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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Foetal hypoxia–ischaemia is a key trigger of meconium aspiration syndrome (MAS). However, many neonates develop MAS without evidence of hypoxia–ischaemia, suggesting the presence of covert but important risk variables. We evaluated the association of MAS with clinical variables, placental histopathologic findings, and inflammatory biomarkers at birth. Of 1336 symptomatic and asymptomatic term singleton neonates with meconium-stained amniotic fluid, 88 neonates (6.6%) developed MAS. Univariate analysis showed that MAS development was associated with low 1- and 5-min Apgar scores, low cord blood pH, funisitis, higher α1-acid glycoprotein levels, and higher haptoglobin levels (all p < 0.001 except for p = 0.001 for haptoglobin). Associations of MAS with caesarean delivery (p = 0.004), premature rupture of the membranes (p = 0.006), chorioamnionitis (p = 0.007), and higher C-reactive protein levels (p = 0.008) were lost when adjusted for multiple comparisons. The final multivariate model to explain MAS development comprised lower cord blood pH (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.47–0.73; p < 0.001), funisitis (OR 2.45; 95% Cl 1.41–4.26; p = 0.002), and higher α1-acid glycoprotein levels (OR 1.02; 95% Cl 1.01–1.03; p = 0.001). Our data from a large cohort of neonates suggested that intrauterine inflammation is one of the key independent variables of MAS development, together with foetal hypoxia–ischaemia. [ABSTRACT FROM AUTHOR]

Background: Newborn infants hospitalised in the neonatal intensive care unit (NICU) are vulnerable to natural disasters. However, publications on evacuation from NICUs are sparse. The 2016 Kumamoto Earthquakes caused serious damage to Kumamoto City Hospital and its level III regional core NICU. Local/neighbour NICU teams and the disaster-communication team of a neonatal academic society cooperated to evacuate 38 newborn infants from the ward. Objective: The aim of this paper was to highlight potential key factors to improve emergency NICU evacuation and coordination of hospital transportation following natural disasters. Methods: Background variables including clinical risk scores and timing/destination of transportation were compared between infants, who subsequently were transferred to destinations outside of Kumamoto Prefecture, and their peers. Results: All but 1 of the infants were successfully evacuated from their NICU within 8 h. One very-low-birth-weight infant developed moderate hypothermia following transportation. Fourteen infants were transferred to NICUs outside of Kumamoto Prefecture, which was associated with the diagnosis of congenital heart disease, dependence on respiratory support, higher risk scores, and longer elapsed time from the decision to departure. There was difficulty in arranging helicopter transportation because the coordination office of the Disaster Medical Assistance Team had requisitioned most air/ground ambulances and only helped arrange ground transportations for 13 low-risk infants. Transportation for all 10 high-risk infants (risk scores greater than or equal to the upper quartile) was arranged by local/neighbour NICUs. Conclusions: Although the overall evacuation process was satisfactory, potential risks of relying on the adult-based emergency transportation system were highlighted. A better system needs to be developed urgently to put appropriate priority on vulnerable infants. [ABSTRACT FROM AUTHOR]

The article presents case study of a 41-year old woman who gave birth to a male neonate who developed a premature rupture of fetal membranes. Topics discussed include several drugs administered to the patient, which include ritodrine hydrochloride, prophylactic antibiotics, and betamethasone, balloon atrial septostomy (BAS), and intubation for surfactant replacement therapy and mechanical ventilation for the newborn baby.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, whiche 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. [ABSTRACT FROM AUTHOR]

Abstract: Neonatal encephalopathy (NE) secondary to intrapartum asphyxia remains a major cause of post-natal death and permanent neurological deficits worldwide. Supportive therapy has been the mainstay of the treatment until recent series of large clinical trials demonstrating benefit of therapeutic hypothermia (TH) in this high risk population. Now the International Liaison Committee on Resuscitation (ILCOR) recommends TH as a standard of care with the protocols used in the large clinical trials as tentative standard protocols. Our goal is to develop a nationwide consensus practice guideline not only consistent with the international standard protocols but also practical and compatible with the current medical system in Japan. In summary, TH should be offered to newborn infants born ⩾36weeks gestational age and birth weight ⩾1800g exhibiting clinical signs of moderate to severe NE as well as evidence of hypoxia–ischemia, i.e. 10min Apgar score ⩽5, a need for resuscitation at 10min, blood pH<7.00, or base deficit ⩾16mmol/L. TH should be conducted in the NICUs capable of multidisciplinary care and under the standard protocols, i.e. utilization of cooling device, target (rectal or esophageal) temperatures at 33.5±0.5 and 34.5±0.5°C for whole body and selective head cooling respectively, duration of TH for 72h, gradual rewarming not exceeding the rate of 0.5°C/h. Long term follow-up with multidisciplinary approach including standardized psychological assessment is warranted. [Copyright &y& Elsevier]

Abstract: Neonatal encephalopathy associated with perinatal hypoxia–ischaemia is one of the most common causes of death and permanent disability worldwide. However, of a wide range of “experimentally neuroprotective treatments” invented so far, only therapeutic hypothermia has been promoted into a standard clinical practice. Such a wide gap in the efficacy of neuroprotective treatments between the experimental setting and clinical practice may be attributed to the strategic flaw in translating basic knowledge into clinical care. When previous clinical studies are carefully reviewed, one may notice that few therapeutic options were chosen based on their track records in experimental studies; protective effects of some drugs had been assumed only based on their pharmacokinetics in adult species; several therapies were chosen merely because clinicians were familiar to these treatments for other purpose; some other therapies were imported too preliminarily from laboratory to clinical practice, potentially ignoring the difference in physiological and pathological backgrounds between rodent models and human patients. When further clinical trials are planned, it is important to ask whether (i) the treatment is supported by pharmacokinetics specific to immature brain, and (ii) the neuroprotective effect of the treatment has consistently been demonstrated using clinically relevant models and study designs. The use of translational large animal models allows the practical simulation and fine-tuning of clinical protocols, which may further assist successful translation of basic knowledge. In addition to the effort to develop alternative therapeutic options, it is important to maximise the effect of the current only neuroprotective option, or therapeutic hypothermia. Independent variables which influence the efficacy of hypothermia have to be elucidated to improve its therapeutic protocol, and to increase the number of patients who will benefit from this treatment. [Copyright &y& Elsevier]

Abstract: Background: Early childhood is an important period for the development of sleep patterns; studies of sleep patterns in young preschool children may help elucidate the mechanism of associated mental/physical conditions and later sleep problems. Aim and methods: The aim of this study was to investigate intrinsic and extrinsic independent variables associated with sleep patterns in preschool children using actigraphy. Forty-eight 5-year-old children from two types of nurseries, which accommodate children with (Type A) or without (Type B) in-home caregivers, were invited to undergo a 7-day actigraphic sleep study. Results: Compared with weekdays, both sleep onset time and sleep end time were later on weekends (28 and 17min later in average, respectively). On weekdays, cultural lessons were associated with a later sleep onset time (22min later); female gender, sports lessons and fixed bathing times were related with an earlier sleep end time (17, 21 and 17min earlier, respectively); sports lessons were also associated with higher sleep efficiency (3.7% higher). During weekends, unfixed bedtimes and daytime naps were related with a later sleep onset time (73 and 54min later, respectively); male gender, Type A nursery and daytime naps were associated with a later sleep end time (33, 37 and 34min later, respectively); sports lessons were associated with higher sleep efficiency (3.6% higher). Conclusions: Our current findings suggested that both intrinsic and extrinsic factors, such as gender, child care, lifestyle and after-nursery lessons, influence the establishment of sleep patterns in young preschool children. Further investigation of these independent variables may help establish a strategy for predicting and preventing sleep disorders later in life. [Copyright &y& Elsevier]

Abstract: Background: The seroprevalence of Human T-cell Leukemia Virus Type 1 (HTLV-1) is female predominant despite the higher incidence of Adult T-cell Leukemia (ATL) in males. If the mother-to-child transmission of HTLV-1 is more common for male infants than in female infants, longer exposure to the virus for males may explain the paradoxically higher incidence of ATL. Objectives: To test the hypothesis that the seroprevalence of HTLV-1 is male predominant during adolescence. Study design: The presence of HTLV-1 antibody in 272,043 blood samples donated to a regional blood bank in an HTLV-1 high-endemic region was assessed. Results: The entire population of female donors had a significantly higher seroprevalence compared to males (2.05% and 1.80%, respectively, p <0.0001). However, compared with male donors, the carrier rate for female donors was lower for the youngest subgroup (16–19 years, p =0.0011); was similar for the next two age subgroups (20–29 years and 30–39 years); and was significantly higher for the last two age subgroups (40–49 years and over 50–64 years, both p <0.0001). In general, older age subgroups led to higher seroprevalence in both genders. Conclusions: HTLV-1 infection is more common for males until after age 20, when male to female sexual transmission becomes likely. This suggests that mother-to-child transmission is more common for males. [Copyright &y& Elsevier]

Phosphorus magnetic resonance spectroscopy (31P MRS) often reveals apparently normal brain metabolism in the first hours after intrapartum hypoxia-ischemia (HI) at a time when conventional clinical assessment of injury severity is problematic. We aimed to elucidate very-early, injury-severity biomarkers. Twenty-seven newborn piglets underwent cerebral HI: 31P-MRS measures ∼2 h after HI were compared between injury groups defined by secondary-energy-failure severity as quantified by the minimum nucleotide triphosphate (NTP) observed after 6 h. For severe and moderate injury versus baseline, [Pi]/[total exchangeable high-energy phosphate pool (EPP)] was increased ( p < 0.001 and < 0.02, respectively), and [NTP]/[EPP] decreased ( p < 0.03 and < 0.006, respectively): severe-injury [Pi]/[EPP] was also increased versus mild injury ( p < 0.04). Mild-injury [phosphocreatine]/[EPP] was increased ( p < 0.004). Severe-injury intracellular pH was alkaline versus baseline ( p < 0.002). For severe and moderate injury [total Mg]/[ATP] ( p < 0.0002 and < 0.02, respectively) and [free Mg] ( p < 0.0001 and < 0.02, respectively) were increased versus baseline. [Pi]/[EPP], [phosphocreatine]/[Pi] and [NTP]/[EPP] correlated linearly with injury severity ( p < 0.005, < 0.005 and < 0.02, respectively). Increased [Pi]/[EPP], intracellular pH and intracellular Mg ∼2 h after intrapartum HI may prognosticate severe injury, whereas increased [phosphocreatine]/[EPP] may suggest mild damage. In vivo31P MRS may have potential to provide very-early prognosis in neonatal encephalopathy. [ABSTRACT FROM AUTHOR]

Abstract: Preterm infants are at significant risk of neuro-developmental disorders at school-age. MRI is a potentially useful screening tool of such disorders. Using FLAIR imaging in the preterm infants at term, here we demonstrate that abnormal low-intensity signal in the white matter predicts the neuro-developmental outcome at 6 years. Study design: Clinical factors associated with white matter appearance on MRI obtained at term were investigated in 210 preterm infants. Results: Low-intensity signal on FLAIR imaging was commonly observed (69%) at <2 months corrected-age. Its incidence correlated with corrected-age at scan, maternal pyrexia and cystic periventricular leukomalacia. Low-intensity signal on FLAIR significantly correlated with performance and full-scale developmental quotients, whereas diffuse high-intensity signal on T2-weighted imaging correlated only with the full-scale developmental quotient at 6 years (n =75, WISC-R). FLAIR imaging, but not T2-weighted imaging, predicted mild neuro-developmental delay. Conclusions: FLAIR appeared to detect subtle white matter injury related with neuro-developmental disorders at school-age, whereas T2-weighted imaging seemed to identify relatively more severe injury. FLAIR is a potentially sensitive screening tool that is readily available and easily interpretable. [Copyright &y& Elsevier]

