scholarly journals Use of Intranasal Insulin as Neuroprotection From Hyperglycemia in Rat Model of Extremely Preterm Infants

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A444-A444
Author(s):  
Lauren McClure Yauch ◽  
Kathleen Ennis ◽  
Ivan Tkac ◽  
Raghavendra Rao
Keyword(s):  
Preterm Infants ◽  
Neuronal Activity ◽  
Rat Model ◽  
Control Group ◽  
Intranasal Insulin ◽  
Long Term Effects ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Neurochemical Profile

Abstract Background: Hyperglycemia is common in extremely preterm infants (EPI) and is a risk factor for increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population. In a rat model of insulinopenic hyperglycemia, abnormal neurochemistry in the hippocampus was found, with lactate, glutamate (Glu):glutamine (Gln) ratio lower and Phosphorylated Creatinine (PCr):Creatinine (Cr) higher. Intranasal insulin has been shown to improve cognitive function in animal models of Alzheimer’s disease and type 2 diabetes mellitus, as well as in adult human studies of Alzheimer’s disease. No study has previous investigated the use of intranasal insulin on preventing the long-term effects of hyperglycemia in the EPI population. Objective: To determine whether administration of intranasal insulin during early postnatal days would negate the effects of hyperglycemia on the developing hippocampus in neonatal rat model of streptozotocin (STZ)-induced hyperglycemia. Design/Methods: STZ (80mg/kg IP) was injected on postnatal day (P) 2, and littermates in the control group were injected with an equivalent volume of citrate buffer. STZ pups were randomized to intranasal insulin, 3U twice daily from P3-P6 (STZ + INS) or left untreated (STZ). Neurochemical profile (consisting of 20 metabolites, PCr:Cr and Glu:Gln ratios) of the hippocampus was evaluated using ultra-high-field (9.4 T) magnetic resonance spectroscopy (MRS) on P7 (acute effects) and P56 (long-term effects) compared with the control group (CON)(N=6/group). Results: Mean glucose values from P3-P6 were higher in STZ groups (STZ = 279.0 +/- 132.2 mg/dL, STZ+INS = 274.4 +/- 89.5 mg/dL, CONT = 128.4 +/- 15.1 mg/dL). The neurochemical profile was different at both P7 and P56. On P7, compared with the control, the taurine (Tau) was higher in the STZ groups (p = 0.007. At P56, PCr:Cr was higher in the STZ group compared to CONT and STZ+INS groups (p = 0.04). No difference noted between the STZ+INS and CONT groups. No other metabolites were altered. Conclusion: Neonatal hyperglycemia alters the acute and long-term neurochemical profile in the hippocampus of developing rats. The increase in PCr:Cr ratio in the STZ group indicates lower demand for ATP and PCr, secondary to decreased neuronal activity, which has been demonstrated in previous studies. PCr:Cr ratio of the STZ+INS group was no different than control, indicating that intranasal insulin reverses the negative effect on neuronal activity caused by neonatal hyperglycemia.

Catheter Patency and Peritoneal Morphology and Function in a Rat Model of Citrate-Buffered Peritoneal Dialysis

2010 ◽  
Vol 30 (6) ◽  
pp. 602-610 ◽  
Author(s):  
Nicola Cavallini ◽  
Magnus Braide
Keyword(s):  
Peritoneal Dialysis ◽  
Rat Model ◽  
Fluid Transport ◽  
Separate Experiment ◽  
Control Group ◽  
Vascular Density ◽  
Long Term Effects ◽  
Catheter Patency ◽  
Peritoneal Morphology

BackgroundSingle-dwell studies in rats and humans have shown that supplementing citrate for lactate in peritoneal dialysis (PD) fluids improves ultrafiltration (UF).MethodsThe long-term effects of citrate-substituted PD fluids on PD catheter patency, UF, and peritoneal morphology were evaluated in a rat model over 5 weeks of daily PD fluid exposure. A standard 2.5% glucose 40 mmol/L lactate PD fluid and a corresponding 10/30 mmol/L citrate/lactate PD fluid were compared. In a control group, rats with catheters received no PD fluid.ResultsThe average patency time (% of 36 days) of silicone rubber PD catheters was significantly longer in the citrate PD group (98.8% ± 1.2%) and the control group (100% ± 0%) compared to the lactate PD group (54.7% ± 9.5%). In a separate experiment, heparin-coated polyurethane catheters were used to study peritoneal morphology and fluid transport. The citrate group had a higher net UF than the lactate group at the beginning and at the end of the 5 weeks. During the experiment, both fluid-treated groups suffered from UF loss; the control group showed the highest net UF at the end of the 5 weeks. Peritoneal vascular density and submesothelial thickness, indicators of angiogenesis and fibrosis, were not significantly different among the groups. Fibrosis was significantly negatively correlated to osmotic UF.ConclusionA positive acute effect of citrate on UF was confirmed and conserved over time. Citrate PD strongly improved PD catheter patency time compared with lactate. Both citrate PD and lactate PD induced negative long-term effects on UF compared with control animals.

