• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.3
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• pp.135-145
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• 2023

Antibiotics are frequently administered during pregnancy. Although necessary to address acute infections, their use facilitates antibiotic resistance. Other associations have also been found with the use of antibiotics, such as perturbations of gut bacteria, delays in microbial maturation, and increased risks of allergic and inflammatory diseases. Little is known about how the prenatal and perinatal administration of antibiotics to mothers affects the clinical outcomes of their offspring. A literature search was conducted of the Cochrane, Embase, and PubMed engines. The retrieved articles were reviewed by two authors and verified for relevance. The primary outcome was the effect of pre- and perinatal maternal antibiotic use on clinical outcomes. Thirty-one relevant studies were included in the meta-analysis. Various aspects are discussed, including infections, allergies, obesity, and psychosocial factors. In animal studies, antibiotic intake during pregnancy has been suggested to cause long-term alterations in immune regulation. In humans, associations have been found between antibiotic intake during pregnancy and different types of infections and an increased risk of pediatric infection-related hospitalization. A dose-dependent positive association between pre- and perinatal antibiotic use and asthma severity has been reported in animal and human studies, while positive associations with atopic dermatitis and eczema were reported by human studies. Multiple associations were identified between antibiotic intake and psychological problems in animal studies; however, relevant data from human studies are limited. However, one study reported a positive association with autism spectrum disorders. Multiple animal and human studies reported a positive association between pre- and perinatal antibiotic use by mothers and diseases in their offspring. Our findings have potentially significant clinical relevance, particularly considering the implications for health during infancy and later in life as well as the related economic burden.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.439-445
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• 2018

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and $GSK3{\beta}$-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

• Toxicological Research
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• v.29 no.3
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• pp.173-179
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• 2013

In-utero exposure to valproic acid (VPA) has been known as a potent inducer of autism spectrum disorder (ASD), not only in humans, but also in animals. In addition to the defects in communication and social interaction as well as repetitive behaviors, ASD patients usually suffer from gastrointestinal (GI) problems. However, the exact mechanism underlying these disorders is not known. In this study, we examined the gross GI tract structure and GI motility in a VPA animal model of ASD. On embryonic day 12 (E12), 4 pregnant Sprague-Dawley (SD) rats were subcutaneously injected with VPA (400 mg/kg) in the treatment group, and with phosphate buffered saline (PBS) in the control group; the resulting male offspring were analyzed at 4 weeks of age. VPA exposure decreased the thickness of tunica mucosa and tunica muscularis in the stomach and ileum. Other regions such as duodenum, jejunum, and colon did not show a significant difference. In high-resolution microscopic observation, atrophy of the parietal and chief cells in the stomach and absorptive cells in the ileum was observed. In addition, decreased staining of the epithelial cells was observed in the hematoxylin and eosin (H&E)-stained ileum section. Furthermore, decreased motility in GI tract was also observed in rat offspring prenatally exposed to VPA. However, the mechanism underlying GI tract defects in VPA animal model as well as the association between abnormal GI structure and function with ASD is yet to be clearly understood. Nevertheless, the results from the present study suggest that this VPA ASD model undergoes abnormal changes in the GI structure and function, which in turn could provide beneficial clues pertaining to the pathophysiological relevance of GI complications and ASD phenotypes.

• The Journal of Korean Academy of Sensory Integration
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• v.7 no.2
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• pp.77-90
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• 2009

Objective : The purpose of this study was to provide evidence for the effectiveness of Sensory Integrative Intervention (SII) through a systematic review. Method : The systematic review was executed using MEDLINE/PubMed, PsycINFO, CINAHL, Cochrane Library, OTSeeker. The key words for search was "effects of sensory integration", "sensory integration therapy", and "sensory integration intervention". 11 studies were used for data analysis, and the level of evidence were level I, leve lII and level IV. The substances of review were subject (population), method (intervention type), effect of the intervention, outcome parameter, and outcome measurement. Results : 1. The subjects of SII were autism spectrum disorders (30.7%), pervasive developmental disorder (15.4%) and preterm infants (15.4%). 2. Most frequently used method was the traditional intervention of J. Ayres (36.5%). The outcome parameters of SII were behavioral outcome (40.63%), motor performance outcome (28.13%), sensory-based outcome (25.0%), and academic outcome (6.35%). 3. The effects of SII were improvement of motor performance (66.7%), sensory-based (62.5%), and behavior problems (61.5%). In most studies, however, academic skill such as writing skill was not a positive outcome parameter in terms of effectiveness of SII. Conclusions : The results implied that the sensory integrative intervention is effective on motor performance, sensory-based and behavioral change, but not on the academic skill. It is suggested that the future research need to be done to examine whether and how the effect of sensory integration intervention can be long-lasting and contribute any academic skill and activities of daily living performance.

• The Journal of Korean Academy of Sensory Integration
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• v.11 no.2
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• pp.27-40
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• 2013

Objective : The aim of this study was to investigate how many studies for sensory integration intervention in Korea reflect the principle of Ayers' sensory integration through a systemic review. Methods : The systemic review was executes using RISS, NDSL, KISS, DBpia. The key words for search were 'sensory integration therapy', 'sensory integration intervention', 'sensory integration program', 'sensory integration training' to search the articles, published in 2000-2012. To analyze ASI fidelity of 49 studies included in the present study, the numbers of items were calculated if the study describe the ASI principle. Results : The IV was the most levels of evidence, and the subjects for the studies were mental intellectual disability (15), developmental disability (14) and autism spectrum disorders (13) etc. It was described the most that presenting sensory opportunities (43), challenging postural, ocular, oral and/or bilateral motor control (37) of ASI fidelity. The studies using more than 4 ASI principle were 26.5%(13), and 7 studies using 8 or more than 8 were studied in OT. Conclusion : In OT, 34 of 49 studies performed, and they used several principles of ASI. To have unity for sensory integration principle and to improve therapy professionalism the study using various data and systematic review study will be needed in the future.

• Journal of Digital Convergence
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• v.19 no.2
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• pp.447-456
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• 2021

This study analyzed 28 domestic and foreign studies related Prompts for Restructuring Oral Muscular Phonetic Targets treatment techniques from 1984 to 2020 to prepare basic data for the development of PROMPT intervention programs and examination tools. According to the analysis, continuous research has been conducted since 1984 when the prompt study was first started, and the method of research was 16 intervention studies, with the highest number of speech disorders, and the target age being 3 to 5 years old, the most frequently conducted for infancy. The treatment was the most frequent in the 16th sessions, and the activities were based on the Motor Speech Hierarchy(MSH), except for the subjects of the non-verbal autism spectrum disorder. According to the analysis of the dependent variables, 'speech production' was the most common, followed by 'speech motor control', 'articulation', and 'speech intelligibility' were highest. Combined with all these studies, it suggests that PROMPT, which are directly useful for exercise spoken word production, are effectively being used outside the country and that it is necessary to develop a PROMPT program that can be applied domestically, in Korea.

• The Journal of Korean Academy of Sensory Integration
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• v.20 no.1
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• pp.55-72
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• 2022

Objective : The purpose of this study was to identify the status and trends of Korean child occupational therapy intervention studies according to the International Classification of Functioning, Disability, and Health, Children and Youth Version (ICF-CY). Methods : In this research, 47 studies on occupational therapy interventions for children that were published between January 2017 and December 2021 in the Journal of Occupational Therapy, registered in the Korea Citation Index, and analyzed the classification of the study type and evidence level to understand the trends. Moreover, intervention objectives and approaches were analyzed on the basis of the ICF-CY. Results : The outcomes of the analysis of the articles published in the Journal of Occupational Therapy were as follows: (1) Level IV was the highest evidence level (53.19%). (2) Among the studies, most (53.7%) included school-age children as subjects. Autism spectrum disorders and developmental delays were the most common diagnoses (14.8%). (3) As for the purpose of intervention according to ICF-CY, activity and participation factors were the most common (48.94%), and a sensory approach was frequently used. Conclusion : This study reviewed articles on occupational therapies for children that were published in the Journal of Occupational Therapy to understand the trends in occupational therapy interventions for children in South Korea. For the development of occupational therapies for children in the future, more qualitative research types and studies on various intervention approaches are needed.

• Journal of Life Science
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• v.33 no.6
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• pp.455-462
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• 2023

