Dr. Olivia Weeks is a researcher and key member of the Collaborative Initiative on FASD (CIFASD). Much of Dr. Weeks’ research involves the connection between prenatal alcohol exposure (PAE) and heart health, including congenital heart defects. Please watch the short video below, in which Dr. Weeks summarizes her research in plain language.
FASD United recently had the opportunity to interview Dr. Weeks about her FASD research and the impact of CIFASD on her work.
FASD United: What is the most valuable impact of CIFASD on you and your work?
Dr. Weeks: One of the most valuable impacts of CIFASD on our work has been the ability to engage with FASD patients and their families, especially through the inclusion of FASD United. Through FASD United events and interactions with FASD Changemakers and the Adult Leadership Committee, we have been able to learn about FASD through individuals with living experience. We often ask, “What do individuals with FASDs want us to know?” This is probably the most important discussion point we have been able to engage with as researchers. We have also been exposed to an excellent language guide from FASD United and lectures on how to help reduce stigma when disseminating information on FASD. I will also add that CIFASD is composed of exceptionally talented and experienced researchers, who constantly challenge us and provide new ideas. This is invaluable for our research!
FASD United: What do you want families and the FASD community to most know about your research?
Dr. Weeks: Members of the FASD community have raised important questions about long-term health risks, but there has been little research following how different parts of the body are affected over time. Our work is driven by these concerns, with a specific focus on the heart. We want to learn what happens to a prenatal alcohol exposed heart from conception through adulthood and share that information broadly with patients, caregivers, and clinicians.
FASD United: Can you expand a bit on what your research shows are the specific ways that PAE impacts heart/cardiovascular health?
Dr. Weeks: We primarily study zebrafish, but we have also conducted retrospective studies in human populations. Here, I will focus on what we have learned from zebrafish, which are a powerful model for understanding early heart development.
In both humans and zebrafish, the heart begins forming very early in development. Two groups of heart precursor cells start on opposite sides of the embryo and must move toward the midline to fuse and form a single, simple heart tube. This early heart tube then bends and twists (a process called looping), expands to form heart chambers, and develops distinct inflow and outflow regions. At the same time, the heart must begin to contract and pump blood. In humans, many of these critical steps occur very early in pregnancy—often within the first few weeks after a missed period, before many people even realize they are pregnant.
When we expose zebrafish to alcohol during these early stages of heart development, we find that the heart precursor cells do not develop normally and fail to migrate properly to the midline. In other words, alcohol interferes with both how cardiac cells mature into functional heart cells and how they move to the correct location. As a result, the formation of the linear heart tube—an essential foundation for all later heart development—is disrupted.
These early problems in cell movement and maturation can lead to congenital heart defects. Importantly, when zebrafish with and without congenital heart defects are allowed to age, we find that those exposed to alcohol early in development are more likely to develop heart muscle disease and impaired heart function later in life. Based on these findings, we believe similar processes may occur in humans, and that individuals with fetal alcohol spectrum disorders may be at increased risk for cardiovascular disease in adulthood.
FASD United: Talk about why biomarkers are important when it comes to FASD and what the latest research shows in that area.
Dr. Weeks: Biomarkers have the potential to play an important role in fetal alcohol spectrum disorder (FASD) research and care for several reasons.
First, most individuals with FASDs are never formally diagnosed. Diagnosis currently relies on a combination of clinical history, physical findings, and neurodevelopmental assessments, which can be difficult to obtain and are not always available. Blood- or tissue-based biomarkers could make identification of individuals affected by prenatal alcohol exposure easier, more objective, and more accessible.
Second, growing evidence shows that some individuals with FASDs are at increased risk for cardiometabolic and cardiovascular conditions later in life. However, we currently have no reliable way to predict who will develop these health problems and who will not. Biomarkers measured from a blood test could help identify individuals at higher risk for future disease, allowing for earlier monitoring or preventive care.
Third, biomarkers could be useful for tracking disease activity over time. Many health conditions associated with FASD evolve across the lifespan. Biomarkers could help clinicians assess whether a patient’s condition is stable, improving, or worsening, and whether new treatments or lifestyle interventions are having a meaningful impact.
Finally, biomarkers can provide insight into the biological mechanisms underlying FASD. If specific genes, proteins, or metabolic pathways are consistently altered, this can tell us which processes are disrupted by prenatal alcohol exposure and point toward potential therapeutic targets.
One of the biomarkers related to FASD that I am familiar with (through an FASD United conference!) is direct testing for ethanol exposure or its metabolites, such as phosphatidylethanol (PEth), in newborn blood. Peth spot testing can indicate recent or late-pregnancy alcohol exposure and can provide rough information about the degree of exposure. However, this approach has important limitations. It can only be used at or near birth, primarily reflects recent exposure, and cannot reconstruct patterns of alcohol use, such as intermittent binge drinking versus daily low-level exposure. Many individuals are never tested, and earlier prenatal exposures may be missed entirely. In addition, these tests can carry stigma and may have legal or social implications for families.
A major gap in the FASD field is the lack of biomarkers that are useful later in life or that can predict specific long-term health outcomes. To address this, recent research has explored noninvasive biomarkers such as circulating microRNAs (CIFASD researchers have explored this), as well as epigenetic markers that reflect long-lasting changes in gene regulation following prenatal alcohol exposure. Other studies, including our own, have used large-scale “omics” approaches to identify genes, proteins, or metabolites that differ between individuals with FASD and those without.
Each of these approaches are promising. My dream is that, in the future, a simple blood test could help identify individuals with FASD who are at higher risk for conditions such as cardiovascular disease, allowing clinicians to intervene earlier and improve long-term health outcomes.
FASD United: Why is early intervention so important when it comes to FASD and heart health, and how is your research advancing this area?
Dr. Weeks: Early intervention is critically important for FASD and heart health because many of the processes that determine lifelong cardiovascular risk begin very early, including before birth.
The earliest possible opportunities for intervention occur even before conception. Advances in genetic sequencing make it possible to identify genetic variants that may increase susceptibility to the harmful effects of prenatal alcohol exposure. One goal of our research is to identify genes that may modify the risk of alcohol-induced congenital heart defects, particularly those that worsen the severity of these defects. Knowing about increased susceptibility could help guide behavioral changes during pregnancy. In addition, understanding the genes and biological pathways involved opens the door to future interventions—such as targeted drugs, vitamins, or other compounds—that might help correct or buffer disrupted developmental pathways.
After birth, early intervention remains important, especially for individuals with FASDs who are born with congenital heart defects. Some heart defects are life-threatening and require diagnosis and treatment within the first days or weeks of life. Others are more subtle and may not be immediately apparent, allowing infants to go home without a diagnosis. When congenital heart defects go unrecognized, they can lead to secondary problems such as low oxygen levels, poor feeding, impaired growth, and altered brain development. A growing body of evidence, including our own work, indicates that prenatal alcohol exposure increases the risk of congenital heart defects. These findings support more comprehensive cardiac screening for individuals with known prenatal alcohol exposure, including with fetal echocardiography before birth.
Our research also addresses a major gap in the field: adult cardiovascular disease in individuals with FASD. This area has been largely understudied. Our work suggests that prenatal alcohol exposure may increase the risk of heart disease, heart muscle dysfunction, and vascular disease later in life. Cardiovascular disease often develops slowly and without obvious symptoms, but it is frequently modifiable through early monitoring, lifestyle interventions, and medical treatment. When left undetected, however, it can lead to significant illness and early mortality. We are advancing this area by identifying the types of cardiovascular conditions that may be more common in individuals with FASD and investigating biomarkers and underlying biological mechanisms that could explain this increased risk.
FASD United: Can you share a personal or professional highlight or standout moment from working with CIFASD?
Dr. Weeks: CIFASD puts on a symposium most years at FASD United’s annual research conference in Seattle. A personal and professional highlight for me last year was having patients and parents with cardiac problems come up and talk to me after the session and tell their stories. I come from an alcohol-affected family myself, and that has really motivated my decision to study alcohol and FASD. Having the work matter to someone is important.
Note:
Research reported in this publication was supported by the National Institute On Alcohol Abuse And Alcoholism of the National Institutes of Health under Award Number U01AA030185. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.