Monitoring of the Healthy Neonatal Transition Period with Serial Lung Ultrasound.

Ultrasound has been used to observe lung aeration and fluid clearance during the neonatal transition period, but there is no consensus regarding the optimal timing of lung ultrasound. We aimed to monitor the trend of the serial lung ultrasound score (LUS) and extended LUS (eLUS) throughout the neonatal transition period (≤1, 2, 4, 8, 24, and 48 h after birth), assess any correlation to the clinical presentation (using the Silverman Andersen Respiratory Severity Score (RSS)), and determine the optimal time of the ultrasound. We found both LUS and eLUS decreased significantly after 2 h of life and had similar statistical differences among the serial time points. Although both scores had a positive, moderate correlation to the RSS overall (Pearson correlation 0.499 [p < 0.001] between LUS and RSS, 0.504 [p < 0.001] between eLUS and RSS), the correlation was poor within 1 h of life (Pearson correlation 0.15 [p = 0.389] between LUS and RSS, 0.099 [p = 0.573] between eLUS and RSS). For better clinical correlation, the first lung ultrasound for the neonate may be performed at 2 h of life. Further research is warranted to explore the clinical value and limitations of earlier (≤1 h of life) lung ultrasound examinations.

The impact of small-for-gestational-age Status on the outcomes in very-Low-birth-weight (VLBW) premature infants: a prospective cohort study in Taiwan.

Background: The impact of small-for-gestational-age (SGA) on very-low-birth-weight (VLBW) premature infants remains inconclusive. This study aimed to assess the effects of being born SGA status on the short-term and long-term outcomes in VLBW preterm infants. Methods: We conducted a population-based, prospective cohort study on VLBW preterm infants born in Taiwan between 2012 and 2017. Sociodemographic, neonatal, growth and neurological data at 2 years of corrected age were collected. A total of 4243 VLBW infants born at 24 through 32 completed weeks' gestation participated in this study, of whom 1,005 had SGA status defined as a birth weight <10th percentile of gestation, and 3,238 did not (the non-SGA group).We compared the risks of short-term outcomes (neonatal mortality and morbidities), long-term outcomes (growth status, including weight, height, and head circumference <10th percentile, and neurodevelopmental impairments at 2 years of age). Subgroup analysis was performed by stratification of gestation age (GA): GA 24-26, 27-29 and 30-32 weeks. Results: In the analysis of short-term outcomes, the SGA group had an increased risk of neonatal mortality [adjusted odds ratio (OR) = 2.66, 2.99, and 2.19, respectively] in all GA subgroups in comparison with the non-SGA group (p < 0.05). The SGA group had a significantly increased risk of bronchopulmonary dysplasia in GA 27-29 and 30-32 weeks (adjusted OR = 2.11 and 1.86, respectively). We also found that there was an increased risk of severe retinopathy of prematurity in GA 24-26 and 27-29 weeks in the SGA group compared with the non-SGA group (adjusted OR = 1.68 and 1.59, respectively).In the analysis of long-term outcomes, the SGA group had a significantly increased risk of NDI throughout all GA subgroups (adjusted = 1.94, 1.33, and 1.35, respectively) in comparison with the non-SGA group. The SGA groups also had an increased risk of growth status <10th percentile at 2 years of age (p < 0.05). Conclusions: SGA VLBW premature infants had higher risks of neonatal death, growth status <10th percentile, and NDI at 2 years of corrected age compared with the non- SGA premature infants. Prenatal surveillance, postnatal attention, and long- term follow-up are warranted to improve the outcomes of VLBW SGA premature infants.

The effect of patient volume on mortality and morbidity of extremely low birth weight infants in Taiwan.

BACKGROUND: To assess whether the number of extremely low birth weight (ELBW) infants treated annually in neonatal intensive care units (NICUs) in Taiwan affects the mortality and morbidity of this patient population. METHODS: This retrospective cohort study included preterm infants with ELBW (≤1000 g). NICUs were divided into three subgroups according to the annual admissions of ELBW infants (low, ≤10; medium, 11-25; and high, >25). Perinatal characteristics, mortality, and short-term morbidities were compared between groups. RESULTS: A total of 1945 ELBW infants from 17 NICUs were analyzed (low-volume, n = 263; medium-volume, n = 420; and high-volume, n = 1262). After risk adjustments, infants from NICUs with low patient volumes were at a higher risk of death. The risk-adjusted odds ratios (aOR) for mortality were 0.61 (95% CI, 0.43-0.86) in the high-volume NICUs and 0.65 (95% CI, 0.43-0.98) in medium-volume NICUs, compared with infants admitted to low-volume NICUs. Infants in medium-volume NICUs had the lowest incidence of prenatal steroid exposure (58.1%, P < 0.001) and were associated with the highest risk of necrotizing enterocolitis (aOR, 2.35 [95% CI, 1.48-3.72]), severe intraventricular hemorrhage (aOR, 1.55 [95% CI, 1.01-2.28]), and bronchopulmonary dysplasia (aOR, 1.61 [95% CI, 1.10-2.35]). However, survival without major morbidity did not differ between the groups. CONCLUSION: The mortality risk was higher among ELBW infants admitted to NICUs with a low annual patient volume. This may emphasize the importance of systematically referring patients from these vulnerable populations to appropriate care settings.

