Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Sustained acute kidney injury as an independent risk factor for neurodevelopmental and growth outcomes in a single NICU center.

PURPOSE: Acute kidney injury (AKI) is commonly seen in neonatal intensive care units (NICUs) and is potentially associated with adverse prognoses in later stages of life. Our study evaluated the impact of sustained AKI (SAKI) on both neurodevelopmental impairment (NDI) and early growth restriction (EGR) in neonates. METHODS: This case-control study retrospectively analyzed the medical records of neonates diagnosed with SAKI in the NICU of a tertiary medical center during the period from January 2007 to December 2020. Cases without subsequent follow-up and those resulting in death were excluded. We analyzed demographic, biochemical, and clinical outcome data. RESULTS: Of the 93 neonates with SAKI, 51 cases (54.8%) were included in this study, while 42 cases (45.2%) were excluded due to a lack of follow-up or death. An age-matched control group comprised 103 neonates, who had never experienced AKI or SAKI, were selected at random. In total, 59 (38.3%) cases were identified as NDI and 43 (27.9%) as EGR. Multivariate analysis revealed that patients with SAKI had significantly higher risks of developing NDI (odds ratio, [OR] = 4.013, p = 0.001) and EGR (OR = 4.894, p < 0.001). The AKI interval had an area under the receiver operating characteristic curve of 0.754 for NDI at 9.5 days and 0.772 for EGR at 12.5 days. CONCLUSIONS: SAKI is an independent risk factor for both NDI and EGR in neonates. Consequently, regular monitoring, neurological development assessments, and appropriate nutritional advice are crucial to these infants who have experienced renal injury.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Antivascular Endothelial Growth Factor Injection.

OBJECTIVE: To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. STUDY DESIGN: Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS: A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P = .008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P = .003), patent ductus arteriosus ligation (OR 10.7, P = .032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P = .018). CONCLUSIONS: All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

The Clinical Characteristics, Microbiology and Risk Factors for Adverse Outcomes in Neonates with Gram-Negative Bacillary Meningitis.

Background: We aimed to describe the clinical features of Gram-negative bacillary (GNB) meningitis in neonates and investigate the risk factors associated with final adverse outcomes of neonatal GNB meningitis. Methods: From 2003 to 2020, all neonates (aged ≤ 90 days old) with bacterial meningitis who were hospitalized in four tertiary-level neonatal intensive care units (NICUs) of two medical centers in Taiwan were enrolled. Neonates with GNB meningitis were compared with those with Streptococcus agalactiae (group B streptococcus, GBS) meningitis. Results: During the study period, a total of 153 neonates with bacterial meningitis were identified and enrolled. GNB and GBS accounted for 40.5% (n = 62) and 35.3% (n = 54) of all neonatal bacterial meningitis, respectively. In neonates with GNB meningitis, the final mortality rate was 6.5% (4 neonates died); 48 (77.4%) had neurological complications, and 26 (44.8%) of 58 survivors had neurological sequelae at discharge. Although the final outcomes were comparable between neonates with GNB meningitis and those with GBS meningitis, neonates with GNB meningitis were more likely to have more severe clinical manifestations initially and have ventriculomegaly at follow-up. After multivariate logistic regression analysis, neonates with seizure at onset, early onset sepsis, and requirement of surgical intervention for neurological complications were independently associated with final adverse outcomes. Conclusions: GNB meningitis was associated with a high risk of neurological complications and sequelae, although it did not significantly increase the final mortality rate. Close monitoring of the occurrence of neurological complications and advanced therapeutic strategies to optimize the outcomes are urgently needed in the future.

Respiratory outcomes in preterm infants following intravitreal bevacizumab for retinopathy of prematurity-a 10-year matched case study.

OBJECTIVES: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). METHODS: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. RESULTS: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. CONCLUSIONS: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.

Invasive Candida parapsilosis Bloodstream Infections in Children: The Antifungal Susceptibility, Clinical Characteristics and Impacts on Outcomes.

