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A New Model to Identify Preterm Neonates at High-Risk for Cognitive Impairments and School Readiness

Award Number: R01NS094200
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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A New Model to Identify Preterm Neonates at High-Risk for Cognitive Impairments and School Readiness - Project Summary/Abstract Children born very preterm (VPT; <32 weeks’ gestation) face a disproportionate burden of neurodevelopmental impairments (NDI). Impairments in the subdomains of mathematics, reading, and behavior are the most common NDI, affecting 25-50% of VPT children. These abilities are critical to school readiness and success at work. In the first cycle of this grant, we assembled the largest North American cohort of VPT infants and performed advanced brain MRI at term corrected age (CA) with longitudinal neurodevelopmental assessments. We demonstrated the clinical importance of diffuse white matter abnormality (DWMA) and multiple other novel MRI biomarkers to enhance prediction of short-term NDI at 2 or 3 years CA. During this second funding cycle, our unique cohort will reach the critical early school ages of 5 to 7 years, when higher-order cognitive abilities in math and reading, emotional self-regulation, and behavior become more apparent and accurately testable. The ability to accurately predict these functions several years earlier could enable early interventions. Assessment of the dynamic trajectories of NDI in VPT children and their modifiable environmental and biologic causes can also accelerate the development of targeted neuroprotective interventions during these critical early years when neuroplasticity is at its peak. The overall objectives of this proposal are to map the early childhood trajectory of brain structural and functional changes and develop early and accurate prognostic models of school readiness. Our rationale is that elucidation of the long-term impact of DWMA, identification of the trajectory and mediators of NDI changes, and robust prognostic models of school readiness will enable novel early intervention trials in targeted VPT infants. To achieve our goals, we will perform morphometric, diffusion, and functional MRI at age 5 and comprehensive developmental testing at 5 and 7 years CA in our cohort of VPT children and a matched group of term-control children. To advance this highly impactful area of research, we propose the following three specific aims: (1) Determine the impact of DWMA at term CA on brain development and functional impairments at age 5; (2) Model individual trajectories of NDI and identify the mediators of neurodevelopmental changes between 3 and 7 years CA; and (3) Develop early prognostic models of school readiness. For the first aim we will correlate objectively quantified DWMA volume at term CA with brain structural and functional connectivity derived from advanced MRI and with higher-order cognitive functions, both at 5 years CA. Under Aim 2, we will plot individual trajectories of neurodevelopmental scores and identify the mediators of trajectory change between 3 and 7 years CA. For the third aim, we will apply the rich collection of clinical, biologic, and neurodevelopmental data collected between birth and 3 years CA to predict our three measures of school readiness at 5 and 7 years CA. This study will provide U.S. population-based prevalence data about the long-term adverse neuroanatomic and functional consequences of VPT birth, identify mediators of NDI change, and facilitate early prediction of school readiness to enable targeted EI and novel randomized clinical trials for VPT children.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $826,976 )
2026	2026	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	3/19/2026	NON-COMPETING CONTINUATION	$826,976
														Subtotal = $826,976

Issue Date FY: 2025 ( Subtotal = $817,515 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/15/2025	NON-COMPETING CONTINUATION	$817,515
														Subtotal = $817,515

Issue Date FY: 2024 ( Subtotal = $965,969 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	6/10/2024	NON-COMPETING CONTINUATION	$69,710
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/31/2024	NON-COMPETING CONTINUATION	$896,259
														Subtotal = $965,969

Issue Date FY: 2023 ( Subtotal = $930,867 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	2/3/2023	NON-COMPETING CONTINUATION	$930,867
2023	2022	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/2/2023	COMPETING CONTINUATION	$0
														Subtotal = $930,867

Issue Date FY: 2022 ( Subtotal = $899,691 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	5/11/2022	COMPETING CONTINUATION	$899,691
2022	2020	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	8/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $899,691

Issue Date FY: 2020 ( Subtotal = $344,116 )
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	3/6/2020	NON-COMPETING CONTINUATION	$344,116
														Subtotal = $344,116

Issue Date FY: 2019 ( Subtotal = $426,013 )
2019	2019	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	12/31/2018	NON-COMPETING CONTINUATION	$426,013
2019	2018	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	10/30/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $426,013

Issue Date FY: 2018 ( Subtotal = $392,181 )
2018	2018	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/22/2018	NON-COMPETING CONTINUATION	$352,962
2018	2018	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/13/2018	NON-COMPETING CONTINUATION	$39,219
														Subtotal = $392,181

Issue Date FY: 2017 ( Subtotal = $512,335 )
2017	2017	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/26/2017	NON-COMPETING CONTINUATION	$51,232
2017	2017	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/18/2017	NON-COMPETING CONTINUATION	$461,103
														Subtotal = $512,335

Issue Date FY: 2016 ( Subtotal = $573,765 )
2016	2016	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/27/2016	NEW	-$573,765
2016	2016	CHILDREN`S HOSPITAL MEDICAL CENTER	3333 BURNET AVENUE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	9/27/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$573,765
2016	2016	Research Institute at Nationwide`s Children`s Hospital	700 CHILDREN`S DRIVE	COLUMBUS	OH	43205	FRANKLIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/18/2016	NEW	$573,765
														Subtotal = $573,765

Grand Total All Awards = $6,689,428

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A New Model to Identify Preterm Neonates at High-Risk for Cognitive Impairments and School Readiness

Award Number: R01NS094200

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/15/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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