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.

Amplification-free Detection of Cytomegalovirus miRNA Using a Modification-free Surface Plasmon Resonance Biosensor.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide; congenital CMV may lead to significant mortality, morbidity, or long-term sequelae, such as sensorineural hearing loss. The current study presents a newly designed surface plasmon resonance (SPR) biosensor for CMV-specific microRNAs that does not involve extra care for receptor immobilization or treatment to prevent fouling on bare gold surfaces. The modification-free approach, which utilizes a poly-adenine [poly(A)]-Au interaction, exhibited a high affinity that was comparable to that of the gold-sulfur (Au-S) interaction. In addition, magnetic nanoparticles (MNPs) were used to separate the analyte from complex sample matrixes that significantly reduced nonspecific adsorption. Moreover, the MNPs also played an important role in SPR signal amplification due to the binding-induced change in the refractive index. Our SPR biosensing platform was used successfully for the multi-detection of the microRNAs, UL22A-5p, and UL112-3p, which were associated with CMV. Our SPR biosensor offered the detection limits of 108 fM and 24 fM for UL22A-5p and UL112-3p, respectively, with an R2 of 0.9661 and 0.9985, respectively. The precision of this biosensor has an acceptable CV (coefficient of variation) value of <10%. In addition, our sensor is capable of discriminating between serum samples collected from healthy and CMV-infected newborns. Taken together, we believe that our newly developed SPR biosensing platform is a promising alternative for the diagnosis of CMV-specific microRNA in clinical settings, and its application for the detection of other miRNAs may be extended further.

Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit.

BACKGROUND: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). METHODS: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. RESULTS: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. CONCLUSIONS: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

Clustered Regularly Interspaced Short Palindromic Repeat Analysis of Clonal Complex 17 Serotype III Group B Streptococcus Strains Causing Neonatal Invasive Diseases.

Group B Streptococcus (GBS) is an important pathogen of neonatal infections, and the clonal complex (CC)-17/serotype III GBS strain has emerged as the dominant strain. The clinical manifestations of CC17/III GBS sepsis may vary greatly but have not been well-investigated. A total of 103 CC17/III GBS isolates that caused neonatal invasive diseases were studied using a new approach based on clustered regularly interspaced short palindromic repeats (CRISPR) loci and restriction fragment length polymorphism (RFLP) analyses. All spacers of CRISPR loci were sequenced and analyzed with the clinical presentations. After CRISPR-RFLP analyses, a total of 11 different patterns were observed among the 103 CRISPR-positive GBS isolates. GBS isolates with the same RFLP patterns were found to have highly comparable spacer contents. Comparative sequence analysis of the CRISPR1 spacer content revealed that it is highly diverse and consistent with the dynamics of this system. A total of 29 of 43 (67.4%) spacers displayed homology to reported phage and plasmid DNA sequences. In addition, all CC17/III GBS isolates could be categorized into three subgroups based on the CRISPR-RFLP patterns and eBURST analysis. The CC17/III GBS isolates with a specific CRISPR-RFLP pattern were more significantly associated with occurrences of severe sepsis (57.1% vs. 29.3%, p = 0.012) and meningitis (50.0% vs. 20.8%, p = 0.009) than GBS isolates with RFLP lengths between 1000 and 1300 bp. Whole-genome sequencing was also performed to verify the differences between CC17/III GBS isolates with different CRISPR-RFLP patterns. We concluded that the CRISPR-RFLP analysis is potentially applicable to categorizing CC17/III GBS isolates, and a specific CRISPR-RFLP pattern could be used as a new biomarker to predict meningitis and illness severity after further verification.

Rapid classification of group B Streptococcus serotypes based on matrix-assisted laser desorption ionization-time of flight mass spectrometry and machine learning techniques.

