Predictive value of the Thompson score for short-term adverse outcomes in neonatal encephalopathy.

BACKGROUND: To explore the predictive value of the Thompson score during the first 4 days of life for estimating short-term adverse outcomes in neonatal encephalopathy. METHODS: This observational study evaluated infants with neonatal encephalopathy (≥36 weeks of gestation) registered in a multicenter cohort of cooled infants in Japan. The Thompson score was evaluated at 0-24, 24-48, 48-72, and 72-90 h of age. Adverse outcomes included death, survival with respiratory impairment (requiring tracheostomy), or survival with feeding impairment (requiring gavage feeding) at discharge. RESULTS: Of the 632 infants, 21 (3.3%) died, 59 (9.3%) survived with respiratory impairment, and 113 (17.9%) survived with feeding impairment. The Thompson score throughout the first 4 days accurately predicted death, respiratory impairment, or feeding impairment. The 72-90 h score showed the highest accuracy. A cutoff of ≥15 had a sensitivity of 0.85 and specificity of 0.92 for death or respiratory impairment, while a cutoff of ≥14 had a sensitivity of 0.71 and a specificity of 0.92 for death, respiratory or feeding impairment. CONCLUSION: A high Thompson score during the first 4 days of life, especially at 72-90 h could thus be useful for estimating the need for prolonged life support. IMPACT: The Thompson score on days 1-4 of age was useful in predicting death and respiratory or feeding impairments. The 72-90 h Thompson score showed the highest predictive capability. Owing to the rarity of withdrawal of life-sustaining treatment in Japan, 43% of infants with persistent severe encephalopathy with a Thompson score of ≥15 at 72-90 h of age could regain spontaneous breathing, be extubated, and survive without tracheostomy. Meanwhile, approximately 50% of infants who survived without tracheostomy required gavage feeding. Our results could provide useful information for clinical decision making regarding infants with persistent severe encephalopathy.

Prolonged requirements for mechanical ventilation and tube feeding support predicted 18-month outcomes for neonatal encephalopathy.

AIM: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia. METHODS: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. RESULTS: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85). CONCLUSION: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia.

Body temperature, heart rate and long-term outcome of cooled infants: an observational study.

BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.

Validation of actigraphy in hospitalised newborn infants using video polysomnography.

Actigraphy has been established as a reliable sleep assessment tool in adults; however, its utility in newborns remains unknown. Validation of actigraphy in newborns may provide a significant insight into the physiological and pathological acquisition process of mature diurnal sleep patterns and subsequent morbidities in both newborns and their mothers. Thus, the present study aimed to evaluate the accuracy of sleep-wake detection by overnight actigraphy in a cohort of newborns. Simultaneous recording of polysomnography and actigraphy data was performed in 40 newborns admitted to a tertiary neonatal intensive care unit (NICU). A mixed-effects logistic regression model to explain the sleep state identified by polysomnography was employed using the actigraphic activity score as a fixed independent variable and the individual newborn's identity as a random effect. To evaluate the usefulness of the actigraphic activity score as a surrogate marker of sleep, a receiver operating characteristic (ROC) curve analysis was performed using the variables that were used in the mixed-effects logistic regression model, and the area under the curve (AUC) was assessed. The results showed that polysomnography-determined sleep epochs were associated with a smaller activity index on actigraphy (odds ratio per 10 activity indices increase 0.81, 95% confidence interval [CI] 0.79-0.84). The AUC for the ROC curve was 0.87 (95% CI 0.87-0.88, range 0.54-0.99). An activity score of 124 showed the maximum overall accuracy (90.2%, 95% CI 87.7-92.1). Our present study suggests that sleep-wake states of NICU-hospitalised newborns can be precisely determined using actigraphy on the ankle.

Early-life respiratory trajectories and neurodevelopmental outcomes in infants born very and extremely preterm: A retrospective study.