Association of mode of delivery with short-term and neurodevelopmental outcomes in periviable singleton infants: A nationwide database study.

OBJECTIVE: To evaluate the association of mode of delivery (MOD) with short-term and neurodevelopmental outcomes at 2 years of corrected age (CA) in periviable singleton infants. METHODS: This retrospective cohort study of the Taiwan Premature Infant Follow-up Network database between 2010 and 2016 compared non-anomalous singleton deliveries (cesarean delivery [CD] vs vaginal delivery [VD]) between 22 0/7 and 25 6/7 gestational weeks. Major morbidities, mortality, and neurodevelopmental outcomes were evaluated at 2-year CA. RESULTS: The CD and VD groups included 354 and 472 infants, respectively. The intraventricular hemorrhage (IVH) rate was lower in the CD group (54% vs 66%, P = 0.001), but severe IVH differed non-significantly between groups (20% vs 26%, P = 0.057). In the small-for-gestational age subgroup, CD was associated with lower IVH (56% vs 84%, adjusted odds ratio [aOR] 0.17, 95% confidence interval [CI] 0.04-0.69) and better survival without neurodevelopmental impairment (29% vs 8%, aOR, 6.64, 95% CI 1.02-43.29) after controlling for potential confounders. CONCLUSION: The optimal MOD for periviable singleton birth and its impact are unclear. CD in periviable singleton births is associated with a decreased IVH risk, without improvement in severe IVH, mortality, or neurodevelopment at 2-year CA. The small-for-gestational age subgroup may benefit from CD for better survival without neurodevelopmental impairment.

Risk Factors of Language Delay at Two Years of Corrected Age among Very-Low-Birth-Weight Preterm Infants: A Population-Based Study.

Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of corrected age in this vulnerable population. VLBW infants, who were assessed at two years of corrected age using the Bayley Scale of Infant Development, third edition, were included using a population-based cohort database. Language delay was defined as mild to moderate if the composite score was between 70 and 85 and severe if the score was < 70. Multivariable logistic regression analysis was used to identify the perinatal risk factors associated with language delay. The study comprised 3797 VLBW preterm infants; 678 (18%) had a mild to moderate delay and 235 (6%) had a severe delay. After adjusting for confounding factors, low maternal education level, low maternal socioeconomic status, extremely low birth weight, male sex, and severe intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (PVL) were found to be significantly associated with both mild to moderate and severe delays. Resuscitation at delivery, necrotizing enterocolitis, and patent ductus arteriosus requiring ligation showed significant associations with severe delay. The strongest factors predicting both mild to moderate and severe language delays were the male sex and severe IVH and/or cystic PVL; thus, early targeted intervention is warranted in these populations.

Effects of erythropoietin in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Minimizing multiple organ dysfunction-related mortality and morbidity is a critical issue for patients with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH). Although erythropoietin (EPO) has demonstrated protective effects on various hypoxic-ischemic organs in animal studies and clinical trials in adults, its effects on neonates with HIE require further investigation. METHODS: This study retrospectively analyzed the medical records of neonates with HIE who received TH with or without EPO (TH+EPO vs TH groups) administration in a tertiary referral hospital from January 2016 to January 2021. Data regarding patient characteristics, medical treatment, and clinical (neurological, cardiac, respiratory, gastrointestinal, hepatic, and renal) function assessments were collected. To control for confounding factors and selection bias between the two groups, a 1:1 propensity matching method was applied. RESULTS: A total of 45 neonates with HIE received TH during the study period, with 24 patients (53%) in the TH+EPO group. After matching, each group enrolled 13 cases. No significant difference in mortality or hospital stay between the two groups was noted. During the first 3 days, the patients in the TH+EPO group showed significantly higher blood pressure (BP) than those in the TH group ( p < 0.05 on day 1). The TH+EPO group showed trends of higher blood hemoglobin ( p > 0.05) and creatinine ( p > 0.05) levels and lower estimated glomerular filtration rate ( p > 0.05) and urine output ( p > 0.05) during the first 2 weeks than TH group. CONCLUSION: The use of EPO in addition to TH is safe for neonates with HIE. The neonates with moderate or severe HIE who received EPO may have a lesser risk of hypotension than those who received TH alone. Further clinical studies on renal and cardiac functions and long-term neurological effects of EPO are required.

