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Review Article
Neonatology (Perinatology)
Neurodevelopmental outcomes of very low birth weight infants in the Neonatal Research Network of Japan: importance of neonatal intensive care unit graduate follow-up
Yumi Kono; on behalf of the Neonatal Research Network of Japan
Clin Exp Pediatr. 2021;64(7):313-321.   Published online November 9, 2020
· Very low birth weight infants remain at high risk of developing neurodevelopmental impairments in early childhood.
· It is important to establish a network follow-up protocol and complete assessments with fewer dropouts to enable clarification of the outcomes of registered infants.
· All possible strategies should be employed to maintain good compliance after neonatal intensive care unit discharge.
Cardiology
Application of CRISPR-Cas9 gene editing for congenital heart disease
Heeyoung Seok, Rui Deng, Douglas B. Cowan, Da-Zhi Wang
Clin Exp Pediatr. 2021;64(6):269-279.   Published online March 2, 2021
Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) system has made a big step in the genome editing which still requires technical developments for the efficient applications in the many fields including congenital heart diseases (CHDs), closely related to the genomic abnormality. In this review, we tried to cover the most updated researches of CRISPR-Cas9 in the CHDs to understand the current technologies, eventually becoming therapeutic bases for the CHD patients.
Gastroenterology
Causes of acute gastroenteritis in Korean children between 2004 and 2019
Eell Ryoo
Clin Exp Pediatr. 2021;64(6):260-268.   Published online September 18, 2020
· Norovirus is the most common virus in Korean children with acute gastroenteritis.
· Escherichia coli and Salmonella spp. are the most common cause of bacterial gastroenteritis in Korean children, with a detection rate of 3%–20%.
· Uncommon bacterial and parasitic gastroenteritis require attention because of increasing international exchange and overseas travel.
Neurology
Myths and truths about pediatric psychogenic nonepileptic seizures
Jung Sook Yeom, Heather Bernard, Sookyong Koh
Clin Exp Pediatr. 2021;64(6):251-259.   Published online October 17, 2020
• Psychogenic non-epileptic seizures (PNES) are events that look like epileptic seizures but are not caused by abnormal electrical discharges.
• PNES are a manifestation of psychological and emotional distress.
• Treatment for PNES does not begin with the psychological intervention but starts with the diagnosis and how the diagnosis is delivered.
• A multifactorial biopsychosocial process and a neurobiological review are both essential components when treating PNES
Genetics and Metabolism
Understanding the genetics of systemic lupus erythematosus using Bayesian statistics and gene network analysis
Seoung Wan Nam, Kwang Seob Lee, Jae Won Yang, Younhee Ko, Michael Eisenhut, Keum Hwa Lee, Jae Il Shin, Andreas Kronbichler
Clin Exp Pediatr. 2021;64(5):208-222.   Published online July 15, 2020
Bayesian false-discovery probability and false-positive report probability are the 2 major Bayesian methods used to evaluate noteworthiness of a genetic variant.
Application of stricter P value is needed to confirm statistical significance in meta-analyses.
Gene network analysis of noteworthy genetic variants shows a blueprint of the genetic background in complex diseases.
Adolescence Medicine
The impacts of exercise on pediatric obesity
Ronald J. Headid III, Song-Young Park
Clin Exp Pediatr. 2021;64(5):196-207.   Published online August 4, 2020
Pediatric obesity contributes to the development of vascular dysfunction and metabolic and cardiovascular diseases which have all been shown to track into adulthood, increasing the risk of early mortality. Early exercise intervention is critical for combating obesity-related comorbidities and the optimal exercise prescription has yet to be well documented. Exercise prescriptions to combat pediatric obesity should incorporate both aerobic and muscle-strengthening exercises with an emphasis on long-term adherence.
Critical Care Medicine
The use of extracorporeal membrane oxygenation in children with acute fulminant myocarditis
Silver Heinsar, Sainath Raman, Jacky Y. Suen, Hwa Jin Cho, John F. Fraser
Clin Exp Pediatr. 2021;64(5):188-195.   Published online August 10, 2020
Acute fulminant myocarditis (AFM) occurs as an inflammatory response to an initial myocardial insult. Its rapid and deadly progression calls for prompt diagnosis with aggressive treatment measures. The demonstration of its excellent recovery potential has led to increasing use of mechanical circulatory support, especially extracorporeal membrane oxygenation (ECMO). Arrhythmias, organ failure, elevated cardiac biomarkers, and decreased ventricular function at presentation...
