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Boron-based multiple-resonance (MR) emitters exhibit the advantages of narrowband emission, high absolute photoluminescence quantum yield, thermally activated delayed fluorescence (TADF), and sufficient stability during the operation of organic light-emitting diodes (OLEDs). Thus, such MR emitters have been widely applied as blue emitters in triplet–triplet-annihilation-driven fluorescent devices used in smartphones and televisions. Moreover, they hold great promise as TADF or terminal emitters in TADF-assisted fluorescence or phosphor-sensitised fluorescent OLEDs. Herein we comprehensively review organoboron-based MR emitters based on their synthetic strategies, clarify structure–photophysical property correlations, and provide design guidelines and future development prospects. [ABSTRACT FROM AUTHOR]

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]

The asymmetric oxidation of a sulfur-containing nine-membered heterocycle was achieved for the late-stage introduction of chirality to the substituents of π-electron systems. The oxidation of the sulfur atom considerably influenced the phase-transition behaviour and crystallinity of the resulting π-electron systems. [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]

Highlights • SiO 2 nanoparticles loaded on spherical porous particles by mechanical processing. • Composite particles fully characterized by BET, FE-SEM and pulsed 1H NMR. • Water droplet drying behavior on powder layer of composite particle was monitored. • 15 wt% loading of nanoparticles successfully increased apparent water drying rate. • Relations between composite particle structure and water drying behavior was discussed. Abstract Nanoscale structured composite particles consisting of spherical porous SiO 2 particles with nanoscaled surface roughness as the core particles and SiO 2 nanoparticles as the depositing particles were designed using a high-shear mechanical composing process to develop a powder material that can form a layer with apparent rapid drying properties. The spherical porous SiO 2 core particles and depositing nanoparticles were selected to enhance the water extension on the core particle surface and amongst the composite particles in the powder layer, respectively. The effects of the composite particle nanoparticle content on the morphology of the composite particles and their relationships with the water droplet extending and drying properties in the powder layer of the designed composite particles were systematically investigated based on FE-SEM observations, characterization of N 2 adsorption/desorption isotherms, and 1H spin-spin relaxation rate measurements of composite particles. The FE-SEM observations show that the pulverized nanoparticles could be successfully attached to porous core particles without the core particles collapsing. The reduction of the specific surface area and increase of the particle specific external surface area after the compositing process strongly supported the fact of nanoparticle attachment. While a small amount of nanoparticle attachment decreased the water droplet extended area, wet area circularity, and apparent drying rate, 15 wt% loading of the pulverized nanoparticles resulted in a drastic increase of the water extended area, wet area circularity, and apparent drying rate. [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]

Purpose: Very low birth weight infants (VLBWIs) are at risk of surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI). We conducted this study to verify whether the timing of stoma closure and that of enteral nutrition establishment after stoma closure in VLBWIs differ among the most common disorders. Methods: A retrospective multicenter study was conducted at 11 institutes. We reviewed the timing of stoma closure and enteral nutrition establishment in VLBWIs who underwent stoma creation for intestinal disorders. Results: We reviewed the medical records of 73 infants: 21 with NEC, 24 with FIP, and 25 with MRI. The postnatal age at stoma closure was 107 (28-359) days for NEC, 97 (25-302) days for FIP, and 101 (15-264) days for MRI ( p = 0.793), and the postnatal age at establishment of enteral nutrition was 129 (42-381) days for NEC, 117 (41-325) days for FIP, and 128 (25-308) days for MRI ( p = 0.855). The body weights at stoma closure were 1768 (620-3869) g for NEC, 1669 (1100-3040) g for FIP, and 1632 (940-3776) g ( p = 0.614) for MRI. There were no significant differences among the three groups. Conclusions: The present study revealed that the time and body weights at stoma closure and the postoperative restoration of bowel function in VLBWIs did not differ among the three diseases. [ABSTRACT FROM AUTHOR]

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]

The aim of this study is to investigate whether it is possible to detect future behavioral and emotional problems in extremely low-birth-weight infants by evaluating the neonatal head magnetic resonance imaging (MRI) using a scoring system. This study included 62 extremely low-birth-weight infants born between April 2015 and March 2017 and those who had undergone MRI at 36 to 42 weeks of gestation. These subjects were administered with the Strength and Difficulties Questionnaire (SDQ) at age 4–5, and the patients who responded to the questionnaire were included in the study. A positive correlation was observed between the Global Brain Abnormality Score and Total Difficulties Score of the SDQ (r = 0.26, p = 0.038). However, no significant difference was observed between the median Global Brain Abnormality Score of the normal and borderline-range group and the Total Difficulties Score of the clinical-range group (p = 0.51). This study demonstrated the relationship between the MRI findings in the newborn period and the emotional and behavioral problems in early childhood, but it is not clinically useful as a predictive marker. [ABSTRACT FROM AUTHOR]

Purpose: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. Methods: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). Results: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. Conclusions: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age. [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]

Introduction: The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). Methods: We asked the responders to an earlier nationwide Japanese survey on pBE to provide additional information. pBE was diagnosed based on the criteria used in the nationwide survey. We collected data on serum total bilirubin (TB), direct bilirubin (DB), albumin, and unbound bilirubin (UB) levels during the first 8 weeks of life, and on phototherapy and exchange transfusion treatments. Results: We obtained clinical data from 75 patients with pBE from 58 hospitals (response rate of 59%), who were born between 2002 and 2016. The average peak TB level was 12.6 mg/dL (215 μmol/L), and the average age at peak attainment was 19.7 days after birth. Albumin level was <2.5 g/dL in 44 patients, and the peak DB level was ≥2 mg/dL (34.2 μmol/L) in 20 patients. The average peak bilirubin/albumin (B/A) (mg/g) ratio was 3.8 (molar ratio of 0.475), and the average age at peak attainment was 18.6 days. The average peak UB level was 0.67 μg/dL (11.5 nmol/L). The median duration of phototherapy was 6 days, and the median day of the last session was 12. The peak TB level occurred after the last day of phototherapy in 30 of the 61 patients available for comparison. Conclusions: Most patients with pBE lacked marked elevations in serum TB levels and the B/A ratio, the peaks of which were sometimes delayed to >4 weeks after birth. [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.

To determine the clinical features of bilirubin encephalopathy in preterm infants (pBE) in Japan. We performed a retrospective, nationwide questionnaire-based survey. The initial survey determined the number of children with pBE who were born after 2000. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including demographic data, neurological symptoms, and MRI and auditory brainstem response (ABR) findings. The initial survey identified 41 pBE infants from 18 institutions. After exclusion of patients included in previous studies, clinical information was collected from 30 patients (21 boys and 9 girls) during the secondary survey. The median gestational age was 26 weeks and the median birthweight was 846 g. Chronic lung disease and symptomatic patent ductus arteriosus were common neonatal complications. Head control was observed in 63% and functional gait in 17% of patients. Purposeful hand use was seen in 57% and verbal communication in 50% of patients. MRI showed T2 hyperintensities in the globus pallidus of 29 of 30 patients. ABR abnormalities were present in 11 of 15 patients. None of the variables were significantly different between the 2017 and 2021 surveys. The pBE infants had severely impaired gross motor function and relatively preserved manual function and verbal communication. MRI and ABR findings aid in the diagnosis of pBE. [ABSTRACT FROM AUTHOR]

Purpose: Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. Methods: A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32 weeks of gestation and weighing ≤ 1500 g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. Results: The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. Conclusion: Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24–31 gestational weeks compared with non-SGA infants. Methods: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. Results: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50–0.88] and 0.62 [0.50–0.78], respectively), respiratory distress syndrome (0.77 [0.69–0.87] and 0.63 [0.58–0.68], respectively), and composite adverse outcomes (0.73 [0.58–0.91] and 0.57 [0.50–0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. Conclusions: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants. [ABSTRACT FROM AUTHOR]

To estimate whether antenatal corticosteroids (ACS) improve short- and long-term preterm offspring outcomes in singleton pregnancies complicated by hypertensive disorders of pregnancy (HDP) similar to pregnancies without HDP. This population-based retrospective study was conducted based on an analysis of data collected by the Neonatal Research Network of Japan on 21,014 singleton neonates weighing ≤1,500 g between 24 and 31 weeks' gestation during 2003–2016. Logistic regression analyses were performed to compare short- and long-term offspring outcomes between mothers receiving ACS treatment and those who did not among pregnancies with HDP and without HDP. Of 21,014 neonates, 4,806 (22.9%) were born to mothers with HDP. ACS treatment was associated with significant decreases in short-term adverse outcomes in the both HDP and non-HDP groups, with similar reduced odds of neonatal death, respiratory distress syndrome, and intraventricular haemorrhage (IVH). However, ACS treatment did not significantly decrease severe IVH (aOR 0.76; 95% CI 0.51–1.13) and periventricular leukomalacia (1.14; 0.78–1.66) in the HDP group. In addition, ACS treatment in mothers without HDP significantly decreased cerebral palsy (aOR 0.70; 95% CI 0.58–084), developmental quotient scores <85 (0.79; 0.69–0.90), and composite adverse outcomes (0.85; 0.75–0.96) at 3 years of age, whereas ACS treatment in mothers with HDP did not significantly improve these outcomes (1.04; 0.69–1.57, 1.11; 0.88–1.39, 0.96; 0.75–1.22, respectively). ACS treatment was associated with significantly decreased major short-term morbidities and mortality among extremely and very preterm neonates of mothers with HDP, with ACS treatment having a decreased effect compared to that observed in neonates of mothers without HDP. Although ACS treatment has no additional effects on offspring outcomes at 3 years of age, our results did not suggest that ACS treatment should be withheld from mothers with HDP. [ABSTRACT FROM AUTHOR]

