Contemporary fluid management, humidity, and patent ductus arteriosus management strategy for premature infants among 336 hospitals in Asia.

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries. Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status. Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation (p < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation (p < 0.001) and on day 14 after birth for infants born at <29 weeks gestation (p < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth (p < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p = 0.012 and <80% vs. 90%-100%, OR of 5.31, p < 0.001). Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

Efficacy and safety of permissive hypercapnia in preterm infants: A systematic review.

CONTEXT: In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, the findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial. OBJECTIVE: To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, and CINAHL STUDY SELECTION: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. DATA EXTRACTION: Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment and Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model. RESULTS: Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR, 1.05; 95% CI, 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR, 1.69; 95% CI, 0.98-2.91; very low CoE), but the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE). LIMITATIONS: The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: Permissive hypercapnia did not have any significant benefit or harm in preterm infants.

Job stress and loneliness among desk workers during the COVID-19 pandemic in Japan: focus on remote working.

BACKGROUND: Previous studies have reported an increase in loneliness since the outbreak of coronavirus disease 2019 (COVID-19), but there are few data on the relationship between job stress and loneliness. This study aimed to assess the relationship between job stress and loneliness among desk workers, with a focus on the impact of remote working. METHODS: This study was part of the Collaborative Online Research on the Novel-coronavirus and Work (CORoNaWork) project in Japan. We extracted data from 13,468 workers who indicated that they were doing desk work. Loneliness was assessed using a single question and job stress was valuated using the Job Content Questionnaire (JCQ). Multiple logistic regression was performed. RESULTS: Participants who worked remotely 4 or more days per week were marginally more likely to report feeling lonely compared with those who did not work remotely (adjusted odds ratio = 1.23, 95% CI: 0.99-5.84, P = 0.066). Remote working did not explain the interaction between JCQ scale scores and loneliness. Among remote workers, the level of support provided by co-workers and supervisors was strongly associated with feelings of loneliness as well as non-remote workers (co-worker support: AOR = 4.06, 95% CI: 2.82-5.84, P < 0.001; supervisor support: AOR = 2.49, 95% CI: 1.79-3.47, P < 0.001). CONCLUSIONS: To reduce loneliness and the risk of associated mental health problems, high-frequency remote workers should interact with supervisors and co-workers using the information and communication technology developed for this purpose.

Prospective cohort study of bedroom heating and risk of common cold in children.

BACKGROUND: In countries with mild winter climates and inadequate heating, the relationship between housing conditions and health outcomes in winter have not been well studied. The purpose of the present study was to evaluate the relationship between heater type and temperature factors in the bedroom and incidence of the common cold among children in Japan. METHODS: In this prospective cohort study, we distributed baseline questionnaires and temperature loggers in December 2019 and administered follow-up questionnaires in March 2020. We recruited children under the age of 15 years. We performed Poisson regression analysis and logistic regression analysis. RESULTS: Of 297 participants, air conditioners were the most prevalent (n = 105, 35%), followed by gas or kerosene heaters (n = 50, 17%), and floor heaters (n = 31, 10%). Air-conditioners were associated with higher incidence of all events related to the common cold, especially having a fever (adjusted incidence rate ratio (aIRR) = 1.84, 95% confidence interval (CI): 1.41-2.40). Gas or kerosene and floor heaters showed a lower incidence rate of some events related to the common cold, such as school or nursery school absence (aIRR = 0.55, 95% CI: 0.37-0.82 and aIRR = 0.39, 95% CI: 0.23-0.67, respectively). Bedroom temperature did not show a positive association, but children who always felt cold showed a higher incidence of some events related to the common cold. CONCLUSIONS: Our findings imply that the heating approach and modal thermal comfort, such as location of heating appliances, humidity, airflow, and radiant heat, may be more important for the onset of common cold in children than bedroom temperature itself.

A Prospective Cohort Study of Bedroom Warming With a Heating System and Its Association With Common Infectious Diseases in Children During Winter in Japan.

