Temporal changes and control variables of growth differentiation factor 15 levels during the first week of life in hospitalised newborn infants.

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.

Video-call based newborn triage system for local birth centres can be established without major instalment costs using commercially available smartphones.

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.

Visual function scale for identification of infants with low respiratory compliance.

AIM: Precise estimation of respiratory function is essential to optimise neonatal respiratory care. However, current clinical scores have not been validated with quantitative measures of respiratory function. The aim of this study was to develop a physiological scoring system to predict low respiratory dynamic compliance of <0.6 ml/cmH2O/kg. METHODS: Forty-four newborn infants were studied before (dynamic compliance) and shortly after scheduled extubation (physiological signs). A novel scoring system was developed based on the association between physiological signs and dynamic compliance. RESULTS: The respiratory rate was identified as the primary independent variable for dynamic compliance in the univariate analysis. The prediction score for low dynamic compliance comprised the presence of nasal flaring, see-saw respiration, suprasternal/intercostal retraction, and the respiratory rate ranks (0-3). The area under the receiver-operating characteristics curve of the composite score had discriminatory capability of 0.86 (95% confidence interval: 0.75-0.97) to predict low dynamic compliance with the optimal cut-off value of ≥3 (sensitivity, 0.882; specificity, 0.667). CONCLUSION: Our novel scoring system might help predict newborn infants with low dynamic compliance, who may require escalation of respiratory support, or transfer to higher level units.

Intrauterine growth and the maturation process of adrenal function.

BACKGROUNDS: Environmental factors during early life alter the hypothalamus-pituitary-adrenal (HPA) axis regulation and increase the risk of diseases in later life. However, adrenal function at each developmental stage has not fully been investigated in relation to pathological antenatal conditions. Cortisol levels of newborns with intrauterine growth restriction (IUGR) are elevated during the neonatal period; however, when studied during early childhood, cortisol levels are reduced compared with their peers, suggesting that the HPA axis regulation might be altered from activation to suppression, the timing of which remains uncertain. AIM: The aim of this study was to assess the presence of an interaction between intrauterine growth and postnatal age on cortisol levels in newborns hospitalised at a neonatal intensive care unit. METHODS: We performed a secondary analysis using a dataset from saliva samples of 62 newborns collected between 30 and 40 weeks corrected age. Interactions between postnatal age and clinical variables with regard to cortisol levels were assessed. RESULTS: The z-score of the birth weight and IUGR showed significant interactions with postnatal age on cortisol levels; cortisol levels were higher ≤5 days of birth and lower >14 days of birth than those in their peers without IUGR. CONCLUSION: The adrenal function of newborns with IUGR might be altered from activation to suppression within the first several weeks of life. Longitudinal studies need to address when/how IUGR alters adrenal functions, and how these responses are associated with diseases during adulthood.

Estimation of elevated intracranial pressure in infants with hydroce-phalus by using transcranial Doppler velocimetry with fontanel compression.

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.

Feeding-Induced Cortisol Response in Newborn Infants.

Context: Understanding the biological rhythms and stress response in sick newborns is important to minimize the negative effects of intensive care. Salivary cortisol has been used as a noninvasive surrogate marker of adrenal function; however, understanding of its control variables is insufficient. Objective: To investigate the presence of feeding-induced cortisol response and its control variables in newborns. Design, Setting, and Patients: Fifty-three newborn infants, who were between 30 and 40 weeks' corrected age and were on 3-hourly regular oral/enteral feeding, were recruited between January 2013 and June 2014. Main Outcome Measure: Saliva samples were collected before and 1 hour after regular feeding. Dependence of cortisol levels (adjusted for postnatal age) and their feeding-related elevation on clinical variables was assessed by using generalized estimating equations. Results: Higher cortisol levels were associated with corrected age ≥37 weeks and saliva samples collected after feeding (both P < 0.001). Oral feeding was associated with a greater feeding-induced cortisol response compared with exclusive enteral feeding (P = 0.034), whereas a prolonged feeding duration (≥30 minutes) was associated with a reduced cortisol response compared with brief feeding (<30 minutes) (P < 0.001). Gestational age, corrected age, antenatal/postnatal glucocorticoids, type of milk, and daily feeding volume had no effect on cortisol response. Conclusions: Feeding-induced cortisol response was observed in newborns. The cortisol response was more prominent following oral feeding and was reduced with prolonged feeding. Future studies may investigate whether feeding-induced cortisol response plays a role in the acquisition of adrenal ultradian and diurnal rhythms.

Insufficient Humidification of Respiratory Gases in Patients Who Are Undergoing Therapeutic Hypothermia at a Paediatric and Adult Intensive Care Unit.

For cooled newborn infants, humidifier settings for normothermic condition provide excessive gas humidity because absolute humidity at saturation is temperature-dependent. To assess humidification of respiratory gases in patients who underwent moderate therapeutic hypothermia at a paediatric/adult intensive care unit, 6 patients were studied over 9 times. Three humidifier settings, 37-default (chamber-outlet, 37°C; Y-piece, 40°C), 33.5-theoretical (chamber-outlet, 33.5°C; Y-piece, 36.5°C), and 33.5-adjusted (optimised setting to achieve saturated vapour at 33.5°C using feedback from a thermohygrometer), were tested. Y-piece gas temperature/humidity and the incidence of high (>40.6 mg/L) and low (<32.9 mg/L) humidity relative to the target level (36.6 mg/L) were assessed. Y-piece gas humidity was 32.0 (26.8-37.3), 22.7 (16.9-28.6), and 36.9 (35.5-38.3) mg/L {mean (95% confidence interval)} for 37-default setting, 33.5-theoretical setting, and 33.5-adjusted setting, respectively. High humidity was observed in 1 patient with 37-default setting, whereas low humidity was seen in 5 patients with 37-default setting and 8 patients with 33.5-theoretical setting. With 33.5-adjusted setting, inadequate Y-piece humidity was not observed. Potential risks of the default humidifier setting for insufficient respiratory gas humidification were highlighted in patients cooled at a paediatric/adult intensive care unit. Y-piece gas conditions can be controlled to the theoretically optimal level by adjusting the setting guided by Y-piece gas temperature/humidity.

