Prepregnancy body mass index and glycated albumin in the third trimester may predict infant complications in gestational diabetes mellitus: a retrospective cohort study.

Background: Maternal hyperglycemia, obesity, and hypertension with gestational diabetes mellitus (GDM) are risk factors for infant complications. This study aimed to investigate maternal factors and glycemic control indicators that affect infant complications in GDM. Methods: We conducted a retrospective cohort study including 112 mothers with GDM and their infants. Multivariate logistic regression analysis was used to investigate the variables associated with good and adverse infant outcomes. We determined the cutoff values of variables that showed a significant difference in the multivariate logistic regression analysis for predicting infant complications by performing receiver operating characteristic curve analysis. Results: In the multivariate logistic regression analysis, prepregnancy BMI and GA in the third trimester were significantly related to good and adverse infant outcomes (adjusted odds ratios [aORs], 1.62; 95% CIs 1.17-2.25, p = 0.003 and aORs, 2.77; 95% CIs 1.15-6.64, p = 0.022, respectively). The cutoff values for prepregnancy BMI and GA in the third trimester were 25.3 kg/m2 and 13.5%, respectively. Conclusions: The importance of weight control before pregnancy and the usefulness of GA in the third trimester to predict infant complications were suggested in this study.

An atypical surge in RSV infections among children in Saitama, Japan in 2021.

Background: In 2021, atypical seasonal respiratory syncytial virus (RSV) outbreaks were observed in several countries. However, the peak, duration, and severity of these outbreaks have not been assessed. Methods: Data were collected from almost all facilities with pediatric wards in Saitama Prefecture, Japan. Variables included the weekly number of patients admitted with RSV infection, their age, and the number of patients who required intubation. The average weekly admission rates (number of patients admitted divided by the number of hospitals) were compared by pre-pandemic year (2018 and 2019) and 2021, using analysis of variance. Results: In 2021, 1354 patients were admitted with RSV infection. The median age of the patients was < 12 months. The admission rate peaked around week 30. The slope of the peak in 2021 was markedly steeper than in the previous years. The mean weekly admission rate did not differ significantly between 2018, 2019, and 2021 (p = 0.77). The proportions of intubated patients did not differ significantly over the 4 years (2018-2021, p = 0.68). Conclusion: The overall number of RSV admissions and intubation rate in 2021 were similar to those in pre-pandemic years.

Comparison of Acute Phase Thymus and Activation-Regulated Chemokine (TARC) Levels in Food Protein-Induced Enterocolitis Syndrome and IgE-Dependent Food Allergy.

Introduction: Patients with food protein-induced enterocolitis syndrome (FPIES) have elevated thymus and activation-regulated chemokine (TARC) levels in the acute phase. However, to the best of our knowledge, no study has evaluated TARC levels in the acute phase of immunoglobulin E-dependent food allergy (IgE-FA). If TARC elevation is a specific response to FPIES among FAs, TARC measurement may help distinguish between FPIES and IgE-FA. Thus, we investigated acute phase TARC levels in patients with FPIES and IgE-FA. Methods: Thirty-one episodes in 16 patients with FPIES and 20 episodes (13 were anaphylaxis) in 20 patients with IgE-FA were included. Patients with eczema were excluded. Serum TARC levels within 6 h of allergic reaction onset and age-adjusted TARC ratios (TARC levels divided by age-specific normal TARC values) were compared between the groups. Results: The median age was 1.1 and 3.6 years in the FPIES and IgE-FA groups, respectively (P < 0.001). The median (range) serum TARC (pg/mL) levels were significantly higher in the FPIES group than in the IgE-FA group [1,283 (410-3,821) versus 377 (109-1,539); P < 0.001]. The median (range) age-adjusted TARC ratios were also significantly higher in the FPIES group [2.56 (0.57-7.86) versus 1.08 (0.15-2.17); P < 0.001]. The area under the curve (AUC) for TARC to distinguish FPIES from IgE-FA was 0.926, and the AUC for the age-adjusted TARC ratio was 0.850. The odds ratio for FPIES diagnosis per 1,000 pg/mL increase in TARC was 31.6 (P = 0.002), and the odds ratio adjusted by age was 17.1 (P = 0.016). Conclusion: Acute phase TARC levels were higher in patients with FPIES than in patients with IgE-FA. The increase in acute phase TARC levels was considered to be a specific response to FPIES among FAs. Measurement of TARC levels in the acute phase may help differentiate FPIES from IgE-FA.

