Sterilization efficacy of a new water-free breast milk pasteurizer.

BACKGROUND: Breast milk, nature's optimum source of nutrition for infants, can contain undesirable microorganisms that cause severe morbidity. After an outbreak of multidrug-resistant Escherichia coli among neonates receiving breast milk donated by another mother in our neonatal intensive care unit (NICU), we were motivated to develop a high-grade breast milk pasteurizer (BMP) designed to thaw and pasteurize breast milk at 63°C for 30 min in a sealed bag without having to open the bag or immerse it in water. METHODS: Pre-existing bacteria and spiked cytomegalovirus (CMV) were measured pre- and post-pasteurization in frozen breast milk donated by mothers of children admitted to the NICU. RESULTS: Among 48 breast milk samples (mean ± standard deviation [SD]), pre-existing bacterial counts of 5.1±1.1 × 104 colony forming units (cfu)/mL decreased to less than 10 cfu/mL (below detection level) in 45 samples after pasteurization for 30 min. In three samples, 10-110 cfu/mL persisted. As no CMV was detected in any of the 48 samples, CMV at ≥5 × 104 pfu/mL was spiked into 11 breast milk samples. After just 10 min of pasteurization, infectious CMV was not detected (threshold <50 pfu/mL) in any sample. CONCLUSION: A new BMP was shown to pasteurize milk effectively with more than a 3-log reduction of microorganisms. Compared to conventional pasteurizers, this device reduces the effort involved in pasteurizing breast milk, avoids various contamination risks, and may reduce the risk of infectious disease transmission via breast milk.

Calmodulinopathy in Japanese Children　- Their Cardiac Phenotypes Are Severe and Show Early Onset in Fetal Life and Infancy.

BACKGROUND: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3.Methods and Results: We screened 195 symptomatic children (age 0-12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1-3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like). CONCLUSIONS: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

Risk factors for discontinuation of exclusive breast feeding within 1month: a retrospective cohort study in Japan.

BACKGROUND: While breastfeeding provides benefits for infants and the mother, many women either do not breastfeed or terminate breastfeeding earlier than recommended. The aim of this analysis was to identify factors associated with early discontinuation of breastfeeding in Japanese women. METHODS: This study used data from medical records of women delivering a singleton live birth between March 2017 and August 2019 in Iwase General Hospital, Fukushima Prefecture, Japan to assess cessation of breastfeeding by the 1-month postpartum appointment. Demographic (age at birth, and employment status), medical (parity, and physical and mental condition of the mother; and infant medical factors, such as sex, Apgar score, and jaundice, among other), and family factors (husband/partner, family members living at the same house, among others) in 734 women who had initiated breastfeeding during their delivery hospital stay were examined, and multiple logistic regression was used to determine significant predictors of early cessation of exclusive breastfeeding. RESULTS: Bivariate analysis revealed that women who were primipara, unmarried, exposed to secondhand smoke, and employed; those who smoked before pregnancy; and those who had asthma were more likely to discontinue exclusive breastfeeding than other women. Infant factors associated with discontinuation were lower birthweight, earlier gestational age, neonatal intensive care unit admission, treatment for jaundice, or lower weight gain. Multivariable analysis revealed that primiparity, passive smoking before pregnancy, maternal employment, and neonatal jaundice therapy were associated with discontinuation of breastfeeding. CONCLUSIONS: In particular, women whose partners smoked before pregnancy may need to be targeted for additional support for breastfeeding.

A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy, associated with high morbidity and mortality, but the role of genetics in cases of fetal-onset has not been fully evaluated. The goal of this study was to identify the genetic background in LVNC fetal-onset patients using next-generation sequencing (NGS). METHODS: Thirty-three fetal-onset Japanese probands with LVNC (20 males and 13 females) were enrolled. In the enrolled patients, 81 genes associated with cardiomyopathy were screened using next-generation sequencing (NGS) retrospectively. RESULTS: Twenty-three patients had congestive heart failure (CHF), and six patients had arrhythmias. Prominent trabeculations were mostly observed in lateral LV, posterior LV, and apex of LV in patients with LVNC. Twelve died; three patients experienced intrauterine death or termination of pregnancy. Overall, 15 variants were found among eight genes in 16 patients. Seven variants were detected in MYH7 and two in TPM1. Sarcomere gene variants accounted for 75.0%. A multivariable proportional hazards model revealed that CHF at diagnosis and a higher ratio of the noncompacted layer/compacted layer in the LV posterior wall were independent risk factors for death in LVNC fetal-onset patients (odds ratio = 4.26 × 106 and 1.36 × 108, p = 0.0075 and 0.0005, respectively). CONCLUSIONS: The present study is the first report focusing on genetic background combined with clinical features in LVNC fetal-onset patients using NGS. Sarcomere variants were most commonly identified in fetal-onset patients, and greater attention should be paid to fetal-onset patients with LVNC having prominent trabeculations in the LV because they are more likely to develop CHF.

