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Indenone azines, in which the exocyclic C=C bond in dibenzopentafulvalene is replaced by an azine moiety (C=N−N=C), have been synthesized as novel electron‐accepting π‐conjugated scaffolds. Structural modulation at the 7,7′‐positions of indenone azines enabled stereoselective syntheses of diastereomers in which the configurations of the two C=N bonds are E,E or Z,Z. X‐ray crystallographic analyses revealed that all the indenone azines exhibit high coplanarity in contrast to the twisted frameworks of dibenzopentafulvalene derivatives, resulting in the formation of densely π‐stacked structures. Electrochemical measurements and quantum chemical calculations revealed the electron‐accepting character of indenone azines comparable to isoindigo dyes. In particular, the intramolecular hydrogen bonds of 7,7′‐dihydroxy‐substituted derivatives impart enhanced electron‐accepting character and significantly red‐shifted photoabsorption. This study demonstrates that indenone azines represent a promising candidate as electron‐accepting building blocks for optoelectronic materials. [ABSTRACT FROM AUTHOR]

Organic light‐emitting diodes (OLEDs) receive considerable attention because of their commercial use in flat panel displays. Herein, highly efficient spiroborate‐based host materials are reported for use in blue OLEDs. Our designed spiroborates (SBOX) were simple to synthesize and exhibited high triplet excitation energies, narrow S‐T gaps, and balanced charge carrier mobilities. A blue OLED containing one of the designed spiroborates, SBON, as a host exhibited a high external quantum efficiency (27.6 %) and low turn‐on voltage (3.7 V) compared to those observed using 3,3′‐di(9H‐carbazol‐9‐yl)‐1,1′‐biphenyl (17.6 % and 4.5 V, respectively), indicating their potential as host materials in OLEDs. [ABSTRACT FROM AUTHOR]

Organic light‐emitting diodes (OLEDs) receive considerable attention because of their commercial use in flat panel displays. Herein, highly efficient spiroborate‐based host materials are reported for use in blue OLEDs. Our designed spiroborates (SBOX) were simple to synthesize and exhibited high triplet excitation energies, narrow S‐T gaps, and balanced charge carrier mobilities. A blue OLED containing one of the designed spiroborates, SBON, as a host exhibited a high external quantum efficiency (27.6 %) and low turn‐on voltage (3.7 V) compared to those observed using 3,3′‐di(9H‐carbazol‐9‐yl)‐1,1′‐biphenyl (17.6 % and 4.5 V, respectively), indicating their potential as host materials in OLEDs. [ABSTRACT FROM AUTHOR]

Background: This nationwide survey aimed to determine the status of jaundice management in Japan. Methods: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. Results: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata‐Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light‐emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata‐Imura criteria. Conclusions: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan. [ABSTRACT FROM AUTHOR]

Dithieno[a,e]penalenes (DTPs) with various substituents were synthesized as a class of antiaromatic compounds. Annulation of thiophene rings imparts the pentalene moiety with high thermal stability even without bulky substituents, while retaining antiaromaticity. The higher magnitude of antiaromaticity in DTPs, in addition to the differences in the electronic structures of the fused aromatic rings, resulted in a narrower HOMO–LUMO gap than that of the corresponding dibenzo[a,e]pentalene analog, giving rise to red‐shifted electronic absorption that reaches the near‐infrared region. Moreover, systematic investigations on the solid‐state packing structure revealed that DTPs prefer offset face‐to‐face packing motifs rather than face‐centered π–π stacking. In particular, the thienyl‐substituted DTP bearing hydrophilic side chains exhibited thermochromic behavior in polar solvents, which was ascribed to the formation of aggregates. [ABSTRACT FROM AUTHOR]

