Neurodevelopmental Outcomes at Age 5 Years After Prophylactic Early High-Dose Recombinant Human Erythropoietin for Neuroprotection in Very Preterm Infants

Natalucci, Giancarlo; Latal, Bea; Koller, Brigitte; Rüegger, Christoph M.; Sick, Beate; Held, Leonhard; Fauchère, Jean‐Claude

doi:10.1001/jama.2020.19395

Cited by 21 publications

(16 citation statements)

References 6 publications

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“…However, more recently, a randomized, double-blind trial of high-dose rEpo administered to extremely preterm infants from 24 h after birth until 32 weeks post menstrual age, had no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age [ 71 ]. Further, a similar study of 448 infants randomized to receive repeated doses of rEpo started within 3 h of very preterm birth found no effect on neurodevelopmental outcomes at 2 and 5 years of age [ 72 , 73 ]. It is possible that the relatively delayed start (within 24 h) and infrequent dosing regimen in Juul et al [ 71 ] may have contributed to the lack of neuroprotection seen in this study as infants received 1000 IU/Kg rEpo every 48 h for a total of 6 doses followed by 400 IU/Kg 3 times per week, whereas the study in preterm fetal sheep showing partial neuroprotection used early initiation of treatment at 30 min and a prolonged infusion to maintain a stable plasma rEpo concentration [ 118 ].…”

Section: Potential Neuroprotective Treatments That Have Been Invesmentioning

confidence: 99%

Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

Yates

Gunn

Bennet

et al. 2021

IJMS

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Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.

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Section: Potential Neuroprotective Treatments That Have Been Invesmentioning

confidence: 99%

Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

Yates

Gunn

Bennet

et al. 2021

IJMS

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“…There were no beneficial effects on any secondary outcomes. While significantly improved neurodevelopment at the age of 3.5 to 4 years has been reported in one RCT ( 11 ), prophylactic high-dose rhEPO had no effect on cognitive scores at 5 years of age in a large Swiss RCT ( 12 ).…”

Section: Discussionmentioning

confidence: 87%

Prophylactic Erythropoietin for Neuroprotection in Very Preterm Infants: A Meta-Analysis Update

et al. 2021

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“…Studies have shown that DR occurs in both type 1 diabetes and type 2 diabetes[ 41 ]. With the increase in the number of diabetic patients, DR has become the main cause of visual impairment in diabetic patients[ 42 ]. The whole pathological process of DR includes important pathological changes such as loss of retinal capillary pericytes, thickening of basement membrane, loss of endothelial barrier function, destruction of blood-retinal barrier, and lead to retinal ischemia, which will increase the level of VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a change in EPO expression is considered as an important factor affecting the retinopathy of prematurity. EPO treatment can effectively protect the nervous system and optic nerve development of premature infants[ 42 , 43 ]. HIF-1α is stably expressed under hypoxia; it can regulate EPO and VEGF expression and promote RNV[ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

Yu¹,

Ren²,

Chen³

2021

WJD

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BACKGROUND As one of the major microvascular complications of diabetes, diabetic retinopathy (DR) is the leading cause of blindness in the working age population. Because the extremely complex pathogenesis of DR has not been fully clarified, the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization (RNV) has great harm to the visual acuity of patients. AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA (piRNA) in proliferative DR mice and select piRNA related to RNV. METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group (CG) and proliferative DR (PDR) group as experimental group (EG), with 50 mice in each group. Samples were collected from both groups at the same time, and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining. The retinal tissues were collected for second-generation high-throughput sequencing, and the differentially expressed piRNA between the CG and EG was detected, and polymerase chain reaction (PCR) was conducted for verification. The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes. RESULTS In the CG there was no perfusion area, neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap. In the EG, there were a lot of nonperfused areas, new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina. There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups. High-throughput sequencing analysis showed that compared with the CG, a total of 79 piRNAs were differentially expressed in EG, among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated. Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation. Ten piRNAs were selected for PCR, and the results showed that the expression of piR-MMU-40373735, piR-MMU-61121420, piR-MMU-55687822, piR-MMU-1373887 were high, and the expression of piR-MMU-7401535, piR-MMU-4773779, piR-MMU-1304999, and piR-MMU-5160126 were low, which were consistent with the sequencing results. CONCLUSION In the EG, the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation, suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.

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Neurodevelopmental Outcomes at Age 5 Years After Prophylactic Early High-Dose Recombinant Human Erythropoietin for Neuroprotection in Very Preterm Infants

Abstract: rapid-exercise-tests-for-exertional-desaturation-in-covid-19/ 6. Rodríguez-Molinero A, Narvaiza L, Ruiz J, Gálvez-Barrón C. Normal respiratory rate and peripheral blood oxygen saturation in the elderly population.

Cited by 21 publications

References 6 publications

Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

Prophylactic Erythropoietin for Neuroprotection in Very Preterm Infants: A Meta-Analysis Update

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

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