AIM: To determine whether early-life respiratory trajectories are associated with neurodevelopmental impairment (NDI) in infants born very and extremely preterm. METHOD: The daily type of respiratory supports in the first 8 weeks after birth were analysed in 546 infants (285 males, 261 females; median gestational age = 28.0 weeks, interquartile range = 3 weeks), comprising 301 infants born very preterm (gestation = 28-30 weeks) and 245 infants born extremely preterm (gestation <28 weeks), who survived to discharge from 2004 to 2018 and received follow-up assessment by Bayley Scales of Infant and Toddler Development at a corrected age of 24 months. NDI included cognition or motor impairment, moderate and severe cerebral palsy, or visual and hearing impairment. RESULTS: Clustering analysis identified three respiratory patterns with increasing severity: improving; slowly improving; and delayed improvement. These were significantly associated with increasing rates of NDI in infants born very and extremely preterm and smaller head circumference in infants born extremely preterm (both p < 0.001). By day 28, the proportion of infants who were under different categories of ventilation support significantly differed according to the three trajectory groups in infants born very and extremely preterm (both p < 0.05). Models that included adverse respiratory trajectories demonstrated more negative impacts on neurodevelopment than those without. INTERPRETATION: An adverse early-life respiratory trajectory was associated with NDI at follow-up, especially in infants born extremely preterm, suggesting a lung-brain axis of preterm birth. WHAT THIS PAPER ADDS: Clustering analysis identified three respiratory trajectories with increasing severity in infants born preterm. Increasing severity of respiratory trajectories was associated with increasing rates of neurodevelopmental impairment. Adverse respiratory trajectories had a significantly negative impact on neurodevelopmental outcomes.

OBJETIVO: Determinar se as trajetórias respiratórias no início da vida estão associadas ao comprometimento do neurodesenvolvimento (CND) em bebês nascidos muito e extremamente prematuros. MÉTODOS: O tipo diário de suporte respiratório nas primeiras 8 semanas após o nascimento foi analisado em 546 bebês (285 meninos, 261 meninas; idade gestacional mediana = 28,0 semanas, intervalo interquartil = 3 semanas), compreendendo 301 bebês nascidos muito prematuros (gestação = 28-30 semanas) e 245 bebês nascidos extremamente prematuros (gestação < 28 semanas), que sobreviveram à alta entre 2004 e 2018 e receberam avaliação de seguimento por meio da Bayley Scales of Infant and Toddler Development na idade corrigida de 24 meses. O CND incluiu deficiência cognitiva ou motora, paralisia cerebral moderada e grave ou deficiência visual e auditiva. RESULTADOS: A análise de agrupamento identificou três padrões respiratórios com gravidade crescente: melhorando; melhorando lentamente; e melhora tardia. Estes foram significativamente associados com taxas crescentes de CND em bebês nascidos muito e extremamente prematuros e menor perímetro cefálico em bebês nascidos extremamente prematuros (ambos p < 0,001). No dia 28, a proporção de bebês que estavam sob diferentes categorias de suporte ventilatório diferiu significativamente de acordo com os três grupos de trajetória em bebês nascidos muito prematuros e extremamente prematuros (ambos p < 0,05). Os modelos que incluíram trajetórias respiratórias adversas demonstraram mais impactos negativos no neurodesenvolvimento do que aqueles sem. INTERPRETAÇÃO: Uma trajetória respiratória adversa no início da vida foi associada ao CND no seguimento, especialmente em bebês nascidos extremamente prematuros, sugerindo um eixo pulmão-cérebro de nascimento prematuro.

Revisions of clinical protocols using the Plan Do Check Act cycle improved outcomes of extremely preterm infants at 2 years.

AIM: Clinical quality improvement is often cumbersome due to established protocols. We aimed to investigate whether outcomes of preterm infants improve with protocol revisions using iteration cycles. METHODS: Preterm infants born <28 weeks gestation between January 2006 and December 2015 were retrospectively analysed. Protocols were revised using Plan Do Check Act cycle. Death and serious adverse events at term were reviewed in six-monthly quality improvement meetings. Adverse outcome of death or motor/sensory impairments at two years was compared before and after two major protocol changes, which were implemented in January 2008 and January 2012. RESULTS: Based on the appraisal for period 2006-2007, strategies for surfactant, narcotics, parenteral nutrition, respiratory gas humidity and prophylactic indomethacin and antibiotics were changed for period 2008-2011. For period 2012-2015, stabilisation of infants was accelerated via very early catheterisation. Of 162 infants (84 males, 25.5 ± 1.5 weeks gestation) within the whole cohort, 63 developed adverse outcomes, which were fewer for periods 2008-2011 (p = 0.013) and 2012-2015 (p = 0.035) compared with period 2006-2007 (adjusted for gestational age, Apgar scores and sex). CONCLUSION: Careful bottom-up revisions of protocols using iteration cycles, accounting for local settings, successfully improved the outcomes of preterm infants.