The Association Between Serum Zinc Levels and Anthropometric Measurements and Nutritional Indicators in Children With Idiopathic Short Stature.

Background Zinc (Zn) is an essential trace element, and its deficiency causes various symptoms, such as anemia, short stature, and poor weight gain, in children. Several studies have reported an association between Zn deficiency and short stature in children. However, few studies have reported on the relationship between serum Zn levels, body mass index (BMI), and nutritional indicators such as albumin, amino acids, and vitamin D. Methods We retrospectively analyzed the data of 56 children with idiopathic short stature. We investigated the mean serum Zn levels and the relationships among serum Zn levels and height standard deviation score (SDS), bodyweight SDS, BMI SDS, hemoglobin (Hb), albumin, alkaline phosphatase (ALP), insulin-like growth factor-1 (IGF-1), 25-hydroxyvitamin D (25(OH)D), and amino acid levels. Results The mean serum Zn levels of the study participants were 70.3±10 µg/dL. Serum Zn levels correlated significantly with weight SDS (r=0.472, p<0.001) and BMI SDS (r=0.416, p<0.001). In contrast, no significant association was found between serum Zn levels and height SDS (r=0.217, p=0.078). We found significant positive correlations between serum Zn levels and Hb and IGF-1 SDS (Hb: r=0.333, p=0.012; IGF-1 SDS: r=0.372, p=0.00478). Serum Zn levels were not correlated with albumin, ALP, 25(OH)D, and amino acid levels. Conclusions Serum Zn levels are associated with anthropometric measurements, especially body weight and BMI. It is important to evaluate Zn levels in children who fail to thrive, even in developed countries.

Differences in Thymus and Activation-Regulated Chemokine and Squamous Cell Carcinoma Antigen 2 Levels in Food Protein-Induced Enterocolitis Syndrome and Atopic Dermatitis.

INTRODUCTION: We previously reported that thymus and activation-regulated chemokine (TARC) levels measured after vomiting are useful predictors of a food protein-induced enterocolitis syndrome (FPIES) diagnosis. However, interpreting TARC levels in patients with eczema is difficult, as the levels are similarly elevated in patients with eczema caused by atopic dermatitis (AD). Therefore, we aimed to investigate whether it is possible to predict whether FPIES or AD is responsible for elevated TARC levels by simultaneously measuring TARC and squamous cell carcinoma antigen 2 (SCCA2), another T-helper type 2 biomarker. METHODS: Twenty-one episodes in 11 patients with FPIES (FPIES group) and 42 age-matched patients with AD (AD group) were included in this study. Serum TARC and SCCA2 levels were measured, and those values and relative ratios were compared between groups. RESULTS: The median age was 1.1 years in the FPIES group and 1.6 years in the AD group (p = 0.492). The median (interquartile range [IQR]) serum TARC concentration was significantly higher in the FPIES group than in the AD group (2,486 [1,815-4,097] pg/mL and 1,451 [1,201-1,751] pg/mL, respectively; p = 0.002). The median (IQR) SCCA2 concentration was significantly higher in the AD group than in the FPIES group (1.9 [1.3-2.9] pg/mL and 0.8 [0.6-1.5] pg/mL, respectively; p < 0.001). After matching, the analysis using stratified TARC values revealed no significant difference in TARC values between the FPIES and AD groups; however, the TARC/SCCA2 ratio was significantly higher in the FPIES group. CONCLUSION: Assessing the relative TARC/SCCA2 ratio may help predict whether elevated TARC levels measured after vomiting are caused by FPIES or AD.

A Pediatric Case of Ketosis-Prone Type 2 Diabetes Requiring Insulin Therapy.

In recent years, cases of diabetic ketoacidosis (DKA) or ketosis as the initial manifestation of diabetes with a similar clinical course to that of type 2 diabetes have been reported. This phenotype has been recognized as ketosis-prone type 2 diabetes (KPD). Most cases of KPD occur in adults, and the typical clinical course is that patients are often able to wean off insulin therapy after initial treatment. We report a pediatric case of ketosis-prone type 2 diabetes requiring insulin therapy with four years of follow-up. Our case suggests that patients with KPD may require strict management, including weight control, compared with patients with typical type 2 diabetes.

