Benefits of a Standardized Enteral Feeding Protocol on the Nutrition and Health Outcomes of Very Low Birth Weight Preterm Infants.

Purpose: To compare nutrition and health outcomes before and after implementing a standardized enteral feeding protocol on nutrition and health outcomes in very low birth weight preterm infants.Methods: A retrospective chart review was performed evaluating preterm infants, born less than 34 weeks gestation and weighing less than 1500 g, before and after the implementation of a standardized enteral feeding protocol. Outcomes included weaning of parenteral nutrition, initiation and advancement of enteral feeds, initiation of human-milk fortifier (HMF), change in weight z-score and neonatal morbidities.Results: Fifty-six infants (30 in pre-group, 26 in post-group) met the inclusion criteria. Infants in the standardized enteral feeding protocol group started enteral feeds earlier (p = 0.039) and received full HMF fortification at lower weights (p = 0.033) than those in the pre-group. Fewer days on continuous positive airway pressure (p = 0.021) and lower rates of bronchopulmonary dysplasia (p = 0.018) were also observed in the post-group. Weaning of parenteral nutrition and weight z-score were not significantly different between groups. There were no differences in other morbidities.Conclusion: Study results suggest that adopting a standardized enteral feeding protocol may promote early initiation of enteral feeds and fortification.

Evaluation of Methods of Breast or Bottle Feeding on Length of Hospitalization of Preterm Infants.

Background: Direct breastfeeding is the optimal method of nourishing preterm infants. Preconceived notions exist among health practitioners that establishment of direct breastfeeding lengthens hospitalization. Thus far, the aforementioned association remains unknown. Research Aim: The objective of this study was to assess the impact of direct breastfeeding establishment on length of hospital stay in preterm infants. Methods: A retrospective chart review on a sample of 101 mother-infant dyads was conducted in the neonatal intensive care unit at Kingston Health Sciences Center (KHSC) in Ontario, Canada. The sample consisted of three groups: (1) modified direct breastfeeding group, defined as infants receiving ≥50% direct breastfeeds during hospitalization, (2) partial breastfeeding group, defined as infants receiving <50% breastfeeds during hospitalization, and (3) bottle feeding group, defined as infants only receiving bottle feeds during hospitalization. A multiple linear regression model was performed to assess the relationship between length of hospitalization and method of oral feeds (modified direct breastfeeds vs. partial breastfeeds vs. bottle feeds) while controlling for infant (gestational age [GA], birth weight, 5 minutes Apgar score, ventilator support) and maternal (age, first-time mother, mental health conditions) factors. Results: GA was inversely associated with length of hospitalization. The number of days on ventilator support was positively associated with length of hospitalization. Method of oral feed, birth weight, 5 minutes Apgar score, maternal age, first-time mother status, and maternal mental health conditions were not associated with duration of hospitalization. Conclusions: Direct breastfeeding establishment does not lengthen hospitalization in preterm infants. This finding may aid health practitioners in increasing direct breastfeeding success in this population.

Determinants of Successful Direct Breastfeeding at Hospital Discharge in High-Risk Premature Infants.

BACKGROUND: Despite a mother's intention to breastfeed, there are many barriers to feeding preterm infants that decrease breastfeeding rates. OBJECTIVE: The objective of this research was to determine factors associated with successful direct breastfeeding (DBF) of the preterm infant at hospital discharge. MATERIALS AND METHODS: A retrospective chart review of 69 preterm (<34 weeks' gestational age) infants in the neonatal intensive care unit, whose mothers intended to breastfeed, was conducted. Infant-, mother-, and feeding-related factors were examined by chi-square or t test for their relationship with breastfeeding success, and by multiple logistic regression to identify predictive factors. RESULTS: Successful DBF at discharge occurred in 64%. Mothers of infants who were breastfed were older (p < 0.0001); had less psychiatric illness (p = 0.03); and were less likely to smoke (p < 0.0001) and use recreational drugs (p = 0.04). The infants had higher birth weights (p = 0.03) and lower incidence of bronchopulmonary dysplasia (p = 0.04). A higher proportion of infants received DBF at their first oral feed (p < 0.001), and were discharged earlier (p = 0.03). Reduced milk supply was cited for breastfeeding failure in 36%. Older maternal age (odds ratio [OR] = 1.24, 95% confidence interval [CI] 1.02-1.51) and DBF at the first oral feed (OR = 7.72, 95% CI 1.37-43.6) were associated with successful DBF at discharge. CONCLUSION: Maternal age and method of first oral feed are critical predictors of breastfeeding success in preterm infants. Mothers should be encouraged to breastfeed at the infant's first oral attempt and strategic breastfeeding support should be provided before initiation of oral feeding.

Does the use of oral nonabsorbable antifungal prophylaxis reduce the incidence of fungal colonization and/or systemic infection in preterm infants?

