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.

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.

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.

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.