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.

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.

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.

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-1βrs1143643 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.

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.