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Background/Objectives: Severe infection (sInfection; either late-onset culture-proven sepsis or necrotizing enterocolitis) in very low birth weight (VLBW) infants increases mortality rates and may show long-term progression. The fecal microbiome composition in VLBW infants with and without sInfection was classified in the sInfection and non-sInfection groups. Methods: Gut microbiomes, secondary information from a previous randomized trial, were analyzed using QIIME 2 software. The biodiversity and abundance of the gut microbiota between the sInfection and non-sInfection groups were compared. Results: Fifty-one neonates were included in the sInfection (n = 9) and non-sInfection (n = 42) groups; no significant differences in the fecal microbiome were observed in both alpha and beta diversities. Analysis of relative abundance revealed that in both groups, the predominant gut microbiota phylum, class, and genus were Proteobacteria, Gammaproteobacteria, and Klebsiella, respectively. The main fecal microbiome in the non-sInfection group included Faecalibacterium, Clostridium butyricum, and Bacteroides fragilis. Clostridium_sensu_stricto _1 was significantly more abundant in the non-sInfection group than in the sInfection group. Conclusions: Clostridium_sensu_stricto_1 was the main gut microbiota in the non-sInfection group. Considering the potential taxa as synbiotics (correlations among prebiotics, probiotics, and postbiotics), therapeutics may be useful for preventing and managing necrotizing enterocolitis or late-onset culture-proven sepsis in VLBW infants.

Background/Objectives: Empirical antimicrobial therapy for neonatal early-onset sepsis (EOS) comprises ampicillin and gentamicin. However, multidrug-resistant organisms are increasing worldwide, thus inflicting a global burden. We identified the incidence and risk factors of neonates with pathogenic isolates that were not susceptible to treatment comprising a combination of ampicillin and gentamicin (non-susceptible group). Methods: This retrospective study included neonates diagnosed with EOS between 2004 and 2023. All patients with EOS and positive culture results within 72 h of birth were reviewed. Patients in the non-susceptible and susceptible groups were analyzed using a multivariable logistic regression model. Results: Sixty pathogenic isolates and 55 neonates with EOS were observed over the course of 20 years. The incidence and case fatality rates of EOS were 0.88 per 1000 live births and 41.8%, respectively. Acinetobacter baumannii was the most common EOS pathogenic isolate (19/60 pathogenic isolates; 12/19 resistant to carbapenems). Pathogenic isolates were susceptible to ampicillin or gentamicin (59%), ampicillin or cefotaxime (42%), and ampicillin or amikacin (72%). Data regarding susceptibility to ampicillin and gentamicin of 49 neonates were available. A multivariable analysis revealed that patients in the non-susceptible group (n = 18) were more likely to experience late-onset EOS (48–72 h; p = 0.01) and require endotracheal intubation on day 1 (p = 0.04) compared to patients in the susceptible group (n = 31). Conclusions: In areas with high multidrug resistance, broader-spectrum antibiotic therapy (ampicillin plus amikacin) should be considered for neonates who develop clinical sepsis within 48–72 h of birth and experience respiratory failure at birth.

Introduction: This study aimed to compare the risks and case fatality rate (CFR) between neonatal multidrug-resistant (MDR) and non-MDR meningitis. Methodology: a secondary analysis of a case-control studies in a Thai neonatal intensive care unit between 1990 and 2018 was performed. The pathogenic organisms causing neonatal meningitis were Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Acinetobacter spp., and Pseudomonas aeruginosa. A MDR organism was defined as an isolate that was non-susceptible to at least 1 agent in at least 3 antimicrobial categories. The multivariate regression was analyzed for MDR and non-MDR samples of neonatal meningitis. Results: Over a period of 29 years, the number of neonatal MDR and non-MDR meningitis cases were 17 and 21, respectively. The medians (interquartile ranges) of gestational age, birthweight and onset of meningitis were 35 (29.5-38) weeks, 1,945 (1,218-2,859) grams and 6.5 (2.8-17.9) days, respectively. The most common organism was Acinetobacter baumannii (32%). By multivariate analysis, neonates who had MDR meningitis were more likely to have a lower Apgar score at 5 minutes (adjusted odds ratio: 95% confidence intervals = 0.66 [0.44-0.99], p = 0.04). The crude CFR of neonatal meningitis was 32%. Non-survivors in MDR meningitis (58.8%) were significantly higher than non-MDR meningitis (9.5%, p = 0.004). The most common pathogen in non-survivors was carbapenem-resistant Acinetobacter baumannii. Conclusions: Neonatal MDR meningitis has an association with lower APGAR scores, and higher CFR as well as Acinetobacter baumannii. Multifaceted infection prevention, and control programs for MDR organisms are crucial, and must be strictly implemented in high MDR areas.

Background: High-frequency oscillatory ventilation (HFOV) minimizes ventilator-induced lung injuries. Spontaneous sigh breathing may augment the functional residual capacity, increase lung compliance, and recruit atelectatic alveoli.Purpose: To evaluate the difference in the partial pressure of carbon dioxide (PaCO2) in neonates receiving invasive HFOV as the primary mode of respiratory support before versus after sigh breaths (Sighs).Methods: This prospective study was conducted between January and December 2023. Intubated preterm and term neonates who underwent HFOV with an available arterial line were enrolled in this study after informed parental consent was obtained. Sighs were set at a frequency of 3 breaths/min and pressure of 5 cmH2O above the mean airway pressure for 2 hours. Arterial blood gas was collected before and after Sighs and analyzed using 2 dependent tests.Results: Thirty neonates with a mean gestational age of 33.6±4.1 weeks and median date of intervention of 1.88 days (interquartile range, 0.87–3.79 days) were enrolled. The mean PaCO2 level was significantly lower in the HFOV with Sighs group (45.2±6.6 mmHg) versus the HFOV alone group (48.8±3.1 mmHg) with a mean difference (MD) of -3.6 mmHg (95% confidence interval [CI], -6.3 to -0.9; P=0.01). Subgroup analyses indicated the ability of Sighs to reduce the PaCO2 level in neonates with respiratory distress syndrome (n=15; MD [95% CI]=-4.2 [-8.2 to -0.2] mmHg; P= 0.04).Conclusion: Sighing can reduce PaCO2 levels in neonates ventilated with HFOV, particularly those with respiratory distress syndrome.

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy.

Background/Objectives: We investigated multimodal strategies to reduce neonatal ventilator-associated pneumonia (VAP) and antimicrobial use across three periods: period 1 (2014–2017), environmental cleaning with sodium hypochlorite, installation of heat and moisture exchangers, elective high frequency oscillatory ventilation (HFOV) as the primary invasive mode, and nasal HFOV after extubation; period 2 (2018–2020), oral care with maternal milk; and period 3 (2021–2024), nasal synchronized intermittent positive pressure ventilation after extubation. Methods: We conducted a quasi-experimental study of all neonates admitted to a neonatal intensive care unit in Thailand. We compared the trends in VAP and antimicrobial use rates using interrupted time-series analysis with segmented regression. Results: During the 11-year study period, 45.6% of neonates were intubated (2470/5414), and the ventilator utilization ratio was 0.19 (17,820 ventilator days/95,151 patient days). The overall VAP incidence was 4.55 per 1000 ventilator days. The yearly VAP incidence density ratio was significantly lower than in 2014. The baseline trend of VAP incidence and colistin use decreased significantly during period 1; nonetheless, the level and slope did not differ significantly between periods 1, 2, and 3. Conclusions: Tailored implementations, namely environmental decontamination, ventilator circuit care, elective HFOV, and nasal HFOV, reduced VAP and colistin use during period 1. Moreover, additive interventions, including oral care in period 2 and nasal synchronized intermittent positive pressure ventilation in period 3, achieved sustained VAP reduction and limited colistin prescriptions in period 1.

Background: Gut-lung crosstalk is a pathway involving interactions between the gastrointestinal, respiratory, and immune systems. The immune responses of the gut and lungs are intricately linked, and previous studies demonstrated that the gut microbiota can influence systemic immune responses in the respiratory system as well as bronchopulmonary dysplasia (BPD).Purpose: To analyze the composition of the gut microbiota in very low birth weight infants with versus without BPD.Methods: Secondary data from a previous randomized controlled trial were analyzed. Microbiomes were analyzed using QIIME 2 software. Gut microbiota diversity and abundance were compared between groups.Results: Fifty-one neonates were classified into the BPD (n=24) and non-BPD (n=27) groups, between which no differences were noted in the alpha and beta diversities of the gut microbiota. In both groups, Proteobacteria, Gammaproteobacteria, and Klebsiella were the predominant phylum, class, and genus in gut microbiota, respectively. Enterococcus, Acinetobacter, Elizabethkingia, Clostridium sensu stricto 1, Bacteroides, Streptococcus, and Serratia were more abundant, whereas Klebsiella, Faecalibacterium, Escherichia-Shigella, Enterobacter, Bifidobacterium, Veillonella, Staphylococcus, and Enterobacteriaceae were less abundant in the BPD versus non-BPD group. Faecalibacterium, Roseburia, Clostridium, Eubacterium, and Coprococcus were significantly more abundant in the non-BPD versus BPD group.Conclusion: The alpha and beta diversities of the gut microbiota did not differ significantly between the BPD and non-BPD groups. However, in terms of relative abundance, the presence of common respiratory pathogens was notable in the BPD group. Conversely, the non-BPD group had a significantly higher prevalence of anaerobic taxa known for their capacity to produce butyrate, a key component of postbiotics.

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury.

Background. Transient hypothyroxinemia of prematurity (THOP) is characterized by low thyroxine (T4) levels with normal thyroid-stimulating hormone (TSH) levels. This study aimed to determine the incidence and factors associated with THOP. Methods. This prospective cohort study included neonates who were born before 37 weeks of gestation in the neonatal intensive care unit (NICU) between April 2017 and December 2020. Serum TSH and free thyroxine (FT4) levels were routinely screened at 3-5 days and 2, 4, and 6-8 weeks postnatally. The criteria for diagnosis of THOP were a TSH level < 7 mU/L with a FT4 level < 0.8 ng/dL at any screening timepoint. Results. The incidence of THOP in infants born before 28, 34, and 37 weeks of gestation was 39.5 (17/43), 8.4% (29/343), and 4.8% (35/722), respectively. A multivariate analysis revealed that a gestational age of < 28 weeks (adjusted odds ratio [aOR]: 5.35, 95% confidence interval [CI]: 1.89-15.13, p=0.002); 5-min Apgar score of ≤3 (aOR: 5.72, 95% CI: 2.2-14.89, p < 0.001); and treatment with aminophylline (aOR: 2.95, 95% CI: 1.08-8.11, p=0.037), dobutamine (aOR: 4.12, 95% CI: 1.55-10.98, p=0.004), or morphine (aOR: 4.91, 95% CI: 1.29-18.74, p=0.011) were associated with an increased risk of THOP. The TSH and FT4 levels in infants with THOP returned to normal ranges by 2 weeks of age. Conclusions. THOP is frequently found in preterm infants. An extremely low gestational age, a low Apgar score, and the use of certain medications in the NICU are risk factors for the development of THOP. Therefore, a thyroid screening program should be implemented for evaluating congenital hypothyroidism (CH) and THOP in preterm neonates in all settings.

Introduction: To identify the risks and outcomes for multidrug-resistant Gram-negative bacilli (MDRGNB) sepsis in neonates. Methodology: This was a retrospective case-case-control study between 1991 and 2016. The control group was selected from the same source records of all neonates with clinical or suspected sepsis but not culture-proven. Results: The numbers of patients in the MDRGNB sepsis, non-MDRGNB sepsis, and control groups were 157, 88, and 218, respectively. MDRGNB sepsis was significantly associated with outborn infants [adjusted odds ratio (aOR) 2.08; p = 0.003] and infants who had a neurologic sequela (aOR 11.58; p = 0.04), lower gestational age (p = 0.03) or previous aminoglycoside use (aOR 2.43; p < 0.001) compared with the control group. Non-MDRGNB sepsis was associated with outborn infants (aOR 2.63; p < 0.001), and infants who had neurologic sequelae (aOR 48.25; p = 0.001) and previous cephalosporin use (aOR 6.28; p < 0.001) or cefoperazone plus sulbactam use (aOR 6.48; p = 0.02) compared with the control group. Case fatality (OR 3.63; p < 0.001) and septic shock (OR 12.81; p < 0.001) rates, length of stay (p < 0.001), and daily hospital costs (p = 0.01) were higher in the MDRGNB sepsis group than in the control group. Conclusions: Smaller preterm neonate with previous aminoglycoside use had a higher MDRGNB than non-MDRGNB sepsis compared with the control group. Intervention to reduce MDRGNB sepsis in the NICU is cost-effective.