Abstract: Background: Therapeutic hypothermia gathers impetus in the developed world as a safe and effective therapy for term asphyxial encephalopathy. Although many questions still remain about the optimal application of hypothermic neuroprotection it is difficult to ignore the developing world where the prevalence of asphyxial encephalopathy is much higher. Experimental studies to optimize high tech cooling need to run in parallel with trials to determine the possible benefits of therapeutic hypothermia in low resource settings. Methods: We used a validated newborn piglet model of transient HI to determine (i) whether optimal neuroprotection occurs at different temperatures in the cortical and deep grey matter; (ii) the effect of body size on regional brain temperature under normothermia and hypothermia; (iii) the effect of insult severity on the therapeutic window duration; (iv) whether cooling using a water bottle is feasible. In this model hypoxia–ischaemia is induced by reversible occlusion of the common carotid arteries by remotely controlled vascular occluders and simultaneous reduction in the inspired oxygen fraction to 0.12. Intensive care can be administered to the piglet maintaining metabolic and physiological homeostasis throughout the experiment, and cerebral energy metabolism is monitored continuously providing quantitative measures of the HI insult, latent phase and secondary energy failure using phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). Results: (i) The optimal temperature for cooling was lower in the cortex than deep grey matter. (ii) Cerebral temperatures were body-weight dependent: a smaller body weight led to a lower brain temperature especially with selective head cooling. (iii) Latent-phase duration is inversely related to insult severity. (iv) Low tech, simple cooling methods using a water bottle can induce and maintain moderate hypothermia. Conclusions: Small shifts in brain temperature critically influence the survival of neuronal cells and body size critically influences brain-temperature gradients — smaller subjects have a larger surface area to brain volume and hence more heat is lost. The clinical implication is that smaller infants may require higher cap or body temperatures to avoid detrimental effects of over-zealous cooling. Latent-phase brevity may explain less effective neuroprotection following severe HI in some clinical studies. “Tailored” treatments which take into account individual and regional characteristics may increase the effectiveness of therapeutic hypothermia in the developed world. Low tech cooling methods using water bottles may be feasible although adequate staffing and monitoring would be required. [Copyright &y& Elsevier]

Abstract: Objective: For optimal neuroprotection following transient perinatal hypoxia–ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window (“latent-phase”; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 °C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI. Methods: Newborn piglets were randomized to: (i) HI-normothermia (n =12), (ii) HI-35 °C (n =7), and (iii) HI-33 °C (n =10). HI-35 °C and HI-33 °C piglets were cooled between 2 and 26 h after HI. Insult and secondary-energy-failure severity and latent-phase duration were evaluated using phosphorus magnetic resonance spectroscopy and compared with neuronal death in cortical-grey and deep-grey matter. Results: More severe HI was associated with shorter latent-phase (p =0.002), worse secondary energy failure (p =0.023) and more cortical-grey-matter neuronal death (p =0.016). Conclusions: Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI. [Copyright &y& Elsevier]

OBJECTIVES. Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the "latent phase" may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33°C or 35°C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI. METHODS. Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal ; n = 12), (2) HI-Trectal 35°C (HI-35; n = 7), and (3) HI-Trectal 33°C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed. RESULTS. Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS. Whole-body hypothermia for 24 hours at either 35 or 33°C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33°C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase. [ABSTRACT FROM AUTHOR]

Background: Neurological disadvantages due to hypoxic ischemic encephalopathy (HIE) are still very serious problems. In order to support the infant with HIE, it is important to evaluate the severity of the brain injury early. The authors performed a magnetic resonance imaging (MRI) study of the neonatal brain in order to assess the clinical value of periventricular low intensities (PVLI) detected on fluid attenuated inversion recovery (FLAIR) imaging. Methods: A total of 451 MRI from 167 preterm and 113 term infants were sorted into groups according to the corrected age at the time of scanning. Intensities in the white matter were then divided into five grades according to the severity of the finding on FLAIR imaging. Chronic abnormalities such as periventricular hyperintensities (PVHI) were also analyzed. Result: In early MRI, which was obtained before 2 months corrected age, the incidence of PVLI was 63%, while it was only 3% and 0% in the middle (2−8 months) and the late (8−18 months) scans, respectively. Instead of PVLI, PVHI were commonly observed both on late FLAIR imaging (89%) and late T2-weighted imaging (72%). The severity of the white matter damage diagnosed on early FLAIR imaging had a significant correlation with that of late FLAIR imaging. Conclusion: F-PVLI on early FLAIR imaging would be a good predictor of chronic white matter damage. FLAIR imaging would be also useful in follow-up of infants because of its high sensitivity to the chronic white matter lesion. [ABSTRACT FROM AUTHOR]