BACKGROUND: Customarily, bedrooms in Japan are left unheated. Although several studies have reported that the use of a heating system has positive outcomes on respiratory infection and asthma, the preventive effect of heating systems against infectious diseases in children is not well known. METHODS: We conducted a cohort study using two questionnaire surveys, one before the winter season in November, 2018 and the second after winter in March, 2019. Participants were 155 children who did not use a heating system in the bedroom and 156 children who did. RESULTS: Having a heated bedroom with a heating system was associated with decreased odds for the frequency of cold (≥3 times) (adjust odds ratio [AOR] 0.35; 95% confidence interval [CI], 0.19-0.65), duration of fever (≥3 days) (AOR 0.38; 95% CI, 0.22-0.66), duration of medicine for a cold (≥3 days) (AOR 0.91; 95% CI, 0.87-0.95), hospital visit due to cold (≥3 days) (AOR 0.54; 95% CI, 0.31-0.94), absence from school or nursery (≥3 days) (AOR 0.43; 95% CI, 0.27-0.70), influenza infection (AOR 0.43; 95% CI, 0.26-0.71), and gastroenteritis (AOR 0.39; 95% CI, 0.21-0.72). Influenza vaccination reduced the odds of influenza infection (AOR 0.36; 95% CI, 0.22-0.59) and absence from school or nursery (≥3 days) (AOR 0.62; 95% CI, 0.39-0.99). CONCLUSION: This study implies that the heating of bedrooms may have a preventive effect against infections among children. Broader dissemination of this knowledge in Japan will require cultural change through public health awareness.

Difference in pyruvic acid metabolism between neonatal and adult mouse lungs exposed to hyperoxia.

OBJECTIVE: Neonatal lungs are more tolerant to hyperoxic injury than are adult lungs. This study investigated differences in the response to hyperoxic exposure between neonatal and adult mouse lungs using metabolomics analysis with capillary electrophoresis time-of-flight mass spectrometry (CE- TOFMS). METHODS: Neonatal and adult mice were exposed to 21% or 95% O2 for four days. Subsequently, lung tissue samples were collected and analyzed by CE-TOFMS. Pyruvate dehydrogenase (PDH) enzyme activity was determined using a microplate assay kit. PDH kinase (Pdk) 1, Pdk2, Pdk3, and Pdk4 mRNA expression levels were determined using quantitative reverse transcription-polymerase chain reaction. Pdk4 protein expression was quantified by Western blotting and Pdk4 protein localization was evaluated by immunohistochemistry. RESULTS: Levels of 3-phosphoglyceric acid, 2-phosphoglyceric acid, phosphoenolpyruvic acid, and lactic acid were significantly elevated in the lungs of hyperoxia-exposed versus normoxia-exposed adult mice, whereas no significant differences were observed with hyperoxia exposure in neonatal mice. PDH activity was reduced in the lungs of adult mice only. Pdk4 mRNA expression levels after hyperoxic exposure were significantly elevated in adult mice compared with that in neonatal mice. Conversely, gene expression levels of Pdk1, Pdk2, and Pdk3 did not differ after hyperoxic exposure in either neonatal or adult mice. Pdk4 protein levels were also significantly increased in adult mouse lungs exposed to hyperoxia and were localized mainly to the epithelium of terminal bronchiole. CONCLUSIONS: Specific metabolites associated with glycolysis and gluconeogenesis were altered after hyperoxia exposure in the lungs of adult mice, but not in neonates, which was likely a result of reduced PDH activity due to Pdk4 mRNA upregulation under hyperoxia.

Validation of the Japanese version of the CDC HRQOL-4 in workers.

BACKGROUND: We set out to investigate the reliability and validity of the Japanese version of the CDC core healthy day measures assessing health-related quality of life (CDC HRQOL-4) in Japanese workers. METHODS: This cross-sectional study was conducted among 1360 Japanese workers of one Japanese company located in Kyushu. Cronbach's alpha was calculated to evaluate the internal consistency of CDC HRQOL-4 items. The concurrent validity was tested by assessing whether the CDC HRQOL-4 items correlated well with the corresponding domains of the SF-8 and the overall WFun score. The construct validity was tested by assessing the ability of the CDC HRQOL-4 to discriminate groups with and without any current disease, pain, mental problem, and sleeping disorder. RESULTS: Cronbach's alpha for three of the four CDC HRQOL-4 items was 0.80, which is greater than the minimal standard (0.70) recommended for internal consistency reliability. Correlation coefficients ranging from 0.25 to 0.67 were obtained between CDC HRQOL-4 items and the SF-8 domains and WFun score. Workers with any current disease, mental problem, pain or sleeping disorder reported higher numbers of unhealthy days, and a higher odd of poor health than those without such problems. Japanese version of the CDC HRQOL-4 shows a good concurrent validity with the SF-8 and the WFun tool and good construct validity among Japanese workers in the current study. CONCLUSIONS: Japanese version of the CDC HRQOL-4 is a reliable and valid instrument that may be used to assess overall health and physically and mentally unhealthy days in Japanese workers.

The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV. METHODS: We conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity. RESULTS: Overall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay. CONCLUSION: Our findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings. PROTOCOL REGISTRATION: PROSPERO CRD42019154761.

Attenuation of Hyperoxic Lung Injury in Newborn Thioredoxin-1-Overexpressing Mice through the Suppression of Proinflammatory Cytokine mRNA Expression.

The role of thioredoxin-1 (TRX), a small redox-active protein with antioxidant effects, during hyperoxic lung injury in newborns remains undetermined. We investigated TRX impact on hyperoxic lung injury in newborn TRX transgenic (TRX-Tg) and wildtype (WT) mice exposed to 21% or 95% O2 for four days, after which some mice were allowed to recover in room air for up to 14 days. Lung morphology was assessed by hematoxylin/eosin and elastin staining, as well as immunostaining for macrophages. The gene expression levels of proinflammatory cytokines were evaluated using quantitative real-time polymerase chain reaction. During recovery from hyperoxia, TRX-Tg mice exhibited an improved mean linear intercept length and increased number of secondary septa in lungs compared with the WT mice. Neonatal hyperoxia enhanced the mRNA expression levels of proinflammatory cytokines in the lungs of both TRX-Tg and WT mice. However, interleukin-6, monocyte chemoattractant protein-1, and chemokine (C-X-C motif) ligand 2 mRNA expression levels were reduced in the lungs of TRX-Tg mice compared with the WT mice during recovery from hyperoxia. Furthermore, TRX-Tg mice exhibited reduced macrophage infiltration in lungs during recovery. These results suggest that in newborn mice TRX ameliorates hyperoxic lung injury during recovery likely through the suppression of proinflammatory cytokines.

Management of bronchopulmonary dysplasia in Japan: A 10-year nationwide survey.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication in very preterm infants. Despite advances in perinatal medicine, the number of BPD patients is increasing in Japan. The aim of this study was to conduct a nationwide survey of the strategies used for the prevention or treatment of BPD. METHODS: Questionnaires assessing the current strategies used to prevent or treat BPD, including neonatal resuscitation, drug therapy, and respiratory supportive care, were sent to secondary or tertiary perinatal units in 2015; responses were compared with those obtained from similar surveys in 2005 and 2010. The annual trend in incidence of BPD among the very low birth weight infants (VLBWIs) was determined using the Neonatal Research Network of Japan database. RESULTS: The response rates in 2005, 2010, and 2015 were 86.8% (230/265), 64.5% (185/287), and 82.8% (236/285) of units, respectively. The use of patient-triggered ventilation for initial management significantly increased from 50% of units in 2005 to 91% in 2015. By contrast, decreased use of high-frequency oscillatory ventilation (HFOV) from 72% to 65% and that of nasal continuous positive airway pressure from 79% to 68% were reported. The proportion of units where the upper limit of targeted blood oxygen saturation before a diagnosis of BPD was set to ≥95% decreased substantially from 92% to 56% over the 10-year period. Despite these changes in management of BPD, the incidence of BPD among VLBWIs in Japan was increasing over a decade. CONCLUSION: This survey demonstrated that there were various changes in practice regarding the prevention or treatment of BPD in Japan. Continuous surveys are required to understand the current clinical situation, and research is needed to develop and evaluate a novel treatment for BPD in premature infants.

Defining the reference range of regional cerebral tissue oxygen saturation using a new portable near-infrared spectroscopy device for term infants.

BACKGROUND: The arterial oxygen saturation of infants requiring resuscitation can be monitored using a pulse oximeter. However, the device cannot provide information about cerebral oxygenation. Thus, we used a new portable near-infrared spectroscopy (NIRS) device that can monitor regional cerebral tissue oxygen saturation (crSO2) with a probe attached to the examiner's finger. AIM: To identify the reference ranges for crSO2 within the first 10 min after birth in term infants who did not receive any medical intervention in the delivery room. RESULTS: crSO2 in the left frontoparietal area of the forebrain was measured within the first 10 min of life in 127 healthy term infants. The median gestational age and birth weight were 37.6 weeks and 2742 g, respectively, and 85% of the infants were delivered via a scheduled cesarean section. The 3rd-97th percentile values for crSO2 ranged from 33.1% to 56.7% at 1 min, from 33.2% to 59.5% at 2 min, and from 38.7% to 66.6% at 5 min after birth. A median of 3.5 min was required to achieve a crSO2 > 50%. CONCLUSIONS: This study showed the reference ranges for crSO2 measured with the new portable NIRS device within the first 10 min after birth in term infants.

