OBJECTIVES-Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results.METHODS-We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998-2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (≥5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death.RESULTS-Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1-36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%-85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death. Copyright © 2009 by the American Academy of PediatricsAddress correspondence to C. Michael Cotten, MD, MHS, PO Box 3179, Duke University, Durham, NC 27710. E-mail: cotte010@mc.duke.edu. The authors have indicated they have no financial relationships relevant to this article to disclose.Reprints Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2010 January 1. Published in final edited form as:Pediatrics. Antibiotics are the most commonly prescribed medications in intensive care nurseries. 1,2 Virtually all extremely low birth weight (ELBW) infants (birth weight of <1000 g) admitted to intensive care nurseries receive empirical antibiotic treatment in the first postnatal days, although cultures from normally sterile sites usually do not yield any bacterial agents and the incidence of culture-proven bacterial sepsis is low in this population. 2,3 A previous study suggested that selection of cefotaxime instead of gentamycin for the first 3 postnatal days was associated with higher mortality risk, even for the most preterm infants. 2 In addition to selecting which antibiotics to use for initial th...
The synbiotic preparation colonized quickly after 3 days of administration and the infants stayed colonized for several months after therapy was stopped. There was an increase in bacterial diversity and gram-positive organisms and a reduction of gram-negative bacterial load in the treatment group. Because a combination preparation was used, it is difficult to specifically attribute the colonization to either the probiotic or prebiotic component in this study. Larger efficacy trials are warranted to examine the mechanism of action and precise effects of these supplements.
Cytokines mediate the host immune response to infectious microorganisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6 and IL-10) and inflammatory cytokines (Interferon-[INF-], tumor necrosis factor-[TNF-], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the 5 sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (P=0.01), and higher levels of the regulatory cytokines, IL-6 (P=0.01) and IL-10 (P<0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population.
Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.
At 18 to 22 months' corrected age, extremely low birth weight infants born with major anomalies have nearly twice the risk for neurodevelopmental impairment, increased risk of poor growth, and > 3 times greater risk of rehospitalization when compared with extremely low birth weight infants without major anomalies. This information may be valuable for counseling parents regarding the outcomes of these infants and for the facilitation of appropriate support and intervention services.
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