Use of Normothermic Default Humidifier Settings Causes Excessive Humidification of Respiratory Gases During Therapeutic Hypothermia.

Adult patients frequently suffer from serious respiratory complications during therapeutic hypothermia. During therapeutic hypothermia, respiratory gases are humidified close to saturated vapor at 37°C (44 mg/L) despite that saturated vapor reduces considerably depending on temperature reduction. Condensation may cause serious adverse events, such as bronchial edema, mucosal dysfunction, and ventilator-associated pneumonia during cooling. To determine clinical variables associated with inadequate humidification of respiratory gases during cooling, humidity of inspiratory gases was measured in 42 cumulative newborn infants who underwent therapeutic hypothermia. Three humidifier settings of 37-default (chamber outlet, 37°C; distal circuit, 40°C), 33.5-theoretical (chamber outlet, 33.5°C; distal circuit, 36.5°C), and 33.5-adjusted (optimized setting to achieve 36.6 mg/L using feedback from a hygrometer) were tested to identify independent variables of excessively high humidity >40.7 mg/L and low humidity <32.9 mg/L. The mean (SD) humidity at the Y-piece was 39.2 (5.2), 33.3 (4.1), and 36.7 (1.2) mg/L for 37-default, 33.5-theoretical, and 33.5-adjusted, respectively. The incidence of excessive high humidity was 10.3% (37-default, 31.0%; 33.5-theoretical, 0.0%; 33.5-adjusted, 0.0%), which was positively associated with the use of a counter-flow humidifier (p < 0.001), 37-default (compared with 33.5-theoretical and 33.5-adjusted, both p < 0.001) and higher fraction of inspired oxygen (p = 0.003). The incidence of excessively low humidity was 17.5% (37-default, 7.1%; 33.5-theoretical, 45.2%; 33.5-adjusted, 0.0%), which was positively associated with the use of a pass-over humidifier and 33.5-theoretical (both p < 0.001). All patients who used a counter-flow humidifier achieved the target gas humidity at the Y-piece (36.6 ± 0.5 mg/L) required for 33.5-adjusted with 33.5-theoretical. During cooling, 37-default is associated with excessively high humidity, whereas 33.5-theoretical leads to excessively low humidity. Future studies are needed to assess whether a new regimen with optimized Y-piece temperature and humidity control reduces serious respiratory adverse events during cooling.

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients.

In ten families with late-onset ornithine transcarbamylase (OTC) deficiency in male patients, three mutant alleles-R40H, R277W, and Y55D-were identified. In a total of 20 informative parent-offspring pairs, father-to-daughter transmission and mother-to-offspring transmission occurred in five (25%) and 15 (75%), respectively, indicating that paternal transmission contributes substantially to the pool of these mutant alleles. Relative reproductive fitness of males and females carrying the mutant alleles was calculated to be 0.49 and 0.89, respectively. Comparison of the life span of the mutant alleles, estimated on the basis of these fitness values with those associated with classic phenotype (neonatal onset) in which reproductive fitness of male patients was nil, revealed that mutant alleles associated with the late-onset phenotype were eliminated more slowly. This would allow the late-onset phenotype mutant alleles to be retained more frequently in a population than those associated with classic phenotype. Although heterozygous females carrying the late-onset phenotype mutant alleles were generally asymptomatic, one female carrying the R40H allele died after a hyperammonemic episode at the age of 18 years. Such heterozygous females should be alerted to possible hyperammonemic crisis.

Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile.

BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis. RESULTS: The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity. CONCLUSION: The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.

In vivo quantitative ultrasonic evaluation of neonatal brain with a real time integrated backscatter imaging system.

We applied the integrated backscatter (IBS) imaging system to the evaluation of the normal neonatal brain of different birth-weights: extremely low-birth-weight (N=13), very-low-birth-weight (N=14), low-birth weight (N=14), and normal birth weight (N=19). The IBS values in six regions of interest, the deep white matter, subcortical white matter, choroid plexus, thalamus, lateral ventricle, and occipital bone, were compared among groups of different birth weights, gestational age, and postnatal age: at the date of birth and 28 approximately 30 days after birth. The IBS values were higher in the order of bone>choroid plexus>deep white matter>subcortical white matter>thalamus>lateral ventricle and were significantly different except for the lateral ventricle in all the groups at days 0 and 28 approximately 30. The IBS values increased with the decrease of birth weight and gestational age. There was a decrease of IBS values at day 28 compared to that of day 0 in the extremely low birth weight and very low birth weight groups; however, they remained the same in infants with low birth weights and in the normal birth weight group. Further studies to evaluate the significance of this technique for the objective diagnosis of brain insults in neonates are necessary.