Intraoperative Transpyloric Tube Insertion for Congenital Diaphragmatic Hernia: Analysis of Japanese Study Group Data.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital disease. Some CDH infants suffer from gastro-esophageal reflux disease (GERD), even after surgical correction of gastric position. A transpyloric tube (TPT) is inserted into CDH patients under direct observation intraoperatively in some hospitals in Japan to establish early enteral feeding. This strategy avoids gastric expansion to maintain a better respiratory condition. However, it is unclear whether the strategy has a secure effect for patient prognosis. This study aimed to evaluate the effectiveness of intraoperative TPT insertion on enteral feeding and postoperative weight gain. METHODS: The Japanese CDH Study Group database was used to identify infants with CDH born between 2011 and 2016, who were then divided into two groups: the TPT group and gastric tube (GT) group. In the TPT group, infants underwent intraoperative TPT insertion; postoperative insertion/extraction of TPT was irrelevant to the analysis. Weight growth velocity (WGV) was calculated using the exponential model. Subgroup analysis was performed using Kitano's gastric position classification. RESULTS: We analyzed 204 infants, of which 99 and 105 were in the TPT and GT groups, respectively. Enteral nutrition (EN) in the TPT and GT groups was 52 ± 39 and 44 ± 41 kcal/kg/day (p = 0.17) at age 14 days (EN14), respectively, and 83 ± 40 and 78 ± 45 kcal/kg/day (p = 0.46) at age 21 days (EN21), respectively. WGV30 (WGV from day 0 to day 30) in the TPT and GT groups was 2.3 ± 3.0 and 2.8 ± 3.8 g/kg/day (p = 0.30), respectively, and WGV60 (WGV from day 0 to day 60) was 5.1 ± 2.3 and 6.0 ± 2.5 g/kg/day (p = 0.03), respectively. In infants with Kitano's Grade 2 + 3, EN14 in the TPT and GT groups was 38 ± 35 and 29 ± 35 kcal/kg/day (p = 0.24), respectively, EN21 was 73 ± 40 and 58 ± 45 kcal/kg/day (p = 0.13), respectively, WGV30 was 2.3 ± 3.2 and 2.0 ± 4.3 g/kg/day (p = 0.76), respectively, and WGV60 was 4.6 ± 2.3 and 5.2 ± 2.3 g/kg/day (p = 0.30), respectively. CONCLUSION: Intraoperative TPT insertion did not improve nutritional intake and WGV30. WGV60 in TPT was less than that in GT. In Grade 2 + 3 subgroup analysis, TPT also had no advantage. We could not recommend routine TPT insertion at surgery. LEVEL OF EVIDENCE: III.

Fluconazole Population Pharmacokinetics after Fosfluconazole Administration and Dosing Optimization in Extremely Low-Birth-Weight Infants.

A prospective single-center study was conducted to characterize the pharmacokinetics (PK) of fluconazole (FLCZ) in extremely low-birth-weight infants (ELBWIs) who received fosfluconazole (F-FLCZ). Intravenous F-FLCZ was administered at a dose of 3 mg/kg of body weight every 72 h during the first 2 weeks of life, every 48 h during the third and fourth weeks of life, and every 24 h after 5 weeks of life. Blood samples from ELBWIs treated with F-FLCZ were collected using scavenged samples. The concentration of FLCZ was determined using liquid chromatography-tandem mass spectrometry. The population pharmacokinetic model was established using Phenix NLME 8.2 software. In total, 18 ELBWIs were included in this analysis. Individual PK parameters were determined by a one-compartment analysis with first-order conversion. Postmenstrual age (PMA), serum creatinine (SCr), and alkaline phosphatase were considered covariates for clearance (CL). The mean population CL and the volume of distribution were 0.011 L/h/kg0.75 and 0.95 L/kg, respectively. Simulation assessments with the final model revealed that the current regimen (3 mg/kg every 72 h) could achieve the proposed target FLCZ trough concentration (>2 µg/mL) in 43.3% and 72.2% of infants with a PMA of ≥37 and 30 to 36 weeks, respectively, and an SCr level of <0.5 mg/dL. Shortened dosing intervals (every 48 or 24 h) might improve the probability of target attainment. This study was the first to assess the PK of F-FLCZ in ELBWI, as well as the first to provide fundamental information about FLCZ exposure after F-FLCZ administration, with the goal of facilitating dose optimization in the ELBWI population. IMPORTANCE Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very-low-birth-weight infants. In order to limit the risk of invasive fungal infections in this population, the administration of fluconazole is generally recommended for extremely low-birth-weight infants admitted to a neonatal intensive care unit with a Candida species colonization prevalence rate of >10%, under the guidelines of the Infectious Diseases Society of America. Fosfluconazole can reduce the volume of solution required for intravenous therapy compared to fluconazole because it has increased solubility, which is a major advantage for infants undergoing strict fluid management. To date, no study has demonstrated the fluconazole pharmacokinetics after fosfluconazole administration in neonates and infants, and this needs to be clarified. Here, we characterized the pharmacokinetics of fluconazole in extremely low-birth-weight infants who received F-FLCZ and explored the appropriate dosage in this patient population.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