Neonatology (Perinatology)
Clinical implications of coronavirus disease 2019 in neonates
Do-Hyun Kim
Clin Exp Pediatr. 2021;64(4):157-164.   Published online February 4, 2021
• Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) was detected in approximately 3% of neonates of mothers with coronavirus disease 2019 (COVID-19).
• Neonatal COVID-19 is relatively benign with 16%–22.4% cases asymptomatic.
• Neonates with pre-existing medical conditions and preterm infants are at a higher risk of severe COVID-19.
• Requirement for neonatal mechanical ventilation is 20%–22.4% (vs. 4% in children)
• Low birth weight (13.9%) and premature birth (22.2%) affect neonates of mothers with COVID-19.
Genetics and Metabolism
Neurofibromatosis type I: points to be considered by general pediatricians
Eungu Kang, Hee Mang Yoon, Beom Hee Lee
Clin Exp Pediatr. 2021;64(4):149-156.   Published online July 15, 2020
Neurofibromatosis type 1 (NF1), a prevalent genetic disease that is transmitted in an autosomal dominant manner, is characterized by multiple cutaneous café-au-lait spots and neurofibromas as well as various degrees of neurological, skeletal, and neoplastic manifestations. The clinical features of NF1 increase in frequency with age, while the clinical diagnosis can remain undetermined in some pediatric patients. Importantly, affected patients...
Review article
Immunology
Systematic review of literature and analysis of big data from the National Health Insurance System on primary immunodeficiencies in Korea
Sohee Son, Ji-Man Kang, Younsoo Hahn, Kangmo Ahn, Yae-Jean Kim
Clin Exp Pediatr. 2021;64(4):141-148.   Published online July 13, 2020
In this article, a systematic review of reported primary immunodeficiency disease (PID) cases in Korea was performed and we attempted to estimate the number of PID patients and healthcare costs for the first time in Korea. Our review revealed that Korean PID cases are greatly underreported in the literature based on health insurance. Physicians in the field and health care policymakers should be aware of the disease burden of PID.
Review Article
Other
Behavioral insomnia in infants and young children
Eun Kyeong Kang, Seung Soo Kim
Clin Exp Pediatr. 2021;64(3):111-116.   Published online July 15, 2020
• Behavioral insomnia is common and affects a child’s daytime functioning and emotions.
• Diagnosing insomnia using the child’s sleep history, a sleep diary/log, and sleep questionnaires is important.
• Behavioral intervention, the main treatment, involves creating positive associations with sleep, establishing a consistent sleep schedule and bedtime routines, and the development of selfsoothing skills.
Neurology
Myelin oligodendrocyte glycoprotein antibody-associated disorders: clinical spectrum, diagnostic evaluation, and treatment options
Yun-Jin Lee, Sang Ook Nam, Ara Ko, JuHyun Kong, Shin Yun Byun
Clin Exp Pediatr. 2021;64(3):103-110.   Published online May 14, 2020
MOG antibody-associated disorder exhibits different pathophysiological and phenotypic findings than both aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder and typical MS. MOG-antibody is of particular interest in pediatric patients with clinical or radiological non-MS typical findings. MOG-antibody was included in a diagnostic algorithm for children recommending for the first time a standardized use in clinical practice except in cases of typical MS.
General Pediatrics
Association between maternal smoking during pregnancy and risk of bone fractures in offspring: a systematic review and meta-analysis
Erfan Ayubi, Saeid Safiri, Kamyar Mansori
Clin Exp Pediatr. 2021;64(3):96-102.   Published online February 5, 2020
Question: What is the effect of maternal smoking during pregnancy (MSDP) on the risk of bone fractures in the offspring?
Finding: After the adjustment for misclassification, MSDP may be associated with a 27% increased risk of bone fracture in the offspring (pooled odds ratio, 1.27; 95% confidence interval, 1.00–1.62; I2=0%; P=0.537)
Meaning: Preventive measures and health education programs should be designed and implemented to encourage women to stop smoking, especially during.
Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019
Ji Hee Kwak, Soo-Young Lee, Jong-Woon Choi; the Korean Society of Kawasaki Disease
Clin Exp Pediatr. 2021;64(2):68-75.   Published online December 30, 2020
Hundreds of cases of children and adolescents with hyperinflammatory responses such as Kawasaki disease have been reported amid the coronavirus disease 2019 (COVID-19) pandemic, leading to coining of the new term COVID-19–associated multisystem inflammatory syndrome in children. In this review article, we introduce the illness and describe its case definitions, epidemiology, pathogenesis, clinical features, treatments, and outcomes.
