Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants caused by multifactorial etiology. Genetic factors are involved in the occurrence of BPD, but studies have found that candidate genes have poor reproducibility and are influenced by ethnic heterogeneity; therefore, more exploration is still needed. We performed whole-exon sequencing in 34 preterm infants with BPD and 32 non-BPD control neonates. The data were analyzed and interpreted by Fisher difference comparison, PLINK and eQTL association analysis, KEGG and GO enrichment analysis, STRING tool, Cytoscape software, ProtParam tool, HOPE online software, and GEOR2 analysis on NCBI GEO dataset. BPD has a highly heterogeneity in different populations, and we found 35 genes overlapped with previous whole-exon sequencing studies, such as APOB gene. Arterial and epithelial cell development and energy metabolism pathways affect BPD. In this study, 24 key genes were identified, and BIVM rs3825519 mutation leads to prolonged assisted ventilation in patients with BPD. A novel DDAH1 mutation site (NM_012137: exon1: c.89 T > G: p.L30R) was found in 9 BPD patients. CONCLUSION: BIVM gene rs3825519 mutation may play a role in the pathogenesis of BPD by affecting cilia movement, and the DDAH1 and APOB genes mutations may have a pathogenic role in BPD. WHAT IS KNOWN: • Genetic factors are involved in the occurrence of bronchopulmonary dysplasia. • The candidate genes have poor reproducibility and are influenced by ethnic heterogeneity, therefore, more exploration is still needed. WHAT IS NEW: • We identified the role of susceptible SNPs in BPD in Shenzhen, China, and identified 24 key genes that influence the pathogenesis of BPD, and also found 35 genes overlapped with previous whole exon sequencing studies, such as APOB gene. • We found that BIVM and DDAH1 genes may play a pathogenic role in the pathogenesis of BPD.

Impacts of delivery mode on very low birth weight infants' oral microbiome.

OBJECTIVES: Initial microbial colonization of the oral after birth provides a vital stimulus for neonatal immune and development. The establishment of the gut microbiota has been shown to differ between very low birth weight (VLBW) infants delivered by caesarian section (C-section) and those delivered vaginally. The objective of this study was to investigate the community structure of the oral microbiota in VLBW infants delivered by the two modes. METHODS: In total, 23 VLBW infants who were hospitalized in the neonatal intensive care unit of Shenzhen BaoAn Maternity & Child Health care Hospital (Shenzhen, China) were recruited for this study: 12 infants delivered vaginally, and the other 11 infants delivered by C-section. The assessment of oral microbiota community was performed using 16S rRNA gene sequence analysis. RESULTS: The results demonstrated that the oral bacterial communities were dominated by the phylum Proteobacteria in both groups. Higher relative abundance of genera Ureaplasma and Pantoea were observed in the vaginal delivery infants, but genera Corynebacterium, Methylobacterium and Variovorax were more prevalent in cesarean-born infants. Furthermore, many metabolic pathways with significant differences between the two groups were detected, mostly related to vitamin, amino acid metabolism and diseases. Additionally, ɑ-diversity and clinical data showed no significant differences between the two groups. CONCLUSIONS: This study indicated that the mode of delivery influences the oral bacterial structure of VLBW infants after birth, but the consequences for neonatal development should be researched in a further study.

Impact of maternal intrapartum antibiotics on the initial oral microbiome of neonates.

OBJECTIVES: Prior studies have proposed that maternal intrapartum antibiotic exposure shapes the gut microbiota and, subsequently the child's health. However, the effect of maternal intrapartum antibiotic exposure and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. The aim of this study was to compare the initial oral microbiota immediately after birth of healthy infants with and without intrapartum antibiotic exposure. METHODS: Twenty-two newborns of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were recruited for this study, 11 born to mothers without intrapartum antibiotic exposure (NT group) and 11 to mothers with intrapartum antibiotic prophylaxis with cefamezin (AT group). Oral microbiome profiles were determined by 16S rRNA sequencing based on the V3V4 hyper-variable regions. RESULTS: Phylum Firmicutes was most frequently detected in subjects both groups and a higher frequency was observed in the NT group than the AT group. Phyla Actinobacteria, Bacteroidetes and Proteobacteria were more abundant after intrapartum antibiotics exposure. Genus Lactobacillus belonging to Firmicutes was predominant in the neonates not exposed to antibiotics, while significantly higher percentages of genera Klebsiella, Roseburia, Propionibacterium, Faecalibacterium, Escherichia/Shigella, Corynebacterium, Bifidobacterium, and Bacteroides were noted in AT infants than NT infants. Further function analysis demonstrated that lipopolysaccharide biosynthesis and amino acid-related metabolic function was enriched in the AT group, and carbohydrate metabolism pathways were more abundant in the NT group. CONCLUSIONS: These findings revealed distinctions in both taxa and metabolic function of oral microbiota between antibiotics-treated and unexposed groups, which indicated that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.

The Initial Oral Microbiota of Neonates Among Subjects With Gestational Diabetes Mellitus.

Objective: The objective was to investigate the potential effect of gestational diabetes mellitus on the initial neonatal oral microbiome community structure. Methods: Oral samples were collected from 20 full-term, vaginally delivered newborns with sterile swabs. Nine of them had mothers diagnosed with gestational diabetes mellitus (GDM group), while 11 had non-diabetic mothers (NDM group). The oral microbiota was analyzed using multi-barcode 16S rRNA sequencing on Illumina MiSeq system. Results: The results showed that the birth weight, gestational age and gestational weight gain were significantly higher in NDM group. There was a significant correlation between gestational age and birth weight. Neonatal oral microbiome was composed of five dominant phyla from Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Tenericutes. Compared to NDM group, a higher alpha diversity and reduction of phylum Firmicutes were observed in GDM group. Genus Lactobacillus dominated in NDM group, while Alistipes, Streptococcus, and Faecalibacterium were overabundant in GDM group. Additionally, carbohydrate metabolism increased in NDM group, whereas amino acid metabolism, vitamin metabolism and lipopolysaccharide biosynthesis were more abundant in GDM group. Conclusions: This study showed a distinct oral microbiota profile in neonates born to mothers with GDM, which indicated that maternal diabetes status played an important role in neonatal initial oral microbiota.

[Association of Ureaplasma urealyticum infection with bronchopulmonary dysplasia in very low birth weight infants with respiratory distress syndrome].

OBJECTIVE: To study the relationship between Ureaplasma urealyticum (UU) infection in the lower respiratory tract and the incidence of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). METHODS: Seventy-three VLBW infants diagnosed with neonatal RDS, who had received at least one dose of pulmonary surfactant, as well as mechanical ventilation, and were hospitalized for over 28 days, were recruited. Endotracheal aspirates were obtained from the lower respiratory tract and examined by real-time PCR to detect UU DNA. The infants were divided into UU infection and non-UU infection groups according to examination results. Clinical characteristics and the incidence of BPD were compared between the two groups. RESULTS: Compared with the non-UU infection group, the UU infection group had a higher rate of maternal vaginal delivery, higher incidence of recurrent nosocomial pulmonary infection and premature rupture of membranes (PROM), and longer durations of PROM, oxygen supplementation, and hospital stay; in addition, the UU infection group had higher plasma IgM level, leukocyte count, and neutrophil count within 3 hours after birth. Among 73 VLBW infants, 45 developed BPD; the incidence of BPD in the UU infection group was 90% (19/21), versus 50% (26/52) in the non-UU infection group (P<0.01). CONCLUSIONS: UU infection in the lower respiratory tract increases the incidence of BPD in VLBW infants with RDS.