Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature.

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review.

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children.

Impacts of routine varicella vaccination program and COVID-19 pandemic on varicella and herpes zoster incidence and health resource use among children in Japan.

PURPOSE: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. RESULTS: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. CONCLUSIONS: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.

Evaluation of the association of birth order and group childcare attendance with Kawasaki disease using data from a nationwide longitudinal survey.

Background: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. Methods: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. Results: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. Conclusions: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

Decreased levels of histidine-rich glycoprotein and increased levels of high-mobility group box 1 are risk factors for refractory Kawasaki disease.

OBJECTIVES: Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD. METHODS: This study was prospectively performed. Patients were divided into two groups and analysed depending on whether KD symptoms improved by Day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards for assessing trends. RESULTS: In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment. CONCLUSIONS: HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.

Neonatal hemochromatosis with εγδß-thalassemia: a case report and analysis of serum iron regulators.

BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδß-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδß-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδß-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan.

BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma.

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Cyclosporine for the treatment of multisystem inflammatory syndrome in children with coronary artery aneurysms.

Multisystem inflammatory syndrome in children (MIS-C) is a newly described syndrome related to the COVID-19, resembling other known aetiologies, including Kawasaki disease. Cardiovascular involvement is common; left ventricle dysfunction and coronary artery aneurysm (CAA) are also observed. Many treatment guidelines recommend using intravenous immunoglobulin (IVIG) alone or with glucocorticoids as the first-line therapy. Biological agents, such as anakinra, are recommended for refractory cases, but the evidence is still accumulating. Moreover, the use of other treatment agents can be beneficial, especially when anakinra is unavailable. Here, we report the case of a 9-year-old girl who presented with MIS-C with CAAs. She received cyclosporine because two rounds of IVIG treatment were ineffective and the use of anakinra is not approved in Japan. Her cytokine profile showed that cyclosporine prevented exacerbation. The case highlights that cyclosporine therapy can be an option for the treatment of refractory MIS-C with CAA.

Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis.

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

Current Insights into Atopic March.

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease.

The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD.

Anaphylaxis after jellyfish ingestion with no history of stings: a pediatric case report.

BACKGROUND: Jellyfish stings are known to induce allergic skin reactions; however, case reports of anaphylaxis after jellyfish ingestion have been increasing, especially in Asian countries. Some cases of anaphylaxis after jellyfish ingestion have been reported in patients with a previous history of frequent jellyfish stings. Herein, we report a pediatric patient with anaphylaxis after jellyfish ingestion with no history of jellyfish stings. CASE PRESENTATION: A 14-year-old girl developed two episodes of anaphylaxis, and her diet diaries revealed that edible jellyfish was common to the meals in both the anaphylaxis events. A skin prick test using five types of edible jellyfish products revealed a positive reaction to some jellyfish, and anaphylaxis was observed after the ingestion of jellyfish in an oral food challenge test. She had no history of jellyfish stings or frequent swimming in the ocean. The basophil activation test showed positive results on stimulation with extracts from various types of edible jellyfish. We observed serum immunoglobulin E (IgE) reactivity to purified jellyfish collagen and jellyfish acid-soluble extracts. Moreover, immunoblotting analysis showed IgE reactivity to two bands at approximately 40 and 70 kDa using purified jellyfish collagen, which may be a causative antigen. CONCLUSIONS: Edible salted jellyfish can be one of the causative foods of anaphylaxis. Clinicians should be aware of the possibility of anaphylactic reactions due to jellyfish ingestion even without a history of jellyfish stings.

Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus.

OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

COVID-19 in Okayama Prefecture: Looking back and looking forward.

In Japan, clinical and experimental studies addressing COVID-19 have been increasing in number since early February 2020, with many case reports being published. Concurrently, many notifications and guidelines have been issued from the government and academic societies. Taking optimal measures at the prefectural level as well as the national level is necessary to prevent the spread of COVID-19. Surveying and analyzing details of the incidences of infected persons in each prefecture is extremely important. This report describes the epidemiological characteristics of COVID-19 observed in Okayama Prefecture, followed by discussion of the direction of public health actions to be taken in the future. We reiterate the crucial importance of reinforcing and maintaining current public health measures, including rapid and detailed compilation of information related to infected persons and their surroundings, appropriate blocking of viral transmission, and early containment of infected persons, to minimize the spread of infection especially during the overlapping epidemic period of influenza in Okayama Prefecture.

Paediatric case of group A streptococcal pharyngitis, arthritis and osteomyelitis associated with dental neglect.

Group A streptococcus (GAS) causes a wide variety of infections in the paediatric population, ranging from pharyngitis to rare but severe invasive diseases, such as bacterial arthritis and osteomyelitis. Dental neglect is a type of child neglect in which caregivers fail to provide adequate care and treatment for dental diseases. This results in poor oral hygiene and can lead to complications including sepsis. We report the case of a 4-year-old boy, suffering from child neglect, presenting with GAS pharyngitis and subsequent bacterial arthritis in the right ankle, osteomyelitis in the right talus and abscess in the right calcaneus. He was first treated with penicillin, which was changed to clindamycin because of a suspected drug-induced rash. He was discharged after 6 weeks of intravenous therapy when symptoms had resolved and inflammatory markers were within the normal range. The case highlights that dental neglect may present a risk for subsequent invasive infections.

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). CASE PRESENTATION: An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. CONCLUSIONS: It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

Prospective Cohort Study of Congenital Cytomegalovirus Infection during Pregnancy with Fetal Growth Restriction: Serologic Analysis and Placental Pathology.

OBJECTIVE: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR). STUDY DESIGN: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth. RESULTS: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine ß-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection. CONCLUSIONS: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection.