Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and neurodevelopmental disorders, and its pathological mechanisms are closely related to disturbed energy metabolism and lipid remodeling. Exploring the spatial heterogeneity of metabolomics is essential to analyze the pathological process of HIE. Methods: In this study, we established a neonatal mouse hypoxic-ischemic brain damage (HIBD) model by the modified Rice method, and analyzed various metabolic pathways such as the tricarboxylic acid (TCA) cycle, purine metabolism, and lipid metabolism in the ischemic edema area, with contralateral and control brain tissues using matrix-assisted laser desorption mass spectrometry imaging (MALDI-MSI) with a spatial resolution of 50 μm. Results: In the HIBD model, key metabolites of the tricarboxylic acid (TCA) cycle (citrate, succinate, L-glutamate, glucose, aspartate, and glutamine) were significantly enriched in the edematous area compared with the control (fold change: 1.52-2.82), which suggests a blockage of mitochondrial function; ATP/ADP/AMP levels were reduced by 53-73% in the edematous area, and xanthine was abnormally accumulated in the hippocampus of the affected side, suggesting energy depletion and altered purine metabolism; lipid remodeling showed regional specificity: some unsaturated fatty acids, such as docosahexaenoic acid, were abnormally accumulated in the hippocampus. In contrast, pentadecanoic acid levels were reduced across the entire brain in the HIBD model, with a more pronounced decrease in the ipsilateral hippocampus, suggesting impaired membrane stability. Conclusions: The neonatal mouse HIBD model exhibits reprogramming of energy metabolism, characterized by a blockage in the tricarboxylic acid (TCA) cycle and ATP depletion, along with an abnormal spatial distribution of lipids. By targeting xanthine metabolic pathways, restoring mitochondrial function, and intervening in region-specific lipid remodeling, brain energy homeostasis may be improved and neurological damage attenuated. Further studies should validate the clinical feasibility of xanthine and lipid imbalance as diagnostic markers of HIBD and explore the critical time window for metabolic intervention to optimize therapeutic strategies.

Aminoglycoside pharmacokinetics is expected to change in premature infant. However, the PK profile of amikacin in Chinese premature infants has not been characterized. The aim of this study was to assess the safety and describe the pharmacokinetics properties of amikacin in Chinese premature infants. This was a two-center, retrospective, pharmacokinetic study. Phoenix NLME was used to construct a pharmacokinetics model. Monte Carlo simulations were performed to screen the optimal dosage regimen. A total of 54 amikacin concentrations from 23 patients were available for population pharmacokinetic analysis. The patients received an amikacin total daily dose (median(range)) of 14.32 (10.34–19.70) mg/kg. The distribution of Cmin (median(range)) was 4.07 (1.01–30.99)µg/mL, and Cmax (median(range)) was 17.45 (4.56-164.72) µg/mL. There were 14 patients achieved target Cmin, and 6 infants achieved Cmax. There were 3 cases occurred acute kidney injury, with Cmax and Cmin all exceeded the recommended range. A one-compartment model with first-order elimination best described the amikacin concentration-time data. The estimated typical values of clearance and volume of distribution for amikacin were 1.43 L/h/70kg and 30.97 L/70kg, respectively. Covariate analyses revealed that statistically significant relationships between amikacin clearance and weight, postmenstrual age and renal function, while there was a statistically significant relationship between volume of distribution and weight. Based on the model-based simulations, the initial recommend dosage regimens prior to therapeutic drug monitoring were suggested as 13 mg/kg q24h, 12 mg/kg q36h and q48h for serum creatinine between 15–22µmol/L; 23–36 and 37–60µmol/L, respectively. Weight, postmenstrual age and renal function have significant influence on the PK of amikacin in Chinese premature infants. The optimal dosage regimens might provide an alternative choice for premature infants in China in the therapy of amikacin.

