# Clinical, Histological, and Transcriptional Associations Between the Diabetic Placenta and Fetal Congenital Heart Defects

> **NIH NIH F30** · UNIVERSITY OF FLORIDA · 2024 · $43,163

## Abstract

PROJECT SUMMARY/ABSTRACT
The primary goal of this proposal is to provide a framework of methodologically-diverse, and clinically-inclined,
investigative training that will prepare the principal investigator for a successful career as a translational
physician-scientist. In addition to MD/PhD-specific professional development and expanded clinical/translational
training, much of this preparation will come from technical education gained from the execution of this proposal’s
research aims. These aims seek to broadly understand the placental correlates of fetal congenital heart defects
(CHDs) in pregnancies affected by pregestational maternal diabetes mellitus (DM). It is recognized that the
placenta plays a critical role in the development of fetal CHDs in early pregnancy, although this role is poorly
understood. DM-affected pregnancies also have a pronounced phenotype of placental dysfunction, although the
mediators of this also remain unknown. Additionally, DM-affected pregnancies are at substantially elevated risk
of developing fetal CHDs and, for certain subtypes of CHD, carry an RR as high as 13.8. These CHDs represent
a large percentage of critical and surgery-necessitating defects and are particularly high-burden, as they come
with risk of additional malformations, neonatal hypoglycemia, preterm birth, and other perinatal complications.
These complications, many of which are also seen in DM pregnancies, come downstream of cyclical
exacerbations of placental dysfunction due to CHD-induced fetal hemodynamic changes. Given this,
investigation of the pronounced changes in placental function seen in DM and/or CHD-affected pregnancies
could yield extremely impactful information for both diagnostic and prognostic management of CHDs in diabetic
pregnancies. The identification of pathway-level molecular changes, and their clinical associations, in
pregnancies affected by DM, fetal CHDs, and both (DM+CHD) will produce novel and foundational information
that could change the paradigm of perinatal care in these pregnancies. The overarching hypothesis of this project
is that similar profiles of angiogenic and inflammatory molecular dysfunction, and resulting clinical pathology, will
be observed in both maternal DM-affected and fetal CHD-affected pregnancies, and that this dysfunction will be
particularly exacerbated in DM-affected pregnancies that also develop fetal CHD. This hypothesis will be tested
via two aims. One aim will use large-scale institutional health data to assess the perinatal risk of common
obstetric and neonatal complications in DM+CHD pregnancies relative to those affected by either pathology in
isolation. The other will characterize the cell type-specific molecular dysfunction of DM, CHD, and DM+CHD
placentas using high-throughput RNA sequencing, western blotting, and immunohistochemistry. In completing
this training plan, and the scientific aims it includes, the applicant will receive critical didactic and experiential
training neces...

## Key facts

- **NIH application ID:** 10823771
- **Project number:** 1F30HL172988-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ADITYA Devidas Mahadevan
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,163
- **Award type:** 1
- **Project period:** 2024-08-16 → 2028-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823771

## Citation

> US National Institutes of Health, RePORTER application 10823771, Clinical, Histological, and Transcriptional Associations Between the Diabetic Placenta and Fetal Congenital Heart Defects (1F30HL172988-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10823771. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*