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Objective To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.Design Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group.Setting Nationwide cohort study.Patients Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database.Interventions Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic.Main outcome measures Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model.Results Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p

Abstract Background The mosquito Aedes aegypti transmits two of the most serious mosquito-borne viruses, dengue virus (DENV) and Zika virus (ZIKV), which results in significant human morbidity and mortality worldwide. The quickly shifting landscapes of DENV and ZIKV endemicity worldwide raise concerns that their co-circulation through the Ae. aegypti mosquito vector could greatly exacerbate the disease burden in humans. Recent reports have indicated an increase in the number of co-infection cases in expanding co-endemic regions; however, the impact of co-infection on viral infection and the detailed molecular mechanisms remain to be defined. Methods C6/36 (Aedes albopictus) cells were cultured in Dulbecco's modified Eagle medium/Mitsuhashi and Maramorosch Insect Medium (DMEM/MM) (1:1) containing 2% heat-inactivated fetal bovine serum and 1× penicillin/streptomycin solution. For virus propagation, the cells were infected with either DENV serotype 2 (DENV2) strain 16681 or ZIKV isolate Thailand/1610acTw (MF692778.1). Mosquitoes (Ae. aegypti UGAL [University of Georgia Laboratory]/Rockefeller strain) were orally infected with DENV2 and ZIKV through infectious blood-feeding. Results We first examined viral replication activity in cells infected simultaneously, or sequentially, with DENV and ZIKV, and found interspecies binding of viral genomic transcripts to the non-structural protein 5 (NS5). When we challenged Ae. aegypti mosquitos with both DENV2 and ZIKV sequentially to probe similar interactions, virus production and vector susceptibility to infection were significantly enhanced. Conclusions Our results suggest that DENV2 and ZIKV simultaneously establishing infection in the Ae. aegypti mosquito vector may augment one another during replication. The data also implicate the homologous NS5 protein as a key intersection between the flaviviruses in co-infection, highlighting it as a potential target for vector control.

Abstract Background Chorioamnionitis is a common cause of preterm birth and leads to serious complications in newborns. The objective of this study was to investigate the role of the Hippo signaling pathway in lung branching morphogenesis under a lipopolysaccharide (LPS)-induced inflammation model. Materials and methods IMR-90 cells and ex vivo fetal lungs were treated with 0, 10, 30, or 50 μg/ml LPS for 24 and 72 h. Supernatant levels of lactate dehydrogenase (LDH), interleukin (IL)-6, IL-8, Chemokine (C-X-C motif) ligand 1(CXCL1), branching and the surface area ratio, Yes-associated protein (YAP), transcription coactivator with PDZ-binding motif (TAZ), fibroblast growth factor 10 (FGF10), fibroblast growth factor receptor II (FGFR2), SRY-box transcription factor 2 (SOX2), SOX9, and sirtuin 1 (SIRT1) levels were examined. Differentially expressed genes in fetal lungs after LPS treatment were identified by RNA-sequencing. Results LPS at 50 μg/ml increased IL-6 and IL-8 in IMR-90 cells and increased IL-6, CXCL1 and LDH in fetal lungs. The branching ratio significantly increased by LPS at 30 μg/ml compared to the control but the increased level had decreased by 50 μg/ml LPS exposure. Exposure to 50 μg/ml LPS increased phosphorylated (p)-YAP, p-YAP/YAP, and p-TAZ/TAZ in IMR-90 cells, whereas 50 μg/ml LPS decreased FGF10 and SOX2. Consistently, p-YAP/YAP and p-TAZ/TAZ were increased in fibronectin+ cells of fetal lungs. Moreover, results of RNA-sequencing in fetal lungs showed that SMAD, FGF, IκB phosphorylation, tissue remodeling and homeostasis was involved in branching morphogenesis following exposure to 50 μg/ml LPS. The p-SIRT1/SIRT1 ratio increased in IMR-90 cells by LPS treatment. Conclusions This study showed that regulation of the Hippo pathway in fibroblasts of fetal lungs was involved in branching morphogenesis under an inflammatory disease such as chorioamnionitis.

Abstract Congenital cytomegalovirus (cCMV) infection is the most prevalent cause of non-genetic sensorineural hearing loss (SNHL) in children. However, the prognostic determinants of SNHL remain unclear. Children with cCMV infection in a tertiary hospital were enrolled. The presence of cCMV-related symptoms at birth, the newborn hearing screening (NHS) results, and the blood viral loads were ascertained. Audiologic outcomes and initial blood viral loads were compared between different groups. Of the 39 children enrolled, 16 developed SNHL. SNHL developed in 60% of children who were initially symptomatic, and in 34.5% of those who were initially asymptomatic with normal hearing or isolated hearing loss, respectively. Failuire in NHS was a reliable tool for early detection of SNHL. The initial viral loads were higher in children who were symptomatic at birth, those who failed NHS, and those who developed SNHL. We observed SNHL deterioration in a patient after CMV DNAemia clearance was achieved, and in another patient with the flare-up of viral load. The presence of cCMV-related symptoms at birth, failure in NHS, and blood viral load might be the prognostic factors for hearing outcomes. Regular audiologic examinations are necessary in all children with cCMV infection even after CMV DNAemia clearance.

Abstract Background Dengue fever is the most rapidly spreading mosquito-borne viral disease globally. More than 2.5 billion people live in dengue-endemic areas. Previous studies suggested an interrelationship between diabetes mellitus (DM) and dengue hemorrhagic fever (DHF). Conversely, glycolysis is a critical metabolic pathway for optimal dengue virus (DENV) replication. However, little is known concerning the effect of glucose on DENV replication in mosquitoes. In this study, we investigated the impact of glucose on DENV replication in mosquitoes Aedes aegypti. Methods Mosquitoes (Ae. aegypti UGAL/Rockefeller strain) were orally infected with DENV (serotype 2, 16681 strain) through infectious blood feeding. The DENV infection and transmission rates were determined by examining mosquito bodies and saliva, respectively, for DENV positivity at different time points after infection. In addition, a reverse genetic approach was applied by introducing double-stranded RNA against genes of interest into the mosquitoes to inhibit gene expression. Results Our data revealed a significant increase of DENV genome levels in mosquitoes consuming an infectious blood meal supplemented with glucose, suggesting that blood glucose is an important factor for viral replication. Interestingly, a significant increase of DENV E protein levels was detected in the saliva 4 days faster in mosquitoes that consumed infectious blood meals supplemented with glucose than in those consuming infectious blood meals alone. Furthermore, we perform RNAi to silence AKT or TOR and investigate the molecular mechanism regulating the glucose-mediated enhancement of viral replication. Silencing of AKT or TOR significantly reduced DENV titers in mosquitoes. Conclusions This study suggested that blood glucose is beneficial to DENV replication and that it facilitates virus transmission in mosquitoes via AKT and TOR signaling. Therefore, our results strengthen our understanding of dengue fever and DM co-morbidity and possibly reveal new targets for specific antiviral therapies. Graphical abstract