Background: Candida parapsilosis is the most common non-albicans candida species that causes invasive candidiasis, but little is known about its impacts on the outcomes of pediatric patients. We aimed to characterize the clinical characteristics, risk factors and outcomes of C. parapsilosis bloodstream infections (BSIs) in children. Methods: All pediatric patients with Candida parapsilosis BSIs between 2005 and 2020 from a medical center in Taiwan were enrolled and analyzed. The antifungal susceptibility, clinical manifestations, management and outcomes were investigated. Cases of Candida parapsilosis BSIs were compared between patients with C. albicans BSIs and other Candida spp. BSIs. Results: During the study period, 95 episodes (26.0% of total cases) of Candida parapsilosis BSIs were identified and analyzed. No significant difference was found between pediatric patients with C. parapsilosis BSIs and those with C. albicans BSIs in terms of patients' demographics, most chronic comorbidities or risk factors. Pediatric patients with C. parapsilosis BSIs were significantly more likely to have previous azole exposure and be on total parenteral nutrition than those with C. albicans BSIs (17.9 vs. 7.6% and 76.8 vs. 63.7%, p = 0.015 and 0.029, respectively). The duration of C. parapsilosis candidemia was relatively longer, and therefore patients often required a longer duration of antifungal treatment when compared with those of C. albicans candidemia, although the candidemia-attributable mortality rates were comparable. Of the C. parapsilosis isolates, 93.7% were susceptible to all antifungal agents, and delayed appropriate antifungal treatment was an independent factor in treatment failure. Conclusions: Pediatric patients with C. parapsilosis BSIs were more likely to have previous azole exposure and be on total parenteral nutrition, and the clinical significances included a longer duration of candidemia and patients often required a longer duration of antifungal treatment.

Outcomes of and factors associated with the development of bronchopulmonary dysplasia with pulmonary hypertension in very low birth weight infants: A retrospective study in a medical center.

Introduction: Bronchopulmonary dysplasia (BPD) with pulmonary hypertension (PH) leads to increased morbidity and mortality in extremely preterm infants. Recent studies have analyzed factors associated with development of PH in BPD; however, this research remains inconclusive, and controversy exists regarding the correlation between BPD and PH. This study aimed to investigate potential associated factors, clinical characteristics, and outcomes of BPD with pulmonary hypertension in very low birth weight (VLBW) preterm infants. Methods: We conducted a retrospective study, reviewing the records of infants with gestational age (GA) <32 weeks and birth weight <1,500 g admitted to a tertiary neonatal intensive care unit between January 2020 and October 2021 who were diagnosed with moderate to severe BPD. Echocardiogram was performed at the postmenstrual age of 36 weeks or before discharge. The diagnosis of PH was based on the findings of echocardiogram. Prenatal and postnatal characteristics, demographic data, treatment details, and outcomes were collected and analyzed. Results: A total of 139 VLBW infants with BPD were enrolled and divided into a PH group (n = 25) and a non-PH group (n = 114). The mean GA was 27.3 ± 2.3 weeks and the mean birth weight of infants with BPD was 927.3 ± 293.3 g. A multivariate logistic regression model revealed that a high positive end-expiratory pressure (PEEP) setting (OR: 2.105; 95% CI: 1.472-3.011; p < 0.001) in established BPD and surgical closure of patent ductus arteriosus (PDA; OR: 6.273; 95% CI: 1.574-24.977; p = 0.009) were associated with BPD-PH. Neonates with BPD who developed pulmonary hypertension remained hospitalized for longer (p < 0.001), received invasive mechanical ventilation support for longer (p < 0.001), had a higher incidence of retinopathy of prematurity (ROP; OR: 4.201; 95% CI: 1.561-11.304; p = 0.003), were more likely to require oxygen support at discharge (OR: 5.600; 95% CI: 2.175-14.416; p < 0.001), and were more likely to undergo tracheostomy (OR: 35.368; 95% CI: 4.03-310.43; p < 0.001). Conclusion: PDA ligation and a higher PEEP setting were associated with BPD-PH in our cohort study. Compared with VLBW infants with BPD but without PH, infants with BPD and PH were hospitalized for longer, and also had a higher incidence of oxygen support after discharge, ROP, and tracheostomy.

