Jin Soo Moon

Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation.

Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1-676 pg/ml vs. median 3.2 pg/ml, range 0.1-408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4-676 pg/ml vs. median 11.7 pg/ml, range 1.3-82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4-676 pg/ml vs. median 8.0, range 0.1-656 pg/ml; p < 0.05 and term: median 11.7, range 1.3-82 pg/ml vs. median 3.1, range 0.1-408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.

Epstein-Barr Virus Infection with Acute Acalculous Cholecystitis

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature.

Impedance-pH monitoring and conventional pH monitoring are complementary methods to detect association between gastroesophageal reflux and apnea-related symptoms in preterm infants and neonates

Objective: To investigate the usefulness of Multichannel intraluminal impedance-pH (MII-pH) monitoring as compared with conventional pH monitoring for detecting Gastroesophageal reflux (GER) episodes and apnea-related symptom association in preterm infants and neonates. Methods: Twenty-three infants (16 preterm and 7 term infants) in hospital, who underwent 24-h MII-pH monitoring, were studied retrospectively. GER indices and apnea-related symptom association were measured by both MII-pH and conventional pH based analysis. Results: Of the total 998 GER episodes assessed by MII-pH monitoring, 407 (40.8%) were acidic and 590 (59.1%) were weakly acidic. A total of 1689 GER episodes were detected by conventional pH based analysis and 270 (16%) were related to retrograde bolus movement. A total of 313 apnea-related symptoms were reported. Five patients had a positive symptom association: 3 by MII-pH, 1 by both MII-pH and conventional pH, 1 only by conventional pH. Conclusions: Addition of MII-pH monitoring to conventional pH monitoring improves the diagnostic yield of symptom association analysis in preterm infants and neonates with apnea-related symptoms. Conventional pH monitoring is still important in the era of impedance measurement.

Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination

We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (P < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (P < 0.001) and modified Vesikari score (P = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (P = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (P < 0.001). Viral co-infection and toxigenic C. difficile co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.

Epidemiology of Biliary Atresia in Korea

Biliary atresia (BA) is the major cause of cholestasis and the leading indication for liver transplantation (LT). However, the incidence of BA in Korea has not been reported. The aim of this study was to investigate the incidence and clinical outcomes of BA in Korea. We used the Korean universal health insurance database and extracted data regarding BA patients younger than 18 years of age admitted between 2011 and 2015. The incidence of BA was calculated by dividing the number of BA patients by the number of live births. Two hundred forty infants were newly diagnosed with BA. A total of 963 BA patients younger than 18 years of age were followed up for 5 years. The overall incidence of BA was 1.06 cases per 10,000 live births. The incidence of BA was 1.4 times higher for female patients than for male patients. Additionally, significant seasonal variation was observed; in particular, the incidence of BA was 2 times higher from June through August than from December through February. Congenital anomalies were found in 38 of 240 patients (15.8%). Congenital heart diseases were major associated congenital anomalies (6.3%). Several complications developed during the study period, including cholangitis (24.0%), varix (6.2%), and gastrointestinal bleeding (4.4%). Three hundred and one of the 963 BA patients under 18 years of age (31.3%) received LT for BA. The incidence of BA is higher in Korea than that in Western countries. We also report significant gender-associated differences and seasonal variation with respect to the incidence of BA.

A mutation analysis of the AGL gene in Korean patients with glycogen storage disease type III

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder that is characterized by the excessive accumulation of abnormal glycogen in the liver and muscles and is caused by a deficiency in glycogen debranching enzyme (amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL)) activity. To investigate the molecular characteristics of GSD III patients in Korea, we have sequenced the AGL gene in eight children with GSD III. All patients were compound heterozygotes. We identified 10 different mutations (five novel and five previously reported). The novel mutations include one nonsense (c.1461G>A, p.W487X), three splicing (c.293+4_293+6delAGT in IVS4, c.460+1G>T in IVS5, c.2682-8A>G in IVS21) and one missense mutation (c.2591G>C, p.R864P). Together, p.R285X, c.1735+1G>T and p.L1139P accounted for 56% of all alleles, while the remaining mutations are heterogeneous. These three mutations can be common in Korea, and further larger studies are needed to confirm our findings.