Allergy
Eosinophils and childhood asthma
Bong Seok Choi
Clin Exp Pediatr. 2021;64(2):60-67.   Published online January 6, 2021
•In allergic eosinophilic asthma, eosinophils act as important effector cells and antigen-presenting cells, while in nonallergic eosinophilic asthma, type 2 innate lymphoid cells play an important role in eosinophil activation.
•Sputum eosinophil counts can be helpful for evaluating allergic airway inflammation in asthma.
• Anti-interleukin-5 has broadened the scope of asthma treatment.
Cardiology
Pediatric heart transplantation: how to manage problems affecting long-term outcomes?
Young Hwue Kim
Clin Exp Pediatr. 2021;64(2):49-59.   Published online April 8, 2020
Since the initial International Society of Heart Lung Transplantation registry was published in 1982, the number of pediatric heart transplantations has increased markedly, reaching a steady state of 500–550 transplantation annually and occupying up to 10% of total heart transplantations. Heart transplantation is considered an established therapeutic option for patients with end-stage heart disease. The long-term outcomes of pediatric heart...
Gastroenterology
Changing prevalence of Helicobacter pylori infection in children and adolescents
Ji Sook Park, Jin Su Jun, Ji-Hyun Seo, Hee-Shang Youn, Kwang-Ho Rhee
Clin Exp Pediatr. 2021;64(1):21-25.   Published online July 15, 2020
Although Helicobacter pylori infection rate in children is unclear due to diversity and limitation of diagnostic tests unlike in adults, investigation the childhood prevalence is important for predicting H. pylori-related diseases in the future.
H. pylori infection occurred in early childhood, and declined during 30 years in our study.
Change in risk factors of H. pylori transmission and consensus for eradication therapy in children might further reduce the infection rate.
Endocrinology
Early menarche and its consequence in Korean female: reducing fructose intake could be one solution
Ji Hyun Kim, Jung Sub Lim
Clin Exp Pediatr. 2021;64(1):12-20.   Published online May 14, 2020
In Korea, the average age of menarche has declined sharply. Early menarche is associated with psychosocial and behavioral problems and cardiometabolic disease. Excess fructose intake has been suggested as one cause of early menarche in recent studies, so reducing fructose intake may be one solution.
Other
Review of epidemiological studies on air pollution and health effects in children
Jong-Tae Lee
Clin Exp Pediatr. 2021;64(1):3-11.   Published online June 10, 2020
This review summarized the accumulated epidemiologic evidence with emphasis on studies conducted in Korea and heterogeneity in the literature. Based on systematic reviews and meta-analyses, there is consistent evidence on the association between exposure to ambient air pollution and children’s health, especially respiratory health and adverse birth outcomes, and growing evidence on neurodevelopmental outcomes.
Infection
The COVID-19 pandemic: an unprecedented tragedy in the battle against childhood obesity
Maximilian Andreas Storz
Clin Exp Pediatr. 2020;63(12):477-482.   Published online November 5, 2020
Large-scale quarantine and home confinement during the coronavirus disease 2019 (COVID-19) pandemic will impose new and unfamiliar stressors on children, thereby worsening the childhood obesity epidemic. Physical, nutritional, and psychosocial factors that promote obesity in children during this special situation complementarily contribute to an unprecedented obesogenic environment. Involved stakeholders, including governments, schools, and families, must make all efforts to minimize the impact of the COVID-19 epidemic on childhood obesity.
Pulmonology
Current perspectives on atypical pneumonia in children
Jung Yeon Shim
Clin Exp Pediatr. 2020;63(12):469-476.   Published online June 10, 2020
Macrolides are the first line treatment in atypical pneumonia caused by M. pneumoniae, C. pneumoniae, and L. pneumophila. Macrolide-resistant mycoplasma pneumonia (MRMP) is emerging worldwide, especially in East Asia. Immune modulators such as corticosteroids or second line antibiotics are treatment options for MRMP. Pediatricians should be careful with empirical therapy of macrolides in children with mild to moderate community-acquired pneumonia not to increase the risk of MRMP.