Towards the development of a human in vitro model of the blood-brain barrier for virus-associated acute encephalopathy: assessment of the time- and concentration-dependent effects of TNF-α on paracellular tightness.

The pathogenesis of virus-associated acute encephalopathy (VAE) involves brain edema caused by disruption of the blood-brain barrier (BBB). We aimed to develop an in vitro VAE model using an in vitro BBB model, to evaluate the dynamics of vascular dysfunction caused by tumor necrosis factor (TNF)-α. A co-culture model, consisting of Transwell®-grown human brain microvascular endothelial cells and pericytes, was treated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using cellZscope®. A permeability assay, using fluorescein isothiocyanate-conjugated sodium or dextran, was performed. Changes in claudin-5 localization and expression after TNF-α treatment were observed using immunofluorescence staining and western blot analysis. The TER decreased and permeability increased after TNF-α treatment; recovery time was dependent on TNF-α concentration. Claudin-5 was delocalized after TNF-α treatment and recovered in a TNF-α concentration-dependent manner. The expression of claudin-5 decreased 24 h after the TNF-α treatment and completely recovered 48 h after TNF-α treatment. Claudin-5 delocalization was likely associated with vascular hyperpermeability. To conclude, we evaluated vascular endothelial cell permeability and injury in VAE using an in vitro BBB model treated with TNF-α. This system can be useful for developing novel therapeutic strategies for VAE and designing treatments that target vascular permeability.

Assessment of a downsized potassium adsorption filter designed to transfuse neonates.

BACKGROUND: During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non-oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF-n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed. STUDY DESIGN AND METHODS: To assess the performance of PAF-n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre-filtration and serial post-filtration (0-30 mL, 30-60 mL, 60-90 mL, and 90-120 mL) samples from 8 RBC components. RESULTS: The average potassium adsorption rate of the PAF-n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%. CONCLUSION: The PAF-n showed an effective potassium ability with negligible RBC dilution.

Perinatal factors affecting platelet parameters in late preterm and term neonates.

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (ß = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (ß = -0.135, P = 0.026) and male sex (ß = -0.185, P = 0.002). PLT was associated with SGA (ß = -0.186, P = 0.002), PIH (ß = -0.137, P = 0.024) and male sex (ß = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates.

Prenatal nicotine exposure affects cardiovascular function and growth of the developing fetus.

AIM: Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined. METHODS: To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline-injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water-administered mice. RESULTS: Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy. CONCLUSION: Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects.

Using Platelet Parameters to Anticipate Morbidity and Mortality Among Preterm Neonates: A Retrospective Study.

Background: Platelets participate in many physiological and pathological functions and some platelet parameters predict adult diseases. However, few studies report whether platelet parameters may reflect neonatal disease and mortality in a large cohort. Objective: We aimed to investigate whether platelet parameters could predict bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and NICU mortality. Study Design and Methods: This retrospective cohort study examined records from 2006 to 2017 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. We retrospectively investigated platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on the first day of life in preterm newborns born <32 weeks' gestation admitted to our NICU from 2006 to 2017. Receiver operating characteristic (ROC) and multiple regression analyses, along with Cox proportional hazard modeling, identified independent predictors of morbidities and mortality in preterm newborns. Results: Of 1,501 neonates admitted to our NICU, a total of 305 preterm newborns were included in this study. Gestational age, birth weight, and Apgar score were significantly lower in non-survivors than in survivors. Platelet count, PCT, PDW and PMI did not differ significantly between the two groups, whereas mean MPV in non-survivors was significantly higher than in survivors (10.5 fl vs. 10.0 fl, p = 0.001). Multivariate Cox hazard modeling showed that shorter GA [HR: 0.628, 95% CI: 0.464-0.840, p = 0.003], male sex [HR: 0.269, 95% CI: 0.113-0.640, p = 0.001], and MPV [HR: 1.469, 95% CI: 1.046-2.063, p = 0.026] independently predicted overall survival. Per receiver operating curve, an MPV threshold of 10.2 fl. MPV predicts prognosis in neonates with a sensitivity of 72.4% and a specificity of 58.6% (AUC = 0.685, 95% CI: 0.600-0.789, p = 0.001). Furthermore, multivariate analysis revealed that platelet parameters were not associated with BPD and NEC, whereas small for gestational age (SGA), Apgar score at 5 min, and low PCT were associated with intraventricular hemorrhage (IVH). Conclusion: This study demonstrates that low PCT predicts IVH, and MPV ≥ 10.2 fL correlates with mortality among infants born after <32 weeks' gestation.