Background: Using regression modeling analysis to investigate the breakpoints of the trends in survival-without-major-neonatal-morbidities (MNM) or -without-neurodevelopmental- impairment (NDI) by year and gestational age (GA) in preterm infants. Methods: We enrolled 2237 preterm infants (GA

Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

Background/Purpose: The aim of this study was to evaluate the efficacy of antenatal corticosteroids for preventing very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) from surfactant use at different gestational ages (GA). Methods: We retrospectively analyzed the VLBW preterm infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2014. Infants at 20–37 weeks' gestation were included, and infants with lethal congenital anomaly, chromosomal anomaly, and congenital infection were excluded. Antenatal corticosteroid courses were classified into two groups (

Background/Purpose: Impaired growth of the corpus callosum (CC) and cerebellar vermis (CV) is associated with poorer neurodevelopmental outcomes in preterm infants. However, references on the postnatal growth rate of the CC and CV by sonography are limited. The aim of this study is to assess the normal linear growth of CC and CV using a serial cranial ultrasound. Methods: We prospectively enrolled preterm infants with very low birth weight from September 2008 to December 2009 after excluding those with congenital anomalies or diseases affecting the brain parenchyma. Serial sonographic measurements of the CC and CV were performed according to the standard protocol. Scheduled comprehensive neurodevelopmental evaluations were performed till the corrected age of 2 years. We excluded those with significant brain damages or poor neurodevelopmental outcomes in the final analysis. The growth rate was estimated using the loess smoothing curve and linear regression analysis. Results: Among the 86 enrolled neonates, 14 with significant brain damage and 8 with poor neurodevelopmental outcomes were excluded from the final analysis. The growth rate of the CC length was 1.72 (95% confidence interval [CI]: 1.24–2.20) and 0.57 (95% CI: 0.33–0.80) mm per week before and after the postmenstrual age of 30.5 weeks, respectively. The growth rate of the CV length was 0.78 (95% CI: 0.68–0.89) mm per week. Conclusion: We proposed reference values of the normal linear growth rate of the CC and CV lengths in very-low-birth-weight preterm infants using the serial cranial ultrasound.

Background: Preterm infants require higher calcium and phosphate intake than term infants to facilitate adequate bone growth, but this is rarely met in parenteral nutrition (PN) solution because of the limited solubility of calcium and phosphate. This study aimed to evaluate the solubility of organic phosphate with calcium gluconate in neonatal PN solutions, simulating its clinical use. Methods: PN solutions were composed of calcium gluconate at 50 mEq/L and sodium glycerophosphate (NaGP) at 25 mmol/L. Another component included 1% or 4% amino acid and 10% or 20% dextrose. For comparison, PN solution composed of potassium phosphate was also evaluated. Each solution was evaluated using the following methods: visual inspection, light obscuration particle count test, and pH measurement. To simulate the clinical condition, the solution was tested after compounding, after being stored at 25 °C for 24 h, and after being stored at 2°C-8°C for 2 or 9 days and subsequently at 25 °C for 24 h. Results: There was no visual deposition in PN solution using NaGP in any of the concentrations and under any stored condition. The solution fulfilled the criteria of physical compatibility as < 25 particles/mL measuring ≥10 μm in diameter and

Background: Exposure to air pollution has been associated with a wide range of adverse health effects; however, few studies addressed the relationship between ambient particulate matter as well as the compositions in particulate matter such as lead and the risk of small for gestational age (SGA) in offspring. The aim of this study is to investigate the effect of maternal exposure to criteria air pollutants and the lead in total suspended particulate matter during pregnancy on SGA births in Taiwan. Methods: This population study consisted of 322,513 singleton live births in Taiwan between 1996 and 2002. Daytime (7 AM–7 PM) exposure to particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), and monthly exposure to lead in total suspended particles (TSP) during each trimester were estimated. Generalized additive model (GAM) was used to assess the association between maternal exposure to particulate air pollutants and SGA births, taking into account potential confounders and gaseous air pollutants. Results: We found significant association between the highest quartile (≥75th) of maternal PM10 exposure and SGA and demonstrated a significant exposure–response relationship. Furthermore, the highest quartile (≥75th) of maternal lead exposure was also associated with SGA during the second and third trimester of pregnancy, and there was a significant exposure–response relationship between maternal lead exposure and SGA during pregnancy. Conclusion: Maternal exposure to PM10 and lead in total suspended particulate matter during pregnancy was associated with an increased risk of SGA in offspring. Key Words: air pollution, lead, pregnancy, small for gestational age

BackgroundMethylxanthines (caffeine; aminophylline/theophylline) are commonly used for apnea of prematurity (AOP) treatment. We aimed to compare the efficacy and adverse effects of caffeine and aminophylline/theophylline.MethodsA retrospective case–control gestational age-matched study investigates patients born between January 2017 and December 2018, 23–35 weeks gestation with birth weights >500 g treating AOP with caffeine or aminophylline/theophylline.ResultsThere were 144 cases (48 in caffeine group and 96 in aminophylline/theophylline group). The median treatment durations were 11 and 17 days in caffeine and aminophylline/theophyllinegroup (p = 0.002). When tachycardia is defined as heart rate ≥160 bpm, the rates were 8.3 and 34.4% in caffeine and control group (p = 0.001). When tachycardia is defined as 10 bpm over baseline heart rate, the rates were 41.7 and 63.5% in caffeine and aminophylline/theophylline group (p = 0.01). Stratified by gestational age and sex, significant reductions in tachycardia rates with caffeine than with theophylline were limited to male infants and infants born at