Low vancomycin trough concentration in neonates and young infants.

BACKGROUND: Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center. METHODS: The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration: <10, 10-15, and >15 mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage. RESULTS: Thirty-three patients were analyzed. The number of patients with <10, 10-15, and >15 mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between <10 versus 10-15 and 10-15 versus >15 mg/L. The numbers of patients with <10, 10-15, and >15 mg/L in the simulation were 26, 6, and 1, respectively. CONCLUSIONS: Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Chylothorax Associated with Congenital Complete Atrioventricular Block.

Introduction Congenital complete atrioventricular block (CCAVB) associated with congenital chylothorax is a rare finding that has been reported in only one case in the literature. We report here the case of an infant with CCAVB complicated by congenital chylothorax. Patient Report We present the case of a male neonate with a birth weight of 2114 g. Fetal bradycardia and right pleural effusion were detected at gestational age of 22 weeks. Maternal serum levels of anti-Sjögren's-syndrome-related antigen A autoantibody were high (4840 U/mL). The neonate was delivered at gestational age of 33 weeks; a temporary external pacemaker was placed immediately after birth that resulted in an improved cardiac output. Milk-colored pleural effusion increased in volume together with the initiation of breast milk feeding. Lymphocytosis and high triglyceride levels in the pleural fluid led to the diagnosis of chylothorax. The pleural effusion resolved in response to prednisolone, octreotide, and total parenteral nutrition. Discussion The causal relationship between CCAVB and congenital chylothorax can be explained by considering the damage to the lymphatic vessels secondary to inflammation due to maternal autoantibodies and venous congestion due to bradycardia. Conclusion In any case of CCAVB associated with atypical pleural effusion, one must consider the possibility of congenital chylothorax.

Randomized Controlled Trial of High-Flow Nasal Cannula in Preterm Infants After Extubation.

OBJECTIVES: Our aim is to compare the efficacy and safety of high-flow nasal cannula (HFNC) against those of nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation (NIPPV) after extubation in preterm infants. METHODS: This prospective, randomized, noninferiority trial was conducted in 6 tertiary NICUs. Infants born at <34 weeks who needed noninvasive ventilation after extubation were enrolled. We randomly assigned infants to an HFNC group when HFNC was used or to an NCPAP/NIPPV group when NCPAP or NIPPV was used. The primary outcome was treatment failure within 7 days after extubation. We then examined clinical aspects of treatment failure with HFNC use. RESULTS: In total, 176 and 196 infants were assigned to the HFNC and NCPAP/NIPPV groups, respectively. The HFNC group showed a significantly higher rate of treatment failure than that of the NCPAP/NIPPV group, with treatment failure occurring in 54 infants (31%) compared with 31 infants (16%) in the NCPAP/NIPPV group (risk difference, 14.9 percentage points; 95% confidence interval, 6.2-23.2). Histologic chorioamnionitis (P = .02), treated patent ductus arteriosus (P = .001), and corrected gestational age at the start of treatment (P = .007) were factors independently related to treatment failure with HFNC use. CONCLUSIONS: We found HFNC revealed a significantly higher rate of treatment failure than NCPAP or NIPPV after extubation in preterm infants. The independent factors associated with treatment failure with HFNC use were histologic chorioamnionitis, treated patent ductus arteriosus, and a younger corrected gestational age at the start of treatment.

