Functional analysis of RRAS2 pathogenic variants with a Noonan-like phenotype.

Introduction: RRAS2, a member of the R-Ras subfamily of Ras-like low-molecular-weight GTPases, is considered to regulate cell proliferation and differentiation via the RAS/MAPK signaling pathway. Seven RRAS2 pathogenic variants have been reported in patients with Noonan syndrome; however, few functional analyses have been conducted. Herein, we report two patients who presented with a Noonan-like phenotype with recurrent and novel RRAS2 pathogenic variants (p.Gly23Val and p.Gly24Glu, respectively) and the results of their functional analysis. Materials and methods: Wild-type (WT) and mutant RRAS2 genes were transiently expressed in Human Embryonic Kidney293 cells. Expression of RRAS2 and phosphorylation of ERK1/2 were confirmed by Western blotting, and the RAS signaling pathway activity was measured using a reporter assay system with the serum response element-luciferase construct. WT and p.Gly23Val RRAS2 were expressed in Drosophila eye using the glass multiple reporter-Gal4 driver. Mutant mRNA microinjection into zebrafish embryos was performed, and the embryo jaws were observed. Results: No obvious differences in the expression of proteins WT, p.Gly23Val, and p.Gly24Glu were observed. The luciferase reporter assay showed that the activity of p.Gly23Val was 2.45 ± 0.95-fold higher than WT, and p.Gly24Glu was 3.06 ± 1.35-fold higher than WT. For transgenic flies, the p.Gly23Val expression resulted in no adults flies emerging, indicating lethality. For mutant mRNA-injected zebrafish embryos, an oval shape and delayed jaw development were observed compared with WT mRNA-injected embryos. These indicated hyperactivity of the RAS signaling pathway. Discussion: Recurrent and novel RRAS2 variants that we reported showed increased in vitro or in vivo RAS signaling pathway activity because of gain-of-function RRAS2 variants. Clinical features are similar to those previously reported, suggesting that RRAS2 gain-of-function variants cause this disease in patients.

Association of cesarean section and infectious outcomes among infants at 1 year of age: Logistic regression analysis using data of 104,065 records from the Japan Environment and Children's Study.

BACKGROUND: There has been a recent decrease in the prevalence of infectious diseases in children worldwide due to the usage of vaccines. However, the association between cesarean delivery and infectious diseases remains unclear. Here, we aimed to clarify the association between cesarean delivery and the development of infectious diseases. METHODS: This study is a cross-sectional study. We used data from the Japan Environment and Children's Study, which is a prospective, nationwide, government-funded birth cohort study. The data of 104,065 records were included. Information about the mode of delivery, central nervous system infection (CNSI), otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastrointestinal infection (GI), and urinary tract infection (UTI) was obtained from questionnaires and medical records transcripts. Multiple logistic regression analysis was used to assess the association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI risk. RESULTS: We included a total of 74,477 subjects in this study, of which 18.4% underwent cesarean deliveries. After adjusting for the perinatal, socioeconomic, and postnatal confounding factors, children born by cesarean delivery did not have an increased risk of developing CNSI (95% confidence interval [CI] 0.46-1.35), OM (95% CI 0.99-1.12), URTI (95% CI 0.97-1.06), LRTI (95% CI 0.98-1.15), GI (95% CI 0.98-1.11), or UTI (95% CI 0.95-1.45). CONCLUSIONS: This nationwide cohort study did not find an association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI. However, further studies are needed to evaluate the role of cesarean delivery in the development of infectious diseases.

Cord blood triglyceride and total cholesterol in preterm and term neonates: reference values and associated factors from the Japan Environment and Children's Study.

This study aimed to investigate the associations between cord serum total cholesterol (TC) and triglyceride (TG)levels and perinatal factors and determine the reference levels of cord blood TC and TG in Japanese neonates. This was a prospective birth cohort study using data from the Japan Environment and Children's Study, which included data on births from 2011 to 2014 in Japan. TC and TG levels were determined in cord blood samples. A total of 70,535 pairs of neonates (male: 36,001, female: 34,524) and mothers were included. The mean cord blood TC and TG levels were 72.2 mg/dL and 24.4 mg/dL, respectively. Multiple regression analyses revealed that gestational age and birth weight were significantly associated with cord blood TC (coefficient -2.35, 95% confidence interval [CI] -2.40 - -2.22 and coefficient 0.002, 95% CI 0.002-0.003, respectively) and TG (coefficient 3.09, 95% CI 3.01-3.17 and coefficient - 0.009, 95% CI - 0.009-0.008, respectively) levels. Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories.    Conclusion: Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term. Furthermore, the mean cord blood TC and TG levels decreased over the entire range of birth weight categories in Japanese newborns. Maternal complications such as maternal parity, HDP, PROM, maternal obesity and income level were associated with cord TC and TG levels. What is Known: • No studies have ascertained the reference levels of cord blood lipid levels in Japan. What is New: • Mean cord blood TG and TC levels decreased over the preterm period; however, these parameters increased during the term.

