Dynamic whole-transcriptome landscape of acute bilirubin encephalopathy in newborns.

Hyperbilirubinemia in newborns may progress to acute bilirubin encephalopathy (ABE), posing short- and long-term health risks. Despite extensive research identifying numerous mRNAs, lncRNAs, circRNAs, and miRNAs associated with brain injury, their roles in neonatal bilirubin-induced brain injury remain elusive. This study employed whole-transcriptome sequencing to ascertain the differentially expressed (DE) RNA profiles in a newborn ABE rat model, followed by bioinformatic analysis. A time-series competing endogenous RNA (ceRNA) regulatory network was established, and the expression trends of 9 arbitrarily chosen RNAs were verified through quantitative real-time polymerase chain reaction(qRT-PCR). In comparison with the control group, we identified 595, 888, and 1448 DE mRNAs; 22, 37, and 37 DE miRNAs; 1945, 1869, and 1997 DE lncRNAs; and 31, 28, and 36 DE circRNAs at 6 h, 12 h, and 24 h, respectively. Predominantly, these DERNAs contribute to biological functions and pathways associated with inflammation, immunity, metabolism, cell death, and neurodevelopmental regulation. Moreover, we constructed ceRNA networks of DE lncRNA/circRNA-DE miRNA-DE mRNA based on time series. The qRT-PCR expression trends for the selected 9 RNAs were generally similar to the RNA-seq outcomes. This investigation uniquely delineated the temporal expression patterns of mRNA and non-coding RNA in ABE, establishing ceRNA networks and identifying potential molecular mechanisms underlying bilirubin-induced hippocampal damage. Nonetheless, further studies are warranted to corroborate these findings in humans.

A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis.

OBJECTIVE: The purpose of this study is to investigate the relationship between single nucleotide polymorphisms of inflammatory cytokines and neonatal sepsis through meta-analysis. METHODS: We collected research literature on the correlation between inflammatory cytokine polymorphisms and neonatal sepsis published before August 2023 through computer searches of databases such as PubMed, Embase, etc. The Stata 14.0 software was utilized for Meta-analysis. To assess heterogeneity, the chi-squared Q-test and I2 statistics were used. The Egger and Begg tests were conducted to determine the possibility of publication bias. RESULTS: After reviewing 1129 articles, 29 relevant articles involving 3348 cases and 5183 controls were included in the study. The meta-analysis conducted on IL-1ßrs1143643 polymorphism revealed significant findings: the T allele genotype has a lower risk of neonatal sepsis(P = 0.000, OR = 0.224, 95% CI: 0.168-0.299), while the TC and TT genotypes showed an increased risk(TC: P = 0.000,OR = 4.251, 95% CI: 2.226-8.119; TT: P = 0.019,OR = 2.020, 95% CI: 1.122-3.639). Similarly, newborns with the IL-6-174 CC genotype had a significantly higher risk of sepsis(P = 0.000,OR = 1.591, 95% CI: 1.154-2.194), while those with the IL-8-rs4073 TT (P = 0.003,OR = 0.467, 95% CI: 0.280-0.777)and TT + AA(P = 0.003,OR = 0.497, 95% CI: 0.315-0.785) genotypes had a significantly lower risk of sepsis. For the IL-10-1082 gene, newborns with the AA genotype(P = 0.002,OR = 1.702, 95% CI: 1.218-2.377), as well as those with the AA + GA genotype(P = 0.016,OR = 1.731, 95% CI: 1.108-2.705), had a significantly higher risk of sepsis. Lastly, newborns carrying the TNF-α-308 A allele (P = 0.016,OR = 1.257, 95% CI: 1.044-1.513)or the AA genotype(P = 0.009,OR = 1.913, 95% CI: 1.179-3.10) have a significantly increased risk of sepsis. Notwithstanding, additional studies must be included for validation. Applying these cytokines in clinical practice and integrating them into auxiliary examinations facilitates the early detection of susceptible populations for neonatal sepsis, thereby providing a new diagnostic and therapeutic approach for neonatal sepsis.

Risk factors of neonatal stroke from different origins: a systematic review and meta-analysis.