IntroductionIn very low birth weight (VLBW) infants, hypothermia immediately following birth is common even in countries rich in medical resources. The purpose of this study is to design a standard prevention bundle that decreases the rate of hypothermia among infants after birth and to investigate efficacy of the bundle and short-term outcomes for VLBW infants.MethodsThis quality improvement project was conducted from February 2017 to July 2018 on all VLBW preterm infants admitted at a single referral level III neonatal intensive care unit. The infants were classified into the pre-intervention (February to September 2017) and post-intervention (October 2017 to July 2018) groups according to the time periods when they were recruited. During the pre-intervention period, we analyzed the primary causes of hypothermia, developed solutions corresponding to each cause, integrated all solutions into a prevention bundle, and applied the bundle during the post-intervention period. Afterwards, the incidence of neonatal hypothermia and short-term outcomes, such as intraventricular hemorrhage (IVH), acidosis, and shock requiring inotropic agents, in each group were compared.ResultsA total of 95 VLBW infants were enrolled in the study, including 37 pre-intervention, and 58 post-intervention cases. The incidence of hypothermia in preterm infants decreased significantly upon the implementation of our prevention bundle, both in the delivery room (from 45.9% to 8.6%) and on admission (59.5% to 15.5%). In addition, the short-term outcomes of VLBW infants improved significantly, especially with the decreased incidence of IVH (from 21.6% to 5.2%, P = 0.015).ConclusionsOur standardized prevention bundle for preventing hypothermia in VLBW infants is effective and decreased the IVH rate in VLBW infants. We strongly believe that this prevention bundle is a simple, low-cost, replicable, and effective tool that hospitals can adopt to improve VLBW infant outcomes.

Background: During one week in September, one index case, followed by two cases of rotavirus gastroenteritis infection, was identified in a neonate intermediate care unit of a tertiary teaching children's hospital. An outbreak investigation was launched to clarify the possible infection source and to stop the spread of infection. Methods: Cohort care and environmental disinfection were immediately implemented. We screened rotavirus in all the unit neonates' stool samples as well as environmental swab samples. The precautionary measures with regard to hand hygiene and contact isolation taken by healthcare providers and family members were re-examined. Results: The fourth case was identified 5 days after commencement of the outbreak investigation. There were total 39 contacts, including 6 neonates, 8 family members, and 25 healthcare providers. Nineteen stool samples collected from other neonates in the units revealed one positive case (the fourth case). However, one sample taken from the computer keyboard and mouse in the ward was also positive. The observation of hygiene precautions and the use of isolation gowns by healthcare workers were found to be inadequate. Following the intensification of infection control measures, no further cases of infection were reported. Conclusions: Hand hygiene and an intensive isolation strategy remained the most critical precautions for preventing an outbreak of healthcare-associated viral gastroenteritis in the neonate care unit. Keywords: Rotavirus, Outbreak, Neonatal care unit, Infection control

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease‐related mortality; however, its sensitivity and compliance are unsatisfactory. Methods This study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result. Results Serum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable. Conclusion Serum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool‐based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening.

Congenital cytomegalovirus (cCMV) infection is the leading environmental cause of childhood hearing impairment. However, its significance remains largely undocumented in many regions of the world. The purpose of this study was to investigate the prevalence and clinical features of cCMV infection in East Asia. Neonates born at a municipal hospital in Taipei were prospectively recruited and underwent concurrent hearing and CMV screenings. Those who failed the hearing screening or screened positive for CMV were subjected to a focused audiological and/or virological surveillance. The characteristics of the newborns and their mothers were compared between the CMV-positive and CMV-negative groups. Of the 1,532 newborns who underwent concurrent hearing and CMV screenings, seven (0.46%) were positive for cCMV infection. All seven CMV-positive newborns were asymptomatic at birth, and none of them developed hearing or other symptoms during a follow-up period of 14.4±6.3 months. The mothers of the CMV-positive newborns demonstrated higher gravidity (2.4 ± 1.4 vs. 2.1 ± 1.2) and parity (2.0 ± 1.2 vs. 1.6 ± 0.7) than those in the CMV-negative group; however, the difference did not reach statistical significance. The prevalence of cCMV infection in Taipei newborns was 0.46%, which is slightly lower than that of other populations and that of a previous report in the Taiwanese population. The relatively low prevalence in this study might be attributed to the improved public health system and decreased fertility rate in Taiwan.

Background: Soluble fms-like tyrosine kinase receptor-1 (sFlt-1)/placental growth factor (PlGF) ratio has been studied extensively as a predictive marker for pre-eclampsia. However, its usefulness for predicting neonatal outcomes remains unknown. This study aimed to evaluate the association of sFlt-1/PlGF ratio with pregnancy outcomes, neonatal morbidities and short-term postnatal growth patterns in pregnant women and their babies. Methods: sFlt-1 and PlGF were measured in women with fetal intrauterine growth retardation (IUGR) or pre-eclampsia during gestational age (GA) of 16â36 weeks. These women were classified into high- and low-ratio groups with a sFlt-1/PlGF cut-off ratio of 85. The maternal and neonatal outcomes were retrospectively reviewed and compared between the two groups. Results: A total of 25 pregnant women were recruited. Thirteen of them had a sFlt-1/PlGF ratio over 85 and twelve had a ratio of less than 85. The median duration from elevation of sFlt-1/PlGF to delivery was 4.5 weeks. Women in the high SFlt-1/PlGF ratio group had higher rates of intrauterine fetal demise (2/13 vs. 0/12) and early termination (1/13 vs. 0/12). The surviving offspring in this group had a higher incidence of preterm birth (GA: 31.4 ± 2.9 weeks vs. 37.3 ± 1.3 weeks, pÂ

Extracorporeal membrane oxygenation (ECMO) was used in neonates with severe cardiopulmonary failure who failed to respond to conventional therapy. We started to apply neck venoarterial ECMO (VA-ECMO) in neonatal patients from 2000. In this study, we have focused on neonates who received ECMO support and described the current status of ECMO in neonates for both cardiac and pulmonary support and the risk factors associated with their outcomes. Methods: Data were retrieved from our ECMO database for the neonates (age < 28 days) who received neck VA-ECMO support from January 2005 to June 2015. Results: In total, 27 neonates, including 21 with respiratory support and six with cardiac support, were enrolled in this study. Sixteen (59.2%) patients survived to hospital discharge, and only one patient had a poor neurological outcome. The survival rate for respiratory support was 61.9% in which meconium aspiration syndrome with persistent pulmonary hypertension of a newborn had a superior outcome (11/13, 84.6%) and congenital diaphragmatic hernia had the worst outcome (4/7, 57.1%). The survival rate in the cardiac support group was only 50%. The median ECMO duration and hospital stay were 6 (1∼35.8) days and 37 (23∼232) days, respectively, for survivors. Furthermore, 11 (52.3%) neonates of 21 outborn patients were put on ECMO in other hospitals by our mobile ECMO team for respiratory support, and their survival (81.8%) was significantly better than those from in-house ECMO institution (40%). Conclusion: This is the first report for ECMO in neonatal disease in Taiwan. We achieved an overall survival rate of 59.2% with good neurological outcomes in this 10-year experience. ECMO could be a useful transportation tool for critical neonates who have a poor response to ventilator support.