Objective: To provide an updated review of the clinical profile and outcomes of delivery room chest compression (DR-CC) in China. Method: Retrospective analysis of prospectively collected data from 23 neonatal intensive care units in Jiangsu, China (2019-2021). Antepartum, delivery room, and postpartum variables in DR-CC-receiving and no-DR-CC groups were compared using uni- and multivariate analyses. The main outcome measure was survival without major morbidities at discharge. Results: Among 2120 preterm infants of <32 weeks gestational age, 112 (5.39%) received DR-CCs. Forty-two (37.50%) DR-CC-group infants survived without major morbidities at discharge, compared with 1299 (66.17%) no-DR-CC-group infants. The DR-CC group had a lower adjusted odds ratio (AOR) of survival without major morbidities (0.53 [0.31, 0.89]). In secondary outcomes, infants who received DR-CCs had more in-hospital mortality (AOR:1.95[1.12, 3.40]) and a significant increase in the rate of grade 3/4 intraventricular hemorrhage / periventricular leukomalacia or death (AOR: 2.35[1.40, 3.95]), moderate bronchopulmonary dysplasia or death (AOR: 2.02[1.21, 3.37]), >= stage 3 retinopathy of prematurity or death (AOR: 2.22[1.33, 3.69]), stage 2 necrotizing enterocolitis or death (AOR: 1.83[1.09, 3.07]) and late-onset sepsis or death (AOR:1.66[1.02, 2.70]). In DR-CC-group infants, use of a T-piece resuscitator, noninvasive respiratory support, and higher gestational age significantly influenced survival without morbidities. Conclusion: This multicenter cohort study revealed the clinical landscape of preterm infants (<32 weeks gestational age) receiving DR-CCs, showing lower survival rates without major morbidities compared to those not receiving DR-CCs.

Background:Late-onset sepsis (LOS) in very low birth weight (VLBW) infants confers substantial mortality risk. While lactate monitoring is standard, validated prognostic thresholds for mortality remain unestablished in this population. Methods:This retrospective cohort study (2014-2024) analyzed 596 VLBW infants (≤32 weeks; <1,500 g) with LOS at a tertiary NICU. Multivariable regression and piecewise linear modeling identified lactate-mortality thresholds, adjusting for gestational age, respiratory failure severity, vasopressor requirement, and multiorgan dysfunction. Bootstrap validation (1,000 iterations) assessed threshold stability. Results:Mortality occurred in 21% (125/596). Nonlinear analysis revealed critical inflection points at 2.2 mmol/L (95%CI: 1.9-2.5) and 4.0 mmol/L (95%CI: 3.7-4.3) (p < 0.001). Lactate ≤ 2.2 mmol/L demonstrated no mortality association (adjusted odds ratio = 1.84, 95%CI: 0.64-5.34; p = 0.260). Within the 2.2-4.0 mmol/L transition zone, each 1 mmol/L increment conferred a 7.0-fold mortality risk (aOR = 7.0, 95%CI: 2.13-22.78; p < 0.001). Beyond 4.0 mmol/L, the relationship attenuated (aOR = 0.90, 95%CI: 0.52-1.43; p = 0.568). Subgroup analyses indicated amplified risk among epinephrine-exposed infants (aOR = 3.40 vs. 1.78; P interaction = 0.094) and those with moderate-to-severe respiratory failure. Conclusion:Lactate reveals phase-specific mortality associations in VLBW infants with LOS. The 7.0-fold mortality risk increase per mmol/L in the 2.2-4.0 mmol/L interval suggests potential metabolic resuscitation targets for precision monitoring in sepsis management.

Pneumocephalus secondary to meningitis is very rare in newborns. Early identification of this disease is challenging, and its prognosis is very poor. However, there is limited information about the management of neonatal pneumocephalus. Here, we report a case of pneumocephalus secondary to meningitis in an 8‑day‑old female newborn and conduct a literature review on reported cases of neonatal pneumocephalus to date. This neonate presented with fever, irritability, and poor feeding. Enterobacter cloacae grew in cerebrospinal fluid (CSF) and blood cultures, and pneumocephalus was detected by a computed tomography (CT) brain scan. The neonate died due to worsening pneumocephalus despite receiving active antibiotic treatment and supportive management. Among the 12 reported cases, the most common initial symptoms were poor feeding, lethargy, and abnormal body temperature, and CSF culture was positive in 11 cases, of which 5 were caused by Citrobacter koseri, 4 were caused by Enterobacter cloacae, 1 was caused by Proteus mirabilis, and 1 was caused by Acinetobacter baumannii. All patients had pneumocephalus according to CT brain scans. Treatment mainly included the administration of broad-spectrum antibiotics and supportive management. Twelve infants died, and the only surviving infant suffered from severe neurodevelopmental disorders. Increased awareness of neonatal pneumocephalus among neonatologists, vigilant monitoring and prompt changes to sensitive antibiotics guided by susceptibility testing may be beneficial for improving the clinical prognosis of the disease.