BACKGROUND: Invasive fungal infection is a significant cause of mortality and morbidity in preterm infants. Oral nonabsorbable agents are used prophylactically, but the literature regarding their effectiveness has not been systematically reviewed. OBJECTIVE: To determine if oral nonabsorbable antifungal prophylaxis reduces the incidence of fungal colonization and/or systemic infection in preterm infants. METHODS: The literature was reviewed using the methodology for systematic reviews for the Consensus on Resuscitation Science adapted from the American Heart Association's International Liaison Committee on Resuscitation. RESULTS: Five studies were reviewed. Three level of evidence 1 studies and two level of evidence 3/4 studies provided evidence that the prophylactic use of oral nonabsorbable antifungal agents can reduce the incidence of fungal colonization and/or systemic fungal infection in preterm infants. CONCLUSION: Prophylactic oral nonabsorbable antifungal medications are an acceptable approach to reduce colonization and invasive fungal infection in preterm infants in units with high baseline colonization rates.

HISTORIQUE: L'infection fongique envahissante est une cause importante de mortalité et de morbidité chez les nourrissons prématurés. Des agents oraux non absorbables sont utilisés en prophylaxie, mais les publications portant sur leur efficacité n'ont fait l'objet d'aucune analyse systématique. OBJECTIF: Déterminer si une prophylaxie antifongique orale non absorbable réduit l'incidence de colonisation fongique ou d'infection systémique chez les nourrissons prématurés. MÉTHODOLOGIE: Les chercheurs ont analysé les publications au moyen de la méthodologie d'analyse systématique du consensus sur la science de la réanimation adaptée du comité de liaison international sur la réanimation de l'American Heart Association. RÉSULTATS: Les chercheurs ont analysé cinq études. Trois études dont la qualité de preuve était de catégorie 1 et deux études dont la qualité de preuve était de catégorie 3 ou 4 ont démontré que l'utilisation prophylactique d'antifongiques oraux non absorbables peut réduire l'incidence de colonisation fongique ou d'infection fongique systémique chez les nourrissons prématurés. CONCLUSION: Une prophylaxie antifongique orale non absorbable est une démarche acceptable pour réduire la colonisation et l'infection fongique envahissante chez les nourrissons prématurés hospitalisés dans une unité où le taux de colonisation de base est élevé.

Hyperthermia amplifies brain cytokine and reactive oxygen species response in a model of perinatal inflammation.

Chorioamnionitis, a perinatal infection of the fetal membranes, and maternal fever, which often accompanies infection are both risk factors for cerebral palsy (CP). Inflammation is a typical reaction to infection. Thus the aim of this study was to determine if hyperthermia alters newborn rat brain inflammatory response and oxidant stress after a maternal rat lipopolysaccaharide (LPS) injection. Since chorioamnionitis can predispose the fetus to perinatal hypoxia, we also explored the interaction with postnatal hypoxia. Exposure of newborn pups to brief hypoxia alone significantly increased brain tumor necrosis factor-alpha (TNF-alpha) and slightly increased levels of nitrite/nitrate. When maternal LPS was combined with postnatal hypoxia, the levels of TNF-alpha in were further increased when compared with hypoxia alone. Exposure of newborn pups to hyperthermia at 39 degrees C following maternal LPS and hypoxia caused yet more significant increases in brain TNF-alpha, nitrite/nitrate, and MDA/4-HAD compared to that under normal temperature conditions. This study supports the hypothesis that fever is a significant modifier of brain inflammatory response in developing brain particularly in a setting of hypoxia.

Corticotropin-releasing hormone potentiates neural injury induced by oxygen-glucose deprivation: a possible involvement of microglia.

While corticotropin-releasing hormone (CRH) has been implicated in a variety of brain disorders such as ischemic injury, the molecular mechanism by which CRH elicits its activities is largely unclear. In the present study, we have determined the effect of CRH on oxygen-glucose deprivation (OGD) induced apoptosis in fetal hippocampal neurons. CRH alone at concentrations of 10-200 nM had no effect on neuronal apoptosis. However, when neurons were co-cultured with microglia, CRH alone at concentrations greater than 100 nM induced neuronal apoptosis and CRH potentiated significant neuronal apoptosis following exposure to OGD. The effect of CRH on neuronal apoptosis was inhibited in the presence of the CRH antagonist astressin. Real-time RT-PCR revealed an increase in mRNA levels of Fas ligand (Fas-L), a membrane protein related to the TNF family, in cultured microglia following OGD exposure. In the presence of CRH, OGD-induced Fas-L expression was significantly increased. The effect of CRH on Fas-L expression was inhibited by specific inhibitors of the extracellular signal-regulated protein kinase (PD98059) and p38 mitogen-activated protein kinase (SB203580). These results suggest that CRH potentiates neuronal apoptosis induced by OGD in the presence of microglia and that this effect may be mediated through the induction of proinflammatory mediators in microglia.