Nasal continuous positive airway pressure (NCPAP) therapy is widely used in neonates, but the clinical practice varies. However, nursing practice differs among individuals, and an inappropriate application method may delay the respiratory therapy, influence the beneficial effect of NCPAP, and increase complications. We introduced a quality improvement project to expedite the application of NCPAP therapy and decrease the incidence of nasal trauma. Methods: A new strategy of mobile NCPAP cart with prepacked fixation kits and a written protocol was implemented from April 2006. All medical staff answered a questionnaire to assess their basic knowledge before and after intensive training. The records of the patients who were treated with NCPAP from October 2005 to November 2006 were reviewed. Results: Fifty-nine medical staff were involved in the project, and their mean score for the questionnaire improved from 69.2 points to 98.3 points after training. From October 2005 to November 2006, 113 infants were recruited in total and 82 of them were admitted after the protocol was implemented. The NCPAP cart dramatically shortened the preparation time (from 520 seconds to 72 seconds) and the application time (from 468 seconds to 200 seconds). The use of the nursing protocol significantly decreased the incidence of nasal trauma in the study population (45.2% vs. 19.6%, p = 0.006), but not in infants with a birth weight of < 1000 g. Risk factors for nasal skin trauma included lower gestational age and birth weight, longer duration of NCPAP use, and lack of standardized nursing care. Conclusion: The mobile NCPAP cart with prepacked fixation kits is a practical way of expediting the initiation of NCPAP therapy. The written nursing protocol decreased the incidence of nasal trauma in infants, except for those with an extremely low birth weight.

Extracorporeal membrane oxygenation (ECMO) is a treatment option for stabilizing neonates with congenital diaphragmatic hernia (CDH) in a critical condition when standard therapy fails. However, the use of this approach in Taiwan has not been previously reported. Methods: The charts of all neonates with CDH treated in our institute during the period 2007–2014 were reviewed. After 2010, patients who could not be stabilized with conventional treatment were candidates for ECMO. We compared the demographic data of patients with and without ECMO support. The clinical course and complications of ECMO were also reviewed. Results: We identified 39 neonates with CDH with a median birth weight of 2696 g (range, 1526–3280 g). Seven (18%) of these patients required ECMO support. The APGAR score at 5 minutes differed significantly between the ECMO and non-ECMO groups. The survival rate was 84.6% (33/39) for all CDH patients and 57.1% (4/7) for the ECMO group. The total ECMO bypass times in the survivors was in the range of 5–36 days, whereas all nonsurvivors received ECMO for at least 36 days (mean duration, 68 days). Surgical bleeding occurred in four of seven patients in the ECMO group. Conclusion: The introduction of ECMO rescued some CDH patients who could not have survived by conventional management. Prolonged (i.e., > 36 days) ECMO support had no benefit for survival.

Although antenatal steroids and early use nasal continuous positive airway pressure (NCPAP) have significantly improved outcomes of neonatal respiratory distress syndrome, intubation with ventilator support is still commonly required in extremely low birth weight (ELBW) infants. The optimal timing of extubation in ELBW infants remains unclear. Methods: We retrospectively analyzed all ELBW preterm infants who were admitted to our neonatal intensive care unit (NICU) from January 2009 to December 2013. Demographic, ventilation, and arterial blood gas analysis results prior to and 2 hours after extubation were collected. Extubation failure was defined as reintubation due to deterioration of respiratory condition within 7 days after extubation. Risk factors for extubation failure were analyzed. Results: In total, 173 ELBW infants were born and admitted to our NICU during these 5 years. Among these 173 infants, 77 (44.5%) used NCPAP only during their hospitalization (20 diagnosed with chronic lung disease (CLD), 25.9%). Among the 95 patients that required intubation, 27 patients expired so extubation was not attempted. Sixteen of 68 (23.5%) survival cases required reintubation within 7 days after extubation. We found that gestational age, birth body weight, and sex ratio did not differ between the successful extubation group and the failed extubation group. Univariate analysis showed that the failed extubation group had a lower arterial pH right before and 2 hours after extubation, with a lower bicarbonate level after extubation. Further multivariate logistic regression analysis revealed an association between poor acid-base homeostasis 2 hours after extubation (pH

Very low birth weight (VLBW) infants account for over 50% of perinatal deaths in Taiwan. This study aimed to identify changes in parental characteristics, perinatal conditions, mortality, and major neonatal morbidities for VLBW infants in Taiwan, and to highlight the challenges faced by patients, families, and caregivers. Methods: We conducted a retrospective cohort study to investigate the mortality and morbidity of VLBW infants registered in the Taiwan Premature Infant Follow-up Network from 1997 through 2011. The exclusion criteria included congenital anomalies and chromosome anomalies. Continuous data was represented as mean ± SD, and changes over time in the variables were tested using one-way analysis of variance, with p < 0.05 considered statistically significant. Results: A total of 13,159 VLBW infants were enrolled. We found significant increases over time in the parental age and educational level, in vitro fertilization, first livebirth, multiple births, maternal transfer, cesarean section, and complete antenatal steroid use. Apgar scores at 1 minute and 5 minutes after birth increased, and the intubation rate decreased gradually. Decreasing mortality over time for each successive period was demonstrated. Incidence of some morbidities increased, such as respiratory distress syndrome and patent ductus arteriosus; in contrast, incidence of others decreased, such as sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and chronic lung disease. However, retinopathy of prematurity (ROP) incidence remained constant. Conclusion: Although the mortality and most of the morbidity of VLBW infants improved over time, the incidence of ROP remained constant. This requires us to further evaluate our strategy for preventing ROP in the future.