Given the persistent ambiguity regarding the etiology of neonatal stroke across diverse origins, our objective was to conduct a comprehensive evaluation of both qualitative and quantitative risk factors. An exhaustive search of eight databases was executed to amass all pertinent observational studies concerning risk factors for neonatal stroke from various origins. Subsequent to independent screening, data extraction, and bias assessment by two researchers, a meta-analysis was conducted utilizing RevMan and Stata software. Nineteen studies, encompassing a total of 30 factors, were incorporated into this analysis. Beyond established risk factors, our investigation unveiled gestational diabetes (OR, 5.51; P < 0.00001), a history of infertility (OR, 2.44; P < 0.05), placenta previa (OR, 3.92; P = 0.02), postdates (OR, 2.07; P = 0.01), preterm labor (OR, 2.32; P < 0.00001), premature rupture of membranes (OR, 3.02; P = 0.007), a prolonged second stage of labor (OR, 3.94; P < 0.00001), and chorioamnionitis (OR, 4.35; P < 0.00001) as potential risk factors for neonatal cerebral arterial ischemic stroke. Additionally, postdates (OR, 4.31; P = 0.003), preterm labor (OR, 1.60; P < 0.00001), an abnormal CTG tracing (OR, 9.32; P < 0.0001), cesarean section (OR, 4.29; P = 0.0004), male gender (OR, 1.73; P = 0.02), and vaginal delivery (OR, 1.39; P < 0.00001) were associated with an elevated risk for neonatal hemorrhagic stroke. CONCLUSIONS: This study provides a succinct overview and comparative analysis of maternal, perinatal, and additional risk factors associated with neonatal cerebral artery ischemic stroke and neonatal hemorrhagic stroke, furnishing critical insights for healthcare practitioners involved in the diagnosis and prevention of neonatal stroke. This research also broadens the conceptual framework for future investigations. WHAT IS KNOWN: • Research indicates that prenatal, perinatal, and neonatal risk factors can elevate the risk of neonatal arterial ischemic stroke (NAIS). However, the risk factors for neonatal cerebral arterial ischemic stroke remain contentious, and those for neonatal hemorrhagic stroke (NHS) and neonatal cerebral venous sinus thrombosis (CVST) are still not well-defined. WHAT IS NEW: • This study is the inaugural comprehensive review and meta-analysis encompassing 19 studies that explore maternal, perinatal, and various risk factors linked to neonatal stroke of differing etiologies. Notably, our analysis elucidates eight risk factors associated with NAIS: gestational diabetes mellitus, a history of infertility, placenta previa, postdates, preterm birth, premature rupture of membranes, a prolonged second stage of labor, and chorioamnionitis. Furthermore, we identify six risk factors correlated with NHS: postdates, preterm birth, an abnormal CTG, the method of delivery, male gender, and vaginal delivery. Additionally, our systematic review delineates risk factors associated with CVST.

Risk factors for infant hearing loss: a meta-analysis.

Hearing loss is a common disability in infants that significantly impacts their cognitive, language, and literacy development. This study aimed to systematically assess the risk factors for the early identification and intervention in infant hearing loss. Databases were searched for meta-analyses of observational studies until November 2023. The quality assessment was performed using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. A meta-analysis identified 14 risk factors significantly associated with infant hearing loss. According to the GRADE approach, there were four factors with moderate-certainty evidence (low birth weight(LBW), congenital anomalies, craniofacial anomalies, intracranial hemorrhages), seven factors with low-certainty evidence (ototoxic medications, family history of hearing loss, mechanical ventilation > 5 days, intrauterine infection, admission to neonatal intensive care unit (NICU) > 5 days, mechanical ventilation and asphyxia) and six with extremely-low-certainty evidence (very low birth weight < 1500 g (VLBW), hyperbilirubinemia, sepsis or meningitis, male sex, premature birth, small for gestational age (SGA)). Nevertheless, no significant association was found between infant hearing loss and factors such as small for gestational age (SGA), male sex, and premature birth (P > 0.05).  Conclusion: The identification of these 14 interrelated risk factors can prove advantageous in clinical practice, as these findings could guide hearing screening and parental counseling. Furthermore, prospective research could be conducted to develop risk-based scoring systems based on these factors. What is Known: • Infant hearing loss is a worldwide issue. • Risk factors for this condition are debated. What is New: • This is the first meta-analysis to comprehensively evaluate perinatal and postnatal risk factors for hearing loss in infants. • Intracranial hemorrhage, mechanical ventilation, and low birth weight are associated with infant hearing loss. However, no evidence of an association was found between premature birth, being small for gestational age, or male sex and hearing loss.

