No abstract

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.

Background: Spontaneous intestinal perforation (SIP) is a devastating complication of prematurity, and extremely low birthweight (ELBW < 1000 g) infants born prior to 28 weeks are at highest risk. The role of nutrition and feeding practices in prevention and complications of SIP is unclear. The purpose of this review is to compile evidence to support early nutrition initiation in infants at risk for and after surgery for SIP. Methods: A search of PubMed, EMBASE and Medline was performed using relevant search terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstracts and full texts were reviewed by co-first authors. Studies with infants diagnosed with SIP that included information on nutrition/feeding practices prior to SIP and post-operatively were included. Primary outcome was time to first feed. Secondary outcomes were incidence of SIP, time to full enteral feeds, duration of parenteral nutrition, length of stay, neurodevelopmental outcomes and mortality. Results: Nineteen articles met inclusion criteria—nine studies included feeding/nutrition data prior to SIP and ten studies included data on post-operative nutrition. Two case series, one cohort study and sixteen historical control studies were included. Three studies showed reduced incidence of SIP with initiation of enteral nutrition in the first three days of life. Two studies showed reduced mortality and neurodevelopmental impairment in infants with early feeding. Conclusions: Available data suggest that early enteral nutrition in ELBW infants reduces incidence of SIP without increased mortality.

Maintenance of healthy pregnancy is reliant on successful balance between the fetal and maternal immune systems. Although maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, though rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined T cells isolated from PV samples may be more proliferative than adult T cells at baseline after T cell receptor (TCR) stimulation. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells.