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.

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.

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.

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.

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.

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.

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.

Influence of Intrauterine Inflammation, Delivery, and Postnatal Feeding on the Temporal Changes of Serum Alpha 1 Acid Glycoprotein Levels in Extremely-Low-Birth-Weight Infants.

Infection remains the primary cause of death in extremely-low-birth-weight infants (ELBWIs). Alpha 1 acid glycoprotein (α1AG), an acute-phase protein, has been shown to be elevated in sporadic cases of septic ELBWIs prior to abnormal clinical signs. To delineate the roles of inflammation, delivery, and feeding in postnatal α1AG changes in ELBWIs, 75 ELBWIs of 26.5 ± 2.2 weeks of gestation born between May 2011 and August 2017 were retrospectively studied. The dependence of α1AG levels obtained on days 0−5 on the clinical variables was examined by incorporating interactions with age, followed by estimations of regression coefficients between clinical variables and α1AG levels at the early and late postnatal ages, defined by their standard deviation. Chorioamnionitis (p < 0.001), funisitis (p = 0.045), vaginal delivery (p = 0.025), enteral feeding (p = 0.022), and probiotics (p = 0.005) were associated with early α1AG elevations. Hypertensive disorder of pregnancy (p < 0.001) and gestational age (p = 0.001) were associated with late α1AG elevation; premature rupture of membranes (p < 0.001), funisitis (p = 0.021), body weight z-scores (p < 0.001), and enteral feeding (p = 0.045) were associated with late α1AG reduction. Postnatal α1AG changes in ELBWIs were associated with variables representative of age, growth, delivery, inflammation, and enteral feeding, potentially reflecting the process of sensitization to extrinsic microbes in utero, at birth, and thereafter.

Near-infrared light scattering and water diffusion in newborn brains.

OBJECTIVE: MRI provides useful information regarding brain maturation and injury in newborn infants. However, MRI studies are generally restricted during acute phase, resulting in uncertainty around upstream clinical events responsible for subtle cerebral injuries. Time-resolved near-infrared spectroscopy non-invasively provides the reduced scattering coefficient ( µ s ' ), which theoretically reflects tissue structural complexity. This study aimed to test whether µ s ' values of the newborn head reflected MRI findings. METHODS: Between June 2009 and January 2015, 77 hospitalised newborn infants (31.7 ± 3.8 weeks gestation) were assessed at 38.8 ± 1.3 weeks post-conceptional age. Associations of µ s ' values with MRI scores, mean diffusivity and fractional anisotropy were assessed. RESULTS: Univariable analysis showed that µ s ' values were associated with gestational week (p = 0.035; regression coefficient [B], 0.065; 95% confidence interval [CI], 0.005-0.125), fractional anisotropy in the cortical grey matter (p = 0.020; B, -5.994; 95%CI, -11.032 to -0.957), average diffusivity in the cortical grey matter (p < 0.001; B, -4.728; 95%CI, -7.063 to -2.394) and subcortical white matter (p = 0.001; B, -2.071; 95%CI, -3.311 to -0.832), subarachnoid space (p < 0.001; B, -0.289; 95%CI, -0.376 to -0.201) and absence of brain abnormality (p = 0.042; B, -0.422; 95%CI, -0.829 to -0.015). The multivariable model to explain µ s ' values comprised average diffusivity in the subcortical white matter (p < 0.001; B, -2.066; 95%CI, -3.200 to -0.932), subarachnoid space (p < 0.001; B, -0.314; 95%CI, -0.412 to -0.216) and absence of brain abnormality (p = 0.021; B, -0.400; 95%CI, -0.739 to -0.061). INTERPRETATION: Light scattering was associated with brain structure indicated by MRI-assessed brain abnormality and diffusion-tensor-imaging-assessed water diffusivity. When serially assessed in a larger population, µ s ' values might help identify covert clinical events responsible for subtle cerebral injury.

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.

Three-year outcome following neonatal encephalopathy in a high-survival cohort.