BACKGROUND: Group B streptococcus (GBS) is an important pathogen that is responsible for invasive infections, including sepsis and meningitis. GBS serotyping is an essential means for the investigation of possible infection outbreaks and can identify possible sources of infection. Although it is possible to determine GBS serotypes by either immuno-serotyping or geno-serotyping, both traditional methods are time-consuming and labor-intensive. In recent years, the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported as an effective tool for the determination of GBS serotypes in a more rapid and accurate manner. Thus, this work aims to investigate GBS serotypes by incorporating machine learning techniques with MALDI-TOF MS to carry out the identification. RESULTS: In this study, a total of 787 GBS isolates, obtained from three research and teaching hospitals, were analyzed by MALDI-TOF MS, and the serotype of the GBS was determined by a geno-serotyping experiment. The peaks of mass-to-charge ratios were regarded as the attributes to characterize the various serotypes of GBS. Machine learning algorithms, such as support vector machine (SVM) and random forest (RF), were then used to construct predictive models for the five different serotypes (Types Ia, Ib, III, V, and VI). After optimization of feature selection and model generation based on training datasets, the accuracies of the selected models attained 54.9-87.1% for various serotypes based on independent testing data. Specifically, for the major serotypes, namely type III and type VI, the accuracies were 73.9 and 70.4%, respectively. CONCLUSION: The proposed models have been adopted to implement a web-based tool (GBSTyper), which is now freely accessible at http://csb.cse.yzu.edu.tw/GBSTyper/, for providing efficient and effective detection of GBS serotypes based on a MALDI-TOF MS spectrum. Overall, this work has demonstrated that the combination of MALDI-TOF MS and machine intelligence could provide a practical means of clinical pathogen testing.

Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity: A Prospective Case-Control Study.

PURPOSE: To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP). DESIGN: Prospective case-control study. PARTICIPANTS: We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2). METHODS: Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups. MAIN OUTCOME MEASURES: Ocular developmental outcomes and Bayley III scores. RESULTS: A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49±0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different. CONCLUSIONS: At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study.

Emerging serotype III sequence type 17 group B streptococcus invasive infection in infants: the clinical characteristics and impacts on outcomes.

BACKGROUND: Group B Streptococcus (GBS) is an important pathogen that causes high mortality and morbidity in young infants. However, data on clinical manifestations between different GBS serotypes and correlation with molecular epidemiology are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, clinical features and molecular characteristics of invasive GBS isolates recovered from Taiwanese infants. METHODS: From 2003 to 2017, 182 non-duplicate GBS isolates that caused invasive disease in infants less than one year of age underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. The clinical features of these infants with GBS disease were also reviewed. RESULTS: Of the 182 patients with invasive GBS disease, 41 (22.5%) were early-onset disease, 121 (66.5%) were late-onset disease and 20 (11.0%) were late late-onset disease (> 90 days of age). All these patients were treated with effective antibiotics on time. Among them, 51 (28.0%) had meningitis, 29 (16.0%) had neurological complications, 12 (6.6%) died during hospitalization, and 15 (8.8%) out of 170 patients who survived had long-term neurological sequelae at discharge. Serotype III GBS strains accounted for 64.8%, followed by serotype Ia (18.1%) and Ib (8.2%). MLST analysis revealed 11 different sequence types among the 182 isolates and ST-17 was the most dominant sequence type (56.6%). The correlation between serotype III and ST17 was evident, as ST17 accounted for 87.3% of all serotype III isolates. There was an obvious increasing trend of type III/ST-17 GBS that caused invasive disease in infants. All isolates were susceptible to penicillin, cefotaxime, and vancomycin, while 68.1 and 65.9% were resistant to erythromycin and clindamycin, respectively. CONCLUSIONS: Despite timely and appropriate antibiotic treatment, a significant proportion of invasive GBS disease still inevitably causes adverse outcomes. Further study to explore preventive strategies and development of serotype-based vaccines will be necessary in the future.

Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates.

BACKGROUND: Invasive candidiasis differs greatly between children and neonates. We aimed to investigate the different therapeutic approaches and their effects on treatment outcomes of these two groups. METHODS: Episodes of neonatal invasive candidiasis were compared with non-neonatal pediatric episodes during a 12-year cohort study. Clinical isolates were documented by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and DNA sequencing, and antifungal susceptibility testing was performed. RESULTS: A total of 342 episodes of invasive candidiasis (113 neonatal and 229 non-neonatal pediatric episodes) in 281 pediatric patients (96 neonates and 185 children) were identified. Candida albicans was the most common pathogen causing invasive candidiasis in neonates and children (47.8% vs. 44.1%). The antifungal susceptibility profiles were not significantly different between neonates and children. More neonates received amphotericin B as therapy, whereas more children received fluconazole or caspofungin. Compared with children, neonates had a significantly longer duration of fungemia, higher rates of septic shock (34.5% vs. 21.8%; P = 0.013), sepsis-attributable mortality (28.3% vs. 17.5%; P = 0.024) and in-hospital mortality (42.7% vs. 25.4%; P = 0.004) than children. Independent risk factors for treatment failure of invasive candidiasis were septic shock (odds ration [OR] 16.01; 95% confidence interval [CI] 7.64-33.56; P <  0.001), delayed removal of intravenous catheter (OR 6.78; 95% CI 2.80-17.41; P <  0.001), renal failure (OR 5.38; 95% CI 1.99-14.57; P = 0.001), and breakthrough invasive candidiasis (OR 2.99; 95% CI 1.04-8.67; P = 0.043). CONCLUSIONS: Neonatal invasive candidiasis has worse outcomes than non-neonatal pediatric candidiasis. Neonatologists and pediatricians must consider age-specific differences when developing treatment and prevention guidelines, or when interpreting studies of other age groups.

Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

BACKGROUND: Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. METHODS: All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. RESULTS: Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). CONCLUSIONS: A considerable proportion of neonatal LOS can be associated with known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with a concurrent focus of infection is significantly different from that of primary bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly more likely to have infectious complications. This association independently leads to sepsis-attributable mortality.

Sleep Problems in Children with Attention Deficit/Hyperactivity Disorder: Current Status of Knowledge and Appropriate Management.

Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder. Current practices on the management of sleep problems for ADHD children are based mostly on expert consensus, whereas more evidence-based literature can be found only recently. Assessment of the sleep conditions in ADHD children before initiation of pharmacotherapy is the currently recommended guideline, and good sleep hygiene can be considered as the first-line treatment option. In addition to modifying the dose regimens, formulation, or alternative stimulants when sleep problems are encountered in ADHD children, atomoxetine, once daily guanfacine extended release, and melatonin are potential choices for ADHD children with more severe sleep problems. In this review, we aimed to provide the most updated information, preferably based on meta-analyses, systemic review, and randomized controlled trials published in the latest 3 years, in order to be clinically useful for practitioners and clinicians.

Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L).

BACKGROUND: Elevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized. METHODS: All episodes of neonatal culture-proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, ≤ 10 mg/L; intermediate, 11-100 mg/L; and high, > 100 mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses. RESULTS: Of 986 episodes of neonatal BSI, 247 (25.1 %) had CRP ≤10 mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase-negative staphylococci (CoNS) were relatively more common (55.9 %, p < 0.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0 %), fungi (2.8 %), or polymicrobial pathogens (3.6 %). Of the BSIs with initial low CRP, 29.1 % were treated with inadequate antibiotics, 13.0 % progressed to septic shock, and 5.3 % had infectious complications. The sepsis-attributable mortality rate was lower in the low CRP group (4.9 %) than in the high CRP group (13.6 %). CONCLUSIONS: A considerable proportion of neonatal BSIs had a normal or low initial CRP level (≤10 mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics.

Sleep and breathing in premature infants at 6 months post-natal age.

BACKGROUND: Poor sleep contributes to the developmental problems seen in preterm infants. We evaluated sleep problems in preterm infants 6 months of post-gestational age using the subjective Brief Infant Sleep Questionnaire (BISQ) and objective sleep tests. We also compared the sleep of premature infants with that of full-term infants. METHODS: The study included 68 6-month-old full-term healthy infants and 191 premature infants born at <37 weeks gestation. All parents completed the BISQ-Chinese version and sleep diaries. At the same time, all premature infants were submitted to one night of polysomnography (PSG) in the sleep laboratory and also were set up with an actigraph kept for 7 days. Statistical analyses were performed using correlation coefficients and the t-test with SPSS version 18 to compare questionnaire responses with other subjective and objective measures of sleep. RESULTS: The sleep problems indicated in the subjective questionnaire for the premature infants, particularly: "the nocturnal sleep duration, number of night awakenings, daytime sleep duration, duration of time with mouth breathing, and loud-noisy breathing" had significant correlations with sleep diaries, actigraphy and PSG results. The BISQ showed that duration of infant's sleeping on one side, nocturnal sleep duration, being held to fall asleep, number of nighttime awakenings, daytime sleep duration, subjective consideration of sleep problems, loud-noisy breathing, and duration spent crying during the night were significantly different between the premature infants and the term infants. PSG confirmed the presence of a very high percentage (80.6%) of premature infants with AHI > 1 event/hour as indicated by the questionnaire. CONCLUSION: Premature infants have more sleep problems than full-term infants, including the known risk of abnormal breathing during sleep, which has been well demonstrated already with the BISQ-Chinese (CBISQ).

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.

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.

Psychosocial and emotional adjustment for children with pediatric cancer and their primary caregivers and the impact on their health-related quality of life during the first 6 months.

PURPOSE: To evaluate caregiver-reported psychosocial adjustment and health-related quality of life (HrQoL) of Taiwanese children with newly diagnosed cancer and their caregivers during the first 6 months of treatment. METHODS: Caregivers of 89 newly diagnosed children completed the child behavior checklist, the pediatric quality of life inventory (PedsQL(™) 4.0), the Parenting Stress Index, and the SF-36 questionnaire at diagnosis, and again 3 and 6 months into treatment. They were compared with a group of age- and sex-matched controls from general community. RESULTS: Significantly worse HrQoL in both children and their caregivers and greater parenting stress were noted in the cancer group than the controls during the first 6 months. Children with cancer were found to have significantly more internalizing behavioral problems and somatic complaints, especially those younger than 12 years old. After starting chemotherapy, significant decrease in parenting stress and improvements of both caregivers and children's HrQoL were noted within the first 6 months, although not to the level comparable with normal controls. CONCLUSIONS: Although children and their caregivers can adjust themselves gradually during the first 6 months after diagnosis of cancer, intervention and efforts aimed at reducing their distress and promoting adjustments are still required during this period.

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.

Correlation Analysis of Attention and Intelligence of Preterm Infants at Preschool Age: A Premature Cohort Study.

OBJECTIVE: Developmental delay in neurocognitive function has been reported in premature children. This cohort study prospectively followed preterm infants following birth, and herein we present the four-year longitudinal follow-up data of cognitive development at preschool age and analyze correlated factors. METHODS: Term and preterm children received regular clinical evaluations and development assessments after birth, and at age 4 ± 1 years, they received the Wechsler-preschool and primary scale of intelligence, Fourth Edition (WPPSI-IV), excluding those with full-scale intelligence quotient < 70. A total of 150 participants received Conners Kiddie Continuous Performance Test (K-CPT), while 129 participants received ophthalmic evaluation. We adopted Chi-square test, ANOVA, and post hoc analysis to compare group differences. Correlations with K-CPT and WPPSI-IV were analyzed using Pearson's correlation. RESULTS: Group 1 consisted of 25 full-term children, group 2 had 94 preterm children with birth-weight of ≥ 1500 g, and group 3 had 159 preterm children with birth-weight of < 1500 g. Group 1 was the healthiest group and had the best performance in attention and intelligence, while group 3 had the worst physical condition and cognitive performance. The correlation analysis revealed that perinatal factors, including gestational age, birth weight, Apgar scores, and physical conditions, significantly correlated with WPPSI-IV and K-CPT variables. Gender significantly correlated with object assembly of WPSSI-IV and clinical index of K-CPT. Among vision-related variables, best corrected visual acuity correlated most with K-CPT, including clinical index, Omission, and hit reaction time standard error of K-CPT, as well as significantly correlated with information and bug search of WPPSI-IV. CONCLUSIONS: Preterm children at preschool age still had poorer cognitive performance than full-term children, especially those with birth BW less than 1500 g. Gender and vision are correlated with cognitive deficits. Continuous monitoring with comprehensive assessments is recommended.

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.

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.

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.