Potential of Thymus and Activation-Regulated Chemokine (TARC) as a Prognostic Biomarker of Food Protein-Induced Enterocolitis Syndrome (FPIES) Caused by Egg Yolk.

BACKGROUND: Several recent studies have reported egg yolk-associated food protein-induced enterocolitis syndrome (FPIES) in Japan. We previously reported the usefulness of post-emetic thymus and activation-regulated chemokine (TARC) levels for the diagnosis and evaluation of symptom severity in FPIES caused by solid foods including egg yolk. However, there are no studies on the usefulness of TARC as a prognostic biomarker. OBJECTIVE: The aim of the study was to evaluate the post-emetic TARC levels, clinical symptoms, and post-index event results of the egg yolk oral food challenge test (OFC), and retrospectively investigate predictive factors of the subsequent OFC result. METHOD: This retrospective study included 12 patients with egg yolk FPIES. The following long-term management protocol for egg yolk FPIES was mandatory for study inclusion: Patients visited the emergency department, met the diagnostic criteria of FPIES, and underwent an egg yolk OFC 6-12 months after complete elimination of egg yolk. If the result of the OFC was positive, the patient underwent the OFC every year until it was negative. We analyzed a total of 20 episodes (12 department visits and eight positive OFCs). The blood test data, including post-emetic TARC level and symptom severity, were compared between the next-OFC-positive group and the next-OFC-negative group. In addition, tolerance development over follow-up was analyzed. RESULTS: The median (range) ages of the next-OFC-positive and negative groups were 11 (6-33) and 10 (7-21) months, respectively. The median (range) serum TARC (pg/mL) level was 5,208 (2,009-8,147) in the next-OFC-positive group, which was significantly higher (p = 0.004) than that in the next-OFC-negative group, which was 1,803 (905-3,754). There were no significant differences in other hematological results. The next-OFC-positive group had greater severity compared to the next-OFC-negative group (p = 0.026). The remission rate was approximately 30% at 24 months and 80% at 36 months. CONCLUSION: Post-emetic TARC levels may predict the short-term prognosis of egg yolk FPIES after approximately 1 year and could be useful for the management of egg yolk FPIES.

Clinical usefulness of glycated albumin and glycated albumin-to-glycated hemoglobin ratio of gestational diabetes mellitus in late pregnancy for predicting infant complications.

BACKGROUND: Gestational diabetes mellitus (GDM) with poorly controlled glycemia is associated with poor pregnancy outcomes. However, adequate markers for glycemic control in GDM have not been fully evaluated. METHODS: We retrospectively studied 77 patients with GDM and their infants. Mean glycated albumin (GA), glycated hemoglobin (HbA1c), and GA/HbA1c in GDM were compared between two groups stratified by the presence or absence of infant complications (complications or non-complications). We assessed the predictability of infant complications in GA, HbA1c, and GA/HbA1c of women with GDM by receiver operating characteristic analysis (ROC). RESULTS: In complications and non-complications, GA and GA/HbA1c were significantly associated with neonatal hypoglycemia (13.9% vs. 13.0%, p < 0.001 and 2.49 vs. 2.33, p < 0.001, respectively), respiratory disorders (13.7% vs. 13.2%, p = 0.013 and 2.48 vs. 2.34, p < 0.001, respectively), myocardial hypertrophy (14.5% vs. 13.0%, p < 0.001 and 2.59 vs. 2.33, p < 0.001, respectively), and large for gestational age (14.5% vs. 13.1%, p < 0.001 and 2.58 vs. 2.34, p < 0.001, respectively). Compared with each infant complication in ROC, GA and GA/HbA1c had higher area under the curve than HbA1c. Especially, GA and GA/HbA1c had highest AUC in predicting myocardial hypertrophy and large for gestational age (GA; 0.92 and 0.92, GA/HbA1c; 0.91 and 0.86, respectively). Although statistically significant positive correlations were found between GA and GA/HbA1c and the number of infant complications (GA: r = 0.417, p < 0.001; GA/HbA1c: r = 0.408, p < 0.001), their correlations were weak. CONCLUSION: Compared with HbA1c, GA and GA/HbA1c of GDM in late pregnancy might be useful for predicting infant complications arising from GDM.