Growth of Very Preterm Infants in a Low-Resourced Rural Setting after Affiliation with a Human Milk Bank.

The extrauterine growth restriction (EUGR) of very preterm infants has been associated with long-term complications and neurodevelopmental problems. EUGR has been reported at higher rates in low resource settings. There is limited research investigating how metropolitan human milk banks contribute to the growth outcomes of very preterm infants cared in rural areas. The setting of this study is located at a rural county in Taiwan and affiliated with the Taiwan Southern Human Milk Bank. Donor human milk was provided through a novel supplemental system. A renewal nutritional protocol was initiated as a quality improvement project after the affiliated program. This study aimed to compare the clinical morbidities and growth outcome at term equivalent age (TEA) of preterm infants less than 33 weeks of gestational age before (Epoch-I, July 2015-June 2018, n = 40) and after the new implementation (Epoch-II, July 2018-December 2020, n = 42). The Epoch-II group significantly increased in bodyweight z-score at TEA ((-0.02 ± 1.00) versus Epoch-I group (-0.84 ± 1.08), p = 0.002). In multivariate regression models, the statistical difference between two epochs in bodyweight z-score changes from birth to TEA was still noted. Modern human milk banks may facilitate the nutritional protocol renewal in rural areas and improve the growth outcomes of very preterm infants cared for. Establishing more distribution sites of milk banks should be encouraged.

An 18-year retrospective study on the epidemiology of early-onset neonatal sepsis - emergence of uncommon pathogens.

BACKGROUND: Nationwide group B Streptococcus agalactiae (GBS) antepartum screening was instituted in Taiwan in 2012. The impact of the policy on early-onset sepsis (EOS) has not been evaluated. This study aimed to examine the impact of the policy on the incidence of neonatal EOS. METHODS: This was a retrospective study conducted at MacKay Children's Hospital. Patients with culture-proven neonatal EOS were enrolled and divided by birth year in relation to the implementation of GBS prevention policy: Epoch 1, 2001-2004 pre-GBS screening; Epoch 2, 2005-2011 elective GBS screening; and Epoch 3, 2012-2018 universal GBS screening. The pathogens and antimicrobial resistance patterns were reviewed and analyzed. The incidence was modeled using Poisson regression. RESULTS: A total of 128 neonates met the enrollment criteria. The observed incidence of EOS was 1.52‰. The incidence rates of EOS, GBS, and Escherichia coli (E. coli) sepsis were similar in Epoch 1 and Epoch 3. E. coli and non-Enterococcal group D Streptococcus (GDS) infection increased significantly in term infants, whereas the EOS-related mortality rate declined in preterm infants. Approximately 72% of the isolated E. coli were ampicillin-resistant, and the antimicrobial sensitivity remained unaltered during the studied period. CONCLUSIONS: The overall EOS incidence has not changed from 2001 to 2018. However, changes in the causative pathogens were observed in both term and preterm infants. Clinicians should be aware of this evolving epidemiology to provide prompt appropriate perinatal management.

Predictive Validity of the Bayley-III Cognitive Scores at 6 Months for Cognitive Outcomes at 24 Months in Very-Low-Birth-Weight Infants.