Background: Transient tachypnea of the newborn (TTN) is a respiratory disorder that results from inadequate or delayed clearance of fetal lung fluid following delivery. At present, supportive care is generally practiced for the treatment of TTN. In this study, we focused on inhaled beta‐agonists for the treatment of TTN, and the aim was to verify the efficacy and the safety of inhaled procaterol for the treatment of TTN. Methods: Inhaled procaterol or normal saline solution was administered to infants. Respiratory rate and mixed venous carbon dioxide (PvCO2) were evaluated as the primary outcomes. The duration of hospitalization, duration of oxygen therapy, and changes in respiratory support were evaluated as secondary outcomes. Results: Thirty‐seven neonates diagnosed with TTN were randomly assigned to the procaterol group (n = 18) or the placebo group (n = 19). There were no differences in PvCO2 or respiratory rate between the two groups before and after intervention. Median duration of oxygen therapy (3 days; IQR, 3–6.5 days vs 2 days, IQR, 2–4.75 days; P = 0.13) and of hospitalization (15 days; IQR, 11.25–20 days vs 11 days, IQR, 8–15.5 days; P = 0.14) were not significantly different. Conclusions: Inhaled procaterol was not effective for the treatment of TTN. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue is the group of Aiko Fukazawa at Kyoto University. The image depicts a N−N component replacing the one originally located between the exocyclic C=C bond of a cross‐conjugated dibenzofulvalene. Read the full text of the article at 10.1002/chem.202300181.“Inserting an azine moiety between the cross‐conjugated system of five‐membered rings has produced a new molecular skeleton… that combines the high planarity of the molecular skeleton with excellent electron‐accepting character.” This and more about the story behind the front cover can be found in the article at 10.1002/chem.202300181). [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue is the group of Aiko Fukazawa at Kyoto University. The image depicts a N−N component replacing the one originally located between the exocyclic C=C bond of a cross‐conjugated dibenzofulvalene. Read the full text of the article at 10.1002/chem.202300181. [ABSTRACT FROM AUTHOR]

Keywords: azine; cross conjugation; electron acceptors; hydrogen bonds; pi conjugation EN azine cross conjugation electron acceptors hydrogen bonds pi conjugation 1 1 1 05/18/23 20230516 NES 230516 B The molecular design b in our manuscript is metaphorically represented by curling, a winter sport played on ice. Front Cover: Stereoselective Synthesis and Characterization of Indenone Azine-Based Electron-Accepting -Conjugated Systems (Chem. Eur. J. 28/2023) Azine, cross conjugation, electron acceptors, hydrogen bonds, pi conjugation. [Extracted from the article]

Ambipolar Charge Transport, High Triplet Energy, Host, Organic Light-Emitting Diodes, Spiroborate Keywords: Ambipolar Charge Transport; High Triplet Energy; Host; Organic Light-Emitting Diodes; Spiroborate EN Ambipolar Charge Transport High Triplet Energy Host Organic Light-Emitting Diodes Spiroborate 1 1 1 03/23/23 20230327 NES 230327 B Organic Electronics b . Spiroborate-based host materials with high triplet energies and ambipolar charge-transport properties are reported by Takuji Hatakeyama et al. in their Communication (e202217512). [Extracted from the article]

Spiroborate-based host materials with high triplet energies and ambipolar charge-transport properties are reported by Takuji Hatakeyama et al. in their Communication (e202217512). Keywords: Ambipolar Charge Transport; High Triplet Energy; Host; Organic Light-Emitting Diodes; Spiroborate EN Ambipolar Charge Transport High Triplet Energy Host Organic Light-Emitting Diodes Spiroborate 1 1 1 03/23/23 20230327 NES 230327 B Organic Electronics b . Ambipolar Charge Transport, High Triplet Energy, Host, Organic Light-Emitting Diodes, Spiroborate. [Extracted from the article]

Background Surgical intestinal disorders, such as necrotizing enterocolitis ( NEC), focal intestinal perforation ( FIP), and meconium-related ileus ( MRI), are serious morbidities in very low-birthweight infants ( VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment ( NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age. Methods A retrospective matched-cohort study was conducted at 11 institutes. We included VLBWI who had undergone laparotomy for NEC, FIP, and MRI. Two control subjects were chosen for every surgical patient and matched for gestational age and birthweight to form the comparison group. Death and neurodevelopmental outcome at 18 months of corrected age were evaluated. Results The number of infants in the NEC, FIP, MRI, and control groups was 44, 47, 42, and 261, respectively. In-hospital mortality was higher in infants with NEC and MRI relative to those in the control group ( P < 0.001). The incidence rate for NDI at 18 months of corrected age was higher in infants with MRI relative to those in the control group ( P = 0.021). On logistic regression analysis, low gestational age, male sex, small for gestational age, intraventricular hemorrhage, and MRI were associated with increased risk of death or NDI at 18 months of corrected age. Conclusions NEC and MRI were associated with in-hospital mortality, and MRI was associated with NDI or death at 18 months of corrected age. [ABSTRACT FROM AUTHOR]

Background Hypoxic-ischemic encephalopathy ( HIE) is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological deficits in later life. We investigated the incidence of term infants with moderate or severe HIE in Japan and identified prognostic risk factors for poor outcome in HIE. Methods Data on 227 infants diagnosed with moderate or severe HIE and born between January and December 2008 were collected via nationwide surveys from 263 responding hospitals. Using logistic regression, we examined the relationship between maternal, antepartum, intrapartum, and neonatal risk factors and clinical outcome at 18 months following birth. Results In Japan, the incidence of moderate or severe HIE was 0.37 per 1000 term live births. Outborn births, low Apgar score at 5 min, use of epinephrine, and low cord blood pH were intrapartum factors significantly associated with neurodevelopmental delay and death at 18 months. Serum lactate, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase (all, P < 0.001) and creatine kinase ( P = 0.002) were significantly higher in infants with poor outcome compared to those with favorable outcomes. Abnormal brain magnetic resonance imaging ( MRI), an important prognostic factor, was significantly associated with poor outcome (odds ratio, 11.57; 95% confidence interval: 5.66-23.64; P < 0.001). Conclusions Risk factors predicting poor outcome in HIE include outborn birth, low Apgar score at 5 min, use of epinephrine, laboratory abnormalities, and abnormal MRI findings. [ABSTRACT FROM AUTHOR]

Background During the last decade, new supportive modalities and new therapeutic strategies to treat congenital diaphragmatic hernia ( CDH) have been introduced. In Japan, the large number of hospitals prevents centralizing infants with CDH in tertiary centers. The aim of this study was to evaluate the correlations between the number of CDH patients, survival rates, and the current strategies employed to treat CDH at the individual hospitals. Methods Eighty-three hospitals with 674 CDH cases were analyzed using questionnaires. We classified the hospitals into three groups according to the number of CDH patients treated: Group 1 ( G1; more than 21 patients), Group 2 ( G2; 11-20 patients), and Group 3 ( G3; fewer than 10 patients). Results The median number of CDH patients in G1, G2, and G3 were 28, 14, and 4, respectively. The overall survival rate was 74.5%. When only the isolated CDH cases with a prenatal diagnosis were included, the overall survival rate was 79.3%. The survival rate of isolated CDH cases with a prenatal diagnosis was significantly higher in G1 than that in G2 or G3 (87.2% vs 75.2% vs 74.3%; P < 0.001). There were no differences in perinatal therapeutic strategies among the three groups. Conclusions We concluded that it might therefore be important to centralize infants with CDH, especially those with isolated CDH with a prenatal diagnosis, to tertiary centers in Japan in order to improve the survival rates. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Aiko Fukazawa and co‐workers at Kyoto University and Nagoya University. The image depicts the π‐electrons as people to highlight the effect of fused aromatic rings in the antiaromatic π‐electron systems. Read the full text of the article at 10.1002/chem.202004244. [ABSTRACT FROM AUTHOR]

Keywords: antiaromaticity; pentalene; thermochromism; thiophene; conjugation EN antiaromaticity pentalene thermochromism thiophene conjugation 1478 1478 1 01/23/21 20210121 NES 210121 B Dancing people parade along the rings b : The cover image depicts the movement of electrons on tetracyclic -conjugated systems under a magnetic field. While the annulation of benzene rings with a pentalene moiety resulted in the local aromatic character in the six-membered rings, the thiophene-fused analog retains the pronounced antiaromatic character of pentalene moiety. While the annulation of benzene rings with a pentalene moiety resulted in the local aromatic character in the six-membered rings, the thiophene-fused analog retains the pronounced antiaromatic character of pentalene moiety. [Extracted from the article]

Citrullinemia is one of the five urea cycle defects. It is caused by argininosuccinate synthetase deficiency (ASSD). In the neonatal form of this disease, severe hyperammonemia develops within 24u48 h of life, with a high rate of mortality. Despite aggressive management with arginine and sodium benzoate, and hemodialysis, acutely ill infants frequently have permanent neurologic sequelae because of the toxic effects of ammonia. Recently, the molecular genetic analysis of citrullinemia has permitted diagnosis. We recently had the opportunity for DNA analysis of severe neonatal citrullinemia, and prenatal diagnosis of the next pregnancy. We report and discuss the necessity of antenatal DNA diagnosis of citrullinemia. [ABSTRACT FROM AUTHOR]