Influences of Initial Empiric Antibiotics with Ampicillin plus Cefotaxime on the Outcomes of Neonates with Respiratory Failure: A Propensity Score Matched Analysis.

Background: Empiric antibiotics are often prescribed in critically ill and preterm neonates at birth until sepsis can be ruled out. Although the current guideline suggests narrow-spectrum antibiotics, an upgrade in antibiotics is common in the neonatal intensive care unit. The impacts of initial broad-spectrum antibiotics on the outcomes of critically ill neonates with respiratory failure requiring mechanical intubation have not been well studied. Methods: A total of 1162 neonates from a tertiary level neonatal intensive care unit (NICU) in Taiwan who were on mechanical ventilation for respiratory distress/failure at birth were enrolled, and neonates receiving ampicillin plus cefotaxime were compared with those receiving ampicillin plus gentamicin. Propensity score-matched analysis was used to investigate the effects of ampicillin plus cefotaxime on the outcomes of critically ill neonates. Results: Ampicillin plus cefotaxime was more frequently prescribed for intubated neonates with lower birth weight, higher severity of illness, and those with a high risk of early-onset sepsis. Only 11.1% of these neonates had blood culture-confirmed early-onset sepsis and/or congenital pneumonia. The use of ampicillin plus cefotaxime did not significantly contribute to improved outcomes among neonates with early-onset sepsis. After propensity score-matched analyses, the critically ill neonates receiving ampicillin plus cefotaxime had significantly worse outcomes than those receiving ampicillin plus gentamicin, including a higher risk of late-onset sepsis caused by multidrug-resistant pathogens (11.2% versus 7.1%, p = 0.027), longer duration of hospitalization (median [IQR], 86.5 [47-118.8] days versus 78 [45.0-106.0] days, p = 0.002), and a significantly higher risk of in-hospital mortality (14.2% versus 9.6%, p = 0.023). Conclusions: Ampicillin plus cefotaxime should not be routinely prescribed as the empiric antibiotics for critically ill neonates at birth because they were associated with a higher risk of infections caused by multidrug-resistant pathogens and final worse outcomes.

Clonal Complex 12 Serotype Ib Streptococcus agalactiae Strain Causing Complicated Sepsis in Neonates: Clinical Features and Genetic Characteristics.

Streptococcus agalactiae (group B Streptococcus [GBS]) is well known to cause serious diseases in infants. A serotype Ib GBS strain has recently emerged and become prevalent in Southeast Asia. We aimed to investigate the clinical and genetic characteristics of this strain. All neonates with invasive GBS diseases from a tertiary-level medical center in Taiwan between 2003 and 2020 were analyzed. The capsule serotyping, multilocus sequence typing, and antimicrobial resistance analyses were performed on all the invasive GBS isolates, and whole-genome sequencing (WGS) was performed specifically on the type Ib GBS strain. A total of 188 neonates with invasive GBS disease during the study period were identified. The type Ib GBS strain accounted for 7.4% (n = 14) of neonatal GBS invasive diseases. Almost all type Ib GBS isolates belonged to sequence type 12 (13/14, 92.9%) and clonal complex 12. Neonates with type Ib GBS disease had a significantly higher rate of complicated sepsis (10/14, 71.4%; P < 0.05) and sepsis-attributable mortality (6/14, 42.9%; P < 0.05). Additionally, type Ib GBS isolates had significantly higher rates of resistance to erythromycin and clindamycin (both 100%; P < 0.05) than other GBS serotypes. WGS revealed the presence of an ~75-kb integrative and conjugative element, ICESag37, comprising multiple antibiotic resistance and virulence genes, and PI-1 plus PI-2a were noted in all type Ib serotype 12 (ST12) GBS isolates; these isolates may be responsible for its high invasiveness and antimicrobial resistance rates. The genomic characteristics of the type Ib clonal complex 12 (CC12) GBS strain may account for the high illness severity associated with this strain and its antibiotic resistance. Continuous monitoring and advanced strategies to control the spread of type Ib CC12 GBS should be considered. IMPORTANCE A type Ib ST12 GBS strain is not a common isolate in neonatal invasive diseases and has been ignored for a long time. However, the recent literature and our data showed that such a GBS strain is associated with a significantly higher risk of severe sepsis, higher illness severity, and a significantly higher rate of sepsis-attributable mortality. This study found a novel gene cluster, including the presence of ICESag37 and specific pilus genes, carrying multiple antimicrobial resistance and virulence genes, which may be responsible for the clinical characteristics. Because of the higher mortality and severity of illness, we concluded that continuous monitoring of the type Ib ST12 GBS strain is warranted in the future.