This study investigated the 3-year clinical outcomes in relation to the severity of encephalopathy in high-survival infants who underwent therapeutic hypothermia. This retrospective observational study was conducted in level II/III neonatal intensive care units in Japan. The nationwide cohort included 474 infants registered in the Baby Cooling Registry of Japan between January 2012 and December 2016. Clinical characteristics, mortality rate and severe neurological impairment at age 3 years were evaluated. Of the infants, 48 (10.4%), 291 (63.1%) and 122 (26.5%) had mild, moderate and severe encephalopathy, respectively, upon admission. By age 3, 53 (11.2%) infants died, whereas 110 (26.1%) developed major disabilities. The mild group survived up to age 3. In the moderate group, 13 (4.5%) died and 44 (15.8%) developed major disabilities. In the severe group, 39 (32.0%) died by age 3. Adverse outcomes were observed in 100 (82.0%) infants. Mortality was relatively low in all subgroups, but the incidence of major disabilities was relatively high in the severe group. The relatively low mortality and high morbidity may be due to Japanese social and ethical norms, which rarely encourage the withdrawal of intensive life support. Cultural and ethical backgrounds may need to be considered when assessing the effect of therapeutic interventions.

Postnatal Serum Total Thyroxine Level Associated with Short- and Long-Term Anthropometric Outcomes in Very Preterm Infants.

Thyroxine (T4) importantly regulates the growth of newborns. Compared to fetuses with equivalent gestational ages, very preterm infants (VPIs) often experience relatively low thyroxinemia, with a normal thyroid-stimulating hormone (TSH) concentration < 10 µIU/mL. However, there is continued debate regarding postnatal thyroxine supplementation for VPIs with normal TSH and transitionally low thyroxinemia. Little research has explored the role of the postnatal total T4 (TT4) serum concentration on the growth of VPIs. In this study, we aim to clarify whether the postnatal thyroxine concentration is associated with the short- and long-term growth outcomes of VPIs. A total of 334 surviving VPIs in our previously reported cohort, born in the period August 2007−July 2016, were enrolled. The exposure variable was the postnatal TT4 concentration at 1 month old. The primary outcomes were body weight increments over 28 days after the screening and anthropometric outcomes at the corrected age of 24 months old. Infants with any hormonal replacement, severe brain injury, congenital anomaly, or cerebral palsy were excluded. In total, 290 (86.8%) VPIs were included for analysis. In the 28 days after thyroid function screening, the TT4 concentration was found to have a significant association with positive increments in body weight (mean increment: 25.7 g per 1 µg/dL; p < 0.001) and a positive body weight z-score (mean increment: 0.039 per 1 µg/dL; p = 0.037), determined by generalized estimating equation analysis. At the corrected age of 24 months old, a higher postnatal TT4 concentration was associated with a lower body mass index (mean coefficient: −0.136; 95% CI: −0.231 to −0.041, p = 0.005) and lower body mass index z-score (mean coefficient: −0.097; 95% CI: −0.170 to −0.024, p = 0.009). Infants with a TT4 concentration > 6.4 ug/dL had significantly lower odds of overweight status (odds ratio: 0.365; 95% CI: 0.177 to 0.754, p = 0.006). We conclude that the postnatal TT4 concentration is associated with a positive increment in body weight in the short term. At the same time, the postnatal TT4 concentration is associated with lower odds of overweight status after long-term follow-up.

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.

A New Quantitative Triage System for Hospitalized Neonates to Assist with Decisions of Hospital Evacuation Priorities.

INTRODUCTION: Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. STUDY OBJECTIVE: To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). METHODS: In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. RESULTS: Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. CONCLUSIONS: Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

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.

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.

Influence of mothers' nighttime responses on the sleep-wake rhythm of 1-month-old infants.

The purpose of this study was to analyze the influence of the mothers' nighttime responses on the sleep-wake rhythm of their 1-month-old infants. This study used an anonymous self-administered survey questionnaire with 1133 mothers of 1-month-old infants. The questionnaire investigated basic information about the parents, growth environment of infants, mothers' sleep patterns during pregnancy, and infants' sleep patterns at the age of one month. Logistic regression analysis was used to analyze the influence of nighttime responses on the risk of infants sleeping longer during the day than at night. Regarding nighttime response behavior, it was found that immediately picking up 1-month-old infants results in longer sleep during the day than at night (OR 1.616 [1.017 - 2.566], p = 0.042), compared to delaying picking up the infant. It was suggested that the stimulation due to picking up an infant may affect sleep-wake rhythm formation.

Foetal growth, birth transition, enteral nutrition and brain light scattering.

If the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (µS') obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether µS' obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of µS', birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher µS' values were associated with higher Apgar scores (p = 0.003) and earlier establishment of enteral feeding (p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.