The author talks about congenital diaphragmatic hernia (CDH) in neonatal medicine by referring to the article “Impact of nutrition in the treatment of congenital diaphragmatic hernia" published within the periodical by Terui et al. Topics discussed include weight gain during infancy in the acute phase of CDH management, physical growth of very-low-birthweight infants, and need for a nutritional strategy in order to improve neurodevelopmental outcomes.

Abstract: The sulfur‐containing nine‐membered heterocycle thiacyclononene (TN) was evaluated as a new type of end‐capping group for π‐conjugated systems. A systematic study on TN‐capped α‐oligothiophenes (TNnTs; n=4–7) revealed that the capping with TN, which adopts a bent conformation, imparts the resulting oligothiophenes with drastically increased solubility at approximately 140 °C and high electrochemical stability, whereas the electronic structure remains virtually unperturbed. The even‐numbered oligothiophenes TN4T and TN6T form characteristic offset herringbone‐type packing structures on account of the steric repulsion between the TN rings and the presence of intermolecular nonbonding S⋅⋅⋅S interactions. This packing mode in combination with the high solubility enabled the solution‐process fabrication of field‐effect transistors based on TN6T, which exhibited a high performance without degradation even upon exposure to air. [ABSTRACT FROM AUTHOR]

Aim: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS‐to‐delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS‐to‐delivery interval on cord blood S100 calcium‐binding protein B (S100B) levels as a biomarker of brain damage. Methods: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS‐to‐delivery interval, retrospectively: non‐ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. Results: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non‐ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). Conclusions: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms. [ABSTRACT FROM AUTHOR]

Background: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short‐term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. Methods: We analyzed the mortality, morbidity, and factors related to short‐term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. Results: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z‐score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. Conclusions: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long‐term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan. [ABSTRACT FROM AUTHOR]

Background Very low-birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium-related ileus (MRI). The aim of this study was to identify disease-specific risk factors for surgical intestinal disorders in VLBWI. Methods A retrospective multicenter case-control study was conducted at 11 institutes. We reviewed VLBWI who underwent laparotomy for intestinal disorders including perforation and intractable bowel obstruction. The surgical disorders were classified into four categories (NEC, FIP, MRI, others) based on the macroscopic findings at operation. In order to identify risk factors, two matched controls for each subject were chosen based on gestational age and birthweight. OR and 95%CI were calculated using a conditional logistic regression model and a multivariate model. Results A total of 150 cases (NEC, n = 44; FIP, n = 47; MRI, n = 42; others, n = 17) and 293 controls were identified. The cases and controls were similar in terms of gestational age and birthweight (cases/controls, 26.7 ± 2.5/26.5 ± 2.6 weeks; 790 ± 256/795 ± 257 g). On multivariate modeling, disease-specific risk factors were as follows: female (OR, 0.23; 95%CI: 0.06-0.89), respiratory distress syndrome (OR, 35.7; 95%CI: 2.48-514) and patent ductus arteriosus (OR, 10.9; 95%CI: 1.51-79.3) for NEC; outborn delivery (OR, 5.47; 95%CI: 1.48-20.2) for FIP; and twin pregnancy (OR, 4.25; 95%CI: 1.06-17.1), PROM (OR, 6.85; 95%CI: 1.33-35.4) and maternal steroid (OR, 0.23; 95%CI: 0.07-0.79) for MRI. Conclusions Different risk factors were identified for NEC, FIP and MRI, suggesting that each disease has a different etiology, and that different strategies are required to prevent these diseases. [ABSTRACT FROM AUTHOR]

The article presents a case study of a female infant that was born at the 44rth week of gestation, having a birth weight of 3404 grams. She was noted of having a variable deceleration on the cardiotocogram. After delivery, the infant was transferred under an intensive care unit due to her respiratory distress secondary to pneumothorax. The infant was found to have a parasagittal injury (PSI), which was characterized by the infarction of the watershed zone, resulting to perinatal asphyxia.