To characterize longitudinal vascular endothelial growth factor (VEGF) trajectories and establish time-discriminative thresholds for bronchopulmonary dysplasia (BPD) severity stratification in extremely preterm neonates. Prospective observational cohort study with serial biomarker assessments. Tertiary neonatal intensive care unit in Suzhou, China (February 2022-January 2023). The cohort comprised 157 infants born at < 30 weeks' gestation with birth weights < 1250 g. After exclusions (n = 21), 136 infants completed the study protocol. BPD severity and weekly plasma VEGF levels (cord blood to postnatal day 28). Analyses included adjusted mixed-effects models for longitudinal trends and Receiver Operating Characteristic (ROC) curves with bootstrap 95% confidence intervals for discriminative accuracy. Infants developing moderate-to-severe BPD (n = 44) exhibited biphasic VEGF dysregulation: elevated cord blood levels (75.8 pg/mL, 95% CI: 63.2-88.4) followed by steep weekly decline (- 56.0 pg/mL/week, 95% CI: -62.5 to - 49.4), whereas no/mild BPD infants (n = 92) maintained stable trajectories (P < 0.001, partial η2 = 0.67). Discriminative performance varied temporally: at birth (AUC 0.88, 95% CI: 0.82-0.93; threshold ≥ 338.6 pg/mL), Day 14 (AUC 0.75, 95% CI: 0.66-0.84; threshold ≤ 232.2 pg/mL) and at Day 21 (AUC 0.91, 95% CI: 0.85-0.96; threshold ≤ 217.5 pg/mL), bootstrap validation confirmed robustness. Longitudinal VEGF trajectories from a parsimonious mixed‑effects model identified infants who developed moderate‑to‑severe BPD, supporting potential for early risk stratification requiring validation.

Background:Sterile gloves, an inexpensive method of hand hygiene, are attributed both protective and useless characteristics concerning neonatal mortality. This study aimed to perform a post hoc secondary analysis of a cluster-randomised controlled trial (cRCT) to examine the association between intrapartum sterile gloves and neonatal mortality. Methods:Data from the Zambia Chlorhexidine Application Trial, a cRCT of 4% chlorhexidine umbilical cord care in Zambia from 2011-2013, were analyzed. A randomised controlled trial (RCT) (NCT01241318) provided pregnant women with clean delivery kits containing sterile gloves. Neonatal mortality was compared between the glove use and nonuse groups. Group differences were evaluated and multivariable logistic regression analyses were performed. Results:Sterile gloves were used in 96.9% of the 37,003 newborns, which varied significantly by place of delivery. The 28-day mortality rates for hospital, health center and nonfacility deliveries were 2.7%, 1.1% and 1.3%, respectively (P<0.001). After adjusting for confounders, logistic regression revealed that the use of sterile gloves was associated with a lower risk of neonatal mortality [odds ratio (OR) =0.10; 95% confidence interval (CI): 0.07-0.15]. The use of perinatal sterile gloves was associated with a reduced risk of immediate neonatal death (<24 hours) (OR =0.47; 95% CI: 0.24-0.91) and early neonatal death (1-6 days) (OR =0.26; 95% CI: 0.16-0.39). Conclusions:The use of perinatal sterile gloves may significantly improve neonatal outcomes in low- and middle-income countries (LMICs). The provision of sterile gloves to promote newborn health may be feasible in LMICs.

The aim of this study was to investigate the association between hypertensive disorders of pregnancy (HDP) and disease progression in preterm infants with necrotizing enterocolitis (NEC), providing a basis for risk-stratified monitoring. We conducted a retrospective cohort study of 237 preterm neonates diagnosed with Bell stage II NEC at a tertiary level teaching hospital in China between January 2015 and January 2025. Statistical analyses included univariate analysis, multivariate logistic regression, smooth curve fitting, and threshold effect analysis. Among the 237 mothers included, 54 (22.78

Background:Accurate prediction of outcomes for extremely preterm infants (EPIs) during the early stage is important to assist clinicians and parents in making decisions. This study aimed to develop and validate models for predicting mortality and survival without major morbidity for EPIs using information available on neonatal intensive care units (NICUs) admission. Methods:Two of the largest contemporary cohorts of EPIs born at 24+0-28+6 weeks' gestation were included in China. Two predictive models were generated separately to predict mortality and survival without major morbidity at discharge. Potential predictors were identified if they had a well-established association with neonatal outcomes in literatures and could be easily obtained on NICU admission, including gestational age, birth weight, sex, inborn, antenatal steroids, 5-min Apgar score, and invasive ventilation on admission. Logistic regression was employed to develop the models. Model performance was assessed via area under the curve (AUC). Results:Among 2,438 EPIs in the development cohort, the mortality rate was 17.7% (431/2,438) and the rate of survival without major morbidity was 52.5% (1,281/2,438). Among the 5,045 infants in the validation cohort, 9.2% (463/5,045) died, and 59.1% (2,981/5,045) survived without major morbidity. Gestational age, birth weight, invasive ventilation on NICU admission, antenatal steroids use, and 5-min Apgar score were selected as predictors in the mortality model, yielding the AUC of 0.77 [95% confidence interval (CI): 0.75-0.79]. For the survival without major morbidity model, predictors were gestational age, birth weight, invasive ventilation on NICU admission, sex, and 5-min Apgar score, and the AUC was 0.72 (95% CI: 0.70-0.74). The validation cohort resulted in AUCs of 0.76 (95% CI: 0.73-0.78) and 0.70 (95% CI: 0.68-0.71) for the mortality and survival without major morbidity models, respectively. Conclusions:Using commonly available predictors on NICU admission including gestational age, birth weight, invasive ventilation on NICU admission, antenatal steroids use, sex, and 5-min Apgar score, we successfully developed and validated two distinct models with acceptable performance, predicting mortality and survival without major morbidity for EPIs.

Background and study aims Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates. In vitro model is an indispensable tool to study the pathogenesis of NEC. This study explored the effects of different stress factors on intestinal injury in vitro. Material and methods Rat intestinal epithelial cell line-6 (IEC-6) cells were exposed to different stressors, including lipopolysaccharide (LPS), cobalt chloride (CoCl2), and a combination of both. We estimated the cell viability, the expression of inflammatory cytokines and tight junction proteins. Results The decrease in IEC-6 cell viability was observed after stimulation by CoCl2 alone or in combination with LPS, but not after stimulation with LPS alone. The expression of interleukin6 (IL-6) and tumornecrosisfactoralpha (TNFα) increased in each group. After stimulation with CoCl2 alone or in combination with LPS, a decrease in Claudin-1 was observed, but an increase was detected after stimulation with LPS alone. Zona occludens 1 (ZO-1) decreased in both mRNA and protein levels after combined stimulation. Conclusion The combined stimulation of LPS and CoCl2 on IEC-6 cells could simultaneously induce severe inflammation and barrier damage, which may better simulate the pathological process of NEC.

ObjectiveThis study aims to develop and validate a nomogram-based scoring system to predict mortality in very low birth weight (VLBW) infants with late-onset sepsis (LOS). Timely risk stratification in this vulnerable population is critical for optimizing clinical outcomes.MethodsWe conducted a retrospective analysis on 202 VLBW infants diagnosed with LOS between January 2018 and December 2022. Predictive models were created at three key time points: 0 h, 6 h, and 12 h post-sepsis onset, utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression for variable selection and multivariable logistic regression for model construction. Internal validation was performed with 1,000 bootstrap resamples to correct for potential overfitting. External validation was conducted on an independent cohort of 71 infants from January 2023 to March 2024. Model performance was assessed using Area Under the Curve (AUC), calibration plots, and decision curve analysis (DCA).ResultsThe models exhibited excellent discrimination with AUCs of 0.83, 0.92, and 0.94 at 0 h, 6 h, and 12 h, respectively, in the development cohort, and 0.95, 0.95, and 0.97 in the validation cohort. Calibration plots showed strong agreement between predicted and observed outcomes. The significant disparity in maternal COVID-19 infection rates between cohorts (1 vs. 89%) may have contributed to the enhanced predictive accuracy in the external cohort.ConclusionThis dynamic, time-specific nomogram demonstrates high predictive accuracy and clinical utility for mortality in VLBW infants with LOS. The impact of maternal COVID-19 infection on neonatal outcomes offers a novel perspective for future research in sepsis prognostication.

Background Neonatal respiratory failure (NRF) is a critical condition with high morbidity and mortality rates. This study aimed to develop a nomogram prediction model to early predict the risk of death in Chinese neonates with NRF. Methods A retrospective analysis was conducted on NRF neonates from 21 tertiary neonatal intensive care units (NICUs) across 13 prefecture-level cities in Jiangsu Province, China, from March 2019 to March 2022. NRF neonates from one random NICU were selected as the external validation set, while those from the remaining 20 NICUs were divided into the training set and the internal validation set at a 7:3 ratio. Death was the primary outcome. LASSO regression and multivariate logistic regression were used to identify the predictive factors from the training set and then the nomogram was constructed. Results A total of 5387 neonates with NRF were included in the analysis. Among them, 3444 were in the training set, 1470 were in the internal validation set, and 473 were in the external validation set. The nomogram was constructed based on the eight predictors of the 1-min Apgar score, birth weight, gestational age, the relationship between birth weight and gestational age, mode of first respiratory support, inhaled nitric oxide, antenatal corticosteroids, and vasoactive drugs. The area under the curve of the nomogram in the training set, internal validation set, and external validation set was 0.763, 0.733, and 0.891, respectively. The P-values of the Hosmer-Lemeshow goodness of fit test were 0.638, 0.273, and 0.253, respectively. Brier scores were 0.066, 0.072, and 0.037, respectively. The decision curve analysis demonstrated a significant net benefit in all cases. These data indicate the good performance of the nomogram. Conclusions This nomogram can serve as a reference for clinicians to identify high-risk neonates early and reduce the incidence of neonatal mortality.

OBJECTIVES:To establish the pharmacokinetic model of linezolid in neonates, and to optimize the administration regimen. METHODS:A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy, and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected, and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. RESULTS:The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination, and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h, respectively. The results of goodness of fit, visualization verification, and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows: 6 mg/kg, q8h, at 28 weeks of gestational age (GA); 8 mg/kg, q8h, at 32 weeks of GA; 9 mg/kg, q8h, at 34-37 weeks of GA; 11 mg/kg, q8h, at 40 weeks of GA. CONCLUSIONS:The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.

BACKGROUND:Being too light at birth can increase the risk of various diseases during infancy. AIM:To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns. METHODS:A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions. RESULTS:Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit (P) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%. CONCLUSION:The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW.

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

There are considerable researches on risk factors for necrotizing enterocolitis (NEC), focusing primarily on the entire course before onset. However, fewer studies address risk factors within the brief period before NEC occurrence. The current study aims to retrospectively analyze the clinical data of NEC patients while focusing on relevant risk factors in the preceding week of NEC onset. Infants born between January 2019 and December 2021 at Suzhou Municipal Hospital and Suzhou University Children’s Hospital with a birth weight < 1500 g or a gestational age < 32 weeks were included. Around 54 NEC patients and 180 controls were recruited in the study. NEC patients satisfying the inclusion criteria formed the case group, while a 1:4 matching principle helped select the control group based on gestational age and birth weight. A statistically significant difference was observed between groups when red blood cell transfusions were compared the week before NEC onset (adjusted OR and 95% CI 2.16 (1.10, 4.24)). Broad-spectrum antibiotic usage before NEC occurrence was significantly lower in the NEC group than in the control group (adjusted OR and 95% CI 0.95 (0.91, 0.99)). A statistically significant difference was observed between groups while comparing patent ductus arteriosus (PDA) (adjusted OR and 95% CI 2.45 (1.23, 4.91)). The indication for packed red blood cell transfusion should be strictly controlled. Moreover, close monitoring of the patient’s condition for NEC occurrence should be conducted within one-week post-transfusion. Accurately identifying infections and using broad-spectrum antibiotics can reduce the incidence of NEC.

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.

BackgroundThe impact of the coronavirus disease 2019 (COVID-19) pandemic on neonatal necrotizing enterocolitis (NEC) is not well characterised. This cross-sectional study evaluated the potential effects of pandemic-related measures on NEC morbidity in premature infants in a neonatal ward during the COVID-19 pandemic.MethodsThis was a retrospective study conducted in a tertiary neonatal ward in eastern and central China over 6 consecutive years (2017, 2018, 2019, 2020, 2021 and 2022). The medical records of 189 premature infants with stage II or III NEC were reviewed for clinical manifestations and aetiologies. The data were analysed and compared between the prepandemic period (2017, 2018, and 2019) and the pandemic period (2020, 2021 and 2022).ResultsA total of 9,903 infants with gestational age (GA) < 37 weeks were enrolled, including 5,382 in the prepandemic period and 4,521 in the pandemic period. A reduction in stage II or III NEC morbidity was observed in infants with GA < 37 weeks, with an average annual morbidity of 2.29% (123/5,382) (95% CI, 1.89%–2.68%) in the prepandemic period and 1.46% (66/4,521) (95% CI, 1.11%–1.81%) in the pandemic period. NEC morbidity showed resurgent characteristics in 2021. When prepandemic coinfections were excluded, most cases of NEC with bloodstream infections in the prepandemic period were attributable to Gram-negative bacteria (27/32, 84.38%), mainly Klebsiella pneumoniae, while in the pandemic period they were attributable to Gram-positive bacteria (10/18, 55.56%), mainly Staphylococcus aureus. Antimicrobial susceptibility testing revealed that Klebsiella pneumoniae was 100% sensitive to meropenem, imipenem, ciprofloxacin and levofloxacin and 100% resistant to ampicillin. Staphylococcus capitis was 100% sensitive to vancomycin, linezolid, tetracycline, cotrimoxazole and cefoxitin and 100% resistant to penicillin and benzathine.ConclusionsCOVID-19 pandemic-related interventions can reduce the morbidity of NEC and change the pathogen spectrum in patients with bloodstream infections. We need to understand the exact factors leading to these changes.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.