Extracellular vesicle miRNA-21 is a potential biomarker for predicting chronic lung disease in premature infants.

Premature infants are often exposed to positive pressure ventilation and supplemental oxygen, which leads to the development of chronic lung disease (CLD). There are currently no standard serum biomarkers used for prediction or early detection of patients who go on to develop CLD. MicroRNAs (miRNAs) are a novel class of naturally occurring, short, noncoding substances that regulate gene expression at the posttranscriptional level and cause translational inhibition and/or mRNA degradation and present in body fluids packaged in extracellular vesicles (EVs), rendering them remarkably stable. Our aim was to evaluate miRNAs identified in serum EVs of premature infants as potential biomarkers for CLD. Serum EVs were extracted from premature infants at birth and on the 28th day of life (DOL). Using a human miRNA array, we identified 62 miRNAs that were universally expressed in CLD patients and non-CLD patients. Of the 62 miRNAs, 59 miRNAs and 44 miRNAs were differentially expressed on DOL0 and DOL28 in CLD and non-CLD patients, respectively. Of these miRNAs, serum EV miR-21 was upregulated in CLD patients on DOL28 compared with levels at birth and downregulated in non-CLD patients on DOL28 compared with levels at birth. In neonatal mice exposed to hyperoxia for 7days, as a model of CLD, five miRNAs (miR-34a, miR-21, miR-712, miR-682, and miR-221) were upregulated, and 7 miRNAs (miR-542-5p, miR-449a, miR-322, miR-190b, miR-153, miR-335-3p, miR-377) were downregulated. MiR-21 was detected as a common miRNA that changed in CLD patients and in the hyperoxia exposed mice. We conclude that EV miR-21 may be a biomarker of CLD.

Pulmonary Artery Banding for Congenitally Corrected Transposition of the Great Arteries With Hydrops Fetalis: A Case Report.

At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

Perinatal Factors Affecting Coagulation Parameters at Birth in Preterm and Term Neonates: A Retrospective Cohort Study.

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time-international normalized ratio correlated with intraventricular hemorrhage (p = 0.000; ß = 0.180) and placental abruption (PA; p = 0.000; ß = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p = 0.000; ß = - 0.217), gestational age (GA; p = 0.000; ß = - 0.282), and PA (p = 0.000; ß = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome (p = 0.007; ß = - 0.114), pregnancy-induced hypertension (p = 0.000; ß = - 0.141), and Apgar score at 1 minute (p = 0.043; ß = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes (p = 0.049). Finally, antithrombin III levels positively correlated with GA (p = 0.000) and BW (p = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates.

Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy.

BACKGROUND: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. CONCLUSIONS: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Neonatal and maternal serum creatinine levels during the early postnatal period in preterm and term infants.

We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman's test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born <29 weeks, pregnancy-induced hypertension (PIH) (p = 0.000, ß = 0.20) and mSCr (p = 0.000, ß = 0.73) were significantly associated with nSCr. In term infants, maternal magnesium administration (p = 0.000, ß = 0.25), respiratory distress syndrome (p = 0.013, ß = 0.16), PIH (p = 0.005, ß = 0.19), and mSCr (p = 0.000, ß = 0.33) were significantly associated with nSCr. nSCr reflected mSCr at all gestational ages. The correlation between nSCr and mSCr in preterm infants (p = 0.000, ß = 0.74) was stronger than in term infants (p = 0.000, ß = 0.34).

Myelomeningocele with Unilateral Right Renal Agenesis: A Case Report.

Congenital anomalies of the spine may occur with malformations of the central nervous, cardiovascular, gastrointestinal, respiratory, and genitourinary systems. This is a case of myelomeningocele with unilateral right renal agenesis in a newborn. The patient suffered complications of cerebrospinal fluid leak and meningitis, but was successfully treated and discharged on day 86. In this case, unilateral right renal agenesis represented a significant surgical risk because failure of the remaining kidney could result in renal failure. Because congenital anomalies of the spine may be associated with malformations of the genitourinary system, and additional surgeries were necessary in our case following birth, it is very important that the presence of genitourinary malformations be evaluated.

