Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE. Using univariate analysis, multivariate analysis and sPLS-DA modelling, we show that newborns with moderate–severe HIE (n = 46) who underwent therapeutic hypothermia (TH) displayed a robust peripheral blood lipidomic signature comprising 29 lipid species in four lipid classes; namely phosphatidylcholine (PC), lysophosphatidylcholine (LPC), triglyceride (TG) and sphingomyelin (SM) when compared with newborns with mild HIE (n = 18). In sPLS-DA modelling, the three most discriminant lipid species were TG 50:3, TG 54:5, and PC 36:5. We report a reduction in plasma TG and SM and an increase in plasma PC and LPC species during the course of TH in newborns with moderate–severe HIE, compared to a single specimen from newborns with mild HIE. These findings may guide the research in nutrition-based intervention strategies after HIE in synergy with TH to enhance neuroprotection.

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Apgar Scores at 10 Minutes and Outcomes in Term and Late Preterm Neonates with Hypoxic-Ischemic Encephalopathy in the Cooling Era

American Journal of Perinatology ◽

10.1055/s-0038-1670637 ◽

2018 ◽

Vol 36 (05) ◽

pp. 545-554 ◽

Cited By ~ 2

Author(s):

Marina Ayrapetyan ◽

Kiran Talekar ◽

Kathleen Schwabenbauer ◽

David Carola ◽

Kolawole Solarin ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Hypoxic Ischemic Encephalopathy ◽

Preterm Neonates ◽

Short Term ◽

Apgar Scores ◽

Significant Difference ◽

The Brain ◽

Ischemic Encephalopathy

Objective To determine the short-term outcomes (abnormal brain magnetic resonance imaging [MRI]/death) in infants born with a 10-minute Apgar score of 0 who received therapeutic hypothermia and compare them with infants with higher scores. Study Design This is a retrospective review of 293 neonates (gestational age ≥ 35 weeks) born between November 2006 and October 2015 admitted with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. Results of brain MRIs were assessed by the basal ganglia/watershed scoring system. Short-term outcomes were compared between infants with Apgar scores of 0, 1 to 4, and ≥5 at 10 minutes. Results Eight of 17 infants (47%) with an Apgar of 0 at 10 minutes survived, having 4 (24%) without abnormalities on the brain MRI and 7 (41%) without severe abnormalities. There was no significant difference in the combined outcomes of “death/abnormal MRI” and “death/severe abnormalities on the MRI” between infants with Apgar scores of 0 and 1 to 4. Follow-up data were available for six of eight surviving infants, and none had moderate or severe neurodevelopmental impairment. Conclusion In the cooling era, 47% of infants with no audible heart rate at 10 minutes and who were admitted to the neonatal intensive care unit survived; 24% without abnormalities on the brain MRI and 41% without severe abnormalities.

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Visual outcomes in children with neonatal hypoxic ischemic encephalopathy treated with therapeutic hypothermia

Journal of Perinatology ◽

10.1038/s41372-021-01101-x ◽

2021 ◽

Author(s):

Jerry Hsu ◽

Noreen Shaikh ◽

Hantamalala Ralay Ranaivo ◽

Andrea C. Pardo ◽

Rebecca B. Mets-Halgrimson

Keyword(s):

Therapeutic Hypothermia ◽

Hypoxic Ischemic Encephalopathy ◽

Visual Outcomes ◽

Ischemic Encephalopathy

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Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy

Scientific Reports ◽

10.1038/s41598-021-83982-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kim V. Annink ◽

Linda S. de Vries ◽

Floris Groenendaal ◽

Rian M. J. C. Eijsermans ◽

Manouk Mocking ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Memory Function ◽

Neurodevelopmental Outcome ◽

Standard Of Care ◽

Hypoxic Ischemic Encephalopathy ◽

School Age ◽

Brain Volumes ◽

Mammillary Bodies ◽

Memory Problems ◽

Ischemic Encephalopathy

AbstractThe mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.

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Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model

International Journal of Molecular Sciences ◽

10.3390/ijms21186801 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6801

Author(s):

Viktória Kovács ◽

Gábor Remzső ◽

Valéria Tóth-Szűki ◽

Viktória Varga ◽

János Németh ◽

...

Keyword(s):

Caudate Nucleus ◽

Therapeutic Hypothermia ◽

Neuroprotective Effect ◽

Fold Increase ◽

Hypoxic Ischemic Encephalopathy ◽

Mrna Levels ◽

Treatment Groups ◽

Apoptosis Inducing Factor ◽

Co2 Treatment ◽

Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H2) or graded restoration of normocapnia with CO2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O2–20%CO2 ventilation; Tcore = 38.5 °C), asphyxia-hypothermia (A-HT, Tcore = 33.5 °C, 2–36 h post-asphyxia), A-HT + H2, or A-HT + CO2 treatment groups. Asphyxia elicited severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H2 or CO2 did not augment TH-induced neuroprotection in any brain areas; rather, CO2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.

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