|Jennifer Armstrong, MD, MPH|
"In-Utero Inflammation and Hypercoagulability as Risk Factors for Perinatal Brain Injury"
Dr. Armstrong-Wells is a child neurologist and studies brain injury, stroke and cerebral palsy (CP) in babies. When she first began her research she hadn't studied these problems as a maternal/pregnancy/fetal issues, but realized that in order to understand brain injury in a baby she needed to understand both the mother and the child.
It has only been in the past 15 years or so that pediatric stroke has been recognized as the major contributor to CP thanks to imaging and higher awareness about looking at stroke and brain injury in children. What actually triggers the stroke is still unknown, and Dr. Armstrong-Wells is working to get to the root of the problem in pregnant women to prevent stroke from happening. Some risk factors are known, but they are all from all retrospective studies. Dr. Armstrong-Wells wants to look forward and understand whether inflammatory markers may be causing it.
Her grant through the CWHR looks at the clotting profile of moms and babies. If she is able to see a link, she hopes to begin looking at the clotting factor in pregnant women because clotting is the biggest factor for stroke even up to one year after the pregnancy. Her ultimate hope is that her research will be able to measure the blood in high risk mothers that will show whether they are at highest risk to have a child with a brain injury, and then to have an actual intervention strategy or therapy to prevent it. Her research also sets the stage for follow up in these mothers' clotting profiles later in life to see if there is increased risk for cardiovascular disease (CVD). This could eventually become a screening tool which could classify women into high and low risk for CVD and get them the treatment they need early on.
|Peter Baker, MD|
Gestational Diabetes and Maternal Obesity: Dysfunctional Offspring Cellular Metabolism and Prevention Through Altered Maternal Diet
Obesity is a major world health concern which has its most basic origins in fetal exposure to maternal over-nutrition. Maternal obesity and gestational diabetes (GDM) place the offspring at risk for obesity and earlier, more severe metabolic syndrome. We hypothesize that the conventional, higher fat GDM therapeutic diet may be detrimental to offspring at the cellular level, programming them to handle and store macronutrients differently than their peers. This highly collaborative project employs a novel model using umbilical cord derived mesenchymal stem cells to examine the effects of maternal GDM dietary therapy in offspring energy metabolism, amino acid utilization, and lipid oxidation in muscle and fat. Outcomes are measured against prenatal exposure and infant adiposity to demonstrate the beneficial effects of a lower fat therapeutic maternal diet, both at the cellular level and clinically in offspring development. Our results may influence the way gestational diabetes is treated, and moreover provide a preventative intervention for fetal programming in obesity.
|Kristen Boyle, PhD|
Maternal Programming of Fetal Stem Cells
The obesity epidemic affects a staggering number of people in our population, and pregnant women and their babies are not untouched. Large observational studies indicate that obese mothers are more likely to give birth to babies who grow up to also be obese. It is apparent that lifestyle and diet heavily affect this correlation, but what is less clear is the genetic mechanism working behind the scenes.
Dr. Boyle is busy working on exciting and timely research to help bridge this connection. She uses a novel research technique stemming from those learned during her doctoral studies. Kristen collects stem cells from the umbilical cords of babies just after birth. In her lab, she coaxes these cells to become fat cells and documents the differences in growth between cells from babies born to healthy weight moms and those born to obese moms. So far, she has identified that cells from babies born to obese moms have a 50% greater capacity to become fat cells. She can also see that there is a correlation between the cells’ fat content and the fat mass of the baby at birth. She is working to determine the mechanism that causes these stem cells to retain their fat-growth characteristics and whether stem cell factors continue to correlate with the children as they grow up.
As she continues her research with support from the Center for Women’s Health Research and a new K-01 NIH Grant, she plans to follow up on the stem cell outcomes as the children grow older. She is collaborating with Dr. Dana Dabelea’s Healthy Start Study in which kids are followed prior to birth for 5 years. Regular blood samples are taken from the children between the ages of 4 and 6, and she is working on ways to culture enough stem cells from the blood sample to carry on her research.
Dr. Boyle has been featured in TIME magazine and interviewed by CBS Denver news about her groundbreaking research. Her eventual hope is that her clinical research will demonstrate a clear cause of the maternal programming of stem cells in unborn babies, and that effective interventions can be put to work to reduce the risk of obesity in kids.
|Laura Brown, MD|
The Impact of Intrauterine Growth Restriction on the Development of Heart Disease and Diabetes Later in Life
Dr. Brown focuses her research on a problem in pregnancy called intrauterine growth restriction (IUGR), a very important problem in terms of fetal growth and nutrition. IUGR occurs in 6 to 8% of all pregnancies, which equals about one in ten women who have either had this happen to them or know someone with that problem. During the pregnancy, the baby does not grow as well as he or she should, often leading to “growth failure” requiring early delivery of the baby.
Many babies with intrauterine growth restriction are born preterm, or if they are born at term they are very low birth weight and their growth patterns don’t necessarily ‘fix’ themselves as they grow into childhood. Therefore their body composition is sometimes not normal. Dr. Brown is interested in how lean body mass (or muscle mass) is impacted in pregnancies affected by IUGR. The muscle and lean mass may not grow proportionally to the growth of fat mass, so that could put the individual at higher risk for diabetes and heart disease later on in life.
The biggest reason this research is important is because there is no real intervention that can be done during pregnancy to improve the growth of the fetus. Doctors can closely follow the pregnancy and deliver the baby once the baby’s growth really slows down (which is determined by following blood flow measurement). By that point though, the baby might already have developed abnormalities in long term growth patterns. Dr. Brown wants to figure out how to intervene early on to decrease the future risk of heart disease and diabetes.
The ultimate ‘cure’ will come from understanding what triggers the problem of intrauterine growth restriction, why it happens in the uterus, and how to intervene during the pregnancy to add to lean mass and prevent the diabetes and heart disease that develops in adulthood.