Iron deficiency, with or without anemia, is common in pregnant women. In fact, nearly 30% of reproductive-age women are anemic worldwide, and anemia in pregnancy has an estimated global prevalence of ...38%. Severe anemia can substantially increase the risk of maternal mortality, and can adversely affect fetal development. In this review, we examine the available data regarding epidemiology and consequences of iron deficiency in mothers and infants, current treatment strategies, and make recommendations for screening and treatment of iron deficiency anemia in gravidas and neonates.
Certain groups of neonates are at high risk of developing long-term neurodevelopmental impairment and might be considered candidates for neuroprotective interventions. This article explores some of ...these high-risk groups, relevant mechanisms of brain injury, and specific mechanisms of cellular injury and death. The potential of erythropoietin (Epo) to act as a neuroprotective agent for neonatal brain injury is discussed. Clinical trials of Epo neuroprotection in preterm and term infants are updated.
Abstract Background In the last two decades, there has been considerable evolution in understanding the role of erythropoietin in neuroprotection. Erythropoietin has both paracrine and autocrine ...functions in the brain. Erythropoietin binding results in neurogenesis, oligodendrogenesis, and angiogenesis. Erythropoietin and its receptor are upregulated by exposure to hypoxia and proinflammatory cytokines after brain injury. While erythropoietin aids in recovery of locally injured neuronal cells, it provides negative feedback to glial cells in the penumbra, thereby limiting extension of injury. This forms the rationale for use of recombinant erythropoietin and erythropoietin mimetics in neonatal and adult injury models of stroke, traumatic brain injury, spinal cord injury, intracerebral hemorrhage, and neonatal hypoxic ischemia. Method Review of published literature (Pubmed, Medline, and Google scholar). Results Preclinical neuroprotective data are reviewed, and the rationale for proceeding to clinical trials is discussed. Results from phase I/II trials are presented, as are updates on ongoing and upcoming clinical trials of erythropoietin neuroprotection in neonatal populations. Conclusions The scientific rationale and preclinical data for erythropoietin neuroprotection are promising. Phase II and III clinical trials are currently in process to determine the safety and efficacy of neuroprotective dosing of erythropoietin for extreme prematurity and hypoxic-ischemic encephalopathy in neonates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy.
In a phase II ...double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7.00 or base deficit ≥15, or resuscitation at 10 minutes); and received hypothermia. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation. Two independent observers rated MRI brain injury severity by using an established scoring system.
The mean age at first study drug was 16.5 hours (SD, 5.9). Neonatal deaths did not significantly differ between Epo and placebo groups (8% vs 19%, P = .42). Brain MRI at mean 5.1 days (SD, 2.3) showed a lower global brain injury score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epo-treated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05).
High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.
Objectives To determine the risks and benefits associated with the transfusion of packed red blood cells (PRBCs) in extremely low birth weight (ELBW) infants. We hypothesized that when ELBW infants ...underwent transfusion with the University of Washington Neonatal Intensive Care Unit (NICU) 2006 guidelines, no clinical benefit would be discernible. Study design We conducted a retrospective chart review of all ELBW infants admitted to the NICU in 2006. Information on weight gain, apnea, heart rate, and respiratory support was collected for 2 days preceding, the day of, and 3 days after PRBC transfusion. The incidence, timing, and severity of complications of prematurity were documented. Results Of the 60 ELBW infants admitted to the NICU in 2006, 78% received PRBC transfusions. Transfusions were not associated with improved weight gain, apnea, or ventilatory/oxygen needs. However, they were associated with increased risk of bronchopulmonary dysplasia, necrotizing enterocolitis, and diuretic use ( P < .05). Transfusions correlated with phlebotomy losses, gestational age, and birth weight. No association was found between transfusions and sepsis, retinopathy of prematurity, or erythropoietin use. Conclusions When our 2006 PRBC transfusion guidelines were used, no identifiable clinical benefits were identified, but increased complications of prematurity were noted. New, more restrictive guidelines were developed as a result of this study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Iron is an essential micronutrient. The majority of iron in the body is used for the production of heme in erythrocytes; however, in the developing neonatal brain, it also plays keys roles in ...synaptogenesis, neurotransmitter production, and myelination 1 . Iron deficiency during critical periods of brain development has been associated with adverse neurodevelopmental outcomes in both preclinical models of iron deficiency 2 and in clinical studies 3 . These neurodevelopmental outcomes may be irreversible despite achieving later iron sufficiency with iron supplementation 3 . Maintaining iron sufficiency for neonates in the neonatal intensive care unit is therefore recognized as an essential part of neonatal neurocritical care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UPCLJ, UPUK, ZAGLJ, ZRSKP
Iron is critical for brain development, playing key roles in synaptogenesis, myelination, energy metabolism and neurotransmitter production. NICU infants are at particular risk for iron deficiency ...due to high iron needs, preterm birth, disruptions in maternal or placental health and phlebotomy. If deficiency occurs during critical periods of brain development, this may lead to permanent alterations in brain structure and function which is not reversible despite later supplementation. Children with perinatal iron deficiency have been shown to have delayed nerve conduction speeds, disrupted sleep patterns, impaired recognition memory, motor deficits and lower global developmental scores which may be present as early as in the neonatal period and persist into adulthood. Based on this, ensuring brain iron sufficiency during the neonatal period is critical to optimizing neurodevelopmental outcomes and iron supplementation should be targeted to iron measures that correlate with improved outcomes.
A working model for hypothermic neuroprotection Wassink, Guido; Davidson, Joanne O.; Lear, Christopher A. ...
The Journal of physiology,
1 December 2018, Volume:
596, Issue:
23
Journal Article
Peer reviewed
Open access
Therapeutic hypothermia significantly improves survival without disability in near‐term and full‐term newborns with moderate to severe hypoxic–ischaemic encephalopathy. However, hypothermic ...neuroprotection is incomplete. The challenge now is to find ways to further improve outcomes. One major limitation to progress is that the specific mechanisms of hypothermia are only partly understood. Evidence supports the concept that therapeutic cooling suppresses multiple extracellular death signals, including intracellular pathways of apoptotic and necrotic cell death and inappropriate microglial activation. Thus, the optimal depth of induced hypothermia is that which effectively suppresses the cell death pathways after hypoxia–ischaemia, but without inhibiting recovery of the cellular environment. Thus mild hypothermia needs to be continued until the cell environment has recovered until it can actively support cell survival. This review highlights that key survival cues likely include the inter‐related restoration of neuronal activity and growth factor release. This working model suggests that interventions that target overlapping mechanisms, such as anticonvulsants, are unlikely to materially augment hypothermic neuroprotection. We suggest that further improvements are most likely to be achieved with late interventions that maximise restoration of the normal cell environment after therapeutic hypothermia, such as recombinant human erythropoietin or stem cell therapy.
The progressive phases of perinatal brain damage after severe hypoxia–ischaemia, and how interventions (i.e. hypothermia, recombinant human erythropoietin (rEpo) and stem cells) interact with deleterious processes induced in these phases. Therapeutic cooling is effective at suppressing damaging mechanisms in the latent and second phases, including inflammation and withdrawal of trophic factors, which helps stabilise neural mitochondria and so provides neuroprotection. This hypothermia‐induced suppression should be continued until cellular homeostasis and prosurvival signalling (e.g. growth factor and electroencephalogram (EEG) restoration) have recovered. Future research should focus on preclinical treatments that further support these survival cues and suppress long‐lasting injurious processes (i.e. persistent inflammation and epigenetic changes) in the third phase. rEpo and stem cells are promising candidates.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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