During pregnancy, maternal immune activation (MIA) from infection increases the risk of neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. MIA induced by polyinosinic-polycytidylic acid (poly (I:C)) and lipopolysaccharide (LPS) in animal experiments has led to offspring with abnormal behaviors and brain development. In addition, it has recently been reported that microglia, which reside in the brain and function as immune cells, play an important role in behavioral abnormalities and brain development in MIA-induced offspring. However, the underlying mechanism remains unclear. In this study, we investigated whether microglia-specific inhibition of GPR56, a member of the G protein-coupled receptor (GPCR) family, causes behavioral abnormalities in brain development. First, MIA induction did not affect the microglia population, but when examining the expression of microglial GRP56 in MIA-induced fetuses, GPR56 expression was inhibited between embryonic days 14.5 (E14.5) and E18.5 regardless of sex. Furthermore, microglial GPR56-suppressed mice showed abnormal behaviors in the MIA-induced offspring, including sociability deficits, repetitive behavioral patterns, and increased anxiety levels. Although abnormal cortical development such as that in the MIA-induced offspring were not observed in the microglial GPR56-suppressed mice, their brain activity was observed through c-fos staining. These results suggest that microglia-specific GPR56 deficiency may cause abnormal behaviors and could be used as a biomarker for the diagnosis and/or as a therapeutic target of behavioral deficits in MIA offspring.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.239-250
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• 2005

Objective : The purpose of this study was obtaining data on the efficacy and safety of risperidone in child and adolescent psychiatric patients. Method : Thirty one children and adolescents (males n=18, females n=13, age ranged from 5.4 to 17.3 years) treated with risperidone were selected among child and adolescent psychiatric inpatients of Seoul National University Hospital from January, 2001 to June, 2002, and charts for them were reviewed retrospectively. Results : The primary psychiatric disorders treated with risperidone were schizophrenia and other psychosis, bipolar I disorder with psychotic features, Tourette's disorder, autism spectrum disorders, mixed receptive and expressive language disorder, attention deficit-hyperactivity disorder, conduct disorder and obsessive-compulsive disorder. twelve of these had comorbid mental retardation. Primary target symptoms of risperidone were psychotic symptoms (n=13 or $41.9\%$), behavioral symptoms (n=10 or $32.3\%$) including aggression, impulsivity, hyperactivity, stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics (n=8, $25.8\%$). The efficacy of risperidone was measured by clinical global improvement (CGI) for target symptoms, $67.7\%$ of subjects showed moderate or marked improvements and its therapeutic effect appeared to be maintained during at least 7.5 months. Mean daily dosage of risperidone was $0.05{\pm}0.01mg/kg$, the group with psychotic symptoms had significantly higher mean daily dosage (0.07mg/kg) compared with other two groups (0.04mg/kg) with behavioral symptoms or tics. A variety of adverse events were reported in this study : weight gain (n=23) most commonly reported, extrapyramidal symptoms (n=15), autonomic symptoms (n=6), sedation (n=5) and symptoms related to hyperprolactinemia (n=2) etc. Although there was no drug change related to the adverse events of risperidone, and $90\%$ of subjects at their last visits were maintained on it, thus its tolerability appeared good. Conclusions Results suggest that risperidone may be relatively safe and effective drug in managing a wide variety of child and adolescent psychopathologies such as psychotic symptoms, behavioral symptoms including aggression, impulsivity, hyperactivity and stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics. Controlled and long-term studies of efficacy and safety of risperidone treatment for children and adolescents are recommended in the future.

• Clinical and Experimental Pediatrics
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• v.52 no.3
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• pp.289-294
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• 2009

Purpose : To assess the usefulness of magnetic resonance imaging (MRI), karyotyping, brainstem auditory evoked potential (BAEP), electroencephalogram (EEG), tandem mass screening test, and newborn metabolic screening test in children with language delay for diagnosing underlying diseases. Methods : From January 2000 to June 2007, a retrospective chart review was performed for 122 children with language delay who visited the Child Neurology Clinic at Yeungnam University Hospital and who underwent neuropsychologic tests and other diagnostic evaluations for underlying diseases. They were grouped into phenomenological diagnostic categories, and test results were analyzed according to the underlying diseases. Results : Of 122 patients, 47 (38.5%) had mental retardation, 40 (32.8%) had developmental language disorders, 23 (18.9 %) had borderline IQ, and 12 (9.8%) had autism spectrum disorder. In 26 (21.3%) cases, the causes or relevant clinical findings to explain language delay were found. Eight (10.4%) of 77 MRIs, 6 (8.0%) of 75 EEGs, and 4 (5%) of 80 BAEPs showed abnormal results. Results directly attributed to diagnosing underlying diseases were 2 hearing defects in BAEPs and 1 bilateral perisylvian cortical dysplasia in MRIs. No abnormal results were found in karyotyping, tandem mass screening tests, and new-born screening tests. Conclusion : Commonly used tests to diagnose the cause of language delay are not very effective and should only be used selectively, according to patient characteristics. However, despite the low diagnostic yields from these tests, because many patients show abnormal results, these tests are useful when conducted in complete evaluation.