Background: Selective head cooling in the newborn infant has been proposed as a neuroprotective treatment with a lower level of systemic adverse effect than that of systemic hypothermia. However, the efficacy is not confirmed as well as that of systemic hypothermia. In order to analyze the safety and efficacy of selective head cooling, 25 newborn piglets were randomly selected for either normothermic or hypothermic treatment. Methods: Global hypoxic insult was induced by lowering the oxygen concentration to the maximal level to maintain the background electroencephalogram (EEG) voltage under 7 µV for 45 min. The core temperature of normothermic piglets was maintained between 38.5°C and 39°C, while prophylactic cooling was applied to the hypothermic piglets at the same time of the insult. Very mild systemic hypothermia by 1°C was induced in addition to selective head cooling with 10°C coolant temperature. Animals were killed for histopathological examination seven hours after the end of the insult. Results: Two normothermic piglets died while all hypothermic piglets survived. Neuropathological findings were significantly severer in the normothermic group than in the hypothermic group. Intracranial pressure was significantly lower, and EEG recovery was significantly better in the hypothermic piglets. There was no significant difference in the lowest oxygen concentration, degrees of acidosis, blood lactate, and blood pressure between the groups, although heart rate was significantly lower in the hypothermic group. Conclusions: We have demonstrated that early head cooling was effective in preventing some of the earliest brain damage due to hypoxic insult even in the absence of profound systemic hypothermia. [ABSTRACT FROM AUTHOR]

Abstract Background: Although selective brain hypothermia is expected to be a promising neuroprotective treatment, the thermal distribution under hypothermia is not fully investigated. We applied selective head cooling to seven newborn piglets under general anesthesia in order to investigate the mechanism of cooling. Methods: Seven healthy, large white piglets aged within 5 days after birth were studied. Temperatures were monitored at the superficial brain (0.5 cm), deep brain (2.0 cm), scalp skin, nasopharynx, tympanum, esophagus, and rectum. A radiant heater and a warmer blanket were used to maintain the normal rectal temperature (38.5-39°C). For the first piglet, the coolant temperature was widely changed from 15C to - 20C in order to define the practical range. Subsequently, the coolant temperature was set at 10C, 0C, and - 10C for the remaining six piglets. The target deep brain temperature was set at 35C, as the same reduction of brain temperature might provide moderate brain hypothermia in the human neonate. Results: With 0C coolant temperature, the deep brain temperature was cooled to 35C; however, the scalp skin attached to the cooling cap became broadly blotchy and injured in all animals. When we induced minimal systemic hypothermia by 1C for a cohort of three piglets, the deep brain temperature decreased in parallel with the rectal temperature, which enabled us to achieve the target temperature with 10°C coolant without injuring the scalp skin. The scalp skin and nasopharyngeal temperatures were good predictors of both superficial and deep-brain temperatures throughout the experiment. Conclusions: Our results suggest that moderate brain hypothermia may be applied to newborn infants without inducing moderate systemic hypothermia. [ABSTRACT FROM AUTHOR]

• GDF15 levels in hospitalised newborns were similar to those in healthy newborns and were higher than in healthy children and adults. • GDF15 levels reduced to approximately 35% of the baseline levels during the first week of life. • GDF15 levels were correlated with postnatal age, Z-score of body weight, N-terminal pro-brain natriuretic peptide and lactate levels. Serum growth differentiation factor 15 (GDF15) is a useful biomarker of mitochondrial diseases; its utility in newborns remains unknown. To investigate the temporal change in GDF15 within the first week of life, and to identify its potential control variables, blood samples were obtained from 18 newborns. The GDF15 levels declined to approximately 35% of the cord blood levels within the first week of life and were negatively correlated with postnatal age and Z-score of birth weight but were positively correlated with N-terminal pro-brain natriuretic peptide and lactate levels. GDF15 levels may reflect the progress of postnatal transition to aerobic metabolism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE. We sought to compare the prognostic utilities of early MRI spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal encephalopathy. METHODS. Twenty-one term infants with neonatal encephalopathy were studied at a mean age of 3.1 days (range: 1-5). Basal ganglia, thalamic and frontal, parietal, and occipital white matter spin-spin relaxation times were determined from images with echo times of 25 and 200 milliseconds. Metabolite ratios were determined from an 8-mL thalamic-region magnetic resonance spectroscopy voxel (¹H point-resolved spectroscopy; echo time 270 milliseconds). Outcomes were assigned at age 1 year as follows: (1) normal, (2) moderate (neuromotor signs or Griffiths developmental quotient of 75-84), (3) severe (functional neuromotor deficit or developmental quotient <75 or died). Predictive efficacies for differentiation between normal and adverse (combined moderate and severe) outcomes were compared by receiver operating characteristic curve analysis and logistic regression. RESULTS. Thalamic and basal ganglia spin-spin relaxation times correlated positively with outcome and predicted adversity. Although thalamic and basal ganglia spin-spin relaxation times were prognostic of adversity, magnetic resonance spectroscopy metabolite ratios were better predictors, and, of these, lactate/N-acetylaspartare was most accurate. CONCLUSIONS. Deep gray matter spin-spin relaxation time was increased in the first few days after birth in infants with an adverse outcome. Proton magnetic resonance spectroscopy was more prognostic than spin-spin relaxation time, with lactate/N-acetylaspartate the best measure. Nevertheless, both techniques were useful for early prognosis, and the potential superior spatial resolution of spin-spin relaxometry may define better the precise anatomic pattern of injury in the early days after birth. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Inappropriate preparation of respiratory gases is associated with serious complications during mechanical ventilation. To develop a temperature monitoring system of respiratory gases within the endotracheal tube, four newborn piglets were studied using an ultra-rapid-response thermometer attached to the closed endotracheal tube suction system. Respiratory gas temperatures were monitored at the mouth-corner level of the endotracheal tube using three thermocouples (Tairway, inserted into the endotracheal tube via the closed suction system; Ttube_centre and Ttube_wall, embedded within the endotracheal tube 0.5 mm and 1.6 mm from the tube wall, respectively). Univariate analysis showed that inspiratory Ttube_centre and inspiratory Ttube_wall were positively correlated with inspiratory Tairway (both p < 0.001). Multivariate analysis showed the dependence of inspiratory Tairway on inspiratory Ttube_centre and Ttube_wall and deflation of endotracheal tube cuff (p < 0.001, p = 0.001 and p = 0.046, respectively). Inspiratory gas temperature within the endotracheal tube can be monitored using a thermometer attached to the closed endotracheal tube suction system. Our system, with further validation, might help optimise respiratory gas humidification during mechanical ventilation. [ABSTRACT FROM AUTHOR]

