412 - Relationship between clinical variables, microbiome, and invasive infection in preterm infants: Comparison between two NICUs in China and the United States

Poster Number: 412
Publication Number: 412.334

Yanping Xu, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China, Hangzhou, Zhejiang, China (People's Republic); Henry Akinbi, Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, OH, United States; Lizhong Du, The Children's Hospital,Zhejiang University, Hangzhou, Zhejiang, China (People's Republic); Liping Shi, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (People's Republic); David B. Haslam, Cincinnati Children's Hospital, Cincinnati, OH, United States

Background: Infants’ microbiota is critical to health and disease. The factors that shape the development of the microbiota in preterm infants are understudied.

Objective: To assess population-level relationships among demographic factors, clinical practices, geographic location, microbiome composition and the microbiology of preterm infant neonatal sepsis.

Design/Methods: DNA was isolated from stool and skin samples collected at 1 and 3 weeks of age from a prospective cohort of infants born < 32 weeks postmenstrual age or birth weight < 2000 g at University of Cincinnati Medical Center (UC) or Children's Hospital, Zhejiang University School of Medicine (ZCH) for metagenomic shotgun sequencing.  Microbiology data were extracted from electronic medical records. Generalized linear mixed-effect model analyses and false discovery rate correction were performed to assess differences between location (UC vs ZCH), gestational age, antibiotic exposure, and sampled body sites. Significance was determined by paired Wilcoxon rank sum test with Bonferroni correction and two-way ANOVA.

Results: A total of 381 samples from 127 infants (ZCH 59, UC 68), median gestational age 30+4 weeks, median birth weight 1380 g, were analyzed. Predominant organisms that accounted for late-onset infections differed between the two locations (Figure 1): UC- Gram-positives were more predominant, particularly Staphylococcus aureus (31% at UC vs 14% at ZCH) and Staphylococcus epidermidis (14% vs 10.2%). In contrast, Gram-negatives were generally more predominant in ZCH, particularly Klebsiella pneumoniae (UC 6% vs ZCH 32%), and Acinetobacter (UC 0.5% vs. ZCH 5%). In each of these cases, metagenomic sequencing revealed that population-level microbial composition corresponded with differences in prevalence among invasive pathogens (Figure 2). Among microbial species, there was variability in the degree to which host and environmental factors contributed to abundance, however across all species geographic location, body site, and postnatal age accounted for the greatest variability, while gestational age and antibiotic exposure had less overall impact.

Conclusion(s): Pathogens causing invasive infection differ between NICUs in ZCH and UC, and these differences correlate with population-level differences in microbiome composition. Our findings support the utility of routine microbiome surveillance in the NICU to help understand microbial ecology, and to inform infection prevention/control practices. 

This work was supported by Nurturing Children’s Development CCHMC and National Natural Science Foundation of China No.81873845.