OBJECTIVE: The objective of this study was to investigate the association between total bilirubin and acute kidney injury (AKI) in neonates admitted to neonatal intensive care units (NICU).
METHODS: All data utilized were extracted from Medical Information Mart for Intensive Care-III (MIMIC-III) in this retrospective cohort study. The primary outcome was the occurrence of AKI during hospitalization in the NICU, and the exposure was the initial measurement of total bilirubin levels within 24 h of neonatal admission to the NICU. The relationship between serum total bilirubin and AKI was evaluated by employing univariate and multivariate logistic regression models. Additionally, subgroup analyses were conducted based on birth weight, sepsis, and mechanical ventilation.
RESULTS: This retrospective cohort study included a population of 1,726 neonates, and 95 neonates developed AKI. Total bilirubin, as a continuous variable, was linked with decreased AKI risk among neonates admitted to the NICU [odds ratio (OR) = 0.77, 95% confidence interval (CI): 0.64-0.92]. Similarly, when total bilirubin levels were categorized by tertiles, tertiles 3 showed a significant association with decreased AKI risk (OR = 0.39, 95%CI: 0.19-0.83). The relationship of total bilirubin level and AKI was also existent among neonates admitted to the NICU who were underweight, had not sepsis, and received mechanical ventilation.
CONCLUSIONS: Total bilirubin level may be a protective factor for the risk of developing AKI.

UNASSIGNED: Parental health literacy is important to children\'s health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy.
UNASSIGNED: This study aimed to determine the effects of a WeChat official account (WOA)-based intervention on parental health literacy of primary caregivers of children aged 0-3 years.
UNASSIGNED: This cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children\'s health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The β coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention\'s effect.
UNASSIGNED: After the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (β=2.51, 95% CI 0.12-4.91) and higher psychological scores (β=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children\'s health outcomes. Furthermore, despite slight subgroup differences in the intervention\'s effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors.
UNASSIGNED: Using a WHO literacy model-based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

OBJECTIVE: To develop a decision-support tool for predicting extubation failure (EF) in neonates with bronchopulmonary dysplasia (BPD) using a set of machine-learning algorithms.
METHODS: A dataset of 284 BPD neonates on mechanical ventilation was used to develop predictive models via machine-learning algorithms, including extreme gradient boosting (XGBoost), random forest, support vector machine, naïve Bayes, logistic regression, and k-nearest neighbor. The top three models were assessed by the area under the receiver operating characteristic curve (AUC), and their performance was tested by decision curve analysis (DCA). Confusion matrix was used to show the high performance of the best model. The importance matrix plot and SHapley Additive exPlanations values were calculated to evaluate the feature importance and visualize the results. The nomogram and clinical impact curves were used to validate the final model.
RESULTS: According to the AUC values and DCA results, the XGboost model performed best (AUC = 0.873, sensitivity = 0.896, specificity = 0.838). The nomogram and clinical impact curve verified that the XGBoost model possessed a significant predictive value. The following were predictive factors for EF: pO2, hemoglobin, mechanical ventilation (MV) rate, pH, Apgar score at 5 min, FiO2, C-reactive protein, Apgar score at 1 min, red blood cell count, PIP, gestational age, highest FiO2 at the first 24 h, heart rate, birth weight, pCO2. Further, pO2, hemoglobin, and MV rate were the three most important factors for predicting EF.
CONCLUSIONS: The present study indicated that the XGBoost model was significant in predicting EF in BPD neonates with mechanical ventilation, which is helpful in determining the right extubation time among neonates with BPD to reduce the occurrence of complications.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.

BACKGROUND: Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.
METHODS: Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses.
RESULTS: For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses.
CONCLUSIONS: An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses.
BACKGROUND: This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.

BACKGROUND: Decision-to-delivery time (DDT), a crucial factor during the emergency caesarean section, may potentially impact neonatal outcomes. This study aims to assess the association between DDT and various neonatal outcomes.
METHODS: A comprehensive search of PubMed, Scopus, Cochrane Library, and Google Scholar databases was conducted. A total of 32 eligible studies that reported on various neonatal outcomes, such as Apgar score, acidosis, neonatal intensive unit (NICU) admissions and mortality were included in the review. Studies were selected based on predefined eligibility criteria, and a random-effects inverse-variance model with DerSimonian-Laird estimate of tau² was used for meta-analysis. Heterogeneity and publication bias were assessed using I² statistics and Egger\'s test, respectively.
RESULTS: The meta-analysis revealed a significant association between DDT < 30 min and increased risk of Apgar score < 7 (OR 1.803, 95% CI: 1.284-2.533) and umbilical cord pH < 7.1 (OR 4.322, 95% CI: 2.302-8.115), with substantial heterogeneity. No significant association was found between DDT and NICU admission (OR 0.982, 95% CI: 0.767-1.258) or neonatal mortality (OR 0.983, 95% CI: 0.565-1.708), with negligible heterogeneity. Publication bias was not detected for any outcomes.
CONCLUSIONS: This study underscores the association between shorter DDT and increased odds of adverse neonatal outcomes such as low Apgar scores and acidosis, while no significant association was found in terms of NICU admissions or neonatal mortality. Our findings highlight the complexity of DDT\'s impact, suggesting the need for nuanced clinical decision-making in cases of emergency caesarean sections.

Objectives: Congenital epiglottic cysts are rare disorders of the larynx with symptoms such as laryngeal stridor and inspiratory dyspnea and are life-threatening in severe cases. This study aimed to investigate the usefulness of low-temperature plasma radiofrequency ablation for congenital epiglottic cysts and provide a reference for clinicians to develop treatment options. Methods: The clinical data of children (n = 7, 4 males and 3 females) with congenital epiglottic cysts, who were admitted to the Second Affiliated Hospital of Wenzhou Medical University and Yuying Children\'s Hospital from March 2018 to March 2023, were analyzed retrospectively. Following preoperative examinations, all patients underwent low-temperature plasma radiofrequency ablation under general anesthesia, and the curative effect was evaluated. Following surgery, regular patient follow-up examinations were conducted to monitor recurrence. Results: The age at the time of operation ranged from 1 day to 99 days, with an average of 37.57 ± 35.01 days. The surgical procedure was successfully completed in all the children; dyspnea disappeared and no surgical complications were observed. In addition, during the postoperative follow-up period of 6 months to 5 years, recurrence was not observed. Conclusions: Low-temperature plasma radiofrequency ablation is a safe and effective procedure for treating congenital epiglottic cysts and deserves clinical application and promotion.

BACKGROUND: Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future.
METHODS: The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared.
RESULTS: Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000-1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05).
CONCLUSIONS: Our retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

BACKGROUND: Genetic disorders significantly affect patients in neonatal intensive care units, where establishing a diagnosis can be challenging through routine tests and supplementary examinations. Whole-exome sequencing offers a molecular-based approach for diagnosing genetic disorders. This study aimed to assess the importance of whole-exome sequencing for neonates in intensive care through a retrospective observational study within a Chinese cohort.
METHODS: We gathered data from neonatal patients at Tianjin Children\'s Hospital between January 2018 and April 2021. These patients presented with acute illnesses and were suspected of having genetic disorders, which were investigated using whole-exome sequencing. Our retrospective analysis covered clinical data, genetic findings, and the correlation between phenotypes and genetic variations.
RESULTS: The study included 121 neonates. Disorders affected multiple organs or systems, predominantly the metabolic, neurological, and endocrine systems. The detection rate for whole-exome sequencing was 52.9% (64 out of 121 patients), identifying 84 pathogenic or likely pathogenic genetic variants in 64 neonates. These included 13 copy number variations and 71 single-nucleotide variants. The most frequent inheritance pattern was autosomal recessive (57.8%, 37 out of 64), followed by autosomal dominant (29.7%, 19 out of 64). In total, 40 diseases were identified through whole-exome sequencing.
CONCLUSIONS: This study underscores the value and clinical utility of whole-exome sequencing as a primary diagnostic tool for neonates in intensive care units with suspected genetic disorders. Whole-exome sequencing not only aids in diagnosis but also offers significant benefits to patients and their families by providing clarity in uncertain diagnostic situations.