Perinatal risk factors for neonatal early-onset sepsis: a meta-analysis of observational studies.

OBJECTIVE: Early-onset neonatal sepsis (EONS) remains an important cause of neonatal mortality and has many risk factors, therefore, this study aimed to investigate the perinatal risk factors for EONS. METHODS: We searched CNKI, Wan Fang, VIP, CBM, PubMed, Embase, and Web of Science to compile studies regarding the incidence of neonatal early-onset sepsis, published up to 1 May 2022. To evaluate the quality of the included studies, we used the Newcastle-Ottawa Scale, and the RevMan5.3 software was used for meta-analysis. RESULTS: A total of 17 studies were included, with 1987 cases in the case group and 4814 cases in the control group. Meta-analysis showed that perinatal asphyxia or intrauterine distress (OR = 3.00, 95% CI: 2.18-4.13), amniotic fluid meconium contamination (OR = 4.51, 95% CI: 2.31-8.81), group B streptococcal (GBS) colonization in pregnant women (OR = 2.13, 95% CI: 1.48-3.05), chorioamnionitis (OR = 4.58, 95% CI: 2.61-8.05), premature rupture of membranes (OR = 2.63, 95% CI: 2.09-3.30), lower gestational age (OR = 1.31, 95% CI: 1.18-1.44), maternal urinary or reproductive tract infection (OR = 3.61, 95% CI: 2.14-6.11), perinatal fever (OR = 3.59, 95% CI: 2.25-5.71), very low birth weight (OR = 3.79, 95% CI: 2.14-6.73), and vaginal examination ≥3 times (OR = 7.95, 95% CI: 4.04-15.64) were the perinatal risk factors for EONS. CONCLUSION: Perinatal asphyxia or intrauterine distress, meconium contamination in amniotic fluid, GBS colonization in pregnant women, chorioamnionitis, premature rupture of membranes, lower gestational age, maternal urinary tract or reproductive tract infection, perinatal fever, very low birth weight, and vaginal examinations ≥3 times may increase the risk of EONS.

MiRNAs as biomarkers for diagnosis of neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: The relationship between circulating miRNAs and neonatal sepsis and the mechanism of action are still unclear at this time. Therefore, the potential diagnostic role of miRNAs in neonatal sepsis (NS) was studied through meta-analysis. METHOD: Web of Science, Cochrane Library, PubMed, and Embase are retrieved, supplemented by manual search, and the search was conducted to find related studies without time limit until May 2022.The quality of the literature was assessed via QUADAS criteria and meta-analyzed via Stata 11.0 software, including the assessment of specificity, sensitivity, likelihood ratio and diagnostic odds ratio. Then, sensitivity analysis and heterogeneity testing were conducted, and finally, the summary receiver operating characteristics (SROC) curve was drawn. RESULT: This study included 14 articles, including 20 miRNAs and 1597 newborns(control group: 727 and case group: 870). Among them, one article was of low quality, three articles were of high quality, and the rest were of medium quality. According to the results of random effects model analysis, the pooled specificity and sensitivity of miRNA for the diagnosis of NS were 0.83 (95%CI: 0.79-0.87) and 0.76 (95%CI: 0.72-0.80), respectively. And negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio were 0.29 (95%CI: 0.24-0.34), 4.51 (95%CI: 3.52-5.78), and 15.81 (95%CI: 10.71-23.35), respectively. The area under the SROC curve was 0.86, and there was no evidence publication bias detected in the funnel plot. CONCLUSION: Circulating miRNAs may be very useful in the development of early diagnostic strategies for neonatal sepsis.

The accuracy of soluble urokinase-type plasminogen activator receptor for the diagnosis of neonatal sepsis: a meta-analysis.

Background: Neonatal sepsis is one of the major causes of morbidity and mortality in newborns. However, atypical clinical manifestations and symptoms make the early diagnosis of neonatal sepsis a challenge. Relatively high-serum soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated as a diagnostic biomarker for adult sepsis. Therefore, the meta-analysis is intended to explore the diagnostic value of suPAR for neonatal sepsis. Methods: The PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Biological Medicine Disk, and Wanfang databases were retrieved from inception to 31 December 2022 to collect diagnostic accuracy studies about suPAR for neonatal sepsis. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool. Then, a meta-analysis was performed using Stata 15.0 software. Results: A total of six articles involving eight studies were included. The results of the meta-analysis showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.89 [95%CI (0.83-0.93)], 0.94 [95%CI (0.77-0.98)], 14 [95%CI (3.5-55.2)], 0.12 [95%CI (0.08-0.18)], and 117 [95%CI (24-567)], respectively. The area under the curve (AUC) of summary receiver operator characteristic (SROC) curves was 0.92 [95%CI (0.90-0.94)]. Sensitivity analysis confirmed the stability of the results, and publication bias was not observed. Fagan's nomogram results demonstrated the clinical availability of the findings. Conclusion: Current evidence suggests that suPAR has potential diagnostic value for neonatal sepsis. Owing to the limited quality of the included studies, more high-quality studies are needed to verify the above conclusion.

The association between mannose binding lectin gene polymorphisms and the risk of neonatal sepsis: an updated meta-analysis.

Objectives: To evaluate the relationship between mannose-binding lectin (MBL) polymorphism and neonatal sepsis to provide ideas for early diagnosis and control of neonatal sepsis using meta-analysis. Methods: The China National Knowledge Infrastructure, WanFang Data, China Biological Medicine Disc, PubMed, Embase, Cochrane Library, and Web of Science databases were electronically searched to collect studies on the association between the MBL gene variants and the risk of neonatal sepsis. Original articles from case-control and cohort studies on the relationship between MBL polymorphisms and neonatal sepsis were considered eligible. Meta-analysis was performed using Stata 15.0 software. The chi-square-based Q test and I2 statistics were used to assess heterogeneity. Forest plots were used to display the results graphically. Potential publication bias was assessed using the Egger and Begg tests and funnel plots. Results: Twenty-two studies, including 4565 cases and 12,746 controls, were included in this meta-analysis. Meta-analysis showed a significant relationship between MBL rs1800450 (codon 54, G > A) and neonatal sepsis in the variant vs. wild types. However, the analysis showed MBL exon 1 gene polymorphism (A/O), MBL rs5030737 (codon 52, C > T), and rs1800451 (codon 57, G > A), involved in existing research, were not associated with the risk of sepsis in neonates. Conclusions: Current evidence shows that MBL rs1800450 is associated with neonatal culture-proven sepsis. Owing to the limited quantity and quality of the included studies, more high-quality studies are required to verify the above conclusion.

Association between high-mobility group box 1 levels and febrile seizures in children: a systematic review and meta-analysis.

The relationship between High-mobility group box 1 (HMGB1) and febrile seizures (FS) in children remains unclear. This study aimed to apply meta-analysis to reveal the correlation between HMGB1 levels and FS in children. Databases including PubMed, EMBASE, Web of science, Cochrane library, CNKI, SinoMed and WanFangData were searched for relevant studies. Pooled standard mean deviation and 95% confidence interval were calculated as effect size since the random-effects model was used when I2 > 50%. Meanwhile, between-study heterogeneity was determined by performing subgroup and sensitivity analyses. A total of 9 studies were finally included. Meta-analysis showed that the children with FS had significantly higher HMGB1 levels compared with healthy children and children with fever but no seizures (P<0.05). Additionally, subgroup analysis showed that the HMGB1 level in children with complex FS was higher than those with simple FS (P<0.05), and children with duration >15 min were higher than those with duration ≤15min (P<0.05). There were no statistical differences between children with or without a family history of FS (P>0.05). Finally, children with FS who converted to epilepsy exhibited higher HMGB1 levels than those who did not convert to epilepsy (P<0.05). The level of HMGB1 may be implicated in the prolongation, recurrence and development of FS in children. Thus, it was necessary to evaluate the precise concentrations of HMGB1 in FS patients and to further determine the various activities of HMGB1 during FS by well-designed, large-scale, and case-controlled trials.

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage.

BACKGROUND: The mechanisms underlying ferroptosis in neonatal hypoxic-ischemic brain damage (HIBD) remain unclear. METHOD: Four microarray datasets were collected from the GEO database (three mRNA datasets GSE23317, GSE144456, and GSE112137, and one miRNA microarray dataset GSE184939). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of HIBD-related genes. The ferroptosis-related genes were extracted from FerrDb, of which closely correlated to HIBD were obtained after the intersection with existing HIBD's DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as protein-protein interaction (PPI) network analysis were subsequently conducted. Cytoscape was used to identify central genes. Immune cell infiltration analysis was performed by the CIBERSORT algorithm. RESULT: Fifty-six ferroptosis-related differentially expressed genes (FRDEGs) were screened, mainly related to ferroptosis, autophagy, hypoxia response, metabolic pathways, and immune inflammation. The seven optimal hub FRDEGs were obtained by intersecting with key modules of WGCNA. Then, the expression levels of the seven optimal hub FRDEGs were validated in the GSE144456 and GSE112137 datasets, and the ferroptosis-related mRNA-miRNA network was established. In addition, this study revealed immune cell infiltration in the HIBD cerebral cortex and the interaction between immune cells. Moreover, notably, specific FRDEGs were strongly positively correlated with immune function. CONCLUSIONS: The mechanism of ferroptosis is intricate and closely related to neonatal HIBD. Therefore, targeting ferroptosis-related gene therapy and immunotherapy may have therapeutic prospects for neonatal HIBD.

Risk factors for metabolic bone disease of prematurity: A meta-analysis.

OBJECTIVE: To investigate the risk factors for metabolic bone disease of prematurity (MBDP), and to provide a reference for the prevention of MBDP. METHODS: The databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, Cochrane Library and other databases were searched for studies on the risk factors for MBDP published up to June 18, 2021. RevMan 5.3 and Stata 14.1 software were used to perform a Meta analysis. RESULTS: A total of 15 articles were included, including 13 case-control studies, 1 current investigation, and 1 retrospective cohort study. There were 1,435 cases in the case group and 2,057 cases in the control group, with a total sample size of 3,492 cases. Meta analysis showed that risk factors for MBDP include birth weight <1000g (OR = 6.62, 95%CI: 2.28-19.25), gestational age <32 weeks (OR = 2.73, 95%CI: 1.07-6.95), septicemia (OR = 2.53, 95%CI: 1.69-3.79), parenteral nutrition time (OR = 4.04, 95%CI: 1.72-9.49), cholestasis (OR = 3.50, 95%CI: 1.49-8.23), intrauterine growth retardation (OR = 6.89, 95%CI: 3.81-12.44), while the birth weight(OR = 0.44, 95%CI: 0.21-0.90) and gestational age (OR = 0.57, 95%CI: 0.44-0.73)are the protective factors of MBDP. CONCLUSION: Factors like birth weight <1000g, gestational age <32 weeks, septicemia, parenteral nutrition time, cholestasis, and intrauterine growth retardation may increase the risk of metabolic bone disease of prematurity.

Mechanisms of Vitamin C Regulating Immune and Inflammation Associated with Neonatal Hypoxic-Ischemic Encephalopathy Based on Network Pharmacology and Molecular Simulation Technology.

BACKGROUND: There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). METHODS: The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. RESULT: Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. CONCLUSION: The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.

Risk factors for necrotizing enterocolitis in neonates: A meta-analysis.