Introduction:  We aimed to establish and validate a risk score for fetuses with congenital diaphragmatic hernia (CDH) using only prenatal ultrasound findings.Material and Methods:  Derivation (2011-2016, n = 350) and validation (2006-2010, n = 270) cohorts were obtained from a Japanese CDH study group database. Using a logistic regression analysis, we created a prediction model and weighted scoring system from the derivation dataset and calculated the odds ratio of an unsatisfactory prognosis (death within 90 days of life or hospitalization duration exceeding 180 days). Five adverse prognostic factors obtained using prenatal ultrasound, including an observed/expected lung area-to-head circumference ratio (o/eLHR) <25%, liver herniation occupying more than one-third of the thoracic space, thoracic stomach, right-side CDH, and severe malformations, were used as predictors. The obtained model was validated using the validation cohort.Results:  The unsatisfactory prognosis prediction model was obtained based on the adjusted odds ratios. The C statistics of the model were 0.83 and 0.80 in the derivation and validation datasets, respectively. The five variables were weighted proportionally to their adjusted odds ratios for an unsatisfactory prognosis (o/eLHR <25%, 1 point; liver herniation occupying more than one-third of the thoracic space, 1 point; thoracic stomach, 1 point; right-side CDH, 2 points; and severe malformations, 3 points). Unsatisfactory prognosis rates for the low- (0-2 points), intermediate- (3-5 points), and high-risk (6-8 points) groups were 17, 46, and 100%, respectively (p < 0.001), in the validation cohort.Conclusion:  Our simple risk score effectively predicted the prognosis of fetuses with CDH. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel. [ABSTRACT FROM AUTHOR]

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]

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C–C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation. [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]

Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats. [ABSTRACT FROM AUTHOR]

Purpose: This study was aimed to evaluate the influence of timing of surgery on patient outcomes, and to clarify appropriate timing of surgery in neonates with congenital diaphragmatic hernia (CDH).Methods: A total of 477 neonates with isolated CDH were included. Patients were classified into two groups by timing of surgery: early repair (ER) (≤48 h) and delayed repair (DR) (>48 h). The primary outcome was 90-day survival, with treatment duration (ventilation, oxygen, and hospitalization) being a secondary outcome. To adjust for disease severity, patients were stratified into three severities by Apgar score 1 min ("mild" 8-10, "moderate" 4-7, and "severe" 0-3), and outcomes were compared between ER and DR within each severity.Results: Although 90-day survival was significantly different among the three severities ("mild" 97%, "moderate" 89%, and "severe" 76%, p = 0.002), there were no differences in 90-day survival between DR and ER within each severity. In "mild", there were no differences in treatment duration between ER and DR. In "moderate", treatment duration was shorter in ER than DR (ventilation 11 vs. 16 days, oxygen 15 vs. 20 days, and hospitalization 34 vs. 48 days). In "severe", treatment duration was shorter in ER than DR, while the best OI was higher in DR than ER.Conclusions: Timing of CDH repair seems to have no influence on 90-day survival regardless of disease severity. Patients with moderate severity may benefit from the early repair by reducing treatment duration. [ABSTRACT FROM AUTHOR]

Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings. [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: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. Case presentation: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy–Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1–qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3–qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. Conclusion: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy–Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). Methods: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. Results: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65–30.89], 11.14 (95% CI 5.19–23.89), and 10.28 (95% CI 3.38–31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. Conclusions: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH. [ABSTRACT FROM AUTHOR]

Purpose: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. Methods: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. Results: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02–13.30) was a favorable prognostic factor for the 90-day survival. Conclusion: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE). Methods: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries. Results: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH. Conclusions: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported. [ABSTRACT FROM AUTHOR]

