Faculty Bibliography

OBJECTIVE: Human milk (HM) has antibacterial properties due to the presence of immune-modulators, including lactoferrin (LF). This study will determine effect(s) of HM maturation, fortification, and storage conditions on LF levels and its antibacterial properties. STUDY DESIGN/METHODS:. RESULTS: The highest level of LF in preterm HM was observed in the first week of lactation. However, storage of preterm HM at 4°C decreased LF levels significantly. Both LF levels and antibacterial activity in preterm HM was lower compared with term HM, but significantly higher than donor HM even after HM-based fortification. LF supplementation of donor HM improved its antibacterial activity. CONCLUSION/CONCLUSIONS: Preterm infants fed donor HM, formula, or stored HM at 4°C may benefits from LF supplementation to improve HM antibacterial properties. KEY POINTS/CONCLUSIONS:· Milk LF levels vary with storage and maturity.. · Donor milk is deficient in LF even after adding HM-based fortification.. · Donor HM and formula fed infants may benefit from LF..

Neonates born prematurely (<37 weeks of gestation) are at a significantly increased risk of developing inflammatory conditions associated with high mortality rates, including necrotizing enterocolitis, bronchopulmonary dysplasia, and hypoxic-ischemic brain damage. Recently, research has focused on characterizing the content of extracellular vesicles (EVs), particularly microRNAs (miRNAs), for diagnostic use. Here, we describe the most recent work on EVs-miRNAs biomarkers discovery for conditions that commonly affect premature neonates.

Introduction/UNASSIGNED:Parenteral Nutrition (PN) can lead to intestinal failure associated liver disease (IFALD). There are no human studies to date studying specifically the benefits of light-protection on neonatal IFALD. Recently, the European Medicines Agency and the American Society for Parenteral and Enteral Nutrition (ASPEN) both recommended full light protection of PN to reduce the risk of adverse clinical outcomes. Objective/UNASSIGNED:The primary objective of this study was to evaluate the impact of light-protecting PN on the incidence of cholestasis and peak direct bilirubin levels in premature infants. Study design/UNASSIGNED:Retrospective chart review of preterm infants requiring PN for a minimum of 2 weeks with or without light-protection. After light protection of the PN solution, primary outcomes (including cholestasis and direct bilirubin levels) of both groups were compared. Secondary outcomes include evaluation of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis and mortality. Results/UNASSIGNED:= 0.0223). There was no difference in NEC, ROP, sepsis or mortality. Conclusion/UNASSIGNED:Our study supports that the practice of light-protecting PN may reduce the incidence of IFALD in premature infants. Moreover, there was a trend toward decreased incidence of severe BPD in the light-protection group. Further light protection studies are needed to confirm these findings.

BACKGROUND:Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring a balance between immunosuppression, which is essential for the maintenance of a semi-allogeneic fetus, and pro-inflammatory host defense to protect the maternal-fetal interface from invading organisms. Adaptation to repeated inflammatory stimuli (endotoxin tolerance) may be critical in preventing inflammation-induced preterm birth resulting from exaggerated maternal inflammatory responses to mild/moderate infections that are common during pregnancy. However, the exact mechanisms contributing to the maintenance of tolerance to repeated infections are not completely understood. miRNAs play important roles in pregnancy, with several miRNAs implicated in gestational tissue function, as well as in pathologic pregnancy conditions. miRNA-519c, a member of the C19MC cluster, is a human-specific miRNA mainly expressed in the placenta. However, its role in pregnancy is largely unknown. OBJECTIVES/OBJECTIVE:To explore the role of "endotoxin tolerance" failure in the pathogenesis of an exaggerated inflammatory response often seen in inflammation-mediated preterm birth. In this study, we investigated the role of miRNA-519c, a placenta-specific miRNA, as a key regulator of endotoxin tolerance at the maternal-fetal interface. STUDY DESIGN/METHODS:-trimester placentas were treated with LPS. After 24 hours, the conditioned media was collected for analysis, and the placental explants were re-exposed to repeated doses of LPS for 3 days. The supernatant was analyzed for inflammatory markers, presence of extracellular vesicles (EVs) and microRNAs. To study the possible mechanism of action of the microRNAs, we evaluated the phosphodiesterase 3 B (PDE3B) pathway involved in TNF-α production using a miRNAs mimic and PDE3B siRNA transfection. Finally, we analyzed human placental samples from different gestational ages and from women affected by inflammation-associated pregnancies. RESULTS:Our data showed that repeated exposure of the human placenta to endotoxin challenges induced a tolerant phenotype characterized by decreased TNF-α and upregulated IL-10 levels. This reaction was mediated by the placenta-specific miRNA-519c packaged within placental EVs. LPS treatment increased the EVs that were positive for the exosome tetraspanin markers, namely CD9, CD63, and CD81, and secreted primarily by trophoblasts. Primary human trophoblast cells transfected with miR-519c mimic decreased PDE3B. While lack of PDE3B, achieved by siRNA transfection, resulted in a decreased TNF-α production. These data supported the hypothesis that the anti-inflammatory action of miRNA-519c was mediated by a downregulation of the phosphodiesterase 3 B pathway, leading to inhibition of TNF-α production. Furthermore, human placentas from normal and inflammation-associated pregnancies demonstrated that decreased placental miRNA-519c level was linked to infection-induced inflammatory pathologies during pregnancy. CONCLUSION/CONCLUSIONS:We identified miRNA-519c, a human placenta-specific miRNA, as a novel regulator of immune adaptation associated with infection-induced preterm birth at the maternal-fetal interface. Our study can serve as a basis for future experiments to explore the potential use of miRNA-519c as a biomarker for infection-induced preterm birth.