Introduction: In extremely and very preterm infants, predicting individual risks for adverse outcomes antenatally is challenging but necessary for risk-stratified perinatal management and parents' participation in decision-making about treatment. Our aim was to develop and validate prediction models for short-term (neonatal period) and medium-term (3 years of age) outcomes based on antenatal maternal and fetal factors alone.Material and Methods: A population-based study was conducted on 31 157 neonates weighing ≤1500 g and born between 22 and 31 weeks of gestation registered in the Neonatal Research Network of Japan during 2006-2015. Short-term outcomes were assessed in 31 157 infants and medium-term outcomes were assessed in 13 751 infants among the 31 157 infants. The clinical data were randomly divided into training and validation data sets in a ratio of 2:1. The prediction models were developed by factors selected using stepwise logistic regression from 12 antenatal maternal and fetal factors with the training data set. The number of factors incorporated into the model varied from 3 to 10, on the basis of each outcome. To evaluate predictive performance, the area under the receiver operating characteristics curve (AUROC) was calculated for each outcome with the validation data set.Results: Among short-term outcomes, AUROCs for in-hospital death, chronic lung disease, intraventricular hemorrhage (grade III or IV) and periventricular leukomalacia were 0.85 (95% CI 0.83-0.86), 0.80 (95% CI 0.79-0.81), 0.78 (95% CI 0.75-0.80), and 0.58 (95% CI 0.55-0.61), respectively. Among medium-term outcomes, AUROCs for cerebral palsy and developmental quotient of <70 at 3 years of age were 0.66 (95% CI 0.63-0.69) and 0.72 (95% CI 0.70-0.74), respectively.Conclusions: Although the predictive performance of these models varied for each outcome, their discriminative ability for in-hospital death, chronic lung disease, and intraventricular hemorrhage (grade III or IV) was relatively good. We provided a bedside prediction tool for calculating the likelihood of various infant complications for clinical use. To develop these prediction models would be valuable in each country, and these risk assessment tools could facilitate risk-stratified perinatal management and parents' shared understanding of their infants' subsequent risks. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid‐ and long‐term disabilities and complications requiring treatment and follow‐up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid‐ and long‐term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence‐based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment. [ABSTRACT FROM AUTHOR]

Aim: To present the feasibility, safety and outcomes of fetoscopic endoluminal tracheal occlusion (FETO) for the treatment of severe congenital diaphragmatic hernia (CDH). Methods: This was a single‐arm clinical trial of FETO for isolated left‐sided CDH with liver herniation and Kitano Grade 3 stomach position (>50% stomach herniation into the right chest). FETO was performed at 27–29 weeks of gestation for cases with observed/expected lung to head ratio (o/e LHR) <25% and at 30–31 weeks for cases with o/e LHR ≥25%. Results: Eleven cases were enrolled between March 2014 and March 2016, and balloon insertion was successful in all cases. The median o/e LHR at entry was 27% (range, 20–33%). The median gestational age at FETO was 30.9 (range, 27.1–31.7) weeks. There were no severe maternal adverse events. One fetus died unexpectedly at 33 weeks of gestation due to cord strangulation by the detached amniotic membrane. There were 3 cases (27%) of preterm premature rupture of membranes. In all 10 cases, balloon removal at 34–35 weeks of gestation was successful. The median gestational age at delivery was 36.5 (range, 34.2–38.3) weeks. The median duration of occlusion and the median interval between balloon insertion and delivery were 26 days (range: 17–49 days) and 43 days (range, 21–66 days), respectively. Both the survival rate at 90 days of age and the rate of survival to discharge were 45% (5/11). Conclusion: The FETO is feasible without maternal morbidity in Japan and could be offered to women whose fetuses show severe isolated left‐sided CDH to accelerate fetal lung growth. [ABSTRACT FROM AUTHOR]

Background: Many small for gestational age (SGA) infants have catch‐up growth during the first 2 years of life, but approximately 10% have no catch‐up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch‐up growth at an early age may be useful for earlier diagnosis and earlier treatment. Methods: This was a retrospective multicenter study. The subjects were SGA infants with very low‐birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch‐up growth were identified on statistical analysis. Results: Of the 217 SGA infants in this study, 181 were in the catch‐up group and 36 were in the no catch‐up group. The catch‐up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch‐up at 3 years. Conclusions: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants. [ABSTRACT FROM AUTHOR]

