Search

Introduction: Diabetes in pregnancy is associated with impaired offspring cardiac function. The objective of this systematic review was to determine the effect of diabetes in pregnancy on cardiac function in the offspring measured by echocardiography., Methods: PubMed, Embase, Cochrane CENTRAL and Web of Science databases were searched from 1992 to June 27, 2023. Studies reporting offspring (age < 18 years) cardiac function by echocardiography compared between any type of diabetes in pregnancy and healthy control pregnancies were included. Study selection, quality assessment and risk of bias was independently performed by two reviewers. Meta-analyses was performed where possible., Results: Thirty-one observational studies were included 1,679 cases and 2,694 controls. In the first week of life (23 studies, n  = 2,663), intraventricular septum diastolic diameter (hypertrophy) was increased, while myocardial performance index (global function) and LV E/A-ratio (diastolic function) were decreased. No difference was found for left ventricular ejection fraction (systolic function). At 1-6 months (4 studies, n  = 454) studies found hypertrophy, and decreased global function, but no difference in systolic or diastolic function. At 1-8 years (7 studies, n  = 1,609) no difference was found. The available data did not allow for sub-analysis based on the type of diabetes, treatment, or glycemic control., Conclusions: Diabetes in pregnancy is associated with cardiac hypertrophy and impaired global cardiac function in infants up to six months old. The few studies reporting on older children found no difference in the parameters investigated. Longitudinal studies employing more advanced echocardiographic measures or MRI are needed to evaluate consequences for long-term cardiac health., Systematic Review Registration: https://www.crd.york.ac.uk/, identifier (CRD42022312471)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Skovsgaard, Møller, Bjerre, Kampmann and Kyng.)

Introduction: Therapeutic hypothermia is the only proven neuroprotective treatment for hypoxic-ischemic encephalopathy. However, studies have questioned whether therapeutic hypothermia may benefit newborns subjected to infection or inflammation before a hypoxic-ischemic insult. We aimed to compare newborn piglets with lipopolysaccharide-sensitized hypoxia-ischemia treated with and without therapeutic hypothermia with regards to measures of neuroprotection., Methods: A total of 32 male and female piglets were included in this randomized experimental study. Lipopolysaccharides from Escherichia coli were infused intravenously before initiation of a standardized global hypoxic-ischemic insult. The piglets were then randomized to either normothermia or therapeutic hypothermia. After 14 h, the piglets were evaluated. Our primary outcome was brain lactate/N-acetylaspartate ratio assessed by magnetic resonance spectroscopy. Secondary outcomes included measures of magnetic resonance imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines., Results: Piglets treated with and without therapeutic hypothermia were subjected to comparable global hypoxic-ischemic insults. We found no difference between the two groups with regards to measures of magnetic resonance spectroscopy and imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines., Conclusion: We found no indication of neuroprotection by therapeutic hypothermia in newborn piglets following lipopolysaccharide-sensitized hypoxia-ischemia. However, interpretation of the results is limited by the short observation period. Further studies are required to determine the potential clinical implications of these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Andersen, Andersen, Andelius, Hansen, Pinnerup, Bjerre, Ringgaard, Schwendimann, Gressens, Kyng and Henriksen.)

Introduction: Hypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls., Methods: Three devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia., Results: Glycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol., Conclusion: This exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Andelius, Bøgh, Pedersen, Omann, Andersen, Andersen, Hjortdal, Pedersen, Rasmussen, Kyng and Henriksen.)

Aim: Neurofilament light Chain (NfL) is a promising brain injury biomarker which may assist diagnosis and prognostication in hypoxic-ischemic encephalopathy (HIE). The aim of this study was to investigate serum NfL levels after hypoxia-ischemia (HI) in a newborn piglet model. Second, to characterize the influence of sex, weight, and treatment with remote ischemic postconditioning (RIPC) on NfL and the correlation between NfL, brain imaging and histologic brain injury., Methods: We used serum from 48 newborn piglets of both sexes subjected to 45 min of global HI, and 4 sham piglets. Blood was collected pre-HI, 2 h post-HI and 72 h post-HI. NfL was measured by single-molecule array (Simoa™). We analysed the temporal profile of NfL after HI, and correlations between NfL, magnetic resonance spectroscopy brain Lac/NAA ratios and histologic brain injury 72 h after HI., Results: Median (IQR) NfL levels were: pre-HI: 66 pg/ml (45-87), 2 h post-HI: 105 pg/ml (77-140), and 72 h post-HI: 380 pg/ml (202-552). The increase in NfL after HI was statistically significant ( p  < 0.0001, mixed-effects ANOVA). Median NfL levels in sham animals were 41.4 pg/ml at baseline and 92.4 pg/ml at 72 h ( p  = 0.11, paired t-test). Neither sex, nor treatment with RIPC influenced NfL levels. Weight had a small, not biologically important, influence. NfL levels at 72 h were moderately correlated with histologic brain injury and brain Lac/NAA ratios. NfL 72 h post-HI > 330 pg/ml had a sensitivity of 89% (95% CI, 57%-99%) and a specificity of 52% (95% CI, 34%-69%) for predicting basal ganglia Lac/NAA ratio in the highest quartile. NfL 72 h post-HI > 445 pg/ml had a sensitivity of 90% (95% CI, 60%-99%) and a specificity of 74% (95% CI, 58%-86%) for predicting cortical brain histopathology injury in the highest quartile., Conclusion: NfL increased after HI, with the largest values at 72 h post-HI. Early NfL was sensitive but not very specific, whereas NfL at 72 h was both highly sensitive and specific for exposure to moderate-severe HI in this model of HI-induced brain injury. This was supported by a moderate correlation of NfL at 72 h with brain Lac/NAA ratio and histopathology., Competing Interests: JK has advised and/or received speaker fees and research & travel support from ECTRIMS, the Swiss MS Society, University of Basel, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Roche, and Teva. SW is Chief Medical Officer and co-founder of Neopredix, a spin-off of the University of Basel, Switzerland. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kyng, Wellmann, Lehnerer, Hansen, Kuhle and Henriksen.)

