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Fetal Congenital Heart Disease and Hypoxia-Induced Inflammation of the Placenta

Award Number: R03HL185218
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Fetal Congenital Heart Disease and Hypoxia-Induced Inflammation of the Placenta - PROJECT SUMMARY Rachel Leon, MD, PhD is an Assistant Professor in the Division of Neonatal-Perinatal Medicine at UT Southwestern Medical Center (UTSW) with a PhD in neuroscience, and she is a current NHLBI K23 Awardee. Her goal is to become an independently funded investigator with expertise in neuroplacentology, a field that focuses on elucidating mechanisms of placental influence on fetal brain development. The long-term goal of her research program is to improve neurodevelopmental outcomes of children with complex congenital heart disease (CCHD) by restoring normal intrauterine brain development and increasing their neurologic reserve before they encounter postnatal physiologic stressors. Dr. Leon is in the 3rd year of her K23 award, which is focused on placental and cerebrovascular hemodynamics in fetuses with CCHD. Specifically, in pregnant patients with fetuses diagnosed with left or right ventricular outflow track obstruction CCHD, and healthy controls, she is using advanced MRI to evaluate placental perfusion longitudinally and determine associated differences in placental size and histopathology, determine the impact of placental perfusion on cerebral autoregulation from the fetal period to the early postnatal adaptation, and determine how placental perfusion affects the trajectory of regional brain growth. Dr. Leon has already made several novel discoveries about the fetal CCHD placenta through this work and successfully competed for both mentored and independent foundation funding. In this R03 proposal, Dr. Leon will branch out to a new study using her advanced MRI techniques to investigate the influence of placental hypoxia on inflammatory markers and mediators, which are known to have deleterious effects on fetal brain development. This study will leverage the robust research infrastructure that Dr. Leon has built to recruit pregnant patients from multiple clinical sites, apply custom advanced MRI protocols, collect placental tissue, and analyze complex multi-omic datasets. Given this research infrastructure and her developing expertise in translational methods of neuroplacentology, Dr. Leon is uniquely positioned to lead this cutting-edge team science investigation. In this proposal, she will test the central hypothesis that fetal CCHD pregnancies have decreased placental oxygenation, leading to a pro-inflammatory environment at the maternal-fetal interface, using the following specific aims: (1) Determine the effects of fetal CCHD on regional placental oxygenation using BOLD MRI; and (2) Define the relationship between placental oxygenation status and markers of inflammation in fetal CCHD placentas. Importantly, this project has been streamlined into the R03 timeframe and budget to create robust preliminary data for an R01 proposal that will be submitted by the end of the award period. The presence of hypoxia-induced inflammation in the placenta will be a paradigm shift in the fetal CCHD field and will provide novel information about the intrauterine environment of fetuses with CCHD. Moreover, by identifying placental hypoxia as a possible trigger for inflammation and inflammation-mediated disruption to fetal brain development, we will be poised to discover unique molecular targets for future interventional trials.


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 = $249,000 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cardiovascular Diseases Research	000	1	5/18/2026	NEW	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

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Fetal Congenital Heart Disease and Hypoxia-Induced Inflammation of the Placenta

Award Number: R03HL185218

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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