Impact of High Flow Nasal Cannula Therapy on Oral Feeding in Very Low Birth Weight Infants with Chronic Lung Disease.

Previous studies on high-flow nasal cannula (HFNC) in very-low-birth-weight infants (VLBWIs) focused on comparing HFNC with nasal continuous positive airway pressure (nCPAP) to determine the usefulness of HFNC as a backup in the case of extubation failure and nasal trauma; however, the studies did not consider oral feeding. This retrospective case-control study aimed at elucidating whether HFNC could prevent the delay in feeding and achievement of full oral feeding in VLBWIs with chronic lung disease (CLD). Forty five VLBWIs were enrolled in this study: an HFNC group (n = 11) that was supported by HFNC at oral feeding initiation, and a non-HFNC group (n = 34) that could start oral feeding without HFNC. The gestational age and birth weight of the HFNC group were lower than those in the non-HFNC group. The median duration of exposure to oxygen and neonatal intensive care unit stay were comparable in both groups. The timings of oral feeding initiation and full oral feeding achievement in both groups were not significantly different: 35.3 (33.0 - 38.1) vs. 35.5 (33.7 - 42.4) weeks (P = 0.91) for the HFNC and 38.6 (34.4 - 42.3) vs. 36.7 (34.6 - 44.4) weeks postmenstrual age (P = 0.29) for the non-HFNC. Clinically significant aspiration pneumonia during the period of oral feeding was not observed in the HFNC group. Respiratory support by HFNC in VLBWIs with CLD might prevent oral feeding delay. Initiation of oral feeding of VLBWIs on HFNC might be safe and might accelerate the achievement of oral feeding milestones.

An in vitro evaluation of the influence of neonatal endotracheal tube diameter and length on the work of breathing.

BACKGROUND: Neonates, particularly premature babies, are often managed with endotracheal intubation and subsequent mechanical ventilation to maintain adequate pulmonary gas exchange. There is no consensus on the standard length of endotracheal tube. Although a short tube reduces resistance and respiratory dead space, it is believed to increase the risk of accidental extubation. There are not entirely coherent data regarding the effect of endotracheal tube length on work of breathing in infants. AIM: The aim of this study was to evaluate the impact of neonatal endotracheal tube diameter and length on the work of breathing using an infant in vitro lung model. METHOD: We assessed the work of breathing index and mechanical ventilation settings with various endotracheal tube diameters and lengths using the JTR100 in vitro infant lung model. The basic parameters of the model were breathing frequency of 20 per minutes, inspiratory-expiratory ratio of 1:3, and positive end-expiratory pressure of 5 cmH2 O. In addition, the diaphragm driving pressure to maintain the set tidal volume was measured as the work of breathing index. The JTR100 was connected to the Babylog 8000plus through the endotracheal tube. Finally, we monitored the peak inspiratory pressure generated during assist-control volume guarantee mode with a targeted tidal volume of 10-30 mL. RESULTS: The diaphragm driving pressure using a 2.0-mm inner diameter tube was twice as high as that using a 4.0-mm inner diameter tube. To maintain the targeted tidal volume, a shorter tube reduced both the diaphragm driving pressure and ventilator-generated peak inspiratory pressure. The difference in the generated peak inspiratory pressure between the shortest and longest tubes was 5 cmH2 O. CONCLUSION: In our infant lung model, a shorter tube resulted in a lower work of breathing and lower ventilator-generated peak inspiratory pressure.

Low-Dose Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-Resistant or Contraindicated Preterm Infants: Three Cases Reports.

Background Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

Measurement of brain tissue oxygen saturation in term infants using a new portable near-infrared spectroscopy device.