Analysis of predictive parameters for extubation in very low birth weight preterm infants.

BACKGROUND: Mechanical ventilation is the primary treatment for preterm infants with respiratory failure. Prolonged intubation may lead to complications; thus, early extubation is desirable. No standard criteria exist for determining the appropriateness of extubating very-low-birth-weight (VLBW) infants. This study explored the predictors of successful extubation in preterm VLBW infants. METHODS: This retrospective cohort study included 60 preterm VLBW infants who underwent their first extubation in the neonatal intensive care unit in a regional hospital in Hsinchu, Taiwan, between January 2017 and November 2020. Successful extubation was defined as having no requirement of reintubation within 3 days of extubation. Potentially predictive variables, including demographics, prenatal characteristics, and ventilator parameters were compared between a successful extubation group and failed extubation group. RESULTS: Of the 60 infants, 47 (78.33%) underwent successful extubation. The successful extubation group had higher Apgar scores at 1 (7 vs. 6, P = 0.02) and 5 min (9 vs. 7, P = 0.007) than those of the failed extubation group. Ventilator inspiratory pressure and mean airway pressure were significantly lower at 24, 16, 8, and 1 h before extubation and upon its completion in the successful extubation group. The areas under a number of the receiver operating characteristic curve curves in this study were moderate, specifically, 0.72, 0.74, and 0.69. Statistical analysis revealed an association between ventilator parameters before 1 h extubation (IP > 17.5cmH2O, MAP >7.5 cmH2O, RSS >1.82) and extubation failure (odds ratio 1.73, 2.27, 2.46 and 95% confidence interval:1.16-2.6, 1.26-4.08, 1.06-5.68, respectively). CONCLUSION: Higher Apgar scores at birth, lower ventilator inspiratory pressure, and mean airway pressure 24, 16, 8, and 1 h and 1 h RSS prior to extubation are associated with successful extubation in VLBW preterm infants.

Platelet parameters and the association with morbidity and mortality in Preterm Infants.

BACKGROUND: There is growing recognition of the role of platelets in inflammation and immune responses, and platelets have been associated with various cardiovascular diseases. It is also known that neonatal morbidities are related to overall platelet activity, and platelet parameters may have the potential to predict morbidities and mortality in preterm infants. This study aimed to assess the initial platelet parameters and the association with major morbidities and mortality in preterm neonates. METHODS: We retrospectively reviewed data from very preterm neonates with a gestational age (GA) <32 weeks who were admitted between June 2020 and May 2021 for platelet parameters (counts, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (platelet counts x MPV/10000(%)) at birth. Major morbidities included early- onset sepsis (EOS) ≤3 days after birth, severe intraventricular hemorrhage (IVH) grade ≥3, and early or overall mortality. RESULTS: A total of 197 very preterm neonates were studied. Their mean (±SD) GA was 28.0 ± 2.4 weeks, birth weight was 990 ± 293 g, platelet counts were 245 ± 81 x1000/µL, MPV was 10.0 ± 0.7 fl, PDW was 11.0 ± 1.6 fl, and plateletcrit was 0.24 ± 0.08%. MPV had a weak negative correlation with both GA (r = -0.234, p = 0.001) and BW (r = -0.343, p <0.001). A lower plateletcrit was associated with EOS (0.14 (0.04-0.22) % vs. 0.23 (0.19-0.30) %, p = 0.027), severe IVH ≤7 days after birth (0.18 (0.14-0.27) % vs. 0.23 (0.20-0.30) %, p = 0.022), and early and overall mortality (0.15 (0.20-0.30) % vs. 0.23 (0.20-0.30) %, p = 0.049; 0.20 ± 0.09 % vs. 0.25 ± 0.07 %, p = 0.008). CONCLUSION: A lower plateletcrit within 24 hours of birth was associated with EOS, severe IVH ≤7 days after birth, and first-week and overall mortality in very preterm neonates.

