# Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics (VICE-MPRINT)

> **NIH NIH P50** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $593,248

## Abstract

PROJECT SUMMARY
In the United States (US), there is a crisis in maternal mortality, which has increased over recent years. The
increasing incidence of severe morbidity and mortality tracks with a rising prevalence of chronic health
problems such as pre-pregnancy obesity (PPO), which itself is a causal driver of adverse pregnancy
outcomes4. Furthermore, observational studies reveal that maternal PPO predicts an offspring’s risks for
obesity, coronary heart disease, stroke, type 2 diabetes mellitus (T2D) and asthma. Obesity also increases the
risk for obstetric complications, including maternal diabetes, preeclampsia, cesarean delivery, and induced
preterm delivery, as well as infant congenital anomalies and macrosomia. In addition, PPO contributes to the
“developmental origins of health and disease” (DOHaD), shaping the future health of offspring during childhood
and later adult life. Thus, maternal obesity is now a serious maternal and pediatric health crisis. Diabetes is
one of the most common comorbidities of PPO, with 1 to 2% of women having type 1 or T2D during pregnancy
and another one in five obese women going on to develop gestational diabetes mellitus (GDM). Metformin (an
orally used biguanide) to treat diabetes has been shown to have more favorable pregnancy outcomes
compared to a controlled diet, however, there is significant debate on its use because metformin crosses the
placental barrier and thus may transport into fetal blood. Many medical professionals have preferred insulin or
a combination of insulin and oral medications for diabetes treatment during pregnancy due to concerns about
the impacts on oral medications on fetal health. Major research gaps we address in this study is include
understanding the impact of PPO on placenta gene expression, as well how pharmacologic treatments for
comorbidities like diabetes, specifically metformin, further alter expression. This proposal’s premise is rooted in
knowledge that mother-to-child transmission of risk for obesity is multifactorial and begins with conception in
utero, but understanding the causal mechanisms of risk transmission at play during gestation requires close
attention to the maternal-fetal interface. We hypothesize that maternal obesity and metformin used to treat
diabetes influence gene transcription in the human placenta in both maternal and fetal tissues. With these
Aims we will also establish the Placental Biobank for Genomics and Outcomes (PB-GO), which we propose as
a new MPRINT Scientific Core. Our specific aims are: Aim 1. Evaluate associations between placental gene
expression, pre-pregnancy BMI. Aim 2. Determine the impact of metformin on placental gene expression. Aim
3. Conduct a phenome-wide association study (PheWAS) in a large clinical population to identify diseases
associated with placental gene expression from fetal derived placental tissue. These data will be the basis of a
future R01 to deeply assess the impact of maternal health and pharmacologic treatm...

## Key facts

- **NIH application ID:** 10584236
- **Project number:** 3P50HD106446-01S2
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** PRINCE Joseph KANNANKERIL
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,248
- **Award type:** 3
- **Project period:** 2022-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10584236

## Citation

> US National Institutes of Health, RePORTER application 10584236, Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics (VICE-MPRINT) (3P50HD106446-01S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10584236. Licensed CC0.

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