Neonates often develop transition problems after low-risk birth, precise assessment of which is difficult at primary birth centres. The aim of this study was to assess whether a video triage system can be established without a specially designed communication system between local birth centres and a tertiary neonatal intensive care unit in a region with a population of 700,000. 761 neonates who were referred to a tertiary neonatal intensive care unit were examined. During period 1 (April 2011-August 2015), only a voice call was available for consultations, whereas, during period 2 (September 2015-December 2017), a video call was additionally available. The respiratory condition was assessed based on an established visual assessment tool. A video consultation system was established by connecting personal smartphones at local birth centres with a host computer at a tertiary neonatal intensive care centre. During period 2, video-based triage was performed for 42.4% of 236 consultations at 30 birth centres. Sensitivity and specificity for predicting newborns with critical respiratory dysfunction changed from 0.758 to 0.898 and 0.684 to 0.661, respectively. A video consultation system for ill neonates was established without major instalment costs. Our strategy might improve the transportation system in both high- and low-resource settings. [ABSTRACT FROM AUTHOR]

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. • Preterm birth is linked to increased incidence of autism spectrum disorder (ASD). • ASD children born very preterm and term had no difference in autistic traits. • Data were obtained from the Autism Diagnostic Observation Schedule, 2nd edition. • Data were from a cohort of very-preterm children with high survival rate. [ABSTRACT FROM AUTHOR]

Aim To assess the developmental characteristics of very low-birth-weight (VLBW) infants using the Kyoto Scale of Psychological Development (KSPD) and to compare with those using the Bayley Scales, third edition (Bayley III). Methods KSPD and Bayley III were performed on 124 Japanese VLBW infants at 18 months of corrected age at a 2-week interval by trained psychologists. The relationships between KSPD and Bayley III in corresponding pairs: Cognitive–Adaptive (C–A) developmental quotient (DQ) and cognitive composite (Cog) scores, Language–Social (L–S) DQ and language composite (Lang) scores, and Postural–Motor (P–M) DQ and motor composite (Mot) scores were analyzed. Results The means [SD] of C–A DQ, L–S DQ, P–M DQ, and overall DQ of KSPD were 94 [15], 90 [17], 89 [15], and 93 [14], respectively. The means [SD] of the Cog, Lang, and Mot scores of Bayley III were 96 [13], 84 [12], and 91 [12], respectively. The DQ of KSPD strongly correlated with the corresponding composite score of Bayley III; Spearman rank correlations between the Cog score and C–A DQ, the Lang score and L–S DQ, and the Mot score and P–M DQ were 0.65, 0.71 and 0.55, respectively. The selected cut-off of the Cog score of <85 accurately identified development delay, defined by KSPD, with sensitivity of 100% and specificity of 85%. Conclusion Although absolute value of the Bayley III score may not represent the degree of impairment, the developmental characteristics on KSPD well correlated with those on Bayley III. The developmental outcomes of Japanese VLBW infants were verified by the two tests. [ABSTRACT FROM AUTHOR]

Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO2 index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO2 index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO2 index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low-cardiac output conditions, fever, and with therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent studies suggest that refractory hypotension from causes other than septicaemia or cardiac failure is common in extremely preterm infants even out of the transitional period. Marked response to low-dose cortisol suggests underlying adrenal insufficiency, although the exact mechanism remains unknown. To investigate potential triggers for and related short-term outcomes of early-onset (

Abstract: Objectives: Perinatal hypoxia–ischaemia affects cognitive outcomes of infants even when clinical symptoms were latent and intensive care was not required. We performed a retrospective analysis in a cohort of term infants who required intensive care (i) to investigate the incidence of abnormal white matter appearances on the magnetic resonance imaging obtained before 2 months corrected age, and (ii) to examine its relationships with other cerebral lesions, clinical backgrounds, and short-term outcome at 12 months. Study design: White matter appearances on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery imaging (FLAIR) were assessed in relationship with other cerebral lesions, clinical backgrounds, established white matter lesions on follow-up scans, and abbreviated developmental outcomes at 12 months in 150 term-born infants who were cared for at a tertiary neonatal intensive care unit with mixed indications for admission (positive pressure ventilation and intravenous inotropes required in 38% and 49% of infants respectively). Results: On T2WI and FLAIR, 14.0% and 41.3% of infants showed abnormal white matter intensities respectively, which were both related with lesions in the internal capsule and deep grey matter. Abnormal T2WI appearances were correlated with low Apgar scores and low blood base-excess whereas abnormal FLAIR appearances were associated with younger corrected age at scan. Follow-up studies in a cohort of infants revealed that abnormal white matter intensities further correlated with chronic long-T2 lesions after 8 months corrected age (n =40) and severe neuro-developmental disability at 12 months (n =104). Conclusions: Abnormal white matter intensities were associated with pathological clinical variables. White matter injury may not be a specific form of cerebral damage in preterm infants. For the precise evaluation of newborn brain imaging, it may be beneficial to account for corrected age even in term infants. [Copyright &y& Elsevier]

Aim: Antenatal stress, maturation and other foetal conditions affect the postnatal cardiovascular function. Atrial- (ANP) and brain-type natriuretic peptide (BNP) play important roles in regulating extracellular fluid volume and blood pressure, which may surrogate the foetal cardiovascular condition. The aim of this study was to investigate the dependence of serum ANP and BNP at birth on antenatal variables in high-risk infants. Methods: Plasma ANP and BNP levels in the umbilical cord blood were compared with antenatal clinical information in 280 infants. Results: High levels of ANP and BNP were associated with multiple pregnancy, antenatal magnesium sulphate and foetal distress. Caesarean section (CS) was paradoxically associated with low ANP and high BNP; low ANP was related with CS before labour whereas high BNP was related with CS after the commencement of labour. High BNP levels further correlated with younger gestational age and intrauteral growth restriction. With regard to short-term postnatal variables, high BNP levels were associated with low Apgar scores and respiratory failure whereas high ANP only correlated with the latter. Conclusion: High natriuretic peptide levels were associated with prematurity at birth, uteral contraction and antenatal stress: cord blood ANP and BNP may be a useful surrogate marker for hidden antenatal stress. [ABSTRACT FROM AUTHOR]

Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and α7β1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system. [Copyright &y& Elsevier]

Measuring bone mineral density (BMD) is important for surveying osteopenia in premature infants. However, the clinical availability of dual-energy X-ray absorptiometry (DEXA) for standard BMD measurement is very limited, and it is not a practical technique for critically premature infants. Developing alternative approaches for DEXA might improve clinical care for bone health. This study aimed to measure the BMD of premature infants via routine chest X-rays in the intensive care unit. A convolutional neural network (CNN) for humeral segmentation and quantification of BMD with calibration phantoms (QRM-DEXA) and soft tissue correction were developed. There were 210 X-rays of premature infants evaluated by this system, with an average Dice similarity coefficient value of 97.81% for humeral segmentation. The estimated humerus BMDs (g/cm3; mean ± standard) were 0.32 ± 0.06, 0.37 ± 0.06, and 0.32 ± 0.09, respectively, for the upper, middle, and bottom parts of the left humerus for the enrolled infants. To our knowledge, this is the first pilot study to apply a CNN model to humerus segmentation and to measure BMD in preterm infants. These preliminary results may accelerate the progress of BMD research in critical medicine and assist with nutritional care in premature infants. [ABSTRACT FROM AUTHOR]