Dependence of Successful Airway Management in Neonatal Simulation Manikins on the Type of Supraglottic Airway Device and Providers' Backgrounds.

Supraglottic airway devices such as laryngeal masks and i-gels are useful for airway management. The i-gel is a relatively new device that replaces the air-inflated cuff of the laryngeal mask with a gel-filled cuff. It remains unclear which device is more effective for neonatal resuscitation. We aimed to evaluate the dependence of successful airway management in neonatal simulators on the device type and providers' backgrounds. Ninety-one healthcare providers performed four attempts at airway management using a laryngeal mask and i-gel in two types of neonatal manikins. The dependence of successful insertions within 16.7 s (75th percentile of all successful insertions) on the device type and providers' specialty, years of healthcare service, and completion of the neonatal resuscitation training course was assessed. Successful insertion (p = 0.001) and insertion time (p = 0.003) were associated with using the i-gel vs. laryngeal mask. The providers' backgrounds were not associated with the outcome. Using the i-gel was associated with more successful airway management than laryngeal masks using neonatal manikins. Considering the limited effect of the provider's specialty and experience, using the i-gel as the first-choice device in neonatal resuscitation may be advantageous. Prospective studies are warranted to compare these devices in the clinical setting.

Intrauterine Inflammation, Excessive Fetal Growth and Respiratory Morbidities in Moderate-To-Late Preterm Neonates.

INTRODUCTION: Respiratory morbidities in neonates are often progressive and life-threatening, and its early prediction is crucial. Intrauterine inflammation is one of the key control variables of respiratory morbidities in both very preterm and term neonates; however, little is known about its effects in the remaining group of moderate-to-late preterm neonates born between 32+0 and 36+6 weeks of gestation. This study aimed to confirm whether intrauterine inflammation is associated with respiratory morbidities in moderate-to-late preterm neonates. METHODS: A single-center retrospective observational study was conducted in neonates born between 32+0 and 34+6 weeks of gestation between April 2013 and March 2018. The correlation between respiratory morbidities (defined as a requirement for invasive mechanical ventilation longer than the median duration of 3 days) and intrauterine inflammation was assessed using multivariable logistic regression analysis. RESULTS: The study population comprised 242 neonates born at 33.7 ± 0.8 weeks of gestation and weighing 1,936 ± 381 g. The multivariable model to predict the outcome comprised respiratory distress syndrome (odds ratio [OR]: 9.1; 95% confidence interval [CI]: 3.7-22.5; p < 0.001), lower gestational age (per week; OR: 0.5; 95% CI: 0.3-0.8; p < 0.005), higher birth-weight z-score (OR: 1.6; 95% CI: 1.2-2.2; p < 0.005), lower cord blood pH (per 0.10; OR: 0.5; 95% CI: 0.3-0.7; p < 0.005), and chorioamnionitis (OR: 2.8; 95% CI: 1.1-7.2; p < 0.05). CONCLUSION: Together with the incidence of respiratory distress syndrome and gestational age, chorioamnionitis and high birth-weight z-scores were associated with an increased incidence of respiratory morbidities in moderate-to-late preterm neonates. The deleterious impact of intrauterine inflammation on the lungs may be common in neonates of virtually all gestational ages. Traditional admission policy of neonatal intensive care units based on a threshold birth-weight, may leave a group of neonates without close observation despite their increased risks for respiratory morbidities.

Body Size, Cerebral Blood Flow, Ambient Temperature, and Relative Brain Temperatures in Newborn Infants under Incubator Care.

Subtle changes in body temperature affect the outcomes of ill newborns. However, the temperature profile of neonatal brains remains largely unknown. In open-cot care, increased cerebral perfusion is correlated with higher superficial brain temperatures. This study investigated the dependence of brain temperature (relative to rectal temperature) on ambient temperature, body size, cerebral perfusion, and metabolism in infants receiving incubator care. Rectal, scalp, and brain temperatures, superior vena cava flow, and brain oxygenation were assessed using echocardiography, thermo-compensatory temperature monitoring, and near-infrared spectroscopy in 60 newborns. These infants had a mean postconceptional age of 36.9 (2.2) weeks and weighed 2348 (609) g at the time of evaluation. The ambient temperature was maintained at 30.0 (1.0) °C. A higher rectal temperature was associated with greater postconceptional age (p = 0.002), body weight (p < 0.001), and head circumference (p < 0.001). Relative scalp, superficial brain, and deep brain temperatures were associated with smaller head circumference (p < 0.001, p = 0.030, and p = 0.015, respectively) and superior vena cava flow (p = 0.002, p = 0.003, and p = 0.003, respectively). In infants receiving incubator care, larger head sizes and increased brain perfusion were associated with lower relative scalp and brain temperatures. When considered alongside previous reports, cerebral perfusion may contribute to maintaining stable cerebral tissue temperature against ambient temperature changes.

Antenatal Growth, Gestational Age, Birth, Enteral Feeding, and Blood Citrulline Levels in Very Low Birth Weight Infants.

Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders.

Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model.

Na⁺/H⁺ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (³¹P) and proton (¹H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model.

Infection surveillance after a natural disaster: lessons learnt from the Great East Japan Earthquake of 2011.

PROBLEM: On 11 March 2011, the Great East Japan Earthquake produced a catastrophic tsunami that devastated the city of Rikuzen-Takata and left it without an effective health infrastructure and at increased risk of outbreaks of disease. APPROACH: On 2 May 2011, a disease-surveillance team was formed of volunteers who were clinicians or members of Rikuzen-Takata's municipal government. The team's main goal was to detect the early signs of disease outbreaks. LOCAL SETTING: Seven weeks after the tsunami, 16 support teams were providing primary health care in Rikuzen-Takata but the chain of command between them was poor and 70% of the city's surviving citizens remained in evacuation centres. The communication tools that were available were generally inadequate. RELEVANT CHANGES: The surveillance team collected data from the city's clinics by using a simple reporting form that could be completed without adding greatly to the workloads of clinicians. The summary findings were reported daily to clinics. The team also collaborated with public health nurses in rebuilding communication networks. Public health nurses alerted evacuation centres to epidemics of communicable disease. LESSONS LEARNT: Modern health-care systems are highly vulnerable to the loss of advanced technological tools. The initiation--or re-establishment--of disease surveillance following a natural disaster can therefore prove challenging even in a developed country. Surveillance should be promptly initiated after a disaster by (i) developing a surveillance system that is tailored to the local setting, (ii) establishing a support team network, and (iii) integrating the resources that remain--or soon become--locally available.

Sleep patterns of Japanese preschool children and their parents: implications for co-sleeping.

AIM: The aim of this study was to investigate the direct relationship of sleep schedule and sleep quality variables between healthy preschool children and their parents, focusing on the influence of the difference in bedtime between each other. METHODS: Forty-seven Japanese 5-year-old children and their primary parent were studied. The parents completed questionnaires including the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The children wore an actigraph for one week. RESULTS: Although sleep patterns of children were generally independent of their parents, late sleep end time and bedtime of children were associated with parents' late sleep end time on weekends. For 87% of children and parents who shared a bedroom, sleep quality was negatively affected by a shorter difference in bedtimes between child and parent, but not by co-sleeping. CONCLUSION: Sleep behaviours of parents can influence those of their children. For parents and children who share a bedroom, the timing of bedtime rather than co-sleeping may be a key factor in modulating sleep patterns. Trying to get children asleep and subsequently falling asleep at a similar time may disturb parents' sleep quality, which may subsequently affect that of their children.

Control variables of serum ferritin concentrations in hospitalized newborn infants: an observational study.

