Huiping Zhu is a member of a team of epidemiologists, statisticians, clinicians, and geneticists working to discover the etiology, the causes, of neural tube defects (NTDs). Using questionnaire data, clinical data, and genetic material collected as part of the Center for Disease Control’s National Birth Defect Prevention Study (NBDPS), Zhu and her colleagues are parsing the complicated and interrelated risk factors—environmental toxins, maternal nutritional status, genetics—for the development of NTDs.
Zhu is a research assistant professor in the Department of Nutritional Sciences and is a member of the Finnell lab at the Dell Pediatric Research Institute (DPRI). Zhu’s work is funded in part by a grant from the National Institutes of Health.
What is already known about NTDs?
Huiping Zhu: Researchers have been studying the role environmental factors play in the etiology of birth defects for many years. They’ve identified several factors with a known connection to NTDs. For example, there are many commonly known drugs that have an established link to NTDs. Recently we’ve learned that diabetes and obesity in the mother are risk factors for the development of birth defects in her baby.
Folic acid protects against many kinds of birth defects. Why doesn’t the story end there?
We’ve known for more than 20 years that folic acid is important for the prevention of birth defects, especially NTDs. Our food is now fortified with folic acid, but we still don’t understand how it works to prevent birth defects. What we do know is that it doesn’t do the same thing for everyone; folic acid offers varying degrees of protection.
There are other environmental exposures linked to birth defects. We’re still studying those. Some of my colleagues are looking closely at the link between arsenic and birth defects. Whether arsenic is teratogenic is still controversial. There appears to be a higher risk for diabetes in areas with high arsenic contamination. As we know, maternal diabetes is an established risk factor for many birth defects.
The anti-epileptic drug valproic acid (VPA) has been established as a risk factor for NTDs. If you take VPA, your body weight is likely to increase. We don’t understand why VPA increases body weight, but we do know that both this drug and obesity cause birth defects. There are some interesting links here. One hypothesis is that arsenic and diabetes share some common mechanisms that cause birth defects. VPA and obesity both cause NTDs and they, too, might have a common mechanism. We are looking at one outcome and trying to identify what all of the various factors have in common.
How common are birth defects?
Birth defects impact 1 in 1000 births or about 324,000 births worldwide.
How will your work benefit women preparing for motherhood?
There are almost 100 genes that have been related to developing obesity, so if you have certain mutations, you tend to develop obesity or diabetes. While you might not be obese or diabetic at the time when you get pregnant, you might have a gene that makes you prone to developing diabetes when you are 50. My hypothesis is, if you have the susceptibility that will ultimately make you obese or diabetic even if you are not obese or diabetic when you are pregnant, your body is already in less than optimal condition. In order to develop to its full potential, the embryo needs the best possible environment. The central nervous system is very sensitive to anything the mother’s body provides; so if the mother has an already-compromised internal environment, she will provide a compromised environment for the developing embryo. She might not know it. She is not obese yet; she is not diabetic yet.
I am testing these genes to see if they predict the outcome of the pregnancies. My work will explain the genetic part of the link between obesity, diabetes, and birth defects. But this is only the beginning part. My next goal is to put the pieces together to have a better understanding of the mechanisms.
What caused you to choose your area of research?
When I was pregnant with my second child, I developed gestational diabetes. I was shocked. I am not overweight; I eat healthy. I did some research which showed that there is a high incidence of gestational diabetes among Asian women. I realized it must also include genetics. I wanted to help women to think about and understand their risk of complications and birth defects before they get pregnant. It will be too late to start after a woman is already pregnant, so I chose to focus on mothers before they become mothers.