Purpose: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes. Methods: We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of <70 and <85 were used to identify lower functioning groups based on the Bayley-III definition. Results: A total of 2,972 VLBW children, born with a mean weight of 1116.4 ± 257.5 g and mean gestational age of 29.0 ± 2.8 weeks, were evaluated. A cognitive score of <70 at 6-month CA had a positive predictive value (PPV) of 27.4% (95% confidence interval [CI]: 19.2-35.7%) for a cognitive score of <70 at 24-month CA, while the negative predictive value (NPV) was 97.3% (95% CI: 96.7-97.9%). A cut-off score of 85 had a PPV of 33.6% (95% CI: 28.1-39.0%) and an NPV of 87.7% (95% CI: 86.4-88.9%). Abnormal muscle tone at 6 months was a risk factor for cognitive function decline at 24 months for both Bayley-III cognitive cut-off scores: scores of 70 (adjusted odds ratio [AOR]: 2.8; 95% CI: 1.5-5.5) and 85 (AOR: 2.6; 95% CI: 1.6-4.1). Lower maternal socioeconomic status was associated with a worsening of the cognitive function in infants at 24 months who scored ≥85 at 6 months (AOR: 1.6; 95% CI: 1.2-2.0). Conclusion: Subnormal Bayley-III cognitive scores at 6-month CA were not predictive of subnormal cognitive function at 24-month CA. In children with normal cognition during early infancy, abnormal muscle tone and lower maternal socioeconomic status may influence the cognitive developing process; this highlighted the importance of early identification of high risk infants and complete preterm infant-associated public health policies to promote an improved neurodevelopmental outcome.

A 12-year-experience with tracheostomy for neonates and infants in northern Taiwan: Indications, hospital courses, and long-term outcomes.

BACKGROUND: Tracheostomy is a valuable procedure in infants and neonates with chronic respiratory failure or severe airway obstruction. The aim of this study is to identify the indication, hospital course, and long-term outcome in a cohort of infants who required tracheostomy in a neonatal and pediatric tertiary care center in northern Taiwan. METHODS: Medical records of infants, who underwent tracheostomy between January 2002 and December 2013, were retrospectively reviewed. Demographics, indication for tracheostomy, hospital course, discharge disposition, further hospitalization and surgery, and long-term outcome data were collected. RESULTS: Fifty-six patients were enrolled. The median gestational age was 38.0 weeks, and median birth weight was 2770 g. he median age at tracheostomy was 104.5 days. The primary indications for tracheostomy were airway obstruction in 35 patients (62.5%), craniofacial anomalies in 7 (12.5%), neuromuscular disorder in 7 (12.5%), cardiopulmonary disorder in 5 (8.9%), and brain injury-related problem in 2 (3.6%). Twenty-two patients (39.3%) were decannulated successfully, and the median time from tracheostomy to decannulation was 2.1 years. Overall mortality rate was 3.6%, but no death was related to tracheostomy. Forty-nine patients underwent regular follow-up at our hospital, and 46 patients (93.9%) required further hospitalization, and 30 (61.2%) underwent further surgery related to a respiratory problem or tracheostomy. Ratio of delayed growth at the time of tracheostomy (28.6%) did not have significant difference at 1 year of age (21.4%) and 2 years of age (25.0%). CONCLUSION: In this study, the most common indication for tracheostomy in neonates and infants was airway obstruction. Excluding patients with neuromuscular diseases, a successful decannulation rate of >50% can be achieved.

Light-gated molecular brakes based on pentiptycene-incorporated azobenzenes.

Three azobenzene derivatives (2 R, 2 OR, and 2 NR) that differed in their terminal substituent (alkyl, alkyloxy, and dialkylamino, respectively) have been synthesized and investigated as molecular brakes, in which the rigid H-shaped pentiptycene group functioned as a rotor and the dinitrophenyl group as a "brake pad". The E and Z isomers of these compounds corresponded to the "brake-off" and "brake-on" states, respectively. The rotation rate of the rotor was evaluated by VT NMR spectroscopy for the brake-on state and by DFT calculations for the brake-off state. The difference between the rotation rates for the rotor in the two states was as large as eight orders of magnitude at ambient temperature. Photochemical switching of the azobenzene moieties afforded efficiencies of 55-67%. A combination of photochemical E→Z and thermal Z→E isomerization promoted the switching efficiency up to 78%. The terminal substituent affected both the photochemical and thermal switching efficiencies. Solvent polarity also played an important role in the lifetimes of the Z isomers. These azobenzene systems displayed similar braking powers but superior switching efficiencies to the stilbene analogue (1O R; ca. 60% vs 20%).

CT-guided transthoracic cutting needle biopsy of intrathoracic lesions: comparison between coaxial and single needle technique.