This single-centered, retrospective cohort study investigated the timing of involution of retinopathy of prematurity (ROP) and retinal vascularization to zone III after intravitreal bevacizumab (IVB) treatment and its possible impacts on postnatal growth and neurodevelopment. Premature infants with birth weight ≤1500 g, born between 2008 to 2014 and diagnosed with ROP were enrolled. All patients with type 1 ROP underwent IVB as 1st line treatment and were recruited as the study group; those with any stage of ROP except type 1 ROP without treatment served as controls. Neurodevelopmental outcomes were assessed using the Bayley Score of Infant Development (BSID) editions II or III. The study group included 35 eyes from 18 patients; the control group included 86 patients. Twenty-three eyes (65.7%) exhibited ROP regression after a single dose of IVB. The majority of plus sign and extraretinal neovascularization regressed within two weeks. The length of time for retinal vascularization to reach zone III was significantly longer in the treatment group compared with the control (mean post-menstruation age 54.5 vs. 47.0 weeks, p

Acute kidney injury (AKI) is common in preterm infants and is associated with high mortality and morbidity. New biomarkers for the early detection of AKI have been identified. Specifically, urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a new and powerful biomarker for AKI and sepsis. Our study evaluated the reference range of uNGAL in healthy neonates in Taiwan. Methods: This study examined 24 preterm and 38 term infants without clinical complications. Urine samples were collected and the uNGAL values were measured at postnatal age (PNA) 3 days, 7 days, 14 days, and 21 days in the preterm infants and at PNA 3 days in the term infants. The uNGAL values were tested using enzyme-linked immunosorbent assay. Results: The median uNGAL values in the preterm infants at PNA 3 days, 7 days, 14 days, and 21 days were 41.52 ng/mL, 35.82 ng/mL, 43.79 ng/mL, and 30.85 ng/mL, respectively. The median value at PNA 3 days in the term infants was 88.1 ng/mL. No significant differences associated with gestational age, birth body weight, or PNA were observed among the preterm infants. However, the uNGAL values in the female term infants were higher than those in the male term infants (p = 0.003). Conclusion: This study presents preliminary data on uNGAL levels in neonates in Taiwan. A large-scale study investigating the correlations between uNGAL and with gestational age, birth body weight, sex, and PNA is recommended.

Chylothorax is a rare condition among neonates, although it is considered clinically significant, as it is difficult to manage in these patients. In addition, the course of chylothorax varies widely. Therefore, we aimed to elucidate the clinical features and effect of prenatal therapy on the prognosis of congenital chylothorax in neonates. Methods: We retrospectively reviewed the medical records of all infants with congenital chylothorax who were admitted to National Taiwan University Hospital, Taipei, Taiwan between January 2000 and December 2012. Their demographic characteristics, as well as their antenatal, perinatal, and postnatal information, were collected for our analysis of the mortality risk. Results: We found 29 infants who were diagnosed with congenital chylothorax during the study period. The median gestational age at birth was 34 weeks (range, 28–41 weeks), and 71% of the infants presented with hydrops fetalis. Most cases of congenital chylothorax were bilateral (bilateral: 86.2%, unilateral: 13.79%), and the overall survival rate was 59.6%. Among the cases with a prenatal diagnosis at ≤ 34 weeks of gestation, infants who received prenatal therapy had a significantly higher survival rate, compared to infants who did not receive prenatal therapy (76.9% vs. 11%, respectively; p = 0.008). Conclusion: We found that infants whose chylothorax was diagnosed ≤ 34 weeks of gestation, and who subsequently received prenatal therapy, experienced a better perinatal condition and exhibited improved postnatal outcomes.

Bronchopulmonary dysplasia (BPD) of prematurity is associated with impaired angiogenesis. Excess soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of vascular endothelial growth factor (VEGF) impaired alveolarization in preterm rats. Overexpression of placenta growth factor (PlGF) in mice caused airspace enlargement, which is similar to BPD pathologically. Our study aimed to clarify whether cord blood levels of these angiogenic factors were associated with the development of BPD in preterm infants. Methods: Preterm infants of gestational age (GA)

The Notch signaling pathway is a highly evolutionarily-conserved cell-cell signaling pathway that regulates many events during development. It plays a pivotal role in the regulation of fundamental cellular processes, such as cell proliferation, stem cell maintenance, and differentiation during embryonic and adult development. However, functions of Notch signaling in Aedes aegypti, the major mosquito vector for dengue, are largely unknown. In this study, we identified a unique feature of A. aegypti Notch (AaNotch) in the control of the sterile-like phenotype in female mosquitoes. Silencing AaNotch with a reverse genetic approach significantly reduced the fecundity and fertility of the mosquito. Silencing AaNotch also resulted in the prevention of micropyle formation, which led to impaired fertilization. In addition, JNK phosphorylation (a signaling molecule in the non-canonical Notch signaling pathway) was inhibited in the absence of AaNotch. Furthermore, treatment with a JNK inhibitor in the mosquito resulted in impaired fecundity and fertility. Taken together, our results demonstrate that non-canonical Notch signaling is essential for controlling fertility in the A. aegypti mosquito.

Nationwide birth weight norms for twins have been reported in several countries across different ethnicities, but such data have not been established in Taiwan. The purpose of this study was to develop reference growth charts that are population-based and contain the information of birth weight percentiles by gestational age for twin neonates in Taiwan. Methods: In this study, we collected nationwide birth weight data for twins by sex and gestational age through the Taiwan Birth Registry. Percentiles, means, and standard deviations of birth weight for each 1-week increment of gestational age from 21 weeks of gestation were estimated and smoothed using weighted polynomial models. Results: The 10th, 50th, and 90th percentiles of birth weight born at the 37th gestational week were 2174 g, 2580 g, and 3125 g for male twins, respectively, and they were 2100 g, 2500 g, and 3000 g for female twins, respectively. The 10th, 50th, and 90th percentiles of birth weight born at the 40th gestational week were 2326, 3285, and 3790 g for male twins, respectively, and they were 2200 g, 2770 g, and 3690 g for female twins, respectively. Conclusion: This is the first nationwide birth weight norm for twins in Taiwan, which is particularly useful for investigation into the predictors and outcomes of altered fetal growth through twin studies in the Taiwanese population.