A sensitive method for analyzing fluconazole in extremely small volumes of neonatal serum.

BACKGROUND: The need for a large volume of serum sample significantly reduces the feasibility of neonatal pharmacokinetic studies in daily practice, which must often rely on scavenged or opportunistic sampling. This problem is most apparent in preterm newborns, where ethical and practical considerations prohibit the collection of large sample volumes. Most of the fluconazole analysis assays published thus far required a minimum serum sample of 50 to 100 µL for a single assay. The purpose of the present study was to develop and validate a sensitive method requiring a smaller sample volume (10 µL) to satisfy clinically relevant research requirements. METHODS: Following simple protein precipitation and centrifugation, the filtrated supernatant was injected into a liquid chromatography system and separated with a C18 reverse-phase column. Fluconazole and the internal standard (IS, fluconazole-d4) were detected and quantified using tandem mass spectrometry. The method was validated with reference to the Food and Drug Administration's Guidance for Industry. Accuracy and precision were evaluated at six quality control concentration levels (ranging from 0.01 to 100 µg/mL). RESULTS: Investigated calibration curves were linear in the 0.01-100 µg/mL range. Intra- and inter-day accuracy (- 7.7 to 7.4%) and precision (0.3 to 6.0%) were below 15%. The calculated limit of detection and the lower limit of quantification (LLOQ) was 0.0019 µg/mL and 0.0031 µg/mL, respectively. Fluconazole in the prepared samples was stable for at least 4 months at - 20 °C and - 80 °C. This method was applied to analyze 234 serum samples from ten neonates who received fosfluconazole, a water-soluble phosphate prodrug of fluconazole which converts to fluconazole in the body, as part of a pharmacokinetic study using daily scavenged laboratory samples. The median (range) concentration up to 72 h after fosfluconazole administration was 2.9 (0.02 to 26.8 µg/mL) µg/mL, which was within the range of the calibration curve. CONCLUSION: Fluconazole was able to be detected in an extremely small volume (10 µL) of serum from neonates receiving fosfluconazole. The method presented here can be used to quantify fluconazole concentrations for pharmacokinetic studies of the neonatal population by using scavenged samples.

Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.

OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.

Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis.

Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use.

Comparison of decision-making in neonatal care between China and Japan.

BACKGROUND: Various differences between China and Japan in approaches to medical treatment have been noted, but a few studies have examined differences in medical decision-making, especially in neonatal care. The aim of this study was to clarify these differences by means of a questionnaire. METHODS: The subjects were physicians on the staff of NICUs in China and Japan. The study questionnaire consisted of three parts dealing with the general characteristics of the participants, questions about treatment strategies for hypothetical, critically ill infants, and general questions about the treatment of foreign patients. The Likert scale was used to assess the treatment strategies and the results were analyzed statistically. Subgroup analysis by age, sex, and medical and NICU experience was also performed. RESULTS: The proportion of respondents in the Chinese and Japanese groups was 26/26 (100%) and 26/31 (84%), respectively. There was a significant difference between the Chinese and Japanese groups for 8 of 75 questions; Chinese physicians chose the positive treatment or examination options for these eight questions unlike their Japanese counterparts. The responses of the younger, less experienced physicians in both countries were more similar to each other, and more positive than those of their older, more experienced colleagues. CONCLUSION: Chinese physicians showed a more positive attitude toward examination and treatment, whereas Japanese physicians showed a more cautious attitude.

Maximization of calcium and phosphate in neonatal total parenteral nutrition.

