Reference values for urinary protein, albumin, beta 2-microglobulin, and the alpha 1-microglobulin-to-creatinine ratio in Japanese children.

BACKGROUND: The importance of the ratio of creatinine to urinary protein, albumin, and low-molecular weight protein as a urinary marker in chronic kidney disease patients is widely recognized. However, no reference values have hitherto been established for these markers in Japanese children. The present study aimed to establish the reference values for these urinary markers in Japanese children. METHODS: The first morning urine was randomly collected from 1712 pupils aged ≥ 3 to < 18 years during school and kindergarten mass urinary screenings. The upper limit of the reference values was set at the 97.5th percentile of the creatinine ratio per marker. RESULTS: The urinary protein-to-creatinine ratio (PCR), urinary albumin-to-creatinine ratio (ACR), urinary beta 2-microglobulin-to-creatinine ratio (BMCR), and urinary alpha 1-microglobulin-to-creatinine ratio (AMCR) showed an age-related decrease at the 50th percentile reflecting an age-related increase in urinary creatinine. The appropriate reference value for the PCR and ACR was 0.12 g/gCr and 35 mg/gCr, respectively, in the entire cohort. The appropriate reference value for the BMCR was 0.5 µg /mgCr for age ≥ 3 to < 6 years and 0.35 µg/mgCr for age 6 years or older. The appropriate reference value for the AMCR was 5.0 µg/mgCr for age ≥ 3 to < 6 years and 3.5 µg /mgCr for age 6 years or older. CONCLUSION: The present study was the first to determine appropriate reference values for the PCR, ACR, BMCR, and AMCR based on an analysis of the first morning urine samples of a large number of children.

Noninvasive respiratory support following extubation in preterm infants.

The use of noninvasive respiratory support is widespread in newborn infants with respiratory distress. As the use of noninvasive respiratory support has increased, so too have the number of modes available. Among these modes, low-flow nasal cannula and nasal continuous positive airway pressure (NCPAP) have been used for a long time and have known efficacy and safety in newborn infants needing respiratory support. High-flow nasal cannula (HFNC) has been newly introduced, and its efficacy and safety are currently being investigated. Bilevel nasal continuous positive airway pressure and nasal intermittent positive-pressure ventilation are often used when NCPAP or HFNC therapy fails. More recently, noninvasive neurally adjusted ventilatory assist and noninvasive high-frequency oscillatory ventilation have been introduced, and their efficacy and safety are currently under evaluation. Comparison of the efficacy and safety among various modes of noninvasive respiratory support after extubation in preterm infants is helping to clarify the position of each mode. The clarification of the strength and characteristics of each device within the same mode will become important as a future direction of noninvasive respiratory support after extubation in such subjects. However, no research has yet reported on long-term outcomes in preterm infants receiving noninvasive respiratory support after extubation. Therefore, further research is needed to evaluate the long-term outcomes.

Small for Gestational Age Affects Outcomes on Singletons and Inborn Births in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: This study aimed to compare the short- and long-term outcomes of extremely preterm small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants in Japan. STUDY DESIGN: We retrospectively assessed 434 SGA and 1,716 AGA infants born at 22 to 27 weeks of gestational age (GA) and examined their outcomes on singletons and inborn births between 2003 and 2012. Infants were followed-up for 3 years, and the clinical characteristics and outcomes were compared. Fisher's exact and Student's t-tests were used for independent sample comparison. Logistic regression was used to identify associated factors. RESULTS: The prevalence of intraventricular hemorrhage ≥ grade 3 was significantly lower (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.11 - 0.72), and the prevalence of bronchopulmonary dysplasia at 36 weeks of GA and the need for home oxygen therapy were significantly higher (aOR: 2.20; 95% CI: 1.66 - 2.91 and aOR: 2.46; 95% CI: 1.75-3.47, respectively) in SGA infants than in AGA infants. SGA infants born at 24 to 25 weeks of GA had a significantly higher prevalence of developmental quotient (DQ) < 70 (aOR: 1.73; 95% CI: 1.08 - 2.77). Those born at 26 to 27 weeks of GA showed a significantly higher prevalence of cerebral palsy (CP) and visual impairment (aOR: 2.31; 95% CI: 1.22 - 4.40 and aOR: 2.61; 95% CI: 1.21 - 5.61, respectively). CONCLUSION: In SGA infants, birth at 24 to 25 weeks of GA is an independent risk factor for DQ < 70, and birth at 26 to 27 weeks of GA is an independent risk factor for CP and visual impairment. However, we did not consider nutritional and developmental factors, and a longer follow-up would help assess neurodevelopmental outcomes. KEY POINTS: · SGA is a risk factor for poor outcomes.. · In SGA infants, birth at 25 to 26 weeks is a risk factor for low a DQ.. · In SGA infants, birth at 26 to 27 weeks is a risk factor for CP..

Video-based neonatal state assessment method for timing of procedures.

BACKGROUND: Procedures should be performed when an infant is most receptive to disruptions in order to reduce the stress on the infant. However, frequent direct observations place a heavy burden on medical staff. There is therefore a need for a method for quantitatively and automatically evaluating the neonatal state. METHODS: Ten infants in our hospital were enrolled in this study. The states of the infants were assessed by medical staff using the Brazelton Neonatal Behavioral Assessment Scale and were recorded on video at the same time. The recorded states were reclassified as activity levels, a new state classification method that includes middle activity, which is the appropriate time for a procedure. Using image analysis, motions of the infant were quantified as two indices: activity and pause time. Activity and pause time were compared for each activity level. The cutoff values of the indices were calculated, and the sensitivity and specificity of the middle activity were calculated. RESULTS: There was a significant difference between all groups of activity level (P < 0.01). The maximum sensitivity and specificity of middle activity were 71.7% and 51.2%, respectively. CONCLUSIONS: The neonatal state of infants can be quantitatively and automatically evaluated using video cameras, and the activity level can be used to determine an appropriate time for procedures in infants. This will reduce the burden on medical staff and lead to less stressful procedures for infants.

Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study.

Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

Brain-type natriuretic peptide level in pregnant women with congenital heart disease predicts SGA offspring.

BACKGROUND: Women with congenital heart disease (CHD) commonly experience complications related to CHD during pregnancy. The clinical features of neonates born to mothers with CHD, however, have not been fully investigated. The frequency of small for gestational age (SGA) is high in infants born to mothers with CHD, but the risk factors have not been examined sufficiently. Therefore, we analyzed the maternal features associated with SGA infants. METHODS AND RESULTS: We enrolled pregnant women with repaired CHD and infants born to them at Tokyo Women's Medical University Hospital between April 2007 and March 2015. Eleven SGA (11%) and 91 non-SGA infants (89%) were included. On multivariate logistic regression, SGA infants were significantly more likely to be associated with a high maternal brain-type natriuretic peptide (BNP) level (OR, 6.7; 95%CI: 1.3-34.5; P = 0.02) and maternal single ventricle disease (OR, 8.4; 95%CI:1.4-51.8; P = 0.02) than were non-SGA infants. CONCLUSIONS: The incidence of SGA infants born to mothers with CHD was not high in this study. High BNP and maternal single ventricle disease, however, are independent predictors of SGA in infants.

Objective evaluation of wheezing in normal infants.

BACKGROUND: To evaluate the frequency of wheezing in infants, the presence of wheezing was examined in normal infants using a breath sound analyzer, METHODS: A total of 443 infants (age range, 3-24 months) were included in the present study. The existence of audible wheezing and faint wheezing/inaudible wheezing-like noises (FW) was confirmed on chest auscultation and a sound spectrogram. The breath sound parameters of the sound spectrum, frequency limiting 99% of power spectrum (F99 ), roll-off from 600 to 1,200 Hz (slope) and spectrum curve indices, total area under the curve of dB data (A3 /AT and B4 /AT ), and ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF50 and RPF75 ) were calculated. Using an original Japanese questionnaire, we examined the characteristics of the airway condition of all infants. RESULTS: Finally, a total of 398 infants were analyzed in the present study, and 283 were in good health while 115 had acute respiratory infection (ARI) in the last 7 days. No infants had audible wheezing on auscultation. Three infants without ARI (1.1%) and 10 infants with ARI (8.7%) had FW. In the evaluation of breath sound parameters, there were no marked differences between the infants with and without FW. CONCLUSIONS: Using a breath sound analyzer, wheezing and FW were recognized in only a few infants in good health. Infants recognized to have audible wheezing in daily practice may be at risk of developing recurrent wheezing/asthma.