This article discusses the study of the therapeutic use of hypothermia as a treatment for neonatal asphyxia. Studies indicating the safety of this procedure in intensive care settings are described. This study sought to develop methods for treating neonatal asphyxia in low-resource medical settings such as Mulago Hospital, Kampala, Uganda. This randomised study added hypothermia treatment to the standard treatment methods for children with asphyxia or neonatal encephalopathy. Questions remaining for further field tests of this treatment are described.

Peripartum depression is a common, serious complication in mothers. To assess the influence of infant care, sleep and growth on the risk of peripartum depression, 1,271 mothers of healthy one-month-old infants completed comprehensive questionnaires including the Edinburgh Postnatal Depression Scale. Relationships between high depression scores and variables related to infants' care, sleep and growth were assessed adjusting for other variables. High depression scores were found in 233 mothers, which were associated with variables related to infants' care (poor satisfaction with infant care support, p < 0.001; mothers' passive response to night-time fussing, p = 0.001), sleep (dim bedroom lighting, p < 0.05; short sleep duration, p < 0.05) and growth (poor weight gain, p < 0.05), as well as maternal variables (primiparas, p < 0.001; poor income satisfaction, p < 0.001; poor sleep satisfaction, p < 0.001; daytime sleepiness, p = 0.001). Considering the observed association between high depression scores and infants' care, sleep and growth, a multidisciplinary approach accounting for infant care would be required to prevent peripartum depression. [ABSTRACT FROM AUTHOR]

For infants with acute progressive hydrocephalus, invasive drainage of cerebrospinal fluid (CSF) is performed until a ventriculo-peritoneal shunt can be inserted. Surrogate markers of intracranial pressure (ICP) may help optimise the timing of invasive procedures. To assess whether RI with/without fontanel compression helps distinguish between infants with normal (<5 cmH2O), mild (5-11 cmH2O), and moderate (>11 cmH2O) ICP elevation, 74 ICP measures before/after CSF removal and 148 related Doppler measures of the middle cerebral artery were assessed. Higher RI was associated with fontanel compression, elevated ICP, and their interaction (all p < 0.001). Without compression, differences in RI were observed between normal and moderate (p < 0.001) and between mild and moderate ICP elevation (p = 0.033). With compression, differences in RI were observed for all pairwise comparisons among normal, mild, and moderate ICP elevation (all p < 0.001). Without compression, areas under the receiver-operating characteristic curve for prediction of mild and moderate ICP elevation were 0.664 (95% confidence interval (CI), 0.538-0.791; p = 0.020) and 0.727 (95% CI, 0.582-0.872; p = 0.004), respectively, which improved to 0.806 (95% CI, 0.703-0.910; p < 0.001) and 0.814 (95% CI, 0.707-0.921; p < 0.001), respectively, with compression. RI with fontanel compression provides improved discrimination of infants with absent, mild, and moderate ICP elevation. [ABSTRACT FROM AUTHOR]

Human sleep-wake cycles are entrained by both natural and artificial light-dark cycles. However, little is known regarding when and how the photoperiod changes entrain the biological clock after conception. To investigate the dependence of sleep patterns in young infants on the natural and artificial light-dark cycles, 1,302 pairs of one-month-old infants and their mothers were asked to answer a questionnaire. Birth in spring, longer daytime sleep duration, early/regular light-off times, and longer maternal nighttime sleep duration were identified as independent variables for longer infant nighttime sleep duration in both univariate and multivariate analyses. Longer maternal nighttime sleep duration was dependent on shorter naps and early/regular bed times but not on the season. We found that nighttime sleep duration depended on both natural and artificial diurnal photoperiod changes in one-month-old infants. Although sleep patterns of infants mimicked those of their mothers, nighttime sleep duration depended on the season, and was positively associated with daytime sleep duration, only in the infants. These specific variables, which render sleep patterns of the infants different from those of their mothers, might be a clue to reveal the covert acquisition process of mature circadian rhythms after birth. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012-2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies. [ABSTRACT FROM AUTHOR]