Background: We have previously investigated neurological outcomes following remote ischemic postconditioning (RIPC) in a newborn piglet model of hypoxic-ischemic encephalopathy. The aim of this study was to further investigate potential mechanisms of neuroprotection by comparing newborn piglets subjected to global hypoxia-ischemia (HI) treated with and without RIPC with regards to measures of cerebral blood flow and oxygenation assessed by functional magnetic resonance imaging., Materials and Methods: A total of 50 piglets were subjected to 45 min global HI and randomized to either no treatment or RIPC treatment. Magnetic resonance imaging was performed 72 h after the HI insult with perfusion-weighted (arterial spin labeling, ASL) and oxygenation-weighted (blood-oxygen-level-dependent, BOLD) sequences in the whole brain, basal ganglia, thalamus, and cortex. Four sham animals received anesthesia and mechanical ventilation only., Results: Piglets treated with RIPC had higher measures of cerebral blood flow in all regions of interest and the whole brain (mean difference: 2.6 ml/100 g/min, 95% CI: 0.1; 5.2) compared with the untreated controls. They also had higher BOLD values in the basal ganglia and the whole brain (mean difference: 4.2 T2*, 95% CI: 0.4; 7.9). Measures were similar between piglets treated with RIPC and sham animals., Conclusion: Piglets treated with RIPC had higher measures of cerebral blood flow and oxygenation assessed by magnetic resonance imaging in the whole brain and several regions of interest compared with untreated controls 72 h after the HI insult. Whether this reflects a potential neuroprotective mechanism of RIPC requires further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kerrn-Jespersen, Andersen, Bennedsgaard, Andelius, Pedersen, Kyng and Henriksen.)

Introduction: Hypoxic ischemic encephalopathy (HIE) is a major cause of death and disability in children worldwide. Apart from supportive care, the only established treatment for HIE is therapeutic hypothermia (TH). As TH is only partly neuroprotective, there is a need for additional therapies. Intermittent periods of limb ischemia, called remote ischemic postconditioning (RIPC), have been shown to be neuroprotective after HIE in rats and piglets. However, it is unknown whether RIPC adds to the effect of TH. We tested the neuroprotective effect of RIPC with TH compared to TH alone using magnetic resonance imaging and spectroscopy (MRI/MRS) in a piglet HIE model. Methods: Thirty-two male and female piglets were subjected to 45-min global hypoxia-ischemia (HI). Twenty-six animals were randomized to TH or RIPC plus TH; six animals received supportive care only. TH was induced through whole-body cooling. RIPC was induced 1 h after HI by four cycles of 5 min of ischemia and 5 min of reperfusion in both hind limbs. Primary outcome was Lac/NAA ratio at 24 h measured by MRS. Secondary outcomes were NAA/Cr, diffusion-weighted imaging (DWI), arterial spin labeling, aEGG score, and blood oxygen dependent (BOLD) signal measured by MRI/MRS at 6, 12, and 24 h after the hypoxic-ischemic insult. Results: All groups were subjected to a comparable but mild insult. No difference was found between the two intervention groups in Lac/NAA ratio, NAA/Cr ratio, DWI, arterial spin labeling, or BOLD signal. NAA/Cr ratio at 24 h was higher in the two intervention groups compared to supportive care only. There was no difference in aEEG score between the three groups. Conclusion: Treatment with RIPC resulted in no additional neuroprotection when combined with TH. However, insult severity was mild and only evaluated at 24 h after HI with a short MRS echo time. In future studies more subtle neurological effects may be detected with increased MRS echo time and post mortem investigations, such as brain histology. Thus, the possible neuroprotective effect of RIPC needs further evaluation., (Copyright © 2020 Andelius, Pedersen, Andersen, Andersen, Hjortdal, Pedersen, Ringgaard, Hansen, Henriksen and Kyng.)