Convolutional neural networks for wound detection: the role of artificial intelligence in wound care.

OBJECTIVE: Telemedicine is an essential support system for clinical settings outside the hospital. Recently, the importance of the model for assessment of telemedicine (MAST) has been emphasised. The development of an eHealth-supported wound assessment system using artificial intelligence is awaited. This study explored whether or not wound segmentation of a diabetic foot ulcer (DFU) and a venous leg ulcer (VLU) by a convolutional neural network (CNN) was possible after being educated using sacral pressure ulcer (PU) data sets, and which CNN architecture was superior at segmentation. METHODS: CNNs with different algorithms and architectures were prepared. The four architectures were SegNet, LinkNet, U-Net and U-Net with the VGG16 Encoder Pre-Trained on ImageNet (Unet_VGG16). Each CNN learned the supervised data of sacral pressure ulcers (PUs). RESULTS: Among the four architectures, the best results were obtained with U-Net. U-Net demonstrated the second-highest accuracy in terms of the area under the curve (0.997) and a high specificity (0.943) and sensitivity (0.993), with the highest values obtained with Unet_VGG16. U-Net was also considered to be the most practical architecture and superior to the others in that the segmentation speed was faster than that of Unet_VGG16. CONCLUSION: The U-Net CNN constructed using appropriately supervised data was capable of segmentation with high accuracy. These findings suggest that eHealth wound assessment using CNNs will be of practical use in the future.

Small for gestational age is a risk factor for the development of delayed thyrotropin elevation in infants weighing less than 2000 g.

OBJECTIVE: Delayed thyrotropin (TSH) elevation (dTSHe) is common in low birthweight infants. We aimed to clarify the risk factors for the development of dTSHe in infants weighing <2000 g at birth. PATIENTS AND METHODS: According to Japanese guidelines, infants with birthweight <2000 g underwent second capillary TSH screening within 30 days, either at 1 month of age; or when weight reached 2.5 kg; or at discharge. dTSHe was defined as TSH >20 mIU/L by venous sampling following a normal result (<15 mIU/L) at first screening aged 4-6 days. For each infant who developed dTHSe three babies without dTSHe were selected and matched for gestational age and birth year. Small for gestational age (SGA) was defined as a birthweight <10th percentile for the gestational age and sex. A multivariate analysis was performed to identify risk factors for the development of dTSHe. RESULTS: Among the 911 study infants, 17 infants (1.9%) had dTSHe. The median (range) birthweight in the dTSHe group (796 [388-1912] g) was significantly smaller than the comparison group (961 [408-1981] g) (P = 0.04). The number (%) of SGA infants was significantly higher in the dTSHe group (12 [71%]) than in the comparison group (13 [25%]) (P = 0.001). The multivariate analysis revealed that SGA was an independent risk factor for the development of dTSHe (adjusted odds ratio, 9.0; 95% confidence interval, 2.5-32.8; P = 0.001). CONCLUSIONS: Small for gestational age is an independent risk factor for the development of dTSHe in infants with a birthweight <2000 g. The influence of prematurity, a matching criterion for this study, on dTSHe requires additional study.

Morphological characterization of pulmonary microvascular disease in bronchopulmonary dysplasia caused by hyperoxia in newborn mice.