Most neonates who reside in the neonatal intensive care unit (NICU) and require surgery are transferred to the operating room (OR) or undergo bedside surgery. However, critically ill neonates who are transferred often encounter the risk of complications. An OR in our NICU was therefore launched in 2009. This study was to appraise the surgeries performed in the NICU OR and compare results with the traditional main OR outside the NICU. Methods: This was a retrospective study in the NICU of a tertiary center. Retrospective chart review was conducted for all neonates who underwent surgical procedures in the NICU OR and the main OR. The information regarding baseline characteristics, surgical procedures and duration, ventilator use, hypothermia, hyperglycemia, instrument dislocations, surgically related infection or complications, and outcomes was obtained. Results: There were a total of 65 patients in this study, 37 in the NCIU OR group and 28 in the main OR group. The presurgical mean airway pressure and the fraction of inspired oxygen (FiO2) were comparable between the two groups, but the postsurgical FiO2 was significantly lower in the NICU OR group (31.0%) than in the main OR group (40.9%; p = 0.027). Furthermore, the NICU OR group required a significantly shorter preoperation waiting time (34.4 minutes vs. 63.6 minutes, p = 0.001) and had a lower incidence of hypothermia than the main OR group (8.1% vs. 39.3%, p = 0.008). However, surgically related complications were similar between groups. Conclusion: The OR within the NICU may reduce the risk of complications during transportation and provide continuity of care to critically ill neonates. It also decreases the disturbance to other NICU patients during operation.

There are limited nationwide data relating to neonatal mortality rate in Taiwan. This study aims to provide updated national birth weight/gestational age-specific neonatal mortality reference rates. Methods: We abstracted the birth registration database from the Ministry of Interior in Taiwan from 1998 to 2002 and linked the data to the death registration database from the Ministry of Health and Welfare in Taiwan between 1998 and 2003. We included 1,331,785 infants born between 20 weeks and 44 weeks of gestation and weighing within the median ± 2 interquartile ranges in their age group in this study. We calculated the birth weight/gestational age-specific neonatal mortality rates of different genders by birth weight increments of 250 g and at gestational age intervals of 1 week. A Poisson regression model was used in modeling the mortality data. Results: A total of 4,169 deaths occurred within 28 days of life out of a total of 1,331,785 live births between 20 weeks and 44 weeks of gestation, giving a neonatal mortality rate (0–27 days) of 3.39 per 1000 live births for males and 2.80 per 1000 for females. The infant mortality rate remained higher in the male (5.91 per 1000) than the female (5.10 per 1000) population within the 1st year of life. Birth weight/gestational age-specific neonatal mortality rates were plotted with curves representing the 10th and 90th birth weight percentiles. The risk of an early neonatal death (0–6 days) does not exceed 50% except for female neonates

Intrauterine exposure to tobacco smoke has been discerned as an important risk factor for low birth weight (LBW), small for gestational age (SGA), and preterm birth infants. In this cohort study, we investigated the association of the amount of parental smoking during the different pregnancy stages with birth weight and the incidence of preterm delivery. Methods: Our study population was acquired from the Taiwan Birth Cohort Study. Between June 2005 and July 2006, 21,248 postpartum women were interviewed 6 months after their deliveries by a structured questionnaire. The parents were divided into four groups according to the amount of smoking during preconception, the first trimester, and the second and third trimesters. The relationships of parental smoking with gestational age and birth weight during the different pregnancy stages were assessed using multivariate linear regression. Multiple logistic regression analyses were performed to estimate the odds ratios and 95% confidence intervals of preterm delivery, LBW, and SGA infants during the different parental smoking status and the different pregnancy stages. Results: After adjusting for the physical and socioeconomic status of the parents and for paternal smoking during the same period, we found that maternal smoking decreased birth weight. Compared with the nonsmoking groups, all the maternal smoking groups had higher incidences of LBW, SGA, and preterm birth infants, especially when the mothers smoked >20 cigarettes/day. The association of paternal smoking with LBW, SGA, and preterm birth infants was insignificant. Conclusion: Maternal smoking is responsible for increased incidences of LBW and preterm delivery of babies, and therefore, smoking cessation/reduction should be advised to pregnant women to reduce morbidities in their neonates. Further studies are needed to clarify the correlation of fetal health with passive smoking, including exposure to environmental tobacco smoke and to other smokers in the family.

Severe pulmonary hemorrhage is a serious complication with a high mortality rate in preterm infants with respiratory distress syndrome (RDS) after surfactant therapy. The aim of this study is to evaluate the efficacy of our current management strategy for neonates with severe pulmonary hemorrhage. Materials and methods: Very-low-birth-weight (VLBW) infants who developed severe pulmonary hemorrhage were studied from January 2006 to August 2011. Treatment for severe pulmonary hemorrhage in our neonatal intensive care unit (NICU) included intratracheal epinephrine spraying/irrigation, blood component therapy, and as necessary, surfactant supplement therapy was administered in cases that secondary RDS was diagnosed. High frequency oscillatory ventilation (HFOV) was utilized when hypoxia or respiratory acidosis persisted under conventional mechanical ventilation (CMV). We then described the clinical courses of severe pulmonary hemorrhage following our management. Results: A total of 18 (3.2%) out of 469 VLBW infants developed severe pulmonary hemorrhage. The mean gestational age was 27 weeks, the mean birth weight was 822 g, and the onset age was 2.5 days after birth. There was no severe pulmonary hemorrhage-associated mortality during this period with the exception of one case, in which an infant died after the parents refused to do further therapy. Sixteen (88.8%) neonates had RDS and 13 received surfactant therapy. Twelve (66.6%) cases developed secondary RDS following the onset of severe pulmonary hemorrhage, and four cases received surfactant supplement therapy. In the surfactant supplement group, alveolar-arterial oxygen difference (AaDO2) and oxygenation index (OI) during the 2–4 hours postpulmonary hemorrhage period showed statistically significant improvement, whereas the other group only showed a tendency toward improvement without reaching statistical significance when compared to the baseline data. Duration of high oxygen requirement [defined as fraction of inspired oxygen (FiO2) > 40%] was also less in the surfactant supplement group. Conclusion: This data suggests that our current strategy is effective for treating severe pulmonary hemorrhage in VLBW infants. Surfactant therapy for severe pulmonary hemorrhage may also be beneficial for improving lung function and may shorten the duration of high oxygen requirement.

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. Methods: We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Results: Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Conclusion: Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness. The pathologies of COPD are due to an abnormal immune response. Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD. We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist α-galactosylceramide (α-GalCer). Our results demonstrated that mice that received repeated intranasal administration of α-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-α. In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis. Furthermore, neutralization of IL-4 reduced α-GalCer induced emphysema. This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism.