Both iron excess and deficiency are deleterious to cellular and organ homeostasis. Serum ferritin levels serve as a biomarker of iron storage; however, their distribution and determinants in sick newborn infants remain unclear. This study aimed to investigate the reference range and independent variables of serum ferritin in hospitalized newborn infants. All newborn infants who were hospitalized at a tertiary neonatal center within 24 h of birth were retrospectively reviewed for the period of April 2015 through March 2017. Serum ferritin levels were assessed using venous blood samples obtained at admission and their independent variables were explored. The study population comprised 368 infants (36.2 ± 2.8 weeks gestation and 2319 ± 623 g at birth), whose median serum ferritin level was 149 µg/L (inter-quartile range: 81-236). The multivariable model used to explain serum ferritin values comprised hemoglobin, lactate dehydrogenase, blood pH, and maternal hypertensive disorders in pregnancy (all p < 0.01, adjusted for sex and birth weight). Serum ferritin values in hospitalized newborn infants were comparable to those previously reported using umbilical cord blood. Our novel findings indicated the association between blood pH, lactate dehydrogenase, and ferritin levels, suggesting the influence of antenatal hypoxia-ischemia and stress to serum ferritin levels.

Autistic traits of children born very preterm assessed using Autism Diagnostic Observation Schedule, Second Edition.

Preterm birth has been linked with increased incidence of autism spectrum disorder (ASD). Despite the remarkable difference in the clinical backgrounds between ASD children born preterm and term, cross-sectional studies have found no striking difference in their autistic traits. To highlight autistic traits related with preterm birth, children born very preterm (prospective birth cohort, n = 50) and term (case cohort, n = 16), who were diagnosed as "Autism" by the Autism Diagnostic Observation Schedule (ADOS), 2nd edition, were compared using the calibrated severity scores of ADOS-2 and T-scores of the Social Responsiveness Scale, 2nd edition. No significant difference was found in the calibrated severity scores between ASD children born preterm and term. There was a trend that T-scores were smaller for the preterm cohort, which did not reach a statistical significance. Even when detailed cross-sectional information was obtained using ADOS-2, no difference in autistic traits was observed between children born very preterm and term. Our findings were consistent with a previous study, which assessed the entire prospective cohort of children born very preterm and found no difference in original ADOS scores. Further studies are warranted to delineate how preterm birth affects the autistic traits and their parental perception in a large prospective cohort.

Furin Regulates the Alveolarization of Neonatal Lungs in a Mouse Model of Hyperoxic Lung Injury.

Despite advances in treatment options, such as corticosteroid administration and less invasive respiratory support, bronchopulmonary dysplasia (BPD) remains an important prognostic factor in preterm infants. We previously reported that furin regulates changes in lung smooth muscle cell phenotypes, suggesting that it plays a critical role in BPD pathogenesis. Therefore, in this study, we aimed to evaluate whether it regulates the alveolarization of immature lungs through activating alveolarization-driving proteins. We first examined furin expression levels, and its functions, using an established hyperoxia-induced BPD mouse model. Thereafter, we treated mice pups, as well as primary myofibroblast cell cultures, with furin inhibitors. Finally, we administered the hyperoxia-exposed mice pups with recombinant furin. Immunofluorescence revealed the co-expression of furin with alpha-smooth muscle actin. Hyperoxia exposure for 10 d decreased alveolar formation, as well as the expression of furin and its target, IGF-1R. Hexa-D-arginine administration also significantly inhibited alveolar formation. Another furin inhibitor, decanoyl-RVKR-chloromethylketone, accumulated pro-IGF-1R, and decreased IGF-1R phosphorylation in myofibroblast primary cultures. Finally, recombinant furin treatment significantly improved alveolarization in hyperoxia-exposed mice pups. Furin regulates alveolarization in immature lungs. Therefore, this study provides novel insights regarding the involvement of furin in BPD pathogenesis, and highlights a potential treatment target for ameliorating the impact of BPD.

Sleep architecture in healthy 5-year-old preschool children: associations between sleep schedule and quality variables.

AIM: Although disturbed sleep quality such as night awakenings and difficulties in falling asleep are common symptoms during sleep in preschool children, relationships between sleep quality and sleep schedule are mostly unknown. This study aimed to evaluate the relationships between sleep schedule and quality variables in preschool children. METHODS: Sleep-wake patterns of 48 healthy 5-year-old children were assessed over 7 consecutive days using actigraphy. RESULTS: Children with longer sleep latency had a lower sleep quality, a later bedtime, a later sleep onset time, a shorter nocturnal sleep period and a longer daytime nap. Children with a longer nocturnal sleep period on weekends compared with weekdays had longer sleep latency and a later sleep onset time on weekdays, resulting in a lower sleep quality on weekends. An irregular bedtime on weekdays was associated with a later sleep onset time and a shorter sleep period on weekends. CONCLUSION: Sleep quality and schedule were linked with each other, which may explain why sleep problems tend to aggregate and form a wider syndrome of disturbed sleep even in young children. Strategies solely targeting the improvement of sleep quantity may not promote ideal sleep; simultaneous considerations for the sleep rhythm and quality may be required.

Hypothermia for neonatal encephalopathy: Nationwide Survey of Clinical Practice in Japan as of August 2010.

BACKGROUND: Therapeutic hypothermia is now recommended as a standard of care for neonatal encephalopathy. Although adherence to standard cooling protocols used in the phase-III trials is essential, empiric approaches have prevailed in Japan. AIM: To elucidate the gap between the standard cooling methods and the current practice in Japan. METHOD: In July 2010, a questionnaire regarding the practice of neonatal encephalopathy was mailed to clinical leads of registered neonatal intensive care units. RESULT: 56.2% of the units were incapable of offering therapeutic hypothermia because of the reasons such as the shortage of human/medical resources (85.1%) and limited number of cases (21.1%). Eighty-nine centres provided therapeutic hypothermia using either selective-head cooling (88.8%) or whole-body cooling (11.2%). Various target temperatures and cooling durations were used; 20.2% of the units cooled infants without using purpose-built equipments, whereas 14.6% did not continuously monitor the body temperature. DISCUSSION: Only 43.8% of the units provided therapeutic hypothermia. Even in centres where hypothermia was offered, adherence to the standard protocols was extremely poor. To secure the safety and efficacy, further promotion of the standard cooling protocols is required; an efficient cooling centre network has to be established by optimizing the work forth distribution and transportation system.

Diagnostic rate of autism spectrum disorder in a high-survival cohort of children born very preterm: A cross-sectional study.

To investigate the diagnostic rate of autism spectrum disorder (ASD) in a high-survival cohort of very preterm children, 77 infants born very preterm (<32 weeks of gestation) were assessed at age 4-6 years old using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Sixteen children (20.8%) were classified as both DSM-5-positive ASD and ADOS-2-identified "autism," which were defined as confirmed ASD in this study. Our result suggests that the prevalence of ASD in very preterm children might be much higher than reported in previous studies when all children were individually evaluated. Further studies in a large sample are required to clarify the true risk of ASD in preterm birth.

Admission temperature of very low birth weight infants and outcomes at three years old.

The lower body temperature of preterm newborns at admission to neonatal intensive care units (NICUs) is inversely associated with their morbidities and mortalities before discharge. This retrospective cohort study aimed to determine whether admission rectal temperature in very low birth weight infants (VLBWIs) is independently associated with a composite outcome of death or moderate-to-severe neurodevelopmental impairments as defined by a performance developmental quotient of < 70 at three years of age. VLBWIs admitted to the NICU between April 2010 and March 2016 were assesed. Developmental assessment was completed in 216 newborns. Nine and two infants died before and after discharge, respectively. A higher admission temperature was associated with a lower incidence of death or moderate-to-severe neurodevelopmental impairments with adjustment for gestational age, sex, antenatal steroid use, Apgar score, severe intraventricular hemorrhage, and severe bronchopulmonary dysplasia (odds ratio [OR] 0.424; 95% confidence interval [CI] 0.250-0.717; p = 0.001). The admission temperature remained as an independent variable of adverse outcome at three years of age even when the study cohort was limited to surviving infants (OR 0.448; 95% CI 0.259-0.774; p = 0.004). Further studies are needed to assess whether avoiding low body temperature at admission results in better long-term neurodevelopmental outcomes in VLBWIs.