PURPOSE: Pulmonary microvascular injury is associated with the pathogenesis of bronchopulmonary dysplasia (BPD). To characterize the mechanisms of pulmonary vascular disease resulting from BPD, we studied the ultrastructural changes affecting pulmonary microvasculature. METHODS: Newborn ICR mice were exposed to 85% hyperoxia or normoxia for 14 days, and then normal air replacement conditions for the following 7 days. At postnatal day (P)14 and P21, lungs were harvested for ultrastructural examination and assessment of pulmonary hypertension. RESULTS: The ultrastructure of pulmonary microvasculature in the hyperoxia-exposed lungs revealed a collapsed capillary lumen. This was due to the abnormal morphology of endothelial cells (ECs) characterized by heterogeneously thick cytoplasm. Compared to normal air controls, the specimens displayed also remarkably thick blood-air barriers (BABs), most of which were occupied by EC layer components. Structural changes were accompanied by increased pulmonary artery medial thickness and right ventricular hypertrophy (RVH). Moreover, abnormalities in ECs persisted even after exposure to 7 days of normal air replacement conditions. Results were confirmed by morphometric quantification. CONCLUSION: Our results suggest that the abnormal morphology of capillary ECs and thick BABs correlates with pulmonary artery remodeling and RVH. These ultrastructural changes might represent possible mechanisms of secondary pulmonary hypertension in BPD.

National survey on concepts for congenital hypothyroidism screening in neonatal intensive care units in Japan.

BACKGROUND: Recently, a revised version of the Guidelines for Mass Screening of Congenital Hypothyroidism (CH) was published in Japan, but it is not known whether the guidelines are used routinely in neonatal intensive care units (NICU). METHODS: To clarify the current status and issues of newborn screening (NBS) for CH in Japanese NICU, we sent a questionnaire by mail or email to neonatologists responsible for 100 tertiary NICU in Japan, and analyzed their responses. RESULTS: The response rate was 92% (92/100). Among respondents, 65% (59/91) performed thyroid function testing separately from NBS for CH. Within this group, 63% (37/59) applied criteria, mostly for very low-birthweight (VLBW) infants (25/37). Only 29% of respondents (26/90), however, used criteria to select VLBW infants for treatment. Furthermore, criteria differed in each NICU. Fifty-seven percent of respondents (50/87) reported issues regarding NBS for CH in NICU, which fell into three main areas: establishment of a clear method for the management of VLBW infants; necessity of simultaneous measurement of thyroid-stimulating hormone and free thyroxine; and overlapping blood collection for NBS and thyroid function tests. CONCLUSIONS: Two-thirds of tertiary NICU performed thyroid function testing separately from NBS for CH. Approximately 60% of neonatologists responded that current NBS for CH had ongoing issues. Further research is needed to establish the optimal NBS protocol for CH in NICU in Japan.

Use of high-flow nasal cannula in neonates: Nationwide survey in Japan.

High-flow nasal cannula is a new modality of respiratory support and is increasing in popularity despite the lack of supporting evidence. We investigated the prevalence of its use in tertiary neonatal units in Japan. A paper-based survey was conducted. The response rate was 83%. High-flow nasal cannula was used in 46/80 units (58%), of which 96% used the high-flow nasal cannula without guidelines. It was used for several indications, including weaning off nasal continuous positive airway pressure and post-extubation respiratory support. The main perceived benefits of the cannula included better access to the neonate and reduced risk of nasal trauma. This survey found that high-flow nasal cannula is used without clear criteria and that clinical practice varies across neonatal units in Japan. Its use in neonates needs to be urgently evaluated.

Differences in mortality and morbidity according to gestational ages and birth weights in infants with trisomy 18.

The aim of this study was to clarify the effects of gestational age and birth weight on outcomes of the infants. Medical records of 36 infants with trisomy 18 admitted to Tokyo Women's Medical University Hospital from 1991 to 2012 were reviewed retrospectively. We compared clinical characteristics between term infants (n = 15) and preterm infants (n = 21). There were one very-low-birth-weight (VLBW) term infant (5%) and 12 VLBW preterm infants (80%). Although there were no significant differences in clinical characteristics and provided management between the two groups, none of the preterm infants achieved survival to discharge. On the other hand, 6 of 21 term infants (29%) achieved survival to discharge (P < 0.05). Similar results were obtained for comparisons between the VLBW infants and non-VLBW infants. Multiple logistic regression analysis revealed that shorter gestational age had a more negative impact than lower birth weight to survival to discharge in infants with trisomy 18. In both preterm and term groups, the infants who died before 30 days commonly died of respiratory failure or apnea. Whereas, the infants who survived more than 30 days mostly died of heart failure.

Bifidobacterium and enteral feeding in preterm infants: cluster-randomized trial.

BACKGROUND: This study evaluated the benefit of Bifidobacterium bifidum OLB6378 (B. bifidum) in very low-birthweight (VLBW) infants (birthweight <1500 g) for the acceleration of enteral feeding. METHODS: A cluster-randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals, divided into two groups: the B group (n = 10 hospitals; B. bifidum given to infants within 48 h of birth) and the P group (n = 9 hospitals; infants received a placebo). The primary outcome was establishment of enteral feeding after birth, defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day). Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge. RESULTS: Overall, 283 VLBW infants were enrolled in the study: B group, n = 153; and P group, n = 130. Enteral feeding was established within 21 days after birth in 233 infants, of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group, at 11.0 ± 3.6 days versus 12.1 ± 3.8 days in P group (P < 0.05). Infant growth during the stay in the neonatal intensive care unit was not different between groups, but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group (3.9%, 6/153) than in the P group (10.0%, 13/130; P < 0.05). No differences were observed in the incidence of other adverse outcomes including mortality. CONCLUSIONS: B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects.

Impact of comprehensive quality improvement program on outcomes in very-low-birth-weight infants: A cluster-randomized controlled trial in Japan.

BACKGROUND: Differences in outcomes among neonatal intensive care units (NICUs) in Japan have been noted, prompting the need for quality improvement. AIM: To assess a comprehensive quality improvement program on outcomes in very-low-birth-weight (VLBW) infants. STUDY DESIGN: A cluster-randomized clinical trial. SUBJECTS: Forty hospitals and VLBW infants born in 2012-2014 and admitted to those hospitals were study subjects. OUTCOME MEASURES: The intervention group (IG) received a comprehensive quality improvement program involving clinical practice guidelines, educational outreach visits, workshops, opinion leader training, audits, and feedback. The control group (CG) was provided only with the guidelines. The primary outcome was survival without neurological impairment at three years of age. RESULTS: IG consisted of 19 hospitals and 1735 infants, while CG included 21 hospitals and 1700 infants. There were no significant differences in gestational weeks, 29.1(26.9-31.3) vs. 29.1(26.7-31.1) or birth weights (g), 1054(789-1298) vs. 1084(810-1309) between the two groups. Both groups showed survival rates without neurological impairment of 67.2 % (1166) and 66.9 % (1137), respectively, without a significant difference. There was no significant difference in mortalities at NICU discharge between the groups, with rates of 4.0 % (70) and 4.2 % (72) respectively. Several clinically relevant improvements were observed in IG, including reduced rates of sepsis, adrenal insufficiency, transfusion for anemia, and a shorter interval to achieve full enteral feeding. However, these did not lead to improvements in the primary outcome. CONCLUSION: The comprehensive quality improvement program to Japanese NICUs did not result in a significant improvement in survival without neurological impairment in VLBW infants.

Subcutaneous Panniculitis-like T Cell Lymphoma Diagnosed with a Slowly Progressive Course: A Case Report.

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Spontaneously Resolved Suspected Hemophagocytic Lymphohistiocytosis or Macrophage Activating Syndrome Associated with Neonatal Lupus Erythematosus: A Case Report.

OBJECTIVES: To present a rare case of neonatal lupus erythematosus (NLE) associated with suspected hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). CASE PRESENTATION: A female infant weighing 2,995 g was born to a mother without medical history of any disease. At birth, the patient had erythematous papules on her face and trunk. She was admitted at 1 day of age with elevated C-reactive protein levels. The patient was diagnosed with NLE based on the presence of anti-Ro/SSA and anti-La/SSB antibodies. Thereafter, it became clear that the antibody levels in her mother were also elevated. At 20 days of age, the infant showed elevated transaminases, ferritin, triglyceride, and soluble interleukin-2 receptor levels. Although HLH or MAS was suspected, she did not fulfill the diagnostic criteria. Thereafter, these abnormal values spontaneously improved, and the skin rash improved with the use of topical steroids. The patient was discharged at 39 days of age. At 1 year of age, the patient's growth and development were normal. CONCLUSION: NLE should be considered in infants with an unexplained skin rash at birth. When a diagnosis is made, close observation of the infant's clinical features is needed to determine whether they will develop HLH or MAS.