BACKGROUND: Appropriate calcium and phosphate supplementation is essential for bone growth in preterm infants. Using Rehabix-K2™ (AY Pharmaceuticals, Tokyo, Japan) and Pleamin-P Injection™ (Fuso Pharmaceutical Industries, Osaka, Japan) as the total parenteral nutrition (TPN) and amino acid solution, respectively, we investigated ways of maximizing calcium and phosphate in the TPN solution. METHODS: Rehabix-K2, Pleamin-P, calcium gluconate, sodium phosphate, 50% glucose, and water were mixed in varying proportions to create 16 formulations. Precipitation assessment was done three times for each of the 16 formulations, and was based on the Japanese Pharmacopeia. RESULT: Precipitation was observed 24 h after mixing when the calcium and phosphate were 60 mEq/L and 30 mmol/L or 80 mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium and phosphate were 20 mEq/L and 10 mmol/L, respectively. Precipitation was observed once out of three times, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13 and 6.26, respectively). No precipitation was observed, however, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 0% and 1% (mean pH, 5.88 and 6.05, respectively). CONCLUSION: Not only the concentration of calcium and phosphate, but also the pH of the TPN solution, are crucial factors for precipitation. Based on these results, a well-balanced TPN solution maximizing calcium and phosphate availability will be able to be formulated.

Bone fracture in severe small-for-gestational-age, extremely low birth weight infants: A single-center analysis.

INTRODUCTION: Bone fracture is a complication of extremely low birth weight infants (ELBWIs). This study aimed to analyze risk factors for bone fracture in a population of severe small-for-gestational-age (SGA) ELBWIs. METHODS: We retrospectively studied data from ELBWIs with a birth weight <1000g and <-2 standard deviations (SDs) born at the National Center for Child Health and Development, Japan, from 2013 to 2015. Infants were divided into fracture and control groups. Serum calcium (Ca) and phosphorus (P) levels, perinatal factors, and previously reported risk factors were analyzed. RESULTS: Of 25 cases of severe SGA ELBWIs, 5 cases of bone fracture were identified. Gestational age was 27.7±2.2, 29.1±2.6weeks (mean difference [MD] -1.4, 95% confidence interval [CI]: -4.0, -1.2, p=0.280), birth weight (BW) 448±105, 673±216g (MD -225, 95% CI: -433, -17, p=0.036) and BW-SD -4.1±0.1, -3.4±0.8 (MD -0.8, 95% CI: -1.5, -0.02, p=0.045) in the fracture and control groups, respectively. Minimums of serum Ca and P were 6.6±1.4, 8.1±0.8mg/dl (MD -1.5, 95% CI: -2.5, -0.6), p=0.003) and 2.3±0.6, 3.5±1.1mg/dl (MD -1.2, 95% CI: -2.2, -0.1, p=0.027) in the fracture and control groups, respectively. CONCLUSION: Lower BW and BW-SD were possible risk factors for bone fracture. Hypocalcemia and hypophosphatemia may also contribute to the condition.

Survival and Neurodevelopmental Outcomes of Very Low Birth Weight Infants in a Regional Core Hospital in Kochi, Japan.

We sought to clarify the survival and neurodevelopmental outcomes of very low birth weight infants (VLBWIs) and to identify risk factors for death or neurodevelopmental impairment (NDI) in VLBWIs at our hospital. The total study population was 217 infants born in 2005-2012 weighing 1,500 g. We compared their outcomes with those from previous reports analyzed the causes of death. Risk factors for death after discharge or NDI were evaluated by a multivariate logistic regression analysis. The incidences of death or NDI reported revealed in this study and the database of Neonatal Research Network of Japan were 25.3% and 19.6% (p＝0.039), respectively. The main causes of death before discharge were intraventricular hemorrhage, sepsis, and persistent pulmonary hypertension of the newborn. The significant risk factors for death after discharge or NDI were early gestational age (weeks) and periventricular leukomalacia (adjusted odds ratio [95% confidence interval, p-value], 0.72 [0.54-0.94, 0.017] and 6.90 [1.35-38.25, 0.021], respectively). These factors must be addressed in order to improve treatment strategies for VLBWIs.

Erythroblastosis of the Donor Twin of Twin Anemia-Polycythemia Sequence.

Twin anemia-polycythemia sequence (TAPS) is a group of disorders in monochorionic twins characterized by a large intertwin hemoglobin difference without amniotic fluid discordance. Reticulocyte count is used to diagnose this condition, but little is known about the role of erythroblasts, which are the prior stage of reticulocytes. In the present case of TAPS, the 25-yr-old Japanese mother showed no signs of oligohydramnios or polyhydramnios throughout gestation. The twins were born at 36 weeks and 6 days, weighing 2,648g and 1,994g. The intertwin hemoglobin difference in umbilical cord blood was (21.1－5.0＝) 16.1g/dL and the donor twin showed signs of chronic anemia, including myocardial hypertrophy and pericardial effusion. Erythroblastosis of the donor twin was prolonged (53,088.5, 42,114.8 and 44,217.9/µL on days 0, 1 and 2, respectively). Erythroblastosis, which indicates chronic anemia, is also a good diagnostic indicator of TAPS.

Importance of Milk Expression for Preterm Infants.

Mothers of preterm infants may find it difficult to express breast milk. There is a low breast milk rate among preterm infants at discharge at our hospital, and here we tested the hypothesis that milk expression factors were the cause of the low rate. The study subjects were born before 33 gestational weeks at our hospital between March 2005 and June 2014. Nutritional evaluation was performed at discharge and noted whether breast milk, infant formula, or a mix of the 2 was being given. We compared the group given breast milk or the mix versus the group given formula. Of the 337 infants, 40 cases were excluded. Data from 297 infants were analyzed. The mean (SD) gestational age and birth weight were 29.5 (2.4) weeks and 1,230 (391) g, respectively. At discharge, 26 (8.8% ), 102 (33.3% ), and 174 (57.9% ) infants were given breast milk, formula, and the mix, respectively. A multivariate logistic regression analysis showed that the first milk expression (h) was the risk factor for the formula group: adjusted odds ratio (95% confidence interval) 1.06 (1.02-1.09) and p=0.002. Delayed first milk expression could affect the low breast milk rate at discharge. Improvement of milk expression should be achieved to promote breastfeeding.

Verification of risk scores to predict i.v. immunoglobulin resistance in incomplete Kawasaki disease.

BACKGROUND: A recent study indicated the efficacy of the addition of prednisolone to i.v. immunoglobulin (IVIG) as initial treatment in patients with higher risk of IVIG resistance. Several different risk scores for predicting IVIG resistance have been proposed, mainly based on typical Kawasaki disease (KD) patients. We investigated the utility of the risk scores to predict IVIG resistance in incomplete KD. METHODS: Clinical records of incomplete KD patients who received a single dose of IVIG between 2005 and 2012 at Kochi Health Sciences Center were retrospectively reviewed. Patients were classified into an IVIG-responsive group and an IVIG-resistant group. The Kobayashi, Egami, and Sano risk scores were calculated for each patient and the proportion of high-risk patients was compared between the two groups for each risk score. RESULTS: For 51 incomplete KD patients, Kobayashi (66.7% vs 47.6%, P = 0.253), Egami (55.6% vs 38.1%, P = 0.274), and Sano (57.1% vs 10.8%, P = 0.068) risk scores identified a higher proportion of high-risk patients in the IVIG-resistant group compared with the IVIG-responsive group, but significant difference was not observed. Sano risk score had the highest OR (6.19; 95%CI: 1.00-38.26). CONCLUSIONS: The proportion of patients identified as being at high risk for IVIG resistance using the Kobayashi, Egami, and Sano risk scores, respectively, was not significantly different between the IVIG-responsive group and the IVIG-resistant group for incomplete KD. Among the three risk scores, the Sano risk score has the best ability to predict IVIG resistance in incomplete KD.

Minimally Conjoined Omphalopagus Twins with a Body Stalk Anomaly.

Introduction This report will discuss a case of minimally conjoined omphalopagus twins (MCOTs) with a body stalk anomaly (BSA). Case Report We experienced monochorionic diamniotic (MD) twins born at 31 weeks. One infant was suspicious of BSA before birth, and another infant was normal. But normal infant had anal atresia with small intestine which was inserted behind the umbilicus. Twins had very short common umbilicus and infant with BSA had intestinal conjunction, two appendixes at the site of the colon, and a blind-ending colon. We diagnosed MCOTs. Discussion On the basis of the Spencer hypothesis, the etiology of MCOTs was that MD twins shared a yolk sac. However, this could not explain the presence of a BSA. It is necessary to consider the possible reasons for a singleton BSA. In addition, intestinal fusion occurred unequally in this case, although two appendixes were found in the same place, which might have occurred because of the balanced fusion.

Weight Growth Velocity and Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants.

INTRODUCTION: This study aimed to assess whether weight growth velocity (WGV) predicts neurodevelopmental outcomes in extremely low birth weight infants (ELBWIs). METHODS: Subjects were infants who weighed 501-1000 g at birth and were included in the cohort of the Neonatal Research Network of Japan (2003-2007). Patel's exponential model (EM) method was used to calculate WGV between birth and discharge. Assessment of predictions of death or neurodevelopmental impairment (NDI) was performed at 3 years of age based on the WGV score, which was categorized by per one increase in WGV. Multivariate logistic regression analysis was used to calculate adjusted odds ratios and their 95% confidence intervals (95%CI). RESULTS: In the 2961 ELBWIs assessed, the median WGV was 10.5 g/kg/day (interquartile, 9.4-11.9). With the categorical approach, the adjusted odds ratios for death or NDI with WGV scores of 6 and 7 were 2.41 (95%CI, 1.60-3.62) and 1.81 (95%CI, 1.18-2.75), respectively, relative to the reference WGV score of 10. WGV scores ≥8 did not predict death or NDI. CONCLUSIONS: WGV scores <8 were significant predictors suggesting that values of WGV during hospitalization in a NICU are associated with neurodevelopmental outcomes. Further investigations is necessary to determine whether additional nutritional support may improve low WGV in ELBWIs.

Changes in the features of invasive pneumococcal disease after introduction of the seven-valent pneumococcal conjugate vaccine in a regional core hospital of Kochi, Japan.

Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2007, invasive pneumococcal disease has declined, but the incidence of Streptococcus pneumoniae serotype 19A has risen worldwide. The present study examined changes in the features of invasive pneumococcal disease since the introduction of the PCV7 in Kochi, Japan. Pediatric cases of invasive pneumococcal disease were investigated before and after vaccine introduction (January 2008 to December 2013). Cases of invasive pneumococcal disease tended to decrease after PCV7 introduction. In addition, before introduction of the vaccine, most serotypes causing invasive pneumococcal disease were those included in the vaccine. However, after the introduction, we found cases infected by serotypes not covered by vaccine. Penicillin-resistant S. pneumoniae was the predominant serotype causing invasive pneumococcal disease before introduction of the PCV7, and the susceptibility of this serotype to antibiotics improved after vaccine introduction. Serotype isolates identified after vaccine introduction were also relatively susceptible to antibiotic therapy, but decreased susceptibility is expected.

Phenotypic Variability and Newly Identified Mutations of the IVD Gene in Japanese Patients with Isovaleric Acidemia.

Isovaleric acidemia (IVA) is an autosomal recessive inborn error affecting leucine metabolism. It is caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), a mitochondrial matrix enzyme that catalyzes the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA. IVD is a FAD-containing enzyme, consisting of four identical subunits. Clinical features of IVA include poor feeding, vomiting, lethargy, developmental delay, metabolic acidosis, and a characteristic "sweaty foot" odor. IVA is one of the target disorders for newborn screening by tandem mass spectrometry (MS/MS). The human IVD gene is located on chromosome 15q. To date, over 50 disease-causing mutations have been reported worldwide. In this study, we searched for IVD mutations in five Japanese patients with IVA (neonatal type, two patients; chronic intermittent type, two patients; and mild biochemical type, one patient). The diagnosis of IVA was confirmed by urinary organic acid analysis using gas chromatography and mass spectrometry. All coding exons and the flanking introns in the IVD gene were amplified by PCR and were directly sequenced. We thus identified six hitherto unknown mutations (p.G94D, p.E116K, p.M167T, p.L243P, p.L246P, and c.696+1G>T) and four previously reported (p.R53P, p.R395C, p.Y403C, and p.E411K) pathogenic mutations. All patients were compound heterozygotes, and each mutation was identified in a single patient. Pathogenicity of newly identified mutations was validated using computational programs. Among them, the p.M167T is believed to influence FAD binding, as the position 167 is present in one of the FAD-binding sites. Our results have illustrated the heterogeneous mutation spectrum and clinical presentation of IVA in the Japanese patients.