Allergy
Pollen-food allergy syndrome in children
You Hoon Jeon
Clin Exp Pediatr. 2020;63(12):463-468.   Published online May 14, 2020
The prevalence of pollen-food allergy syndrome (PFAS) in Korean children with pollen allergy was recently reported to be 42.7%. PFAS can cause a wide range of symptoms from mild allergy to severe anaphylaxis depending on the nature of food allergens that share the epitopes with pollen. Cases of anaphylaxis caused by PFAS have recently increased. Treatments for PFAS should be individualized for patients according to the severity of symptoms.
Neurology
Health effects of electromagnetic fields on children
Jin-Hwa Moon
Clin Exp Pediatr. 2020;63(11):422-428.   Published online May 26, 2020
· The nervous systems of children are more vulnerable to the effects of electromagnetic waves than adults.
· The exposure to electromagnetic fields (EMFs) among children should be minimized.
· According to International Agency for Research on Cancer EMFs are possibly carcinogenic, it should not be overlooked or interpreted with bias.
Other
Comparison of diagnostic and treatment guidelines for undescended testis
Jaeho Shin, Ga Won Jeon
Clin Exp Pediatr. 2020;63(11):415-421.   Published online March 23, 2020
Primary caregivers should consider surgical specialist referral of patients with undescended testis if no descent occurs by 6 months, undescended testis is newly diagnosed after 6 months of age, or testicular torsion is suspected. Orchiopexy is recommended between 6 and 18 months at the latest. The original location of the testes and the age at orchiopexy are predictive factors for infertility and malignancy later in life.
Endocrinology
Air pollution and childhood obesity
Moon Young Seo, Shin-Hye Kim, Mi Jung Park
Clin Exp Pediatr. 2020;63(10):382-388.   Published online March 27, 2020
Questions: What are the possible effects of air pollution on the occurrence of childhood obesity and what are the mechanisms?
Finding: Epidemiologic studies suggest that air pollutants might act as obesogens in the pediatric population, and their possible mechanisms include oxidative stress, physical inactivity, and epigenetic modulation.
Meaning: This paper reviews updated information on air pollution, one of the modifiable environmental factors in childhood obesity.
Allergy
Montelukast use over the past 20 years: monitoring of its effects and safety issues
Yong Ju Lee, Chang-Keun Kim
Clin Exp Pediatr. 2020;63(10):376-381.   Published online February 5, 2020
Although the efficacy of montelukast is inferior to that of ICS, both physicians and parents prefer montelukast to ICSs.
EDN may be a useful biomarker for the treatment and monitoring of preschool children with asthma.
The US FDA requires boxed warning about serious neuropsychiatric events of montelukast, therefore, physicians should consider the benefits and risks of montelukast before prescribing it.
Pulmonology
Overview of management of children with COVID-19
Dyah Kanya Wati, Arya Krisna Manggala
Clin Exp Pediatr. 2020;63(9):345-354.   Published online July 17, 2020
The specific treatments for COVID-19 in children remain inconclusive and debatable despite effectively decreasing its signs and symptoms.
The need for clinical trials and reports should be investigated.
Gastroenterology
Increasing incidence of inflammatory bowel disease in children and adolescents: significance of environmental factors
Sowon Park, Yunkoo Kang, Hong Koh, Seung Kim
Clin Exp Pediatr. 2020;63(9):337-344.   Published online December 6, 2019
Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may...
Nutrition
Components of human breast milk: from macronutrient to microbiome and microRNA
Su Yeong Kim, Dae Yong Yi
Clin Exp Pediatr. 2020;63(8):301-309.   Published online March 23, 2020
Human breast milk (HBM) is essential for the infant’s growth and development right after birth and is an irreplaceable source of nutrition for early human survival. Various infant formulas have many similarities to HBM in many components, but there is no perfect substitute for HBM. Recently, various breast milk components and their roles have been studied according to the development...
Neurology
Autoimmune encephalitis and epilepsy: evolving definition and clinical spectrum
Joo Hee Seo, Yun-Jin Lee, Ki Hyeong Lee, Elakkat Gireesh, Holly Skinner, Michael Westerveld
Clin Exp Pediatr. 2020;63(8):291-300.   Published online August 16, 2019
Advances in autoimmune encephalitis studies in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to the disorder. The disorder or syndrome has been linked to a wide variety of pathologic processes associated with the neuron-specific autoantibodies targeting intracellular and plasma membrane antigens. However, current criteria for autoimmune encephalitis...
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