Factors associated with long-term mechanical ventilation in extremely preterm infants

2018 ◽  
Vol 11 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Lina Yossef ◽  
Edward G. Shepherd ◽  
Susan Lynch ◽  
Kristina M. Reber ◽  
Leif D. Nelin
Keyword(s):  
Mechanical Ventilation ◽  
Preterm Infants ◽  
Factors Associated ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

scholarly journals Short- and Long-Term Outcomes of Extremely Preterm Infants in Japan According to Outborn/Inborn Birth Status*

2019 ◽  
Vol 20 (10) ◽  
pp. 963-969 ◽  
Author(s):  
Yoshihito Sasaki ◽  
Kaoru Ishikawa ◽  
Akira Yokoi ◽  
Tomoaki Ikeda ◽  
Kazuo Sengoku ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Long Term Outcomes ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Short And Long Term

scholarly journals Bronchopulmonary Dysplasia: Can We Agree on a Definition?

2018 ◽  
Vol 35 (06) ◽  
pp. 537-540 ◽  
Author(s):  
Deepak Jain ◽  
Eduardo Bancalari
Keyword(s):  
Respiratory Failure ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Nasal Cannula ◽  
Clinical Practices ◽  
Unique Challenge ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Respiratory Outcomes

AbstractThe advances in obstetric and neonatal care over the last half century have resulted in changes in pathophysiology and clinical presentation of bronchopulmonary dysplasia (BPD). In contrast to the original description of BPD by Northway et al as a severe lung injury in relatively mature preterm infants, the most common form of BPD currently is characterized by chronic respiratory insufficiency in extremely preterm infants. This evolution in the presentation of BPD, along with changes in respiratory support strategies such as increased use of nasal cannula oxygen, has presented a unique challenge to find a definition that describes the severity of lung damage and predict the long-term respiratory outcomes with some accuracy.The limitations of current definitions of BPD include inconsistent correlation with long-term respiratory outcomes, inability to classify infants dying from severe respiratory failure prior to 36 weeks' postmenstrual age, and potential inappropriate categorization of infants on nasal cannula oxygen or with extrapulmonary causes of respiratory failure. In the long term, the aim for a new definition of BPD is to develop a classification based on the pathophysiology and objective lung function evaluation providing a more accurate assessment for individual patients. Until then, a consensus definition that encompasses current clinical practices, provides reasonable prediction of later respiratory outcomes, and is relatively simple to use should be achieved.

Early inhaled budesonide in extremely preterm infants decreases long‐term respiratory morbidity

2020 ◽  
Vol 55 (5) ◽  
pp. 1124-1130 ◽  
Author(s):  
Jana Tukova ◽  
Jan Smisek ◽  
Blanka Zlatohlavkova ◽  
Richard Plavka ◽  
Daniela Markova
Keyword(s):  
Preterm Infants ◽  
Respiratory Morbidity ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Inhaled Budesonide

scholarly journals Effects of Early Vocal Contact in the Neonatal Intensive Care Unit: Study Protocol for a Multi-Centre, Randomised Clinical Trial

2021 ◽  
Vol 18 (8) ◽  
pp. 3915
Author(s):  
Manuela Filippa ◽  
Elisa Della Casa ◽  
Roberto D’amico ◽  
Odoardo Picciolini ◽  
Clara Lunardi ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Neonatal Intensive Care Unit ◽  
Preterm Infants ◽  
Neonatal Intensive Care ◽  
Sensitive Period ◽  
Control Group ◽  
Long Term Effects ◽  
Infant Neurodevelopment

Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and environmental factors, as they are exposed to an atypical auditory environment and simultaneously, long periods of early separation from their parents. The short-term effects of early vocal contact (EVC) on an infant’s early stability have been investigated. However, there is limited evidence of its impact on the infant’s autonomic nervous system maturation, as indexed by heart rate variability, and its long-term impact on infant neurodevelopment. Our multi-centric study aims to investigate the effects of EVC on a preterm infant’s physiology, neurobehaviour, and development. Eighty stable preterm infants, born at 25–32 weeks and 6 days gestational age, without specific abnormalities, will be enrolled and randomised to either an intervention or control group. The intervention group will receive EVC, where mothers will talk and sing to their infants for 10 min three times per week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator and observe the infant’s behaviour through a standard cluster of indicators. Infants will be assessed at baseline; the end of the intervention; term equivalent age; and 3, 6, 12, and 24 months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Early interventions in the neonatal intensive care unit have demonstrated effects on the neurodevelopment of preterm infants, thereby lowering the negative long-term effects of an atypical auditory and interactional environment. Our proposed study will provide new insight into mother–infant early contact as a protective intervention against the sequelae of prematurity during this sensitive period of development. Early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and maternal sensitivity and stress are still unclear. Trial Registration: NCT04759573, retrospectively registered, 17 February 2021.

scholarly journals Extreme Prematurity and Pulmonary Outcomes Program in Saitama (EPOPS): A Study Protocol of a Prospective Multicenter Cohort Study of Extremely Preterm Infants in Japan (Preprint)

2020 ◽  
Author(s):  
Fumihiko Namba ◽  
Kosuke Tanaka ◽  
Sayu Omori ◽  
Kazushige Ikeda ◽  
Ken Kawabata ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Infants ◽  
Developed Countries ◽  
Respiratory Morbidity ◽  
Extreme Prematurity ◽  
Multicenter Cohort Study ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Definition Of

UNSTRUCTURED Introduction: Because of the improvements in survival rates for preterm infants, not only the rates of bronchopulmonary dysplasia (BPD) but also that of long-term respiratory complications of premature birth are increasing, which results in financial and health burdens in developed countries. Thus far, risk factors of respiratory morbidities of extremely preterm infants remain unknown. Furthermore, the definition, as well as the predictive ability, of BPD for long-term respiratory outcomes are yet to be determined. Therefore, Extreme Prematurity and Pulmonary Outcomes Program in Saitama (EPOPS) aims to develop the diagnostic criteria for BPD and to determine the prognostic factors contributing to the long-term pulmonary outcomes manifested in extremely preterm infants. Methods and analysis: The EPOPS is an observational prospective cohort study performed by a consortium of six neonatal intensive care units (NICUs) in Saitama, Japan. The subjects included in this study were infants (from each clinical center) with gestational ages 22 to 27 weeks, having an expected target of 400 subjects. This study aims to determine the definition of BPD and other perinatal factors which accurately predict the long-term pulmonary outcomes in survivors of extreme prematurity. Moreover, association between BPD and post-prematurity respiratory disease (PRD) will also be investigated using generalized linear models. Discussion: The EPOPS incorporates the aspects of neonatal care in secondary- and tertiary-level NICUs to develop the existing research studies on the definition of BPD, objective biomarkers, and outcome measures of respiratory morbidity in extremely preterm infants beyond the NICU hospitalization, thereby leading to a novel understanding of the nature and natural history of BPD and of potential mechanistic and therapeutic targets among at-risk subjects. Ethics and Dissemination: The protocol and consent forms were evaluated and approved by institutional review boards at each EPOPS center. Registration details: Not registered because of an observational study without any interventions.

scholarly journals Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants. A protocol for the SafeBoosC randomised clinical phase III trial

2019 ◽  
Author(s):  
Mathias Hansen ◽  
Adelina Pellicer ◽  
Christian Gluud ◽  
Eugene Dempsey ◽  
Jonathan Mintzer ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Preterm Infants ◽  
Near Infrared ◽  
Control Group ◽  
Severe Brain Injury ◽  
Treatment As Usual ◽  
Opt Out ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Postmenstrual Age

Abstract Background: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC-III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants. Methods/Design: SafeBoosC III is an investigator-initiated multinational randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using ‘opt-out’ or deferred consent). Exclusion criteria will be no parental informed consent (or if ‘opt-out’ is used, lack of record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record of parents’ decision to opt-out in the infants clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 hours after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 hours of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants. Discussion: Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates. Trial registration: ClinicalTrial.gov NCT03770741 (registered 10/12-2018), https://clinicaltrials.gov/ct2/show/NCT03770741?recrs=b&cond=cerebral+near+infrared+spectroscopy&rank=3

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