Purpose: The carbonic anhydrase inhibitor dorzolamide can increase optic nerve blood flow. The aim of the study reported here was to investigate the effect of dorzolamide on isolated rabbit ciliary arteries that supply the optic nerve. Methods: Changes in ciliary artery isometric tension and intracellular Ca concentration ([Ca]) were recorded to elucidate the underlying pharmacologic mechanisms by which dorzolamide regulates blood flow to the optic nerve. Results: Dorzolamide induced concentration-dependent relaxation of rabbit ciliary arteries that had been precontracted by exposure to a high potassium (high-K) solution. Neither pretreatment with 10 µM KB-R 7943, an Na/Ca exchanger inhibitor, nor alkalinization of the high-K solution had an effect on the dorzolamide-induced relaxation. Pretreatment with 100 µM N-nitro- l-arginine methylester, a nitric oxide synthase inhibitor ( n = 10), 10 µM indomethacin, a prostacyclin inhibitor ( n = 9), or 0.1 µM iberiotoxin, an inhibitor of endothelium-derived hyperpolarizing factor ( n = 7), did not change the concentration-dependent relaxation induced by dorzolamide. Incubation with 3 mM dorzolamide in a Ca-free solution did not change the transient contractions of the rabbit ciliary arteries induced by 1 µM histamine ( n = 9). However, 3 mM dorzolamide significantly suppressed the increase in [Ca] induced by the reintroduction of Ca to a calcium-free extracellular medium ( P < 0.05). Furthermore, 3 mM dorzolamide significantly suppressed the [Ca] increase induced by the high-K solution ( P < 0.05). Conclusions: Taken together, our results reveal a novel role for dorzolamide in relaxing the ciliary arteries. Our data support the hypothesis that the vasodilatory action of dorzolamide is mediated by inhibition of Ca entry through voltage-dependent Ca channels. [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]

Purpose: Predicting lethal pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH) before extracorporeal membrane oxygenation (ECMO) initiation is difficult. This study aimed to predict lethal pulmonary hypoplasia in patients with CDH prior to ECMO. Methods: This was a multicenter cohort study involving neonates prenatally diagnosed with isolated unilateral CDH (born 2006–2020). Patients who required ECMO due to respiratory insufficiency were included in this study. Patients who underwent ECMO due to transient disorders were excluded from analysis. Blood gas analysis data within 24 h of birth were compared between survivors and non-survivors. Predictive abilities were assessed for factors with significant differences. Results: Overall, 34 patients were included (18 survivors and 16 non-survivors). The best pre-ductal PaO2 was significantly lower in non-survivors than in survivors (50.4 [IQR 30.3–64.5] vs. 67.5 [IQR 52.4–103.2] mmHg, respectively; p = 0.047). A cutoff PaO2 of 42.9 mmHg had a sensitivity, specificity, and positive predictive value of 50.0%, 94.4%, and 88.9%, respectively, to predict mortality. Conclusion: The best PaO2 within 24 h after birth predicted mortality following ECMO initiation. This should be shared to families and caregivers to optimize the best interests of the infants with CDH. [ABSTRACT FROM AUTHOR]

Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain. We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of <85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging. The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient. The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions. [ABSTRACT FROM AUTHOR]

Purpose: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). Methods: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. Results: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. Conclusions: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR. [ABSTRACT FROM AUTHOR]

Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation. [ABSTRACT FROM AUTHOR]

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]

Purpose: To date, there is no compelling evidence of the optimal timing of surgery for congenital diaphragmatic hernia (CDH). This study aimed to establish the optimal timing of surgery in neonates with isolated left-sided CDH. Methods: This multicenter cohort study enrolled 276 patients with isolated left-sided CDH at 15 institutions. Based on the timing of surgery, the patients were classified into four groups [< 24 h (G1), 24–47 h (G2), 48–71 h (G3), and ≥ 72 h (G4)]. The clinical outcomes were compared among the groups using a logistic regression model, after adjusting for potential confounders, such as disease severity. Results: Multivariate analyses showed that G2 also had a lower mortality rate than the other groups. In mild and severe cases, there were no significant differences in mortality across the four groups. In moderate cases, G2 resulted in significantly increased survival rates, compared with G1. Conclusion: The study results suggest that surgery within 24 h of birth is not recommended for patients with moderate severity CDH, that there is no benefit in the delay of surgery for more than 72 h in mild severity CDH patients, and that there is no definite optimal time to perform surgery in severe cases of CDH. [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]

Purpose: Growth retardation is a severe morbidity in infants with congenital diaphragmatic hernia (CDH). This study aimed to determine when catch-up growth starts in infants with CDH and to determine the adequate amount of nutrition required during catch-up growth. Methods: This was a multicenter retrospective cohort study involving neonates with isolated CDH (born 2006–2010; n = 98). Weight gain velocity (WGV) was calculated using body weight Z-scores. The minimum required weight gain was defined as WGV ≥ 0. Patients were dichotomized into severe and non-severe cases according to diaphragmatic defects. Results: Average monthly WGV changed from < 0 to ≥ 0 at 2 months of age. Total caloric intake at 2 months of age was lower when the WGV between 1 and 3 months was < 0 in both severe cases [122 (95% confidence interval (CI) 116–128) vs. 97 (95% CI 84–110) kcal/kg/day, p = 0.02] and non-severe cases [115 (95% CI 110–120) vs. 99 (95% CI 87–111) kcal/kg/day, p < 0.001)]. Conclusion: Catch-up growth started at approximately 2 months of age. During this period, total caloric intake of > 122 kcal/kg/day was needed to avoid decreases in the body weight Z-score in severe cases. [ABSTRACT FROM AUTHOR]