Background: The optimum enteral (EN) and parenteral nutrition (PN) regimens during acute management of congenital diaphragmatic hernia (CDH) remain unclear. We examined the effects of EN and PN on weight gain in CDH patients. Methods: A multicenter retrospective cohort study of neonates with CDH (born 2006–2010; n = 105) who survived to discharge was conducted. Patients were divided as receiving PN ≥ or <50 kcal/kg/day at 1 week of age, and EN ≥ or <60 kcal/kg/day at 2 weeks of age. Changes in bodyweight at 30, 60, and 90 days of age were compared. Results: The higher EN group (n = 39) had greater mean weight gain than the lower EN group (n = 66; 90 days: 2,501 g, 95% CI: 2,294–2,710 g vs 1,706 g, 95% CI: 1,553–1,861 g; P <0.001). When patients received lower EN, the higher PN group (n = 24) had greater mean weight gain than the lower PN group (n = 42; 90 days: 1,768 g, 95% CI: 1,574–1,961 g vs 1,411 g, 95% CI: 1,264–1,558 g; P = 0.004). Conclusion: The amount of EN in the acute phase of CDH management is essential for weight gain during infancy. When patients are intolerant to adequate EN, supportive PN is also essential. [ABSTRACT FROM AUTHOR]

Background Hydrops fetalis ( HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion. Methods All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. Prenatal, perinatal, and postnatal information was obtained from the medical records and was retrospectively analyzed. Results Forty-one HF patients with pleural effusion were included, and 28 patients (68%) survived. On multivariate logistic stepwise analysis, gestational birth week ( OR, 0.71; 95% CI: 0.52-0.96, P = 0.027) and standard deviation ( SD) score of the birthweight ( OR, 1.74; 95% CI: 1.01-2.99, P = 0.045) were significant factors for postnatal death. All patients with both ≥32 gestational weeks and <3.0 birthweight SD score survived. Conclusions Combined with the gestational weeks data, birthweight SD score may be useful to estimate the prognosis of HF with pleural effusion. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to clarify how extracorporeal membrane oxygenation ( ECMO) is used to treat congenital diaphragmatic hernia ( CDH) in Japan. Methods We completed a nationwide survey of CDH involving 614 infants. The subjects included 43 patients who underwent ECMO. We compared the clinical data of the patients who did and did not survive ≥90 days, and analyzed the 24 h blood gas data in isolated CDH cases in both groups. Results Of the 43 CDH patients, non-isolated CDH associated with other life-threatening or chromosomal anomalies was diagnosed in six patients. Only one of these six patients was able to discontinue ECMO and survived, and the other five died shortly after birth. The other 37 patients all had isolated CDH. The reason for initiating ECMO in 31 of these patients was persistent pulmonary hypertension of the newborn ( PPHN). In the 37 patients with isolated CDH, ECMO was initiated within 24 h after birth. Sixteen patients (37%) survived ≥90 days, and intact discharge was possible in eight cases. Among the isolated CDH patients, on ROC analysis of the lowest oxygenation index ( OI) to predict 90 day survival, the cut-off was 15. Conclusions ECMO is used to treat PPHN starting from an early period after birth, but the mortality and morbidity are not favorable. For lowest OI, the index used to predict survival following ECMO, the cut-off was 15. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to clarify the outcome of patients with cardiovascular malformation ( CVM) among those with congenital diaphragmatic hernia ( CDH) who are indicated for the Fontan procedure. Methods The subjects included 76 CDH patients with CVM recruited from a national survey of 614 CDH patients. The outcomes were evaluated between two groups divided according to indication for the Fontan procedure. Patients with functional univentricular disease were considered to be candidates for the Fontan procedure. Results Sixteen (21.1%) of the 76 patients were candidates for the Fontan procedure, accounting for 2.6% of all 614 patients with CDH. None of these patients, however, underwent the Fontan procedure. Among the 16 patients, the absence of obstruction of the left ventricular outflow tract ( LVOTO) was significantly associated with better 90 day survival (71.4%, 5/7, for those without LVOTO vs 0.0%, 0/9, for those with LVOTO, P = 0.0007). After excluding 22 patients with chromosomal and/or genetic abnormalities or syndromes, the 90 day survival rate was significantly better in neonates without than with indication for the Fontan procedure (62.5%, 25/40 vs 28.6%, 4/14, P = 0.0271). Conclusions Patients with indications for the Fontan procedure are rare, and the outcome of patients with LVOTO among those with CDH is especially poor. [ABSTRACT FROM AUTHOR]

Background Congenital cytomegalovirus ( CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. Methods A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. Results Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction ( IUGR) or other specific findings on fetal ultrasonography ( US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (<60 mg/kg per day). Conclusions This secondary survey has identified the risk factors associated with outcome and important issues in diagnosis and treatment of two mother-to-child infections: congenital CMV and neonatal herpes, in Japan. [ABSTRACT FROM AUTHOR]

Background Congenital diaphragmatic hernia is associated with cardiovascular malformation. Many prognostic factors have been identified for isolated congenital diaphragmatic hernia; however, reports of concurrent congenital diaphragmatic hernia and cardiovascular malformation in infants are limited. This study evaluated congenital diaphragmatic hernia associated with cardiovascular malformation in infants. Factors associated with prognosis for patients were also identified. Methods This retrospective cohort study was based on a Japanese survey of congenital diaphragmatic hernia patients between 2006 and 2010. Frequency and outcome of cardiovascular malformation among infants with congenital diaphragmatic hernia were examined. Severity of congenital diaphragmatic hernia and cardiovascular malformation were compared as predictors of mortality and morbidity. Results Cardiovascular malformation was identified in 76 (12.3%) of 614 infants with congenital diaphragmatic hernia. Mild cardiovascular malformation was detected in 19 (33.9%) and severe cardiovascular malformation in 37 (66.1%). Their overall survival rate at discharge was 46.4%, and the survival rate without morbidity was 23.2%. Mortality and morbidity at discharge were more strongly associated with severity of cardiovascular malformation (adjusted OR 7.69, 95% CI 1.96-30.27; adjusted OR 7.93, 95% CI 1.76−35.79, respectively) than with severity of congenital diaphragmatic hernia. Conclusions The prognosis for infants with both congenital diaphragmatic hernia and cardiovascular malformation remains poor. Severity of cardiovascular malformation is a more important predictive factor for mortality and morbidity than severity of congenital diaphragmatic hernia. [ABSTRACT FROM AUTHOR]

Aim To explore a less invasive way of assessing preload in neonates than fitting catheters to measure central venous pressure ( CVP). This study evaluated the relationship between inferior vena cava ( IVC) measurements and gestational age ( GA) or body weight ( BW) in term and premature infants and the correlation between those measurements and CVP in sick infants under mechanical ventilation. Methods We studied 57 clinically stable infants, together with14 sick infants fitted with central venous catheters to measure CVP. Subcostal transverse views were recorded at the level of the left branch of portal vein, and the minimum ( DS) and maximum ( DL) diameters of the IVC were measured. We evaluated the values of DS and DL and the S/L ratio ( DS divided by DL) in the clinically stable infants and the correlation between S/L and CVP in the sick infants with central catheters. Results DS and DL correlated positively and strongly with both GA and BW, whereas S/L was almost independent of both GA and BW and correlated strongly with CVP. Conclusion At the subcostal transverse views, S/L is much less affected by either GA or BW than DS or DL and correlates strongly with CVP in mechanically ventilated infants. [ABSTRACT FROM AUTHOR]

This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near-term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS). We investigated 17 term and near-term infants with HIE. Inclusion criteria were as follows: ≥35 weeks of gestation, clinical signs of HIE, magnetic resonance imaging (MRI) lesions corresponding to HIE, assessment of outcome at >18 months of age, depression of EEG, and serial EEG examinations. The 17 infants were divided into the following two groups: Group A (n = 4) with prolonged EEG depression over 21 days of age, and group B (n = 13) with disappearance of EEG depression by 21 days of age. WS developed in all four infants in group A, but in only one of 13 infants in group B. WS occurred significantly more frequently in group A than in group B. For the prediction of subsequent development of WS, prolonged EEG depression over 21 days of age showed sensitivity of 0.80 and specificity of 1.0. In both groups, abnormal irregular faster waves with or without EEG depression were seen in 11 infants between 2 and 28 days of age. They had no significant relationship with WS, but were significantly related to an adverse developmental outcome. Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of the later development of WS. [ABSTRACT FROM AUTHOR]

The article presents several case studies of brain damage caused by severe fetomaternal hemorrhage (FMH). The first case was about a male infant born during a 38 week of gestation having a birth weight of 2625 grams which was found with a remarked anemia with increased reticulocytosis at mild elevated transaminase levels. Another was a case of a female infant born during 39th week of gestation with birth weight of 2720 grams having anemia, low blood glucose at mild elevated transaminase level.