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.

Differences in response to treatment in children with severe IgA nephropathy according to patient age.

AIM: To clarify whether the response to treatment of IgA nephropathy (IgAN) differs depending on patient age, we examined the response to treatment according to age of onset in children with IgAN. METHODS: We collected data for 44 children with severe IgAN. The children were retrospectively divided into three groups based on their age at disease onset. Group 1 consisted of 24 children under 11 years old, group 2 consisted of 9 children aged 12 to 13 years, and group 3 consisted of 11 children aged over 14 years old. The clinical features and prognosis were analyzed for each group. RESULTS: The urinary protein excretion and serum IgA values in group 3 were higher than those in groups 1 and 2 at the most recent follow up, and histological findings showed that the MESTCG scores in group 3 were higher than those in group 1. Furthermore, the incidence of patients with persistent nephropathy or renal insufficiency in group 3 was higher than those in groups 1 and 2. CONCLUSIONS: Patients aged 14 years and older with IgAN may respond poorly to treatment compared with those younger than 14 years old. Therefore, care must be taken regarding response to treatment and relapse when treating older children.

Maternal triglyceride levels and neonatal outcomes: The Japan Environment and Children's Study.

BACKGROUND: Although maternal triglyceride (TG) is important for fetal growth, there are few large cohort studies investigating the relationships between maternal TG during pregnancy and neonatal outcomes. OBJECTIVES: The objective of this study was to investigate the associations between maternal TG during the second and third trimesters and neonatal outcomes including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA). METHODS: This was a prospective birth cohort study using data of the Japan Environment and Children's Study included data of births from 2011-2014 in Japan including 79,519 pairs. Participants were divided into tertiles according to maternal TG in the second or third trimesters. Multiple logistic regression modeling was used to examine the risks of LBW, SGA, LGA and PTB in association with maternal TG levels in the second or third trimesters RESULTS: In the second trimester, compared with reference TG group (T2), women in higher TG group (T3) and lower TG group (T1) were also at increased risk of LGA (aOR 1.20, 95% CI 1.11-1.29) and SGA (aOR 1.25, 95% CI 1.10-1.41), respectively. In the third trimester, women in T3 and T1 were at increased risk of LGA (aOR 1.27, 95% CI 1.17-1.38) and SGA (aOR 1.17, 95% CI 1.02-1.34), respectively. CONCLUSION: In this study, higher maternal TG levels in the second or third trimesters were associated with risks of LGA, however, lower maternal TG levels in the second or third trimesters were conversely associated with risks of SGA.

Serum zinc and copper levels in infants admitted to the neonatal intensive care unit.

OBJECTIVES: Zinc and copper are trace elements, but their reference values during the neonatal and infant periods are not clear. We aimed to determine the trend of serum zinc levels in infants admitted to the neonatal intensive care unit and compare serum zinc and serum copper levels at admission between small-for-gestational-age (SGA) and non-SGA infants. METHODS: From 406 patients admitted to the neonatal intensive care unit from January 2009 to September 2012, 339 patients were included in this retrospective study. Blood samples were collected on admission, and serum zinc and serum copper levels were measured. Serum zinc was tested every month until discharge. RESULTS: Serum zinc levels of infants born at <30 wk of gestation decreased by 46% in the first month of life. All infants born at ≤34 wk of age became zinc deficient at 2 mo of age. The relationship between gestational age and serum zinc level at admission had a negative correlation (Spearman's rank correlation cofficients) = -0.66; P < 0.001). There was a negative correlation between serum zinc and serum copper at admission (rs = -0.49; P < 0.001). Serum copper levels of SGA infants at admission were significantly higher than those of non-SGA infants (P < 0.001). CONCLUSIONS: All of the infants admitted to the neonatal intensive care unit at ≤34 wk of gestation were zinc deficient by 2 mo of age, suggesting the need for enteral zinc administration. Serum copper was higher in SGA infants than in non-SGA infants on admission, but further studies are needed to determine whether excess copper affects development.

Predicting neonatal mortality with a disseminated intravascular coagulation scoring system.

BACKGROUND: Although disseminated intravascular coagulation (DIC) is a critical disease, its mortality in neonates is hard to predict. The aim of this study was to investigate underlying conditions associated with neonatal DIC to see if a scoring system could predict mortality. METHODS: We retrospectively evaluated the DIC scores of neonates diagnosed on or after the second day of life, in conjunction with underlying conditions associated with DIC. The diagnosis of DIC was made according to Japan Society of Obstetrical, Gynecological & Neonatal Hematology (JSOGNH) 2016 neonatal DIC criteria. RESULTS: Among 23 neonates with DIC, 8 had gastrointestinal perforation with necrotizing enterocolitis and 6 had congenital heart disease. Although factors such as birth weight, gestational age, D-dimer, and fibrinogen were not predictive of mortality, median PT-INR differed significantly between the two groups (survived 1.69 vs died 2.37, P = 0.004). Furthermore, median DIC scores differed significantly by survival outcome (P = 0.013). CONCLUSION: DIC scores based on JSOGNH 2016 neonatal DIC criteria are predictive of mortality in infants diagnosed with DIC on or after the second day of life.

Involvement of miRNA-34a regulated Krüppel-like factor 4 expression in hyperoxia-induced senescence in lung epithelial cells.

BACKGROUND: Premature infants, subjected to supplemental oxygen and mechanical ventilation, may develop bronchopulmonary dysplasia, a chronic lung disease characterized by alveolar dysplasia and impaired vascularization. We and others have shown that hyperoxia causes senescence in cultured lung epithelial cells and fibroblasts. Although miR-34a modulates senescence, it is unclear whether it contributes to hyperoxia-induced senescence. We hypothesized that hyperoxia increases miR-34a levels, leading to cellular senescence. METHODS: We exposed mouse lung epithelial (MLE-12) cells and primary human small airway epithelial cells to hyperoxia (95% O2/5% CO2) or air (21% O2/5% CO2) for 24 h. Newborn mice (< 12 h old) were exposed to hyperoxia (> 95% O2) for 3 days and allowed to recover in room air until postnatal day 7. Lung samples from premature human infants requiring mechanical ventilation and control subjects who were not mechanically ventilated were employed. RESULTS: Hyperoxia caused senescence as indicated by loss of nuclear lamin B1, increased p21 gene expression, and senescence-associated secretory phenotype factors. Expression of miR-34a-5p was increased in epithelial cells and newborn mice exposed to hyperoxia, and in premature infants requiring mechanical ventilation. Transfection with a miR-34a-5p inhibitor reduced hyperoxia-induced senescence in MLE-12 cells. Additionally, hyperoxia increased protein levels of the oncogene and tumor-suppressor Krüppel-like factor 4 (KLF4), which were inhibited by a miR-34a-5p inhibitor. Furthermore, KLF4 knockdown by siRNA transfection reduced hyperoxia-induced senescence. CONCLUSION: Hyperoxia increases miR-34a-5p, leading to senescence in lung epithelial cells. This is dictated in part by upregulation of KLF4 signaling. Therefore, inhibiting hyperoxia-induced senescence via miR-34a-5p or KLF4 suppression may provide a novel therapeutic strategy to mitigate the detrimental consequences of hyperoxia in the neonatal lung.

Maternal hemoglobin levels and neonatal outcomes: the Japan Environment and Children's Study.

BACKGROUND: Low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB) are important neonatal outcomes that may affect infant morbidity and mortality. The aim of this study is to investigate associations between maternal hemoglobin (Hb) concentrations and pregnancy outcomes of LBW, SGA, and PTB. METHODS: This was a prospective birth cohort study using data of the Japan Environment and Children's Study. Participants were divided into five groups according to maternal Hb (g/dL) in the first and second trimesters: group 1, Hb < 9; group 2, 9 ≤ Hb < 11.0; group 3, 11.0 ≤ Hb < 13.0; group 4, 13.0 < Hb < 14.0; and group 5, 14.0 ≤ Hb. We examined the relationships between LBW, PTB, SGA, and maternal Hb in the first and second trimesters. RESULTS: Excluding 29,673, a total of 74,392 newborns (first trimester: n = 39,084, second trimester: n = 35,308) were included. We obtained adjusted odds ratios (aORs) (95% confidence intervals (CIs)) using multivariate analysis; compared with group 3 in the first trimesters, women in group 1 were at increased risk of PTB (aOR, 3.20; 95% CI, 1.69-6.09), LBW (aOR, 2.21; 95% CI, 1.19-4.09). In the second trimester, multivariate analysis revealed that, compared with group 3 in the second trimester, women in group 1 were at increased risk of PTB (aOR, 2.30; 95% CI, 1.19-4.42) and women in group 5 were at increased risk of LBW (aOR, 1.87; 95% CI, 1.24-2.81) and PTB (aOR, 1.73; 95% CI, 1.06-2.83). CONCLUSIONS: Elevated maternal Hb in the second trimester was associated with risks of PTB and LBW.

Association between preconception dietary inflammatory index and neurodevelopment of offspring at 3 years of age: The Japan Environment and Children's Study.

OBJECTIVES: We investigated the relationship between the daily dietary inflammatory index (DII) score 1 y before pregnancy and offspring neurodevelopment. METHODS: Data of singleton pregnancies from the Japan Environment and Children's Study involving live-term births from 2011 to 2014 were extracted. Individual meal patterns during 1 y before pregnancy obtained from food frequency questionnaires were used to calculate DII scores. Participants were stratified by DII quintiles (quantile [Q] 1 and Q5 represented the most anti- and proinflammatory dietary groups, respectively) and by sex of the newborn. Q3 (middle inflammatory diet group) was the reference for the multiple logistic regression model used to estimate the effect of anti- or proinflammatory diet on impaired neurodevelopment at age 3 y. RESULTS: During this study, 68 479 maternal and neonatal pair records were obtained (34 817 male and 33 662 female offspring). Male offspring in the Q1 group exhibited decreased delayed development in communication (adjusted odds ratio [aOR]: 0.79; 95% confidence interval [CI], 0.67-0.93), fine motor (aOR: 0.86; 95% CI, 0.76-0.98), problem-solving (aOR: 0.83; 95% CI, 0.73-0.94), and social (aOR: 0.75; 95% CI, 0.63-0.90) skills. Offspring in the Q5 group exhibited increased delay in fine motor skill development (aOR: 1.23; 95% CI, 1.10-1.39). Female offspring in the Q1 group exhibited decreased delayed development in problem-solving skills (aOR: 0.81; 95% CI, 0.67-0.98), and those in the Q5 group exhibited an increased delay in gross motor skill development (aOR: 1.24; 95% CI, 1.01-1.53). CONCLUSIONS: An antiinflammatory diet 1 y before pregnancy may decrease the risk of impaired neonatal neurodevelopment, and a proinflammatory diet may increase this risk.

Diagnostic reference value of antibody levels measured using enzyme immunoassay for subacute sclerosing panencephalitis.

High measles-specific antibody titers in the cerebrospinal fluid (CSF) have important diagnostic significance for subacute sclerosing panencephalitis (SSPE), a progressive neurological disorder caused by measles virus variants. However, the diagnostic reference value of antibody levels and the usefulness of the CSF/serum ratio measured using enzyme immunoassays (EIAs) for SSPE diagnosis remain unclear. To facilitate SSPE diagnosis using EIAs, measles immunoglobulin G (IgG) titers in the CSF and serum of patients with and without SSPE were measured and their CSF/serum antibody ratios evaluated. Serum and CSF antibody levels were compared among three patients with SSPE (59 paired samples), 37 non-SSPE patients, and 2618 patients of unknown backgrounds. Of the 59 paired samples from three patients with SSPE, 56 paired samples (94.9%) showed CSF measles IgG levels ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, whereas non-SSPE cases showed CSF measles IgG levels <0.1 IU/mL and a CSF/serum ratio <0.03. Of the 2618 CSF samples with unknown backgrounds, 951 showed measurable IgG levels with EIA, with a CSF/serum ratio peak of 0.005-0.02, with a 90th percentile of 0.05. Assuming the SSPE criteria as CSF measles IgG ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, only 20 samples (0.8%) with unknown backgrounds were categorized as having SSPE. Conversely, assuming the non-SSPE criteria as CSF measles IgG <0.1 IU/mL and a CSF/serum ratio <0.03, 2403 samples (92%) with unknown backgrounds were categorized as not having SSPE. In conclusion, high CSF/serum ratios (≥0.05) and high measles CSF IgG levels (≥0.5 IU/mL) may be useful for diagnosing SSPE.

Gene expression profile and injury sites in mice treated with Shiga toxin 2 and lipopolysaccharide as a Shiga toxin-associated hemolytic uremic syndrome model.

Shiga toxin 2 (Stx2) and lipopolysaccharide (LPS) contribute to the development of hemolytic uremic syndrome (HUS). Mouse models of HUS induced by LPS/Stx2 have been used for elucidating HUS pathophysiology and for therapeutic development. However, the underlying molecular mechanisms and detailed injury sites in this model remain unknown. We analyzed mouse kidneys after LPS/Stx2 administration using microarrays. Decreased urinary osmolality and urinary potassium were observed after LPS/Stx2 administration, suggestive of distal nephron disorders. A total of 1,212 and 1,016 differentially expressed genes were identified in microarrays at 6 h and 72 h after LPS/Stx2 administration, respectively, compared with those in controls. Ingenuity pathway analysis revealed activation of TNFR1/2, iNOS, and IL-6 signaling at both time points, and inhibition of pathways associated with lipid metabolism at 72 h only. The strongly downregulated genes in the 72-h group were expressed in the distal nephrons. In particular, genes associated with distal convoluted tubule (DCT) 2/connecting tubule (CNT) and principal cells of the cortical collecting duct (CCD) were downregulated to a greater extent than those associated with DCT1 and intercalated cells. Stx receptor globotriaosylceramide 3 (Gb3) revealed no colocalization with DCT1-specific PVALB and intercalated cell-specific SLC26A4 but did present colocalization with SLC12A3 (present in both DCT1 and DCT2), and AQP2 in principal cells. Gb3 localization tended to coincide with the segment in which the downregulated genes were present. Thus, the LPS/Stx2-induced kidney injury model represents damage to DCT2/CNT and principal cells in the CCD, based on molecular, biological, and physiological findings.

Can serum periostin predict bronchopulmonary dysplasia in premature infants?

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD. METHODS: A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006). CONCLUSIONS: Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants. IMPACT: This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.

Biomarker Potential of the Soluble Receptor for Advanced Glycation End Products to Predict Bronchopulmonary Dysplasia in Premature Newborns.

Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants. The soluble receptor for advanced glycation end products (sRAGE) is implicated in the development of various pulmonary diseases. The objectives of the current study were to investigate perinatal factors associated with serum sRAGE levels at birth and to establish whether serum sRAGE could be a biomarker for BPD. This retrospective single-center study was conducted at Fukushima Medical University Hospital's Department of Pediatrics Neonatal Intensive Care Unit from April 2014 to September 2020. Mechanically ventilated or oxygenated neonates born at <32 weeks gestational age and healthy control neonates were included in this study. Serum sRAGE levels in cord blood were measured using an enzyme-linked immunosorbent assay. Eighty-four preterm infants born at <32 weeks and 40 healthy infants were identified. The 84 born at <32 weeks were categorized as BPD (n = 34) or non-BPD (n = 50) neonates. The median gestational age (GA) and birthweight (BW) were significantly lower in BPD vs. non-BPD neonates (24.4 vs. 27.6 weeks, P < 0.001, 634 vs. 952 g, P < 0.001, respectively). Serum sRAGE at birth in all 124 preterm and term infants significantly correlated with BW (r = 0.417, P < 0.0001) and GA (r = 0.415, P < 0.0001). Among those born at <32 weeks, median serum sRAGE levels at birth were significantly lower in infants with BPD than without (1,726 vs. 2,797 pg/mL, P = 0.0005). Receiver operating characteristic analysis for sRAGE levels at birth in infants with and without BPD revealed that the area under the curve was 0.724 (95% confidence interval 0.714-0.834, P = 0.001). However, serum RAGE levels were not associated with severity of BPD. Serum sRAGE levels at birth were significantly correlated with BW and GA. Furthermore, serum sRAGE levels at birth could serve as a biomarker for predicting BPD, but not its severity.

Perinatal diagnosis of a fetus with an unbalanced translocation 46,XY,der(10)t(6;10)(p22;q26.1) with multiple malformations:a case report and literature review.

The phenotype of an unbalanced translocation is characterized by the dosage effects of the affected genes in the translocated chromosome. We present the case of a fetus with a paternally derived unbalanced 46,XY,der(10)t(6;10)(p22;q26.1) translocation, detected following growth retardation and cardiac malformation. In trisomy 6p and 10q26 monosomy, external surface malformations, including characteristic facial abnormalities, and neurological or higher effects have been reported. Developmental delay and hypotonia are reported in ≤ 80% of cases of 10q monosomy. Herein, low birth weight, cephalic abnormalities including microcephaly, low-set ears and a high arched palate, ambiguous genitalia including scrotal hypoplasia and cryptorchidism, and congenital heart defects, including ventricular septal defect and pulmonary atresia, were observed. Neurological impact was not evaluated due to neonatal death. The mortality rate and frequency of low birth weight in such translocations has been seldom reported. In this case, severe cardiac malformation and low birth weight may have caused early neonatal death. Whilst Trisomy 6 is associated with low birth weight and perinatal death, few studies have reported these outcomes in 10q26 deletion syndrome. Our findings therefore contribute to the evidence base regarding unbalanced translocations and may improve the clinical management of such patients.

Cytokine Profiles Before and After Exchange Transfusions in Severe Late-Onset Neonatal Group B Streptococcus Meningitis: A Case Report.

Streptococcus agalactiae or group B streptococcus (GBS) is a pathogen that causes severe neonatal infections, resulting in sepsis, pneumonia, and meningitis. Neonatal GBS meningitis has a poor neurological prognosis and a high mortality rate. GBS disease is classified as early- and late-onset if the onset age is 0-6 and 7-89 days after birth, respectively. There is currently no effective preventive strategy against late-onset GBS (LOGBS) disease. Here, we report a case of female infant with LOGBS meningitis who recovered from the septic shock by two exchange transfusions (ExTs) but still experienced severe neurological sequela. She was born at a gestational age of 39 weeks via caesarian section due to oligohydramnios and had fever 11 days after birth. GBS was detected in her cerebrospinal fluid (CSF) and blood but not in the vaginal or breast-milk cultures of the mother. The patient was treated with intravenous antibiotic administration; however, she suddenly developed pulseless ventricular tachycardia and asystole the next day. Her heart rate was normalized via cardiopulmonary resuscitation. We also performed two ExTs, and she recovered from the septic shock. Cytokine-profile analysis revealed that the serum and CSF levels of various pro-inflammatory and anti-inflammatory cytokines were elevated before the ExTs, after which the serum levels of several of these cytokines decreased. Two ExTs were effective in saving the life of the patient but did not improve the neurological prognosis. Given that neonatal GBS meningitis has high fatality and sequela rates; thus, it is necessary to establish a preventive strategy.

Red cell distribution width as a predictor for bronchopulmonary dysplasia in premature infants.

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at < 30 weeks were included in this study. They were categorized into BPD (n = 85) and non-BPD (n = 91) infants. RDW at birth and 14 days and 28 days of life (DOL 14, DOL 28) were measured. Clinical data were obtained from all subjects at Fukushima Medical University (Fukushima, Japan). The mean RDW at birth, DOL 14 and DOL 28 were 16.1%, 18.6%, 20.1%, respectively. Small for gestational age (SGA), chorioamnionitis (CAM), hypertensive disorders of pregnancy (HDP), gestational age and birth weight were significantly associated with RDW at birth. SGA, BPD and red blood cell (RBC) transfusion before DOL 14 were associated with RDW at DOL 14. BPD and RBC transfusion before DOL 14 were associated with RDW at DOL 28. Compared with non-BPD infants, mean RDW at birth DOL 14 (21.1% vs. 17.6%, P < 0.001) and DOL 28 (22.2% vs. 18.2%, P < 0.001) were significantly higher in BPD infants. Multivariate analysis revealed that RDW at DOL 28 was significantly higher in BPD infants (P = 0.001, odds ratio 1.63; 95% CI 1.22-2.19). Receiver operating characteristic analysis for RDW at DOL 28 in infants with and without BPD yielded an area under the curve of 0.87 (95% CI 0.78-0.91, P < 0.001). RDW at DOL 28 with mild BPD (18.3% vs. 21.2%, P < 0.001), moderate BPD (18.3% vs. 21.2%, P < 0.001), and severe BPD (18.3% vs. 23.9%, P < 0.001) were significantly higher than those with non-BPD, respectively. Furthermore, there are significant differences of RDW at DOL 28 between mild, moderate, and severe BPD. In summary, we conclude that RDW at DOL 28 could serve as a biomarker for predicting BPD and its severity. The mechanism by which RDW at DOL 28 is associated with the pathogenesis of BPD needs further elucidation.