Establishment of a method for evaluating endothelial cell injury by TNF-α in vitro for clarifying the pathophysiology of virus-associated acute encephalopathy.

BACKGROUND: Virus-associated acute encephalopathy (VAE) is a severe central nervous system complication caused by common viral infections in children. The pathophysiology of VAE is thought to be endothelial injury. This study was designed to establish an in vitro VAE model for evaluating endothelial injury caused by the proinflammatory cytokine TNF-α. METHODS: Transwell-grown human umbilical vein endothelial cells (HUVECs) monolayers were incubated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using impedance spectroscopy. Permeability changes of HUVECs after TNF-α treatment were determined by fluorescein isothiocyanate (FITC)-conjugated dextran. Moreover, TNF-α-induced morphological changes in claudin-5 and apoptosis were observed by immunofluorescent staining. RESULTS: The decrease in TER, time of TER recovery to baseline, and increase in permeability were all dependent on TNF-α concentration. Immunofluorescent staining showed that claudin-5 was delocalized after TNF-α treatment in a dose-dependent manner. In addition, some apoptotic cells were observed at high TNF-α concentrations. CONCLUSION: TER measurement combined with a permeability assay could be useful for evaluating vascular endothelial cell permeability in an in vitro model. These evaluation methods will contribute to both the development of specific treatments focusing on vascular permeability, and the search for a novel therapeutic strategy in VAE treatment.

The Microbiome of the Lower Respiratory Tract in Premature Infants with and without Severe Bronchopulmonary Dysplasia.

Aim We determined whether the bacteria in the lower respiratory tract (LRT) in extremely premature infants with severe bronchopulmonary dysplasia (BPD) are different from those with nonsevere BPD. Study Design We conducted a retrospective study of extremely premature infants who were admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Japan between April 2005 and March 2014. We screened for the bacterial colonization of the LRT using tracheobronchial aspirate fluid. Results A total of 169 extremely premature infants were included. Overall, 102 did not experience severe BPD, whereas the remaining 67 experienced severe BPD. Corynebacterium species (Cs) were more frequently detected in the severe BPD than nonsevere BPD infants (p = 0.03). There were significant differences between infants with and without severe BPD in the duration of endotracheal ventilation (p = 0.00, odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), the duration of supplemental oxygen (p = 0.00, OR, 1.02; 95% CI, 1.01-1.03) before 36 weeks of postmenstrual age, and the frequency of sepsis after 7 postnatal days (p = 0.01, OR, 1.73; 95% CI, 1.18-2.54). Conclusion Cs are more likely to be present in the severe BPD infants with longer duration of endotracheal ventilation.

Volumetric Analysis of Gallbladder in Extremely Premature Infants.

BACKGROUND: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants. METHODS: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W. RESULTS: Intotal, 30 infants were included. Themediangestationalageoftheinfantswas 26 weeks 5 days (range, 23 weeks 1 day-28 weeks 6 days), and the median birth weight was 731 g (range, 398-1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05 -0.59) in infants on admission and constantly < 0.05 in those between Day 10 and Day 56 after birth. There was no correlation of GV/W with clinical variables after birth. CONCLUSION: It is considered that GB volume is not affected by serial changes without nonfavor-able course of enteral nutrition.

Early Postnatal Seizures in a Neonate with Wolf-Hirschhorn Syndrome.

Background Wolf-Hirschhorn syndrome (WHS), which is characterized by a typical facial appearance, growth retardation, mental retardation, seizures, and congenital cardiac defects, has an estimated incidence of 1 per 50,000 births. Case We report a case of a low birth weight neonate with WHS and seizures, as well as persistent pulmonary hypertension in the early neonatal period. Apgar scores were 6 (1 minute) and 8 (5 minutes) with evident retraction. After admission to the neonatal intensive care unit, the patient had tonic-clonic seizures with epilepticus 30 minute after birth. Although the seizures were uncontrollable, continuous thiopental administration was effective for seizure mitigation. Conclusion Neonatal seizures with WHS occur rarely. This is the first case report on seizures just after birth in a neonate with WHS.

Plasma TGF-ß1 Levels Are Elevated in Down Syndrome Infants with Transient Abnormal Myelopoiesis.

Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-ß1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-ß1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-ß1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-ß1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis.