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| ID | Type | Description | Link |
|---|---|---|---|
| 05-17-23 | Other Identifier | UHCMC IRB |
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This observational study will investigate whether differences in birth events and oxygen levels during the newborn period affects the brain activity of children during the middle childhood years.
The investigators will conduct an observational study comparing two groups of children to determine whether differences in birth events and oxygen levels during the newborn period lead to structural and functional impairment within the brain's dopaminergic pathways and the cortical regions innervated by those pathways. The dopaminergic system is involved in modulating motor control and cognitive function.
Using magnetic resonance diffusion tensor imaging, structural integrity of dopaminergic circuits will be quantified and compared in post-hypoxic former preterm children versus healthy control children born at term closely matched by age/sex/race.
Functional activity during executive function tasks will be quantified and compared in post-hypoxic former preterm children versus healthy control children born at term using functional magnetic resonance imaging-blood oxygen level dependent (fMRI-BOLD). Assessment of motor function (grooved pegboard task) will also be performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Post-hypoxic former preterm | Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging and Cognitive Performance Testing. |
| |
| Healthy term-born children | Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging and Cognitive Performance Testing. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnetic Resonance Imaging | Other | MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. |
| Measure | Description | Time Frame |
|---|---|---|
| Structural Integrity of Dopaminergic Circuits | Assessment of dopaminergic circuits originating in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Includes right and left nucleus accumbens, right and left mamillary body, right and left hippocampus. Measured using Magnetic Resonance T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans with three-dimensional volumetrics analysis | 30 minutes |
| Functional Activity During Executive Function Tasks | Subjects in each group were evaluated for changes in functional connectivity between the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), as evaluated by functional magnetic resonance imaging blood oxygen level dependent (fMRI-BOLD), using whole brain analysis. The measurement is increase/decrease of MRI signal intensity in a given region, thresholded at p <0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects' scans were combined/mapped onto a standard MNI brain. Only clusters of over 50 voxels were included, and the size of the region is reported in voxel size. The averaged brains for prematurely born fMRI was subtracted from the full term treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only brain regions innervated by primary or collateral dopaminergic pathways are reported. | 30 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Performance-Fine Motor Function | Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand) | 20 minutes |
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Inclusion Criteria:
Exclusion Criteria:
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Study Group Children (n=11) will be drawn from a cohort currently maintained by the investigators.
Healthy Control Children will be recruited using various strategies: (1) study flyers given to the parents of the prematurely born cohort children to pass along to parents of other children with ages similar to their own child. (2) study flyers posted in the hospital's primary care pediatric clinics asking interested children/families to contact us to learn more about the study; (3) study flyers distributed by professional colleagues/pediatric physicians to potential candidate children/families meeting study inclusion criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Michael J Decker, PhD | Case Western Reserve University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Case Western Reserve University | Cleveland | Ohio | 44106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8038285 | Background | Poets CF, Samuels MP, Southall DP. Epidemiology and pathophysiology of apnoea of prematurity. Biol Neonate. 1994;65(3-4):211-9. doi: 10.1159/000244055. | |
| 11230582 | Background | Huppi PS, Murphy B, Maier SE, Zientara GP, Inder TE, Barnes PD, Kikinis R, Jolesz FA, Volpe JJ. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics. 2001 Mar;107(3):455-60. doi: 10.1542/peds.107.3.455. |
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Because this is a vulnerable population and a small sample size from a known cohort of children, it is unclear of the institutional requirements for sharing individual participant data in any format other than peer-reviewed publications. The investigators will make datasets from this study available upon completion of the study. Those who are interested will submit a brief research plan to the Principal Investigators. Qualified investigators whose research question can be appropriately addressed by the requested dataset will be invited to discuss their plan and finalize details with the investigators via phone or in person.
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| ID | Title | Description |
|---|---|---|
| FG000 | Post-hypoxic Former Preterm | Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
| FG001 | Healthy Term-born Children | Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Post-hypoxic Former Preterm | Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Structural Integrity of Dopaminergic Circuits | Assessment of dopaminergic circuits originating in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Includes right and left nucleus accumbens, right and left mamillary body, right and left hippocampus. Measured using Magnetic Resonance T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans with three-dimensional volumetrics analysis | All participants who had a usable structural magnetic resonance imaging (MRI) scan | Posted | Mean | Standard Deviation | mm^3 | 30 minutes |
|
1 week
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Post-hypoxic Former Preterm | Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Cognitive Performance Testing: For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
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Insufficient numbers of children studied due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic research shut-down. When research protocols were permitted to resume, parents were reluctant to bring children for a voluntary research study. Data collection also terminated early for technical reasons; the magnetic resonance imaging (MRI) scanner was replaced during the pandemic shut-down with a different model that did not produce comparable results to the earlier scans.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael J. Decker | Case Western Reserve University | 2163682467 | mjd6@case.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 13, 2021 | Dec 15, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 22, 2021 | Dec 15, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D002534 | Hypoxia, Brain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
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MRI neuroimages
|
| Cognitive Performance Testing | Other | For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
|
|
| 10802746 | Background | Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol. 2000 Feb;5(1):3-16. doi: 10.1053/siny.1999.0112. |
| 26262797 | Background | Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A, Nelson H; Canadian Oxygen Trial Investigators. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015 Aug 11;314(6):595-603. doi: 10.1001/jama.2015.8841. |
| 15329741 | Background | Janvier A, Khairy M, Kokkotis A, Cormier C, Messmer D, Barrington KJ. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol. 2004 Dec;24(12):763-8. doi: 10.1038/sj.jp.7211182. |
| 23428277 | Background | Perna R, Cooper D. Perinatal cyanosis: long-term cognitive sequelae and behavioral consequences. Appl Neuropsychol Child. 2012;1(1):48-52. doi: 10.1080/09084282.2011.643946. |
| 26920003 | Background | Smith TF, Schmidt-Kastner R, McGeary JE, Kaczorowski JA, Knopik VS. Pre- and Perinatal Ischemia-Hypoxia, the Ischemia-Hypoxia Response Pathway, and ADHD Risk. Behav Genet. 2016 May;46(3):467-77. doi: 10.1007/s10519-016-9784-4. Epub 2016 Feb 26. |
| 12614682 | Background | Decker MJ, Hue GE, Caudle WM, Miller GW, Keating GL, Rye DB. Episodic neonatal hypoxia evokes executive dysfunction and regionally specific alterations in markers of dopamine signaling. Neuroscience. 2003;117(2):417-25. doi: 10.1016/s0306-4522(02)00805-9. |
| 16171240 | Background | Decker MJ, Jones KA, Solomon IG, Keating GL, Rye DB. Reduced extracellular dopamine and increased responsiveness to novelty: neurochemical and behavioral sequelae of intermittent hypoxia. Sleep. 2005 Feb;28(2):169-76. doi: 10.1093/sleep/28.2.169. |
| 28828549 | Background | Decker MJ, Jones KA, Keating GL, Rye DB. Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system. Sleep Breath. 2018 May;22(2):547-554. doi: 10.1007/s11325-017-1558-6. Epub 2017 Aug 22. |
| 27047695 | Background | Rocha-Ferreira E, Hristova M. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury. Neural Plast. 2016;2016:4901014. doi: 10.1155/2016/4901014. Epub 2016 Mar 7. |
| 8817697 | Background | Nyakas C, Buwalda B, Luiten PG. Hypoxia and brain development. Prog Neurobiol. 1996 May;49(1):1-51. doi: 10.1016/0301-0082(96)00007-x. |
| 20053379 | Background | Stollstorff M, Foss-Feig J, Cook EH Jr, Stein MA, Gaillard WD, Vaidya CJ. Neural response to working memory load varies by dopamine transporter genotype in children. Neuroimage. 2010 Nov 15;53(3):970-7. doi: 10.1016/j.neuroimage.2009.12.104. Epub 2010 Jan 4. |
| 23489778 | Background | Langer N, von Bastian CC, Wirz H, Oberauer K, Jancke L. The effects of working memory training on functional brain network efficiency. Cortex. 2013 Oct;49(9):2424-38. doi: 10.1016/j.cortex.2013.01.008. Epub 2013 Jan 31. |
| 22022357 | Background | Allin MP, Kontis D, Walshe M, Wyatt J, Barker GJ, Kanaan RA, McGuire P, Rifkin L, Murray RM, Nosarti C. White matter and cognition in adults who were born preterm. PLoS One. 2011;6(10):e24525. doi: 10.1371/journal.pone.0024525. Epub 2011 Oct 12. |
| 17599699 | Background | Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. doi: 10.1016/j.nurt.2007.05.011. |
| 18309087 | Background | D'Ardenne K, McClure SM, Nystrom LE, Cohen JD. BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science. 2008 Feb 29;319(5867):1264-7. doi: 10.1126/science.1150605. |
| 22395207 | Background | Kim SG, Ogawa S. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab. 2012 Jul;32(7):1188-206. doi: 10.1038/jcbfm.2012.23. Epub 2012 Mar 7. |
| 16290018 | Background | Goncalves SI, de Munck JC, Pouwels PJ, Schoonhoven R, Kuijer JP, Maurits NM, Hoogduin JM, Van Someren EJ, Heethaar RM, Lopes da Silva FH. Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject variability. Neuroimage. 2006 Mar;30(1):203-13. doi: 10.1016/j.neuroimage.2005.09.062. Epub 2005 Nov 14. |
| 15904191 | Background | Galan RF, Ermentrout GB, Urban NN. Efficient estimation of phase-resetting curves in real neurons and its significance for neural-network modeling. Phys Rev Lett. 2005 Apr 22;94(15):158101. doi: 10.1103/PhysRevLett.94.158101. Epub 2005 Apr 19. |
| BG001 | Healthy Term-born Children | Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Birth gestation | gestational at birth (maternal pregnancy weeks completed) | Mean | Standard Deviation | weeks |
|
| OG001 | Healthy Term-born Children | Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. |
|
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| Primary | Functional Activity During Executive Function Tasks | Subjects in each group were evaluated for changes in functional connectivity between the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), as evaluated by functional magnetic resonance imaging blood oxygen level dependent (fMRI-BOLD), using whole brain analysis. The measurement is increase/decrease of MRI signal intensity in a given region, thresholded at p <0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects' scans were combined/mapped onto a standard MNI brain. Only clusters of over 50 voxels were included, and the size of the region is reported in voxel size. The averaged brains for prematurely born fMRI was subtracted from the full term treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only brain regions innervated by primary or collateral dopaminergic pathways are reported. | All participants who met criteria for a technically acceptable functional magnetic resonance imaging scan (less than 3mm movement artifact) were included in these analyses. FSL (FMRIB Software Library)-defined cluster sizes greater than 50 voxels, with p<0.05, within cognitive areas of interest are included in the outcome table. That table provides the number of voxels in clusters that showed increased or decreased connectivity. | Posted | Number | Cluster size (voxels) | 30 minutes |
|
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|
|
| Secondary | Cognitive Performance-Fine Motor Function | Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand) | Posted | Mean | Standard Deviation | seconds | 20 minutes |
|
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| 0 |
| 9 |
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Healthy Term-born Children | Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Cognitive Performance Testing: For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots. | 0 | 7 | 0 | 7 | 0 | 7 |
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| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |