Pauline Kromann Reim - PhD Scholarship 2021

Project summary:
Is future health determined in fetal life?

Understanding genetic factors in the association between fetal growth and cardiometabolic disease risk

This research project will investigate if mechanisms driving cardiometabolic disease (CMD) can be detected during fetal life.
We aim to determine the effects of known maternal and fetal genetic variants and protein biomarkers associated with CMD on fetal growth and blood flow during pregnancy. We hypothesize that genetic variants and protein biomarkers associated with CMD will cause early changes in the intrauterine environment, the fetal growth potential, as well as the maternal and fetal vessels, ultimately leading to altered fetal growth and blood flow.

Project Title

Fetal growth and cardiometabolic diseases – an in-depth evaluation of the underlying genome, transcriptome, and proteome.

Background

Throughout pregnancy an interplay between both maternal and fetal genetic, environmental, and physiologic factors takes place – all affecting the growth of the fetus and ultimately the weight of the newborn baby. The weight of the newborn is known to have a substantial impact on future health, as previous studies have demonstrated a significant association between both high and low birth weight and increased risk of CMD later in life. The mechanisms driving this association are complex and not yet fully disclosed.

Aim

We aim to evaluate the genetic background of the association between fetal growth throughout pregnancy and CMD later in life. Uncovering this association will contribute to the identification of individuals early in life with an increased risk of CMD in adulthood. This may lead to improvement of preventative strategies and prognosis of some of the most common chronic diseases worldwide such as type 2 diabetes and cardiovascular disease.

Methods

This study differs from previous research by investigating fetal growth throughout pregnancy in contrast to weight measured at birth as a surrogate measure of fetal growth.

In a cohort of 1200 pregnant women and 700 newborns with genotype data, blood samples, as well as detailed ultrasound scans throughout pregnancy, we will investigate

  • Associations between genetic variants of CMD and fetal growth
  • Time specific gene expression (RNA) related to fetal growth
  • Associations between known cardiovascular and inflammatory protein biomarkers and fetal growth

By shedding light on the association between very early life conditions and disease risk later in life we hope to be able to contribute to the development of personalized medicine which among other efforts offers more focused, precise, and effective preventative strategies.

Pauline Kromann Reim

  • MD
  • Novo Nordisk Foundation Centre for Basic Metabolic Research
  • University of Copenhagen, Human Genomics and Metagenomics in Metabolism
  • Herlev Hospital, Department of Obstetrics and Gynecology

Mentors:

Louise Kelstrup, MD, PhD, Associate Clinical Professor, Department of Obstetrics and Gynecology, Herlev Hospital

Torben Hansen, MD, PhD, Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism, University of Copenhagen

Line Engelbrechtsen, MD, PhD, Department of Obstetrics and Gynecology, Hillerød Hospital

Partners:

  • Professor Estrid Høgdall, Department of Pathology, Herlev Hospital

  • Torben Hansen's group, Novo Nordisk Foundation Center for Basic Metabolic Research, Human Genomics and Metagenomics in Metabolism, University of Copenhagen

Contact: