Dataset Information

Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

ABSTRACT: Septicemia is a leading cause of death among neonates in low-income settings, a situation that is deteriorating due to high levels of antimicrobial resistance. Novel interventions are urgently needed. Iron stimulates the growth of most bacteria and hypoferremia induced by the acute phase response is a key element of innate immunity. Cord blood, which has high levels of hemoglobin, iron and transferrin saturation, has hitherto been used as a proxy for the iron status of neonates. We investigated hepcidin-mediated redistribution of iron in the immediate post-natal period and tested the effect of the observed hypoferremia on the growth of pathogens frequently associated with neonatal sepsis. Healthy, vaginally delivered neonates were enrolled in a cohort study at a single center in rural Gambia (N?=?120). Cord blood and two further blood samples up to 96?hours of age were analyzed for markers of iron metabolism. Samples pooled by transferrin saturation were used to conduct ex-vivo growth assays with Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and Klebsiella pneumonia. A profound reduction in transferrin saturation occurred within the first 12?h of life, from high mean levels in cord blood (47.6% (95% CI 43.7-51.5%)) to levels at the lower end of the normal reference range by 24?h of age (24.4% (21.2-27.6%)). These levels remained suppressed to 48?h of age with some recovery by 96?h. Reductions in serum iron were associated with high hepcidin and IL-6 levels. Ex-vivo growth of all sentinel pathogens was strongly associated with serum transferrin saturation. These results suggest the possibility that the hypoferremia could be augmented (e.g. by mini-hepcidins) as a novel therapeutic option that would not be vulnerable to antimicrobial resistance. Trial registration: The original trial in which this study was nested is registered at ISRCTN, number 93854442.

SUBMITTER: Prentice S

PROVIDER: S-EPMC6851364 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

Prentice Sarah S Jallow Amadou T AT Sinjanka Edrissa E Jallow Momodou W MW Sise Ebrima A EA Kessler Noah J NJ Wegmuller Rita R Cerami Carla C Prentice Andrew M AM

Scientific reports 20191112 1

Septicemia is a leading cause of death among neonates in low-income settings, a situation that is deteriorating due to high levels of antimicrobial resistance. Novel interventions are urgently needed. Iron stimulates the growth of most bacteria and hypoferremia induced by the acute phase response is a key element of innate immunity. Cord blood, which has high levels of hemoglobin, iron and transferrin saturation, has hitherto been used as a proxy for the iron status of neonates. We investigated ...[more]

PMID: 31719592

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Project description:BackgroundNewborns delivered in healthcare facilities in low- and middle-income countries are at an increased risk of healthcare associated infections. Facility-based studies have focused primarily on healthcare worker behaviour during labour & delivery with limited attention to hygiene practices in post-natal care areas and largely ignore the wide variety of actors involved in maternal and neonatal care.MethodsThis exploratory mixed-methods study took place in six healthcare facilities in Nigeria where 31 structured observations were completed during post-natal care, discharge, and the first 6 hours after return to the home. Frequency of hand hygiene opportunities and hand hygiene actions were assessed for types of patient care (maternal and newborn care) and the role individuals played in caregiving (healthcare workers, cleaners, non-maternal caregivers). Qualitative interviews with mothers were completed approximately 1 week after facility discharge.ResultsMaternal and newborn care were performed by a range of actors including healthcare workers, mothers, cleaners and non-maternal caregivers. Of 291 hand hygiene opportunities observed at health facilities, and 459 observed in home environments, adequate hand hygiene actions were observed during only 1% of all hand hygiene opportunities. Adequate hand hygiene prior to cord contact was observed in only 6% (1/17) of cord contact related hand hygiene opportunities at healthcare facilities and 7% (2/29) in households. Discharge advice was infrequent and not standardised and could not be remembered by the mother after a week. Mothers reported discomfort around telling non-maternal caregivers to practice adequate hand hygiene for their newborn.ConclusionsIn this setting, hand hygiene practices during post-natal care and the first 6 hours in the home environment were consistently inadequate. Effective strategies are needed to promote safe hand hygiene practices within the post-natal care ward and home in low resource, high-burden settings. Such strategies need to target not just mothers and healthcare workers but also other caregivers.

Project description:Aim: Characterizing the response to myocardial infarction (MI) in the regenerative sheep fetus heart compared to the post-natal non-regenerative adolescent heart may reveal key morphological and molecular differences that equate to the response to MI in humans. We hypothesized that the immediate response to injury in (a) infarct compared with sham, and (b) infarct, border, and remote tissue, in the fetal sheep heart would be fundamentally different to the adolescent, allowing for repair after damage. Methods: We used a sheep model of MI induced by ligating the left anterior descending coronary artery. Surgery was performed on fetuses (105 days) and adolescent sheep (6 months). Sheep were randomly separated into MI (n = 5) or Sham (n = 5) surgery groups at both ages. We used magnetic resonance imaging (MRI), histological/immunohistochemical staining, and qRT-PCR to assess the morphological and molecular differences between the different age groups in response to infarction. Results: Magnetic resonance imaging showed no difference in fetuses for key functional parameters; however there was a significant decrease in left ventricular ejection fraction and cardiac output in the adolescent sheep heart at 3 days post-infarction. There was no significant difference in functional parameters between MRI sessions at Day 0 and Day 3 after surgery. Expression of genes involved in glucose transport and fatty acid metabolism, inflammatory cytokines as well as growth factors and cell cycle regulators remained largely unchanged in the infarcted compared to sham ventricular tissue in the fetus, but were significantly dysregulated in the adolescent sheep. Different cardiac tissue region-specific gene expression profiles were observed between the fetal and adolescent sheep. Conclusion: Fetuses demonstrated a resistance to cardiac damage not observed in the adolescent animals. The manipulation of specific gene expression profiles to a fetal-like state may provide a therapeutic strategy to treat patients following an infarction.

Dataset Information

Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

Publications

Hepcidin mediates hypoferremia and reduces the growth potential of bacteria in the immediate post-natal period in human neonates.

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