Incidence of Neonatal Seizures in China Based on Electroencephalogram Monitoring in Neonatal Neurocritical Care Units.

Importance: Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. Objectives: To determine the incidence of neonatal seizures in infants with high risk in China. Design, Setting, and Participants: A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. Main Outcomes and Measures: The incidence of neonatal seizures, categorized by etiology, and seizure burden. Results: A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). Conclusions and Relevance: This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Identification and verification of feature biomarkers associated with immune cells in neonatal sepsis.

BACKGROUND: Neonatal sepsis (NS), a life-threatening condition, is characterized by organ dysfunction and is the most common cause of neonatal death. However, the pathogenesis of NS is unclear and the clinical inflammatory markers currently used are not ideal for diagnosis of NS. Thus, exploring the link between immune responses in NS pathogenesis, elucidating the molecular mechanisms involved, and identifying potential therapeutic targets is of great significance in clinical practice. Herein, our study aimed to explore immune-related genes in NS and identify potential diagnostic biomarkers. Datasets for patients with NS and healthy controls were downloaded from the GEO database; GSE69686 and GSE25504 were used as the analysis and validation datasets, respectively. Differentially expressed genes (DEGs) were identified and Gene Set Enrichment Analysis (GSEA) was performed to determine their biological functions. Composition of immune cells was determined and immune-related genes (IRGs) between the two clusters were identified and their metabolic pathways were determined. Key genes with correlation coefficient > 0.5 and p < 0.05 were selected as screening biomarkers. Logistic regression models were constructed based on the selected biomarkers, and the diagnostic models were validated. RESULTS: Fifty-two DEGs were identified, and GSEA indicated involvement in acute inflammatory response, bacterial detection, and regulation of macrophage activation. Most infiltrating immune cells, including activated CD8 + T cells, were significantly different in patients with NS compared to the healthy controls. Fifty-four IRGs were identified, and GSEA indicated involvement in immune response and macrophage activation and regulation of T cell activation. Diagnostic models of DEGs containing five genes (PROS1, TDRD9, RETN, LOC728401, and METTL7B) and IRG with one gene (NSUN7) constructed using LASSO algorithm were validated using the GPL6947 and GPL13667 subset datasets, respectively. The IRG model outperformed the DEG model. Additionally, statistical analysis suggested that risk scores may be related to gestational age and birth weight, regardless of sex. CONCLUSIONS: We identified six IRGs as potential diagnostic biomarkers for NS and developed diagnostic models for NS. Our findings provide a new perspective for future research on NS pathogenesis.

Congenital tuberculosis in a neonate following in vitro fertilization-embryo transfer: A case report.

Background: Congenital tuberculosis is becoming increasingly common, but congenital tuberculosis infection in neonates following in vitro fertilization and embryo transfer (IVF-ET) has been rarely reported; a diagnosis of congenital tuberculosis is often delayed due to the non-specificity of maternal IVF treatments and clinical manifestations during pregnancy-particularly in low-birth-weight preterm infants. Case presentation: We herein report a case of congenital tuberculosis. The infant was born at 27+5 weeks of gestation and was admitted to the hospital due to hypopnea after birth. Due to a poor response to treatment, we conducted pathogenic microorganism metagenomic analysis to assess the nucleotide sequences within the Mycobacterium tuberculosis complex. After collecting sputum, the strains from the tuberculosis analysis were isolated and confirmed. From a detailed examination of the mother and in accordance with the child's congenital tuberculosis, we confirmed the diagnosis of pelvic tuberculosis. Conclusion: IVF treatment and pregnancy can exacerbate latent tuberculosis, especially in women from a family with a history of tuberculosis infections. We posit that the optimal way to prevent neonatal congenital tuberculosis in IVF-ET is to procure a detailed maternal medical or family history and to identify and treat maternal tuberculosis during IVF treatment.

Weighted Gene Co-expression Network Analysis of Key Biomarkers Associated With Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from interactions between genes and the environment. The accurate molecular etiology of BPD remains largely unclear. This study aimed to identify key BPD-associated genes and pathways functionally enriched using weighted gene co-expression network analysis (WGCNA). We analyzed microarray data of 62 pre-term patients with BPD and 38 pre-term patients without BPD from Gene Expression Omnibus (GEO). WGCNA was used to construct a gene expression network, and genes were classified into definite modules. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of BPD-related hub genes were performed. Firstly, we constructed a weighted gene co-expression network, and genes were divided into 10 modules. Among the modules, the yellow module was related to BPD progression and severity and included the following hub genes: MMP25, MMP9, SIRPA, CKAP4, SLCO4C1, and SLC2A3; and the red module included some co-expression molecules that displayed a continuous decline in expression with BPD progression and included the following hub genes: LEF1, ITK, CD6, RASGRP1, IL7R, SKAP1, CD3E, and ICOS. GO and KEGG analyses showed that high expression of inflammatory response-related genes and low expression of T cell receptor activation-related genes are significantly correlated with BPD progression. The present WGCNA-based study thus provides an overall perspective of BPD and lays the foundation for identifying potential pathways and hub genes that contribute to the development of BPD.

Altered Urinary Amino Acids in Children With Autism Spectrum Disorders.