Objective: The objective is to identify the risk factors for necrotizing enterocolitis (NEC) in neonates by a meta-analysis, and to provide a reference for the prevention of NEC. Methods: The databases, including Chinese Biomedical Literature Datebase, China National Knowledge Infrastructure, Wanfang database, and Weipu Periodical database, PubMed, Web of Science, Embase, Cochrane Library, were searched for studies on the risk factors for NEC in neonates. The meta-analysis was carried out with the aid of Stata software. Results: A total of 52 studies were included, with 48 case-control studies and 4 cohort studies. There were 166,580 neonates in total, with 33,522 neonates in the case group and 133,058 neonates in the control group. The meta-analysis showed that gestational diabetes (OR = 3.62, 95% CI:1.77-7.41), premature rupture of membranes (OR = 3.81, 95% CI:1.16-12.52), low birth weight (OR = 3.00, 95% CI:2.26-3.97), small for gestational age (OR = 1.85, 95% CI:1.15-2.97), septicemia (OR = 4.34, 95% CI:3.06-6.15), blood transfusion (OR = 3.08, 95% CI:2.16-4.38), congenital heart disease (OR = 2.73, 95% CI:1.10-6.78), respiratory distress syndrome (OR = 2.12, 95% CI:1.24-3.63), premature birth (OR = 5.63, 95% CI:2.91-10.92), pneumonia (OR = 4.07, 95% CI:2.84-5.82) were risk factors for NEC in neonates. Breastfeeding (OR = 0.37, 95% CI:0.23-0.59), take probiotics (OR = 0.30, 95% CI:0.22-0.40), prenatal use of glucocorticoids (OR = 0.39, 95% CI:0.30-0.50), Hyperbilirubinemia (OR = 0.28, 95% CI:0.09-0.86) were protective factors for NEC in neonates. Conclusions: Gestational diabetes, premature rupture of membranes, low birth weight, small for gestational age, septicemia, blood transfusion, congenital heart disease, respiratory distress syndrome, premature birth, and pneumonia may increase the risk of NEC in neonates. Breastfeeding, taking probiotics, prenatal use of glucocorticoids, and Hyperbilirubinemia may reduce the risk of NEC in neonates.

No association between children's febrile seizures and S100B protein levels: A meta-analysis.

BACKGROUND: In recent years, studies have examined the relationship between febrile seizures in children and S100B protein with contradictory results. We systematically evaluated the relationship between children's febrile seizures and S100B protein levels. METHODS: We used Stata 11.0 software to conduct a meta-analysis of the included studies published in The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and EMBASE databases as well as clinical trial registries in China, Europe, and the United States. RESULTS: Six case-control studies were finally included in the meta-analysis. The results of the meta-analysis showed that the serum S100B protein level of children with febrile seizures was 0.72 higher than the serum S100B protein level of healthy children (Z=6.85, 95% CI 0.52∼0.93, P<0.05). There was no difference in the serum S100B protein level between the children with febrile seizures and children with fever but without seizures (Z=0.70, 95% CI -0.20∼0.41, P>0.05). CONCLUSION: The level of serum S100B protein in children with febrile seizures was higher than that of healthy children and was statistically significant, whereas the increase in children with higher fever without seizures was not statistically significant. Because there was only a difference in serum S100B protein levels between children with febrile seizures and healthy children but not in febrile children without seizures as the strongest confounding factors for the results, febrile seizures do not elevate the level of S100B protein levels any more than fever.

Correlation between neonatal hyperbilirubinemia and vitamin D levels: A meta-analysis.