Point-of-care ultrasound for children.

Most diseases in children are acute, and ultrasonography should be performed in emergency cases rather than X-ray or computed tomography (CT) as children are more sensitive to radiation than adults. Therefore, point-of-care ultrasound (POCUS) is especially useful in children. The target organs of pediatric ultrasound are the same as in adults, and the infant brain can also be observed with ultrasound because the fontanel magna is still open. However, there are a number of points that physicians should be aware of regarding pediatric POCUS. There are some diseases specific to children, which are not found in adults. A higher frequency probe and higher frame rate are needed for children than for adults because of their small body size and rapid heart rate. Infants are not compliant, which necessitates the use of various measures to ensure that they remain still during the imaging examination. Pediatric POCUS is useful not only for diagnosis but also to ensure the safety of medical procedures, which is usually more difficult in children than in adults. POCUS has become a powerful tool for improving the success of such procedures and patient safety. The usefulness of POCUS is clearly evident, and it is being widely adopted across all disciplines in clinical medicine. Nevertheless, adoption of pediatric POCUS has been limited, and therefore educational programs for pediatric POCUS are needed.

Implementation and assessment of a pediatric point-of-care ultrasound training course in Japan: a pilot study.

PURPOSE: The popularity of point-of-care ultrasound (POCUS) has led to the creation of educational guidelines for its use. In Japan, however, a comprehensive training course for POCUS use in pediatric emergency medicine has yet to be developed. The present study aimed to implement a pilot course for pediatric POCUS training in Japan and to compare participants' self-efficacy level before and after the course. METHODS: A half-day training course in pediatric POCUS was implemented at a meeting of the Japan Society of Point-of-Care Ultrasound. A standardized training course, including pre-learning materials, live lectures, and hands-on sessions, was developed based on the US consensus educational guidelines. Physicians interested in pediatric POCUS were recruited for participation and completed a self-evaluation survey before and after the course to access their background, self-efficacy in performing selected ultrasound procedures before and after the course, and their overall satisfaction with the course. RESULTS: In total, 31 physicians participated. Of these, 25 completed the survey. Ten participants were in post-graduate year (PGY) 1-2, 13 were in PGY 3-5, and eight were in PGY 6 or higher. The post-training self-efficacy score was significantly higher than the pre-course assessment score (86.0 [standard deviation (SD): 19.2] vs. 35.6 [SD 17.6], p = < 0.05, mean difference: 49.6 [95% confidence interval 39.6-61.2]). Furthermore, overall satisfaction with the course was high at 8.6 (SD 1.8). CONCLUSION: The present study implemented a pilot training course in pediatric POCUS and found the participants' self-efficacy level to be significantly higher after the course.

Stratified therapy for Kawasaki disease using a new scoring system to predict the response to a lower dose of intravenous immunoglobulin therapy.

BACKGROUND: Several studies have reported treatment options for patients with Kawasaki disease refractory to standard immunoglobulin therapy; however, no studies have reported low-dose immunoglobulin therapy for patients with a low risk of Kawasaki disease. METHODS: A total of 277 patients with Kawasaki disease were included in this study. We used Kobayashi score and our Less high-risk score to divide the patients into three groups. Patients in the high-risk group (Kobayashi score ≥ 5 points) received 2 g/kg intravenous immunoglobulin and prednisolone. Patients in the moderate-risk group (Kobayashi score < 5 points and Less high-risk score ≥ 2 points) received 2 g/kg intravenous immunoglobulin treatment. Patients in the low-risk group (Kobayashi score < 5 points and Less high-risk score < 2 points) received 1 g/kg intravenous immunoglobulin treatment. The response rate and the incidence of coronary artery lesions at 4 weeks after treatment were evaluated in each group. RESULTS: The treatment response rates in the high-risk (n = 110), moderate-risk (n = 80), and low-risk (n = 87) groups were 74.5, 72.5, and 77.0%, respectively. Coronary artery lesions occurred in 7.3, 3.8, and 2.3% of patients in the high-, moderate-, and low-risk groups, respectively. There were no significant differences between the groups regarding treatment response or coronary artery lesion rate. CONCLUSION: The therapeutic response rate and the therapeutic effect of low-dose intravenous immunoglobulin in the low-risk group identified with our new scoring were satisfactory. Stratified therapies for patients with Kawasaki disease based on the scoring system may be useful.