BACKGROUND: A small oximeter with the probe attached to the examiner's finger has been developed. The aim of this study was to determine the feasibility of measuring regional oxygenation of the brain tissue using this device in healthy term infants immediately after birth. METHODS: We conducted a prospective observational study. Using a new near-infrared spectroscopy (NIRS) device, we measured changes in regional cerebral tissue oxygen saturation (crSO2 ) during the first 10 min of life in 32 healthy term infants after delivery. Arterial oxygen saturation (SpO2 ) was also simultaneously measured. RESULTS: Median crSO2 increased from 43% (1 min after birth) to 49% (4 min after birth); thereafter, no significant changes were observed. Median SpO2 increased constantly from min 3 to min 7, from 77% to 92% and did not change significantly after 8 min. A stable oxygen saturation signal was measured in 59% of infants (crSO2 ) and in 0% of infants (SpO2 ) at 1 min, and in 97% (crSO2 ) and in 78% (SpO2 ) at 3 min. CONCLUSIONS: During the transition after birth, crSO2 can be more easily and quickly measured in healthy newborn infants using the novel NIRS device than SpO2 .

Analysis of the Physiological Variation in Neutrophil CD64 Expression during the Early Neonatal Period.

Background Several biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variations. The aim of this study was to investigate the physiological variation in neutrophil CD64 (nCD64) expression during the early neonatal period and the change in nCD64 expression in neonates with noninfectious diseases. Methods Of 71 neonates enrolled in this prospective study, 5 and 51 were diagnosed as having bacteremia and noninfectious diseases, respectively. Fifteen healthy neonates were enrolled as normal controls. Peripheral white blood cell counts, serum C-reactive protein and procalcitonin levels, and nCD64 expression were examined at birth and on the first and fifth day of life in neonates with noninfectious diseases and healthy neonates. In neonates with bacteremia, these markers were measured at onset. Results nCD64 expression was significantly higher in neonates with bacteremia (median, 1,992) than in those with noninfectious diseases (1,823, p < 0.001) and healthy neonates (1,848, p = 0.002). Unlike other biomarkers, no differences in nCD64 expression were observed on the same days between neonates with noninfectious diseases and healthy neonates. Conclusion nCD64 expression may be a useful marker for the diagnosis of bacterial infection in the early neonatal period, because it does not show any physiological variations.

West syndrome in a patient with Schinzel-Giedion syndrome.

Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed.

Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants.

BACKGROUND AND AIMS: Protein convertase subtilisin/Kexin type-9 (PCSK9) is a substantial player in lipoprotein metabolism. This study was designed to elucidate the role of PCSK9 in the regulation of lipoprotein during the fetal period. STUDY DESIGN AND SUBJECTS: This study was a cross-sectional study. Eighty-one neonates (45 males, 36 females) who were admitted to the neonatal intensive care unit were enrolled in the study. The median age in gestational weeks and weight at birth were 37.1 weeks and 2493 g, respectively. There were no gender differences, but the proportion of infants who were small-for-gestational age (SGA) was significantly higher among females than males. The prefed serum PCSK9 level was assayed with ELISA kits. RESULTS: The median PCSK9 concentration in male newborns was significantly lower than that in females (148.2 ng/ml vs. 171.4 ng/ml, respectively, p<0.001). Circulating serum PCSK9 levels were positively correlated with total cholesterol (r=0.281, p<0.05) and low-density lipoprotein cholesterol (LDL-C; r=0.272, p<0.05). However, there were no correlations between PCSK9 levels and birth weight, gestational age or SGA. Multivariate forward stepwise linear regression analysis revealed that gestational age and circulating PCSK9 levels were independent predictors of the serum LDL-C levels in newborn infants. CONCLUSION: Our first quantitative analysis of neonatal serum PCSK9 levels at birth showed that circulating PCSK9 levels show gender-based differences and are significantly correlated with LDL-C. These results suggest that PCSK9 could play an important role in regulating LDL-C levels during the fetal period.

Urine screening for patients with developmental disabilities detected a patient with creatine transporter deficiency due to a novel missense mutation in SLC6A8.

Creatine transporter deficiency (CTD) is an example of X-linked intellectual disability syndromes, caused by mutations in SLC6A8 on Xq28. Although this is the second most frequent genetic cause of intellectual disabilities in Europe or America after Fragile X syndrome, information on the morbidity of this disease is limited in Japan. Using the HPLC screening method we have established recently, we examined samples of urine of 105 patients (73 males and 32 females) with developmental disabilities at our medical center. And we have found a family with three ID boys with a novel missense mutation in SLC6A8. This is the second report of a Japanese family case of CTD. A systematic diagnostic system of this syndrome should be established in Japan to enable us to estimate its frequency and treatment.