Stepwise Endoscopy Based on Sigmoidoscopy in Evaluating Pediatric Graft-versus-Host Disease

Purpose The aim of our study was to establish a safe and convenient diagnostic method for acute gastrointestinal (GI) graft-versus-host disease (GVHD) in children by determining the sensitivity and negative predictive values of upper and lower endoscopic biopsies for children suspected of GI GVHD. Methods Patients suspected of GI GVHD who received endoscopic evaluation within 100 days after stem cell transplantation and endoscopies between January 2012 and March 2014 in Seoul National University Childrens Hospital were included in our study. Results Fifteen patients with a total of 20 endoscopic procedures were included in our study. Sensitivity at the esophagus, stomach, and duodenum were 22.2%, 30.0%, and 80.0%, respectively. Negative predictive values at the esophagus, stomach, and duodenum were 22.2%, 30.0%, and 60.0%, respectively. Overall sensitivity and negative predictive values of upper endoscopic biopsy for GVHD were 77.8% and 50.0%, respectively. Overall sensitivity and negative predictive values of lower endoscopic biopsy for GVHD were 88.9% and 66.7%, respectively. Conclusion We recommend flexible sigmoidoscopy as a safe and accurate diagnostic tool for GVHD, similar to other studies reported previously. However, if there is no evidence of GVHD on sigmoidoscopy with high index of suspicion of GI bleeding, full colonoscopy and upper endoscopy should be considered.

Diencephalic syndrome: a frequently neglected cause of failure to thrive in infants.

Purpose Diencephalic syndrome is an uncommon cause of failure to thrive in early childhood that is associated with central nervous system neoplasms in the hypothalamic-optic chiasmatic region. It is characterized by complex signs and symptoms related to hypothalamic dysfunction; such nonspecific clinical features may delay diagnosis of the brain tumor. In this study, we analyzed a series of cases in order to define characteristic features of diencephalic syndrome. Methods We performed a retrospective study of 8 patients with diencephalic syndrome (age, 5-38 months). All cases had presented to Seoul National University Childrens Hospital between 1995 and 2013, with the chief complaint of poor weight gain. Results Diencephalic syndrome with central nervous system (CNS) neoplasm was identified in 8 patients. The mean age at which symptoms were noted was 18±10.5 months, and diagnosis after symptom onset was made at the mean age of 11±9.7 months. The mean z score was -3.15±1.14 for weight, -0.12±1.05 for height, 1.01±1.58 for head circumference, and -1.76±1.97 for weight-for-height. Clinical features included failure to thrive (n=8), hydrocephalus (n=5), recurrent vomiting (n=5), strabismus (n=2), developmental delay (n=2), hyperactivity (n=1), nystagmus (n=1), and diarrhea (n=1). On follow-up evaluation, 3 patients showed improvement and remained in stable remission, 2 patients were still receiving chemotherapy, and 3 patients were discharged for palliative care. Conclusion Diencephalic syndrome is a rare cause of failure to thrive, and diagnosis is frequently delayed. Thus, it is important to consider the possibility of a CNS neoplasm as a cause of failure to thrive and to ensure early diagnosis.

Reappraisal of Regional Growth Charts in the Era of WHO Growth Standards

After the WHO Growth Standards (WHOGS) was published in 2006, many countries in the world endorsed and adopted the new growth references as a standard measure for the growth of infants and young children. Certainly, the WHOGS has an impact on the global policy about obesity and underweight in children. Such WHOGS innovation has influenced many regional health authorities and academies, which have managed their own growth charts for a long time, in changing their strategies to develop and use regional growth charts. In Korea, along with the tradition to create a national growth chart every decade, we now face a new era of advancing with the WHOGS.

Molecular Analysis of the UGT1A1 Gene in Korean Patients with Crigler-Najjar Syndrome Type II

Purpose Crigler-Najjar syndrome type II (CN-2) is characterized by moderate non-hemolytic unconjugated hyperbilirubinemia as a result of severe deficiency of bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The study investigated the mutation spectrum of UGT1A1 gene in Korean children with CN-2. Methods Five Korean CN-2 patients from five unrelated families and 50 healthy controls were enrolled. All five exons and flanking introns of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced. Results All children initially presented with neonatal jaundice and had persistent indirect hyperbilirubinemia. Homozygous p.Y486D was identified in all five patients. Three patients had an associated homozygous p.G71R and two a heterozygous p.G71R. The allele frequency of p.Y486D and p.G71R in healthy controls was 0 and 0.16, respectively. No significant difference in mean serum bilirubin levels was found between homozygous carriers of p.G71R and heterozygous carriers. Conclusion The combination of homozygous p.Y486D and homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be screened for the mutation analysis of UGT1A1 in Korean CN-2 patients.