20p11.23-p11.21 deletion in a child with hyperinsulinemic hypoglycemia and GH deficiency: A case report.

Some neonatal hypoglycemias have genetic origins. For instance, mutation in forkhead box protein A2 (FOXA2), located on chromosome 20p11.21, has recently been reported to cause hyperinsulinemic hypoglycemia and hypopituitarism. Here, we report a case of hyperinsulinemic hypoglycemia and GH deficiency (GHD) with 20p11.23-p11.21 deletion, which included FOXA2. The boy was diagnosed with hyperinsulinemic hypoglycemia during the neonatal period and subsequently administered diazoxide for treatment. His blood glucose levels gradually stabilized, and the diazoxide dosage was slowly reduced and ultimately fully weaned. The patient was discharged at the age of 29 d. Unfortunately, the patient experienced recurrent hypoglycemia at 3 mo, and diazoxide administration was re-initiated. Further examination, including chromosomal microarray analysis, revealed a 2.48-Mb 20p11.23-p11.21 deletion that encompassed FOXA2. In addition, severe GHD was detected, and magnetic resonance imaging of the brain revealed pituitary stalk interruption. Accordingly, GH replacement therapy was started at 0.175 mg/kg/wk, and blood glucose levels were stabilized. Our report suggests that there are pathological conditions that can cause both hyperinsulinemic hypoglycemia and hypopituitarism and reaffirms the importance of evaluating not only insulin and congenital metabolic disorders but also pituitary function in patients with hypoglycemia.

[EVALUATION OF THE RELATIONSHIP BETWEEN THE SEVERITY OF SOLID FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME AND POST-EMETIC SERUM THYMUS AND ACTIVATION-REGULATED CHEMOKINE LEVELS].

BACKGROUND: We reported that post-emetic serum thymus and activation-regulated chemokine (TARC) levels may be a potential biomarker to diagnose solid food protein-induced enterocolitis syndrome (FPIES). However, there are no reports on the relationship between FPIES severity and serum TARC levels. METHODS: The subjects were 13 cases of FPIES (hen's egg=10, Wheat=1, rice=1, short-neck clam=1) for a total of 22 events (7 emergency outpatient visits, 9 positive and 6 negative results of oral food challenge test). Serum TARC levels at 6 and 24 h after antigen ingestion were compared between the symptomatic and asymptomatic events and the mild-moderate and severe events. We also evaluated the correlation between vomiting duration and serum TARC levels. RESULTS: The median serum TARC (pg/ml) in the asymptomatic, mild-moderate, and severe events were 546, 1093, and 3127 at 6 h after ingestion, and 910, 2053, and 6496 at 24 h after ingestion, respectively. The serum TARC level was significantly higher in the symptomatic events than the asymptomatic events, and it was significantly higher in the severe events than the mild-moderate events (p < 0.01). There was a moderate correlation between serum TARC levels and vomiting duration. CONCLUSION: Post-emetic serum TARC correlates with the severity of FPIES. It is expected that this information will lead to an objective evaluation of the severity of FPIES.

Evaluation of the Diagnostic Accuracy of Thymus and Activation-Regulated Chemokine to Discriminate Food Protein-Induced Enterocolitis Syndrome from Infectious Gastroenteritis.