Systemic adrenocorticotropic hormone administration down-regulates the expression of corticotropin-releasing hormone (CRH) and CRH-binding protein in infant rat hippocampus.

Systemic adrenocorticotropic hormone (ACTH) administration is a first-line therapy for the treatment of infantile spasms, an age-specific seizure disorder of infancy. It is proposed that exogenous ACTH acts via negative feedback to suppress the synthesis of corticotropin-releasing hormone (CRH), a possible endogenous convulsant in infant brain tissue. The aim of this study was to determine whether systemic ACTH treatment in infant rats down-regulates the hippocampal CRH system, including CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R1 and CRH-R2). Daily i.p. injection of ACTH for 7 consecutive days (postnatal days 3-9) elevated serum corticosterone levels 20-fold measured on postnatal day 10, indicating systemic absorption and circulation of the ACTH. Semiquantitative reverse transcriptase-PCR demonstrated that both CRH and CRH-BP mRNA obtained from the hippocampi of ACTH-injected infant rats was significantly depressed relative to saline-injected animals. Comparable reductions in both CRH and CRH-BP synthesis were further demonstrated with radioimmunoassay. In contrast, neither CRH-R1 nor CRH-R2 mRNA was altered by ACTH treatment, relative to saline-injected rats. This latter finding was confirmed electrophysiologically by measuring the enhancement of hippocampal population spikes by exogenous CRH, also showing no differences between ACTH- and saline-injected rats. The results of this study support the proposal that systemic ACTH treatment down-regulates CRH expression in infant brain, perhaps contributing to the therapeutic efficacy observed during treatment of infantile spasms.

Corticotropin-releasing hormone induces proliferation and TNF-alpha release in cultured rat microglia via MAP kinase signalling pathways.

We have previously demonstrated that corticotropin-releasing hormone (CRH) receptor 1 (CRH-R1) is functionally expressed in rat microglia. In the present study, we show that CRH, acting on CRH-R1, promoted cell proliferation and tumour necrosis factor-alpha (TNF-alpha) release in cultured rat microglia. Exogenous CRH resulted in an increase in BrdU incorporation compared with control cells, which was observed in a range of concentrations of CRH between 10 and 500 nm, with a maximal response at 50 nm. The effect of CRH on BrdU incorporation was inhibited by a CRH antagonist astressin but not by a cAMP-dependent protein kinase inhibitor H89. Exposure of microglial cells to CRH resulted in a transient and rapid increase in TNF-alpha release in a dose-dependent manner. In the presence of astressin, the effects of CRH on TNF-alpha release were attenuated. CRH effects on TNF-alpha release were also inhibited by specific inhibitors of MEK, the upstream kinase of the extracellular signal-regulated protein kinase (ERK) (PD98059) or p38 mitogen-activated protein kinase (SB203580), but not by H89. Furthermore, CRH induced rapid phosphorylation of ERK and p38 kinases. Astressin, PD98059, and SB230580 were able to inhibit CRH-induced kinase phosphorylation. These results suggest that CRH induces cell proliferation and TNF-alpha release in cultured microglia via MAP kinase signalling pathways, thereby providing insight into the interactions between CRH and inflammatory mediators.

Functional expression of corticotropin-releasing hormone (CRH) receptor 1 in cultured rat microglia.

Corticotropin-releasing hormone (CRH), known as a key regulator of the hypothalamic-pituitary-adrenal axis response to stress, elicits its biological effects by binding to two membrane receptors (CRH-R1 and CRH-R2). The present studies examined the presence of functional expression of CRH receptors in cultured microglia of rat. CRH-R1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR), western blotting and receptor chemical cross-linking assay in cultured microglia. CRH-R2 mRNA was undetectable by RT-PCR. The radioligand binding analysis using [125I]Tyr-rat/human CRH revealed a high affinity binding site (Kd of 1.2 nm and Bmax of 84 fmol/mg of protein). Competition studies using CRH and related peptides indicated kinetic and pharmacological characteristics consistent with the CRH-R1 receptor subtype. Receptor chemical cross-linking assay demonstrated a single band of CRH receptor with a molecular weight of -77 kDa, which was inhibited in the presence of excess unlabeled rat/human CRH in a dose-dependent manner and inhibited by a CRH receptor antagonist astressin. Functional coupled cAMP production in cultured microglia was stimulated by exogenous addition of CRH and related peptides in a dose-dependent manner and blocked by astressin. Our findings suggest the functional expression of CRH-R1 receptor in rat microglia, indicating an important mechanism of interaction between immune and neuroendocrine systems in brain physiological and pathological conditions.