The incidence of neonatal hyperbilirubinemia in our hospital has increased since the implementation of breastfeeding promotion. Inadequate breastfeeding results in reduced calorie intake, weight loss and neonatal hyperbilirubinemia. Supplementary feeding is required if breastfeeding proves inadequate. However, the optimal weight loss cut-off value for supplementary feeding is unknown. Methods: We collected records for all healthy neonates with a gestational age ≥35 weeks and birth body weight (BBW) above 2500 g, born between March 2002 and July 2005, from our nursery. A total of 1979 neonates were reviewed, 874 of whom were exclusively breastfed and subsequently enrolled in this study. Only infants who were breastfed exclusively were enrolled; 219 of these infants (25.1%) presented significant hyperbilirubinemia after 72 hours of age. Infants with early-onset (

Arterial blood gas analysis is the gold standard for assessing the adequacy of ventilation. However, arterial blood sampling may be associated with serious complications in neonates. The aim of the study was to utilize the side-stream capnometry measurement of end-tidal carbon dioxide (PetCO2) via nasal cannula circuits and to verify the reliability of PetCO2 in reflecting the arterial blood carbon dioxide (PaCO2) level in nonintubated neonates. Methods: A retrospective medical record review analysis was performed in nonintubated neonates admitted to the neonatal ward in a medical center. Simultaneous arterial PaCO2 and PetCO2 levels were evaluated. PaCO2 and PetCO2 levels were compared by paired t test and were correlated using Pearson's correlation. The PetCO2 bias was defined as the difference between PaCO2 and PetCO2, and was assessed by Bland-Altman plot analysis. Results: A total of 34 neonates were recruited, and data of 54 pairs of PaCO2 and PetCO2 levels were available for comparison. The average (mean ± SD) gestational age was 32.5 ± 4.2 weeks, and the average birth weight was 1881 ± 1077 g. There was a good correlation between PetCO2 and PaCO2 levels among all paired samples (r = 0.809, p < 0.001). When the data were divided into those with respiratory disease (n = 34) and those without (n = 20), significant correlation between PetCO2 and PaCO2 levels were both noted in the former group (r = 0.823, p < 0.001) and the latter group (r = 0.770, p < 0.001). The overall average mean value of PetCO2 was lower than that of PaCO2 (39.4 ± 8.8 mmHg vs. 41.3 ± 9.2 mmHg, p = 0.014). The difference between PetCO2 and PaCO2 levels was significant only among those with respiratory disease (38.8 ± 9.8 mmHg vs. 41.2 ± 10.3 mmHg, p = 0.027), but not among those without (40.5 ± 7.0 mmHg vs. 41.6 ± 7.2 mmHg, p = 0.289). Conclusions: End-tidal CO2 measurement by side-stream capnometry through nasal cannula could provide an accurate and noninvasive estimate of PaCO2 levels in nonintubated neonates.

Patients with congenital duodenal obstruction (CDO) predominantly have a postampullary lesion site and a high association with Down syndrome, according to previous reports from Western countries. This study aimed to determine whether there are racial differences in the clinical characteristics of congenital duodenal obstruction, based on the experience from a Taiwanese medical center. Methods: The charts were retrospectively reviewed among neonates with CDO who received surgery at National Taiwan University Hospital during the period 1985- 2008. Patients were grouped into a preampullary or postampullary group according to the obstruction in relation to the ampulla of Vater. Other characteristics, including sex, time of diagnosis, operative findings, as well as associated anomalies, were recorded for further analysis. Results: A total of 30 patients with CDO including 16 with atresia, 10 with mucosal webs, and 4 with stenosis, were recruited; among them, 16 were boys and 14 were girls. In 15 patients (50%), the diagnosis of duodenal obstruction was made prenatally. A total of 11 of the 30 patients (37%) were in the preampullary group and 19 (63%) were in the postampullary group. Seventeen patients (56.7%) had at least one additional anomaly, including four (13%) who had trisomy 21. The preampullary group had significantly fewer associated congenital anomalies than in the postampullary group (27% vs. 74%, p = 0.012). Conclusion: Our cohort showed a relatively lower incidence of postampullary lesions and associated Down syndrome in patients with CDO compared with Western countries. Additionally, patients with preampullary lesions had significantly less association with other anomalies.

Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental anomalies. Early surgical excision is becoming an increasingly common option. We investigated the clinical features and management of patients with CCAM and BPS at the National Taiwan University Hospital. Methods: We conducted a retrospective review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995 to January 2008. Prenatal examination, postnatal presentation, management and patient outcome were analyzed. We also propose a concise algorithm for the practical management of these conditions. Results: Sixteen patients were recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%) with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed antenatally at a median gestational age of 20 weeks. Eleven (69%) patients underwent surgical resection before 6 months of age because of respiratory distress or repeated pulmonary infection. There were no surgery-related complications among the seven patients who underwent early surgery within 1 month of age. Five (31%) patients remained asymptomatic and did not undergo surgery. All patients survived with no limitations to daily activity during follow-up periods of 1–8 years. Conclusion: The high proportion of mixed-type lesions suggests that CCAM and BPS may share the same developmental ancestry. Early surgical resection within 1 month of age is safe in symptomatic patients.

Antiphospholipid syndrome (APS) in pregnancy is characterized by the presence of maternal autoantibodies in association with recurrent fetal loss and severe obstetric complications such as prematurity, intrauterine growth retardation, or placental insufficiency. This study aimed to assess the perinatal outcomes in neonates born to mothers with APS. Methods: The medical records of pregnant women with APS and their offspring were retrospectively collected between January 1997 and July 2007. Maternal and perinatal histories including demographic data, medications, obstetric histories, and neonatal clinical manifestations and laboratory data were analyzed. Results: Eleven women with a diagnosis of primary APS were included. Eight of these patients had experienced frequent spontaneous abortions (72.7%), and four had unexplained fetal deaths (36.3%). None of them had vascular thrombosis. Specific autoimmune antibodies were detected, including anticardiolipin antibody (n = 6), anti-β2 glycoprotein I (n = 3), and antiphospholipid antibody (n = 7). Among the pregnancies, five had preterm births (45.4%), two had intrauterine growth retardation (18.1%), and one had intrauterine fetal demise (9.1%). Thrombocytopenia was noted in three babies, all of whose mothers had lower platelet counts. One patient with neonatal thrombocytopenia developed intracranial hemorrhage, seen on brain images. Conclusions: This limited study suggests that neonates born to mothers with primary APS are at risk of prematurity, being small for gestational age, and having thrombocytopenia. Further large, prospective studies are required to better define the perinatal outcomes.

Neonatal sepsis is the most serious problem in neonatal intensive care, resulting in significant morbidity and mortality. We evaluated the causative pathogen, drug sensitivity, hematological parameters, clinical course and mortality rate of neonatal sepsis in a Taiwanese medical center and compared our results to those of previous studies conducted in Taiwan. Methods: Neonates admitted to the neonatal intensive care unit (NICU) at National Taiwan University Hospital (NTUH) between January 2001 and December 2006 were included in this study. Patients were divided into early-onset sepsis and late-onset sepsis groups if their culture tested positive within the first 7 days of life or later, respectively. Results: A total of 109 episodes of sepsis were identified in 100 neonates. The incidence of sepsis was 4.06% among all NICU admissions. Most neonates with early-onset sepsis were term infants, while very low birth weight (VLBW) and preterm infants accounted for the majority of cases of late-onset sepsis. In early-onset sepsis, the most common pathogens responsible included group B streptococci (GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was associated with more meningitis involvement but lower incidence of mortality compared with E. coli. The most common causative micro organisms in late-onset sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The sepsis-related mortality rates were higher in early-onset sepsis (10%) than in late-onset sepsis (7%). Conclusion: Unlike previous reports from Taiwan, in the present study, GBS was found to be the leading pathogen in early-onset sepsis. GBS screening and intrapartum antibiotic prophylaxis guidelines should be used in Taiwan to prevent early neonatal sepsis. The most common causative microorganisms of late-onset sepsis were CONS and Candida species. Candida parapsilosis was associated with a high mortality rate.

Pneumomediastinum usually occurs after assisted ventilation. Spontaneous pneumomediastinum without preceding assisted ventilation, and presenting as a huge cystic mass in a term newborn infant has rarely been reported. We report a term baby who developed respiratory distress at 2 days of age. A huge cystic tumor of the thymus or a congenital mediastinal cystic tumor was initially suggested by chest radiography and computed tomography. Follow-up chest film revealed a “spinnaker sail sign” which is a typical radiographic presentation of pneumomediastinum.

Fetuses with upper airway obstruction have a high mortality rate if proper airway management is not immediately administered after delivery. The EXIT (ex utero intrapartum treatment) procedure is a new technique that establishes the fetal airway while uteroplacental circulation is still maintained. The prognosis of such neonates has much improved after the introduction of this procedure. We report two neonates with prenatal diagnosis of upper airway obstruction; they were born smoothly via the EXIT procedure. The first was a case of epignathus, a rare type of nasopharyngeal or oropharyngeal teratoma derived from all three germ cell layers with variable maturity. The second was a case of giant lymphangioma that resulted from localized malformations in the development of the lymphatic system. Furthermore, compared with routine cesarean section, the short-term maternal outcomes were not different with regard to infection rate, estimated blood loss, wound complication, and postpartum hospital stay.

Two major forms of biliary atresia, the embryonic and perinatal type, are considered to have different pathogeneses and distinct prognoses. Embryonic biliary atresia is associated with worse prognosis. We report a case of embryonic biliary atresia in a preterm male infant of 31 weeks of gestation and weighing 1375 g, with the initial manifestation of intermittent acholic stool 5 days after birth. Kasai portoenterostomy was performed at the age of 51 days when he weighed 2164 g. Nevertheless, poorly restored bile flow and progressive cholestasis led to early liver transplantation at the age of 8 months. Liver function had recovered to normal levels by the age of 12 months. Diagnosis of biliary atresia in preterm infants is difficult and requires a high index of suspicion and careful workup. This case illustrates the poor outcome of embryonic biliary atresia and that early liver transplantation may be necessary to improve the prognosis. [J Formos Med Assoc 2007;106(1):78-81]

In Western developed countries, Listeria monocytogenes is not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocyto-genes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals. [J Formos Med Assoc 2007;106(2):161-164]

Congenital central hypoventilation syndrome (CCHS) is a rare disease that is characterized by failure in the autonomic control of breathing. Recent reports have identified mutation of the paired mesoderm homeobox protein 2b (PHOX2B) gene as playing a major role in CCHS. Increasing polyalanine repeat number is associated with a more severe clinical phenotype. We report a newborn male infant with the clinical manifestations of apnea and cyanosis requiring immediate endotracheal intubation at the age of 1 day. Recurrent hypoventilation with hypercapnia and hypoxemia occurred during sleep after weaning from the ventilator. No primary cardiopulmonary disease was identified. These clinical manifestations are compatible with CCHS. PHOX2B gene mutation analysis performed at the age of 4 months revealed expanded alleles containing polyalanine 26 repeats, further supporting the diagnosis of CCHS. Continuous ventilator support was necessary and tracheostomy was ultimately performed at the age of 5 months due to ventilator dependence. He was discharged with home ventilator support at the age of 6 months. [J Formos Med Assoc 2007;106(1):69-73]

Preeclampsia and retinopathy of prematurity (ROP) are associated with impaired angiogenesis. Previous studies on the relationship between preeclampsia and ROP have produced conflicting results. The goal of this study was to evaluate the association between maternal preeclampsia and ROP using a large population-based cohort of very-low-birth-weight (VLBW) infants from 21 neonatal departments registered in the database of the Premature Baby Foundation of Taiwan. Multivariable logistic regression analysis was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for preeclampsia with reference to ROP and severe ROP. A total of 5,718 VLBW infants (844 cases with maternal preeclampsia) were included for analysis. The overall incidences of mild and severe ROP were 36.0% and 12.2%, respectively. Univariable analysis showed lower GA and lower birth weight, vaginal delivery, non-SGA, RDS, PDA, sepsis, transfusion, and absence of maternal preeclampsia to be associated with mild and severe ROP development. However, OR (95% CI) adjusted for the variables that were significant according to univariable analysis showed the risks of developing any-stage ROP and severe ROP for maternal preeclampsia to be 1.00 (0.84-1.20) and 0.89 (0.63-1.25), respectively. The results remained unchanged in stratified analyses according to SGA status. Our data showed that maternal preeclampsia was not associated with the subsequent development of any stage or severe ROP in VLBW infants.