OBJECTIVE: Hyperbilirubinemia is a common disease in the neonatal period, and hyperbilirubinemia may cause brain damage. Therefore, prevention and diagnosis and management of hyperbilirubinemia is very important, and vitamin D may affect bilirubin levels. To evaluate the relationship between neonatal hyperbilirubinemia and vitamin D levels. METHOD: The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and Embase databases as well as clinical trial registries in China and the United States were searched for relevant studies from inception to September 2020 without restrictions on language, population, or year. The studies was screened by two reviewers independently, the data were extracted, and the risk of bias of the included studies was evaluated using the NOS. A meta-analysis was conducted on the included studies using Stata11 software. RESULTS: Six case-control studies were included, and the methodological quality of the studies was high (grade A). The studies included 690 newborns; more than 409 were diagnosed with hyperbilirubinemia. The means and standard deviations were calculated. Meta-analysis results showed that neonatal vitamin D levels were 7.1 ng/ml lower among infants with hyperbilirubinemia than among healthy newborn levels (z = 6.95, 95% CI 9.10 ~ 5.09, P < 0.05). Subgroup analysis was conducted based on whether the bilirubin levels were concentrated in the 15 to 20 mg/dl range. Vitamin D level of infants with hyperbilirubinemia (the bilirubin levels were concentrated in the 15 to 20 mg/dl range) was 9.52 ng/ml (Z = 15.55, 95% CI-10.72~-8.32, P<0.05) lower than that of healthy infants. The bilirubin levels in four cases were not concentrated in the 15-20 mg/dl range. The results showed that the vitamin D level of hyperbilirubinemia (The bilirubin levels were not concentrated in the 15-20 mg/dl range) neonates were 5.35 ng/ml lower than that of healthy neonates (Z = 6.43, 95% CI-6.98~-3.72, P<0.05). CONCLUSION: Vitamin D levels were observed to be lower in neonates with hyperbilirubinemia as compared to term neonates without hyperbilirubinemia in this study. This can possibly suggest that neonates with lower vitamin D levels are at higher risk for developing hyperbilirubinemia.

[Role of fecal calprotectin in the diagnosis of neonatal necrotizing enterocolitis: a Meta analysis].

OBJECTIVE: To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis. METHODS: Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted. RESULTS: A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95%CI:0.78-0.82) and a sensitivity of 0.86 (95%CI:0.83-0.89) in the diagnosis of NEC, with a negative likelihood ratio of 0.19 (95%CI:0.14-0.26), a positive likelihood ratio of 4.71 (95%CI:3.57-6.23), and a diagnostic odds ratio of 29.56 (95%CI:17.98-48.61). The area under the SROC curve was 0.9131 and the Q* index was 0.8456. The Fagan diagram showed that the post-test probability of NEC indicated by negative FC was 13%, while that indicated by positive FC was 86%. The Meta regression analysis showed that the heterogeneity came from other non-threshold factors. CONCLUSIONS: FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.

Effect of erythropoietin on Fas/FasL expression in brain tissues of neonatal rats with hypoxic-ischemic brain damage.

Hypoxic-ischemic brain damage (HIBD) occurs due to intrauterine hypoxia ischemia influencing the energy supply for fetal brain cells, which affects the metabolism of the brain to make the brain suffer a severe damage. Erythropoietin (EPO), which regulates hemacytopoiesis, is a kind of cytokine. EPO is sensitive to hypoxia ischemia. In this study, we aimed to investigate the effect of EPO on the expression of Fas/FasL in brain tissues of neonatal rats with HIBD. Neonatal rats were assigned randomly to sham, HIBD, and EPO groups. Five time points for observation were 6, 12, 24, 48, and 72 h after the HIBD rat model had been established, respectively. In the HIBD group, Fas/FasL expression began to rise at 6 h, reached the peak at 12-24 h, and dropped from 24 h. In the EPO group, the expression of Fas/FasL was lower than those in HIBD group at 12, 24, and 48 h (P<0.05). Our findings suggest that EPO may reduce cell apoptosis after hypoxic-ischemic damage through reduction of the expression of Fas and FasL, and that optimal therapeutic time window is 6-24 h after HIBD.

Ultrasound measurement of the corpus callosum and neural development of premature infants.

Length and thickness of 152 corpus callosa were measured in neonates within 24 hours of birth. Using ultrasonic diagnostic equipment with a neonatal brain-specific probe, corpus callosum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus callosum length as well as thickness of the genu and splenium increased with tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus callosum velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus callosum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose gestational age was 34 weeks or less. Corpus callosum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus callosum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus callosum growth in premature infants is associated with neurobehavioral development during the early extrauterine stage.