BACKGROUND: Post-emetic elevation in thymus and activation-regulated chemokine (TARC) levels has been reported in patients with food protein-induced enterocolitis syndrome (FPIES); however, no studies have investigated differences in TARC levels between FPIES and other diseases. OBJECTIVES: We evaluated the clinical usefulness of TARC measurement in differentiating between FPIES and infectious gastroenteritis. METHODS: This study included 8 patients with solid-food FPIES (FPIES group; hen's egg [n = 6], rice [n = 1], and short-neck clam [n = 1]; a total of 11 episodes necessitating emergency department visit or positive result of oral food challenge test) and 17 patients with infectious gastroenteritis (control group), and all patients had no eczema. Post-emetic serum TARC levels and modified TARC levels (serum TARC value - normal mean for each age) were compared between the 2 groups. RESULTS: The median (range) ages for the FPIES and control groups were 0.7 (0.5-6.2) and 1.8 (0.1-4.4) years, respectively (p > 0.05). In the FPIES and control groups, median (range) TARC levels were 2,911 (1,062-7,816) and 600 (277-2,034) pg/mL, and median (range) modified TARC levels were 2,204 (355-7,109) and 129 (0-1,314), respectively. The TARC and modified TARC levels were significantly higher in the FPIES group than in the control group (p < 0.001 for both). CONCLUSION: In the absence of eczema, post-emetic serum TARC levels might be a potential diagnostic biomarker for distinguishing FPIES from infectious gastroenteritis.

A new index of ultrasonography for estimating cerebral circulation in newborn infants.

PURPOSE: To quantitatively estimate the influence of ductal shunt on cerebral blood flow and establish a new index of ultrasonography for estimating cerebral circulation without the influence of ductal shunt in newborn infants. METHODS: We retrospectively examined the records of anterior cerebral artery (ACA) and left pulmonary artery (LPA) blood flow velocity curves recorded by pulsed Doppler ultrasonography within 6 h after birth in 123 newborn infants without asphyxia (normal group) and in 31 newborn infants with asphyxia (asphyxia group). RESULTS: In the normal group, the resistance index (RI) of the ACA showed a positive correlation with the ratio of LPA diastolic-to-systolic flow velocities (LPAD/LPAS) (P < 0.001, r = 0.58), and the estimated RI (eRI) of the ACA was calculated using the following formula: Y = 0.47X + 0.67 (Y estimated RI; X LPAD/LPAS). In the asphyxia group, the RI of the ACA showed a weak correlation to base excess (BE) (P < 0.05, r = 0.46). The eRI of the ACA was calculated by the LPAD/PLAS in the asphyxia group, and the difference between the RI and eRI showed a better correlation to BE than RI (P < 0.001, r = 0.64). CONCLUSION: We determined the relation between cerebral blood flow RI and ductal shunt, and (RI - eRI) may be a new useful ultrasonographic index indicating cerebral circulation without the influence of ductal shunt in newborn infants.

Comparison of methemoglobin levels in food protein-induced enterocolitis syndrome and other gastrointestinal diseases in neonates.

INTRODUCTION AND OBJECTIVES: Methemoglobinemia has been reported to be associated with severe food protein-induced enterocolitis syndrome (FPIES). However, no reports have evaluated methemoglobin (MHb) levels in FPIES without symptomatic methemoglobinemia or the usefulness of MHb measurement for the diagnostic prediction of FPIES. To evaluate the MHb levels of patients with neonatal-onset FPIES and determine whether MHb levels are higher in FPIES than in other gastrointestinal diseases. PATIENTS AND METHODS: Eleven neonates with severe acute FPIES (FPIES group) and 139 neonates with other gastrointestinal diseases (non-FPIES group) were included in this study. Patient characteristics, symptoms, and venous blood test values (MHb, pH, HCO3-, and C-reactive protein) were evaluated. RESULTS: The median age at onset was 16 days vs. 1 day; males comprised 64% vs. 46%, the median gestational age was 38 weeks vs. 38 weeks, the median birth weight was 2710g vs. 2880g, and the median hospitalization duration was 31 days vs. 6 days for the FPIES vs. non-FPIES groups, respectively. MHb (%) was higher in the FPIES group than in the non-FPIES group [median (range), 1.1 (0.6-10.9) and 0.6 (0.3-1.2), respectively, p<0.001]. There were no differences in terms of pH, HCO3-, and C-reactive protein (p>0.05). In the receiver operating characteristic analysis for FPIES diagnosis based on MHb (%), the area under the curve was 0.885, specificity was 97.1%, and sensitivity was 72.7% at a MHb cutoff of 1.0. CONCLUSION: High MHb levels may help diagnose severe acute FPIES in neonates, but careful evaluation is needed.