PURPOSE: To evaluate the complication rates and diagnostic accuracy of two different CT-guided transthoracic cutting needle biopsy techniques: coaxial method and single needle method. METHODS: This study involved 198 consecutive subjects with 198 intrathoracic lesions. The first 98 consecutive subjects received a single needle cutting technique and the next 100 consecutive subjects received a coaxial technique. Both groups were compared in relation the diagnostic accuracy and complication rates. RESULTS: No significant difference was found between the two groups concerning patient characteristics, lesions and procedure variables. There was a borderline statistical difference in the incidence of pneumothorax at within 24-h post biopsy between patients in the single needle group (5%) and the coaxial group (13%) (P=0.053). Little difference was found in the pneumothorax rate at immediately post biopsy between the two groups, which was 28% in the single needle group and 31% in the coaxial group. There was no significant difference in the hemoptysis rate between the two groups, which was 9.2% in the single needle group and 11% in the coaxial group. Both techniques yielded an overall diagnostic accuracy of 98% for malignant lesions with similar sensitivity (single needle: 96.9% vs. coaxial: 96.4%) and specificity (single needle: 100% vs. coaxial: 100%). CONCLUSION: There is little difference in the pneumothorax rates and bleeding complications between patients who either received a single needle or a coaxial transthoracic cutting biopsy. Both techniques produce an overall diagnostic accuracy of 98% for malignant lesions.

An acidic extracellular pH disrupts adherens junctions in HepG2 cells by Src kinases-dependent modification of E-cadherin.

We have previously shown that culturing HepG2 cells in pH 6.6 culture medium increases the c-Src-dependent tyrosine phosphorylation of beta-catenin and induces disassembly of adherens junctions (AJs). Here, we investigated the upstream mechanism leading to this pH 6.6-induced modification of E-cadherin. In control cells cultured at pH 7.4, E-cadherin staining was linear and continuous at cell-cell contact sites. Culturing cells at pH 6.6 was not cytotoxic, and resulted in weak and discontinuous junctional E-cadherin staining, consistent with the decreased levels of E-cadherin in membrane fractions. pH 6.6 treatment activated c-Src and Fyn kinase and induced tyrosine phosphorylation of p120 catenin (p120ctn) and E-cadherin. Inhibition of Src family kinases by PP2 attenuated the pH 6.6-induced tyrosine phosphorylation of E-cadherin and p120ctn, and prevented the loss of these proteins from AJs. In addition, E-cadherin was bound to Hakai and ubiquitinated. Furthermore, pH 6.6-induced detachment of E-cadherin from AJs was blocked by pretreatment with MG132 or NH(4)Cl, indicating the involvement of ubiquitin-proteasomal/lysosomal degradation of E-cadherin. An early loss of p120ctn prior to E-cadherin detachment from AJs was noted, concomitant with a decreased association between p120ctn and E-cadherin at pH 6.6. PP2 pretreatment prevented the dissociation of these two proteins. In conclusion, pH 6.6 activated Src kinases, resulting in tyrosine phosphorylation of E-cadherin and p120ctn and a weakening of the association of E-cadherin with p120ctn and contributing to the instability of E-cadherin at AJs.

Protein kinase C-Fyn kinase cascade mediates the oleic acid-induced disassembly of neonatal rat cardiomyocyte adherens junctions.

Oleic acid (OA) affects assembly of gap junctions in neonatal cardiomyocytes. Adherens junction (AJ) regulates the stability of gap junction integrity; however, the effect of OA on AJ remains largely unexplored. The distribution of N-cadherin and catenins at cell-cell junction was decreased by OA. OA induced activation of protein kinase C(PKC)-alpha and -epsilon and Src family kinase, and all three kinases were involved in the oleic acid-induced disassembly of the adherens junction, since it was blocked by pretreatment with Gö6976 (a PKCalpha inhibitor), epsilonV1-2 (a PKCepsilon inhibitor), or PP2 (a Src family kinase inhibitor). Src family kinase appeared to be the downstream of PKC-alpha and -epsilon, as blockade of either PKC-alpha or -epsilon activity prevented the OA-induced activation of Src family kinase. Immunoprecipitation analyses showed that OA activated Fyn and Fer. OA promoted the association of p120 catenin/beta-catenin with Fyn and Fer and caused increased tyrosine phosphorylation of p120 catenin and beta-catenin, resulting in decreased binding of the former to N-cadherin and of the latter to alpha-catenin. Pretreatment with PP2 abrogated this OA-induced tyrosine phosphorylation of p120 catenin and beta-catenin and restored the association of N-cadherin with p120 catenin and that of beta-catenin with alpha-catenin. In conclusion, these results show that OA activates the PKC-Fyn signaling pathway, leading to the disassembly of the AJ. Therefore, inhibitors of PKC-alpha/-epsilon and Src family kinase are potential candidates as cardioprotection agents against OA-induced heart injury during ischemia-reperfusion.