Association of serum levels of inflammatory cytokines with retinopathy of prematurity in preterm infants.

Introduction: Retinopathy of prematurity (ROP) is a retinal vascular developmental disease associated with risks factors such as supplementary oxygen use or low birth weight/early gestational age. Multiple studies have reported associations between ROP and systemic inflammation. In this study, we investigated serum cytokines associated with ROP development and severity and assessed their applicability as potential biomarkers of ROP. Methods: This prospective study was conducted at an institutional referral center between 2019 and 2021. To measure the serum levels of 40 inflammatory cytokines in eligible premature patients, we collected their serum samples during the enrollment of patients or the intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and after 2 and 4 weeks. Results: Fifty patients were enrolled. In patients with type 1 ROP who received anti-VEGF agents (n = 22), the levels of serum intercellular adhesion molecule-1 decreased significantly (p < 0.05) at 4 weeks compared with the baseline level, whereas those of serum granulocyte-macrophage colony-stimulating factor increased significantly (p < 0.05). In patients with ROP who did not require any treatment (n = 14), no significant change was noted in the level of any of the 40 inflammatory cytokines. In control infants without ROP (n = 14), the serum levels of tumor necrosis factor-α, interleukin (IL)-15, and IL-12p40 increased significantly (p < 0.05) at 4 weeks. The changes in the levels of serum inflammatory cytokines did not vary significantly among the aforementioned three groups. A generalized estimating equation indicated that zone 1 ROP, stage 3 ROP, older postmenstrual age, respiratory distress syndrome, necrotizing enterocolitis, and sepsis were associated with the changes in serum cytokine levels. Conclusions: Although significant changes (compared with baseline) were observed in the serum levels of certain inflammatory cytokines in patients with type 1 ROP and infants without ROP, no significant difference in cytokine level fluctuations were noted among the three groups. Changes in serum inflammatory cytokine levels may not predict ROP development or severity. Additional comprehensive studies are warranted to establish their definitive role and significance in ROP, emphasizing the need for continued research in this area.

Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection-An 11-Year Multicenter Cohort Study in Taiwan.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Pediatric Candida Bloodstream Infections Complicated with Mixed and Subsequent Bacteremia: The Clinical Characteristics and Impacts on Outcomes.

Background: Pediatricians face a therapeutic challenge when patients with Candida bloodstream infections (BSIs) simultaneously have positive bacterial culture. We aim to characterize the clinical characteristics of pediatric Candida BSIs complicated with mixed bacteremia and subsequent bacterial infections, risk factors and impacts on outcomes. Methods: All episodes of pediatric Candida BSIs between 2005 and 2020 from a medical center in Taiwan were reviewed. Mixed Candida/bacterial BSIs were defined as isolation of a bacterial pathogen from blood cultures obtained within 48 h before or after the onset of Candida BSI. The clinical features and impacts of mixed Candida/bacterial BSIs were investigated. Results: During the study period, 320 patients with a total of 365 episodes of Candida BSIs were identified and analyzed. Mixed Candida/bacterial BSIs were 35 episodes (9.6%). No significant difference was found between mixed Candida/bacterial BSIs and monomicrobial Candida BSIs in terms of patient demographics, Candida species distributions, most chronic comorbidities or risk factors. Patients with mixed Candida/bacterial BSIs were associated with a significantly higher risk of subsequent bacteremia (51.4% vs. 21.2%, p < 0.001) and a relatively higher candidemia-attributable mortality rate (37.2% vs. 22.4%, p = 0.061) than those with monomicrobial Candida BSIs. Mixed Candida/bacterial BSIs were not an independent risk factor of treatment failure or final mortality according to multivariate logistic regression analyses. Conclusions: The clinical significance of mixed Candida/bacterial BSIs in children included a longer duration of septic symptoms, significantly higher likelihood to have subsequent bacteremia, and relatively higher risk of candidemia attributable mortality.

Effects of Probiotics on Gut Microbiomes of Extremely Preterm Infants in the Neonatal Intensive Care Unit: A Prospective Cohort Study.

Background: Probiotics have been previously reported to reduce the incidence of necrotizing enterocolitis (NEC) in extremely preterm infants, but the mechanisms by which the probiotics work remain unknown. We aimed to investigate the effects of probiotics on the gut microbiota of extremely preterm infants. Methods: A prospective cohort study was conducted on 120 extremely preterm neonates (gestational age ≤ 28 weeks) between August 2019 and December 2021. All neonates were divided into the study (receiving probiotics) and the control (no probiotics) groups. Multivariate logistic regression analysis was performed to investigate the significantly different compositions of gut microbiota between these two groups. The effects of probiotics on the occurrence of NEC and late-onset sepsis were also investigated. Results: An increased abundance of Lactobacillus was noted in neonates who received the probiotics (AOR 4.33; 95% CI, 1.89-9.96, p = 0.009) when compared with the control group. Subjects in the probiotic group had significantly fewer days of total parenteral nutrition (median [interquartile range, IQR]) 29.0 (26.8-35.0) versus 35.5 (27.8-45.0), p = 0.004) than those in the control group. The probiotic group had a significantly lower rate of late-onset sepsis than the control group (47.1% versus 70.0%, p = 0.015), but the rate of NEC, duration of hospitalization and the final in-hospital mortality rates were comparable between these two groups. Conclusions: Probiotic supplementation of extremely preterm infants soon after the initiation of feeding increased the abundance of Lactobacillus. Probiotics may reduce the risk of late-onset sepsis, but further randomized controlled trials are warranted in the future.

Novel CNNM2 Mutation Responsible for Autosomal-Dominant Hypomagnesemia With Seizure.

CNNM2 is primarily expressed in the brain and distal convoluted tubule (DCT) of the kidney. Mutations in CNNM2 have been reported to cause hypomagnesemia, seizure, and intellectual disability (HSMR) syndrome. However, the clinical and functional effect of CNNM2 mutations remains incompletely understood. We report our clinical encounter with a 1-year-old infant with HSMR features. Mutation screening for this trio family was performed using next-generation sequencing (NGS)-based whole exome sequencing (WES) with the identified mutation verified by Sanger sequencing. We identified a de novo heterozygous mutation c.G1439T (R480L) in the essential cystathionine ß-synthase (CBS) domain of CNNM2 encoding CNNM2 (cyclin M2) without any other gene mutations related to hypomagnesemia. The amino acid involved in this missense mutation was conserved in different species. It was also found to be pathogenic based on the different software prediction models and ACGME criteria. In vitro studies revealed a higher expression of the CNNM2-R480L mutant protein compared to that of the wild-type CNNM2. Like the CNNM2-wild type, proper localization of CNNM2-R480L was shown on immunocytochemistry images. The Mg2+ efflux assay in murine DCT (mDCT) cells revealed a significant increase in intracellular Mg2+ green in CNNM2-R480L compared to that in CNNM2-WT. By using a simulation model, we illustrate that the R480L mutation impaired the interaction between CNNM2 and ATP-Mg2+. We propose that this novel R480L mutation in the CNNM2 gene led to impaired binding between Mg2+-ATP and CNNM2 and diminished Mg2+ efflux, manifesting clinically as refractory hypomagnesemia.