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Hyperglycemia and Adverse Pregnancy Outcome Study-Cardiovascular Health of HAPO Offspring (HAPO CVH)

Award Number: R01HL160921
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Hyperglycemia and Adverse Pregnancy Outcome Study-Cardiovascular Health of HAPO Offspring (HAPO CVH) - Project Summary Halting the intergenerational transfer of cardiovascular disease (CVD) risk is a priority for NHLBI and the American Heart Association (AHA). Yet, limited understanding around the timing, pathways, and mechanisms underlying the observed associations between maternal gestational health and offspring cardiovascular health (CVH) remains a significant barrier to developing targeted, timely interventions. We propose to leverage the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort to substantially advance understanding of the in utero origins of offspring CVH and CVD, as measured during the critical period of young adulthood. The original HAPO study recruited ~25,500 women in 2000-2006 to prospectively and uniformly examine the association of gestational glycemia, uncomplicated by treatment, with maternal and neonatal outcomes. Eleven years later, 4,832 offspring returned to study effects of GDM on offspring adiposity and glycemia. We hypothesize that there are significant independent associations of maternal adiposity, glycemia, BP, and lipids at ~28 weeks gestation with CVH and arterial injury among offspring at age 18-25 years, and that DNA methylation (DNAm) will be associated with upstream intrauterine exposures and downstream CVH and arterial injury. HAPO CVH will include a comprehensive CVH assessment of 1,000 HAPO FUS offspring from 4 HAPO centers. We will measure BP, adiposity, lipids, glycemia, and lifestyle behaviors, characterize total CVH with AHA’s ‘Life’s Simple 7’ framework, and obtain carotid ultrasonography to identify the earliest changes of subclinical CVD. We will also analyze existing cord blood DNAm data and will acquire new epigenome-wide association data from young adult DNA using the Illumina 850K chip. We will achieve our objectives through the following specific aims: Specific Aim 1: Define associations of the in utero cardiometabolic milieu at ~28 weeks’ gestation with offspring CVH and subclinical CVD in young adulthood. Hypothesis 1a: Poorer maternal gestational metabolic health is associated with poorer offspring CVH (Co-primary outcome) in young adulthood. Hypothesis 1b: Poorer maternal gestational metabolic health is associated with higher carotid IMT (Co-primary outcome), lower carotid distensibility, and unfavorable carotid artery grayscale features in young adulthood. Hypothesis 1c: Poorer maternal gestational metabolic health is associated with worsening of cardiovascular health from childhood to young adulthood. Specific Aim 2: Examine the role of epigenetic mechanisms in the association of upstream intrauterine cardiometabolic exposures and downstream CVH and subclinical CVD. Hypothesis 2a: Poorer maternal gestational metabolic health is associated with differential DNAm in aging-related pathways (measured as accelerated epigenetic aging) in cord blood and young-adult offspring. Hypothesis 2b : Poorer maternal gestational metabolic health is associated with differential DNAm in specific cardiometabolic pathways in young- adult offspring blood cells, and this differential DNAm partly statistically mediates the association of adverse intrauterine exposures with later CVH status and carotid arterial injury in young adulthood


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: 2025 ( Subtotal = $1,873,668 )
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	001	3	9/19/2025	NON-COMPETING CONTINUATION	$187,365
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	000	3	3/3/2025	NON-COMPETING CONTINUATION	$1,686,303
														Subtotal = $1,873,668

Issue Date FY: 2024 ( Subtotal = $1,844,703 )
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	001	2	4/25/2024	NON-COMPETING CONTINUATION	$0
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	000	2	3/2/2024	NON-COMPETING CONTINUATION	$1,694,117
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	002	2	6/21/2024	NON-COMPETING CONTINUATION	$150,586
														Subtotal = $1,844,703

Issue Date FY: 2023 ( Subtotal = $1,941,677 )
2023	2023	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	000	1	2/22/2023	NEW	$1,940,403
2023	2023	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Cardiovascular Diseases Research	001	1	6/30/2023	NEW	$1,274
														Subtotal = $1,941,677

Grand Total All Awards = $5,660,048

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Hyperglycemia and Adverse Pregnancy Outcome Study-Cardiovascular Health of HAPO Offspring (HAPO CVH)

Award Number: R01HL160921

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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