Pregnancy Complications Linked to Lifelong Cardiovascular Disease Risk for Mothers

Pregnant women who develop a common complication called pre-eclampsia are twice as likely to develop heart problems later in life. Now a University of Alberta postdoctoral fellow is working to understand why and to develop prevention strategies.

Amanda de Oliveira, a researcher in Sandra Davidge’s lab in the Department of Obstetrics & Gynecology, has won a prestigious Banting Postdoctoral Fellowship to carry out the research, funded by the Canadian Institutes of Health Research. Her project will focus on how pre-eclampsia in pregnant women increases their risk of cardiovascular complications, such as high blood pressure, heart attacks and stroke later in life.

Pre-eclampsia occurs during or shortly after pregnancy and is characterized by persistent high blood pressure, protein in the urine and organ damage. It affects five to eight per cent of all pregnancies and is a major risk factor for severe illness and death among pregnant women and their babies.

The risks don’t end with pregnancy, however. Having pre-eclampsia doubles a woman’s risk for  cardiovascular problems later in life, including a four times higher risk of having hypertension than in women who did not have pre-eclampsia. There is also evidence that the children of pre-eclamptic mothers are at higher risk of cardiovascular issues.

All pregnant women have higher levels of cholesterol, which is necessary to support production of important hormones and fetal development. But in a subset of women, cholesterol levels are excessively high, leading to pre-eclampsia. de Oliveira is looking at the processes underway in the blood vessels of mothers with the condition, both during and after pregnancy. Her pre-clinical research involves feeding pregnant rats a diet abnormally high in cholesterol to mimic the condition in women.

We are still talking about pre-clinical research, but we are trying to understand the mechanism, and hopefully by understanding we have a better idea of how to move forward.

One of the goals is to develop potential prevention strategies. With that in mind, de Oliveira is studying a protein in the immune system called toll-like receptor 4 (TLR4) that, when activated, can lead to blood vessel dysfunction. It may be possible eventually to develop a therapy that could target the receptor to prevent the development of pre-eclampsia.

She is also studying the efficacy of using Aspirin (acetylsalicylic acid) to target an enzyme that has a role in blood vessel damage in pregnancy. Aspirin is already known to reduce the incidence of pre-eclampsia in high-risk women if taken before week 16 of gestation, but it is not known whether this can also prevent cardiovascular disease later in life. If her study shows that using Aspirin in pregnant rats prevents pre-eclampsia more broadly, as well as its consequences later in life, this would provide evidence that more women — especially those with abnormally high levels of cholesterol — might benefit from taking Aspirin.

“We are still talking about pre-clinical research,” she says, “but we are trying to understand the mechanism, and hopefully by understanding we have a better idea of how to move forward. Maybe there is a subpopulation of women with excessively high levels of cholesterol in pregnancy who would also benefit from receiving Aspirin, but at this point, we don’t know that.”

This new project builds on de Oliveira’s postdoctoral work, funded by the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute (WCHRI).

“I am an immigrant to Canada, so for me it was very important to receive the support from WCHRI,” says de Oliveira, who did her undergraduate studies in Brazil and her PhD at the Florida Institute of Technology. “I am honoured to have my work recognized, at the local level by WCHRI and now at the national level.”