Transient leukaemia (TL) in neonates with Down syndrome (DS) is characterized by the transient appearance of blast cells in the peripheral blood that resolves spontaneously. Some TL patients die at an early age due to organ failure. Seventy DS patients with TL were studied retrospectively to identify clinical and laboratory characteristics associated with early death (<6 months of age). Sixteen of 70 patients (22·9%) died early. The main causes of death were organ failure, particularly hepatic and cardiopulmonary failure. On univariate analysis, early gestational age (EGA), high white blood cell (WBC) count (≥100 × 109/l), percentage of peripheral blasts, elevated aspartate transaminase (AST), elevated direct bilirubin (DB), and low Apgar score were significantly associated with poor survival. On multivariate analysis, EGA, WBC count, and DB were independent predictors of poor outcome. A simple risk stratification system combining EGA and WBC count was devised to predict poor outcome. Term infants (EGA ≥ 37 weeks) whose WBC count was lower than 100 × 109/l had the best outcome [7·7% (3/39) died early], while preterm infants (EGA < 37 weeks) whose WBC count was higher than 100 × 109/l had the worst outcome [54·5% (6/11) died early]. This stratification system may be useful for identifying high-risk patients who need early therapeutic interventions. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate (CS) is a major microenvironmental molecule in the CNS, and there have been few reports about its neuroprotective activity. As neuronal cell death by excitotoxicity is a crucial phase in many neuronal diseases, we examined the effect of various CS preparations on neuronal cell death induced by the excitotoxicity of glutamate analogs. CS preparations were added to cultured neurons before and after the administration of glutamate analogs. Then, the extents of both neuronal cell death and survival were estimated. Pre-administration of a highly sulfated CS preparation, CS-E, significantly reduced neuronal cell death induced by not only NMDA but also ( S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate. Neither CS preparations other than CS-E nor other highly sulfated polysaccharides such as heparin and dextran sulfate exerted any neuroprotective effects. NMDA-induced current in neurons was not changed by pre-administration of CS-E, but the pattern of protein-tyrosine phosphorylation was changed. In addition, the elevation of caspase 3 activity was significantly suppressed in CS-E-treated neurons. These results indicate that CS-E prevents neuronal cell death mediated by various glutamate receptors, and suggest that phosphorylation-related intracellular signals and the suppression of caspase 3 activation are implicated in neuroprotection by CS-E. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate the natural history and associated predictors of musculoskeletal deformities in congenital diaphragmatic hernia (CDH) survivors. Methods A multicenter retrospective survey was conducted among CDH patients between January 2006 and December 2010 in Japan, and a follow-up survey was performed between September 2013 and October 2013. One hundred and eighty-two (79.8%) of the 228 patients were alive. An orthopedic survey of 159 survivors without severe coexisting congenital anomalies was subsequently carried out, and the rates of pectus excavatum (PE), scoliosis and chest asymmetry were evaluated. Results Scoliosis, PE and chest asymmetry were found in 20 (12.6%), 19 (11.9%) and 12 (7.5%) patients, respectively. In total, 44 patients (27.7%) developed orthopedic abnormalities. Reduction in the oxygenation index within 24 h after birth ( P = 0.044), large diaphragmatic defects ( P = 0.047) and patch repair ( P = 0.014) were predictive for scoliosis. In addition, Apgar score at 5 min was significantly lower in the patients who developed PE ( P = 0.034); and stomach herniation ( P = 0.004) and liver herniation ( P = 0.013) at prenatal diagnosis and large diaphragmatic defects ( P = 0.036) were predictive of chest asymmetry. Conclusions Approximately one-quarter of the survivors developed musculoskeletal abnormalities in the present survey of CDH patients. These data suggest that each musculoskeletal abnormality has its own specific predictors. [ABSTRACT FROM AUTHOR]