Autism spectrum disorders (ASD) affect 1% of children. Although there is no cure, early diagnosis and behavioral intervention can relieve the symptoms. The clinical heterogeneity of ASD has created a need for improved sensitive and specific laboratory diagnostic methods. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis of the metabolome has shown great potential to uncover biomarkers for complex diseases such as ASD. Here, we used a two-step discovery-validation approach to identify potential novel metabolic biomarkers for ASD. Urine samples from 57 children with ASD and 81 matched children with typical development (TD) were analyzed by LS-MS/MS to assess differences in urinary amino acids and their metabolites (referred to as UAA indicators). A total of 63 UAA indicators were identified, of which 21 were present at significantly different levels in the urine of ASD children compared with TD children. Of these 21, the concentrations of 19 and 10 were higher and lower, respectively, in the urine of ASD children compared with TD children. Using support vector machine modeling and receiver operating characteristic curve analysis, we identified a panel of 7 UAA indicators that discriminated between the samples from ASD and TD children (lysine, 2-aminoisobutyric acid, 5-hydroxytryptamine, proline, aspartate, arginine/ornithine, and 4-hydroxyproline). Among the significantly changed pathways in ASD children were the ornithine/urea cycle (decreased levels of the excitatory amino acid aspartate [p = 2.15 × 10-10] and increased arginine/ornithine [p = 5.21 × 10-9]), tryptophan metabolism (increased levels of inhibitory 5-hydroxytryptamine p = 3.62 × 10-9), the methionine cycle (increased methionine sulfoxide [p = 1.46 × 10-10] and decreased homocysteine [p = 2.73 × 10-7]), and lysine metabolism (reduced lysine [p = 7.8 × 10-9], α-aminoadipic acid [p = 1.16 × 10-9], and 5-aminovaleric acid [p = 1.05 × 10-5]). Collectively, the data presented here identify a possible imbalance between excitatory and inhibitory amino acid metabolism in ASD children. The significantly altered UAA indicators could therefore be potential diagnostic biomarkers for ASD.

Relationship of plasma S100B and MBP with brain damage in preterm infants.

To study the relationships of MBP and S100B with PVH-IVH and PVL in preterm infants. 385 cases of preterm infants, whose gestational age was less than 34 weeks, were enrolled in the study. The plasma levels of S100B and MBP were detected within 24 hours and on the 3rd, 7th, 14th day after birth. Cranial ultrasound was preformed 2-3 d, 1 week, 2 weeks, 3 weeks and 4 weeks after birth. They also received Cranial MRI examination before discharge or when the correct gestational age reached 40 weeks. According to the exclusion standard, 73 cases were excluded. The included 312 cases were divided into 3 groups (no brain damage group, PVH-IVH group and PVL group) according to the result of cranial ultrasound and MRI. The differences of plasma levels of S100B and MBP among groups were compared, and the relationships of the plasma levels of S100B and MBP with gestational age in no brain damage group were analyzed. The results of cranial ultrasound and/or MRI showed: 204 cases had no brain damage (enrolled in no brain damage group); 69 cases had PVH-IVH (enrolled in PVH-IVH group); 27 cases had PVL and 12 cases had PVL and PVH-IVH (both enrolled in PVL group). The plasma level of S100B: within 24 h and on the 3rd d after birth, the serum levels of S100B in PVH-IVH group were significantly higher than those in no brain damage group (P < 0.05); and the plasma levels of S100B in PVL group were significantly higher than those in no brain damage group and PVH-IVH group (all P < 0.05). On 7th d and 14th d after birth, there were no significant differences between PVH-IVH group and no brain damage group (P > 0.05); and the plasma levels of S100B in PVL group were still significantly higher than those in no brain damage group and PVH-IVH group (all P < 0.05). The plasma levels of MBP: within 24 h and on the 3rd d, 7th d and 14th d after birth, there were no significant differences between PVH-IVH group and no brain damage group (all P > 0.05); and the plasma levels of MBP in PVL group were significantly higher than those in no brain damage group and PVH-IVH group (all P < 0.05). Correlation analysis of gestational age and S100B, MBP: the plasma level of S100B in no brain damage group had a negative correlation with gestational age (r = -0.483, P = 0.006), and that of MBP had no correlation with gestational age (r = -0.295, P = 0.105). The plasma levels of S100B and MBP increased significantly in preterm infants with brain damage within 24 h after birth, and the plasma levels of S100B and MBP in PVL infants were higher than those in PVH-IVH infants. The increased plasma levels of S100B and MBP in PVL infants lasted longer than in PVH-IVH infants. The increased plasma levels of S100B and MBP in preterm infants would have certain clinical significance for judging whether early brain damage and PVL would happen.

[Effects of feeding patterns after hospital discharge on increase rates of growth indices in preterm and low-birth-weight infants within 3 months after birth].

OBJECTIVE: To study the effects of post-discharge formula (PDF) for preterm infants, breast milk (BM) and term infant formula (TF) on increase rates of body weight, length and head circumference in preterm and low-birth-weight infants (PLBWIs) from discharge to 3 months after birth, and to provide a reference for the choice of feeding pattern for PLBWIs. METHODS: A total of 407 PLBWIs discharged from the newborn departments of ten hospitals in Guangzhou City and Foshan City in Guangdong Province, China were chosen for this study. According to feeding pattern, they were assigned to three groups: PDF-fed (n=258), BM-fed (n=58) and TF-fed (n=91). Their body weight, length and head circumference were measured at 3 months after birth, and the increase rates of growth indices relative to baseline values (at birth) were calculated and compared. RESULTS: At 3 months after birth, the PDF-fed group had significantly greater body weight, length and head circumference than the BM-fed and TF-fed groups (P<0.05). The increase rates of body weight and length were significantly higher in the PDF-fed group than in the BM-fed and TF-fed groups (P<0.05). CONCLUSIONS: Compared with those fed with BM and TF after discharge, the PDF-fed PLBWIs have higher increase rates of body weight and length and show greater body weight and length at 3 months after birth. However, further study is needed to investigate the long-term effects.