatr. 2024;67(2):92-103.   Published online May 24, 2023
· Review of articles that investigated the applications of virtual, augmented, or mixed reality in pediatric clinical settings and in the training of pediatric medical professionals was conducted.
· A total of 89 studies were retrieved, with 36 randomized controlled trials.
· In most studies, intervention using the novel technology was at least as effective or more effective than the traditional method.
· Use of virtual, augmented, and mixed reality has potential in pediatrics.
Clinical Note
Neurology
Expanding association between BICD2 variants and brain malformations and associated lissencephaly
Jaeso Cho, Haeryung Kim, Seoungbok Lee, Jihoon G Yoon, HyeJin Kim, Minhye Kim, Seoyun Jang, Woojoong Kim, Soo Yeon Kim, Jong Hee Chae
Clin Exp Pediatr. 2024;67(1):54-56.   Published online December 21, 2023
Review Article
Nephrology (Genitourinary)
X-linked hypophosphatemic rickets: from diagnosis to management
Eujin Park, Hee Gyung Kang
Clin Exp Pediatr. 2024;67(1):17-25.   Published online June 14, 2023
· X-linked hypophosphatemia (XLH), the most common cause of hypophosphatemic rickets, affects 1/20,000 people.
· XLH is caused by a loss-of-function mutation of the PHEX gene.
· Its main pathogenesis is elevated fibroblast growth factor-23 (FGF23) level.
· Burosumab, an FGF23 inhibitor, was developed in the early 2000s.
· Burosumab was approved in Korea in 2020 for XLH patients aged 1+ years with radiographic evidence of bone disease.