An observational study in Perinatal Hypoxia, Dopamine and Neurobehavioral Manifestations, sponsored by Case Western Reserve University. Completed at 1 site in United States. Open to participants aged 8 Years to 15 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-10-10.
Sponsored by Case Western Reserve University · Observational
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.
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.
Exclusion Criteria:
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.
Other: Magnetic Resonance Imaging · Other: Cognitive Performance Testing
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.
Other: Magnetic Resonance Imaging · Other: Cognitive Performance Testing
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.
Also known as: T-1 MPRAGE, fMRI-BOLD
For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Also known as: Grooved pegboard task
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
Time frame: 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.
Time frame: 30 minutes
Cognitive Performance-Fine Motor Function
Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand)
Time frame: 20 minutes
| Milestone | Post-hypoxic Former Preterm | Healthy Term-born Children |
|---|---|---|
| Started | 11 | 10 |
| Completed | 9 | 7 |
| Not completed | 2 | 3 |
| Withdrew: Lost to follow-up | 2 | 0 |
| Withdrew: Unable to schedule | 0 | 3 |
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
| mm^3 | Post-hypoxic Former Preterm | Healthy Term-born Children |
|---|---|---|
| left nucleus accumbens | 148.90 ± 50.12 | 175.93 ± 25.41 |
| right nucleus accumbens | 177.25 ± 31.46 | 192.78 ± 16.48 |
| left mamillary body | 89.34 ± 18.18 | 54.78 ± 18.02 |
| right mamillary body | 67.78 ± 17.34 | 44.70 ± 15.03 |
| left hippocampus | 2741.09 ± 511.83 | 3419.48 ± 619.00 |
| right hippocampus | 3329.34 ± 682.48 | 4241.03 ± 659.36 |
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.
| Cluster size (voxels) | Post-hypoxic Former Preterm | Healthy Term-born Children |
|---|---|---|
| Left thalamus | 310 | 358 |
| Left middle temporal gyrus | 95 | 75 |
Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand)
| seconds | Post-hypoxic Former Preterm | Healthy Term-born Children |
|---|---|---|
| Cognitive Performance-Fine Motor Function | 102.11 ± 42.77 | 82.71 ± 15.59 |
Collected over 1 week. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Post-hypoxic Former Preterm | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) |
| Healthy Term-born Children | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) |
| Age, Categorical(Participants) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| <=18 years | 9 | 7 | 16 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| Mean | 11.15 ± 0.93 | 12.13 ± 2.06 | 11.58 ± 1.55 |
| Sex: Female, Male(Participants) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| Female | 6 | 3 | 9 |
| Male | 3 | 4 | 7 |
| Ethnicity (NIH/OMB)(Participants) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 9 | 7 | 16 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 7 | 3 | 10 |
| White | 1 | 4 | 5 |
| More than one race | 1 | 0 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| United States | 9 | 7 | 16 |
| Birth gestation(weeks) | Post-hypoxic Former Preterm | Healthy Term-born Children | Total |
|---|---|---|---|
| Mean | 26.11 ± 1.90 | 39.00 ± 1.00 | 31.75 ± 6.78 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided — 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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Neurobehavioral Manifestations→
Case Western Reserve University