Text Alternative: Role of Research in Understanding, Preventing, & Treating Birth Defects

To view the original video and read the News Release, please go to http://www.nichd.nih.gov/news/releases/Pages/032112-birth-defects.aspx

Video/Graphics Audio



Alan E. Guttmacher, M.D.

Eunice Kennedy Shriver National Institute of Child Health and Human Development

January 2012



Dr. Alan Guttmacher on camera

Dr. Alan Guttmacher: Hello, I'm Alan Guttmacher. I'm the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. And I'm going to talk with you today about birth defects and about the role of research in understanding birth defects, in treating them, and in preventing them.



  • Some basic facts about birth defects
  • An example of how research has made a difference
  • Model systems to study development
  • The role of systems biology
  • The role of chemical genomics
  • Future research opportunities

Dr. Guttmacher: First I'm going to say something about the basic facts about birth defects, then talk with you about an example where research has already made a difference in terms of preventing birth defects.  I'm also going to talk about how we use model systems to study development, which is very important in understanding birth defects.  And I'll talk then about the role of systems biology and of chemical genomics in understanding birth defects and in coming up with new treatment and prevention measures for them. And finally, I'll talk with you some about other research opportunities in birth defects.  Probably the first basic fact to get across about birth defects . . .

Dr. Guttmacher on camera

Dr. Guttmacher:  . . . is that the term "birth defects" is a terrible term in many ways. It's the one that we've used scientifically for years, it's the one we still use, but the problem with it is that by calling it a defect, first of all we give, I think, unneeded stigma to kids and families who are born with a birth defect. But also, sometimes it keeps science from advancing. This is really about human variation.  And part of human variation can be to be born with certain problems, which we label as "birth defects."


Defining Birth Defects

Major Birth Defects:

  • Cause structural changes in one or more parts of the body
  • Are present at birth
  • Have a serious, adverse effect on health, development, or functional ability

Dr. Guttmacher: What we mean when we say "birth defect" is something that causes structural changes in one or more parts of the body and, of course, is present at birth. We distinguish major from minor birth defects: major birth defects being those that have a serious adverse effect on health, development, or functional ability.


Prevalence, Severity

  • In the U.S., about 3% of babies are born with major birth defects.
  • Birth defects account for more than 20% of infant deaths.
  • Birth defects are associated with higher risks of illness and long-term disability.
  • Major structural defects include those of the heart, limb, face, and nervous system.

Dr. Guttmacher: In the U.S. about 3% of all babies are born with one of these major birth defects. Birth defects account for greater than 20% of all infant deaths in the U.S.  They are also associated with higher risks of illness and of long term disability— for those who are born with birth defects and survive. Major structural birth defects include those that affect the heart, the limb, the face, the nervous system, and sometimes other parts of the body as well. What those numbers don't show, what those definitions don't tell us, is about the impact of birth defects in the lives of . . .

Dr. Guttmacher on camera

Dr. Guttmacher:  . . . individuals who have birth defects and their families, which of course, can be major or can be less major.  And that's not just depending upon the nature of the birth defect itself, but it also depends upon the individual and their resiliency, it depends upon the family, and how they view the specific birth defect. So birth defects— while they have biological causes in terms of their impact upon the lives on individual and families-- it's not just a question of biology, it's a question of other aspects of the human condition as well, really.


Role of Research

  • Research plays a critical role in better understanding, preventing, and ameliorating birth defects.

Dr. Guttmacher: Research has played a critical role for many years in better understanding birth defects and already in terms of treating them and even preventing some birth defects.

Dr. Guttmacher on camera

Dr. Guttmacher: One recent research success story relates to neural tube defects. Neural tube defects are multifactoral, that is, they're caused by . . .


Past Research Success Story

  • Problem: Neural tube defects(NTDs)
  • Causes: Multifunctional, only partially understood
  • Research: Showed that folic acid supplementation can prevent 50-70% of NTDs.
  • Outcome: Findings informed health recommendations, led to mandatory fortification of grain products in U.S.; NTD prevalence declined more than 25%


Picture of a baby

Picture of a pregnant woman

Dr. Guttmacher:  . . . a combination of many different things. Some of them dietary, we believe. Certainly there are some genes that are involved and people who are born with certain genetic variations have an increased likelihood for being born with a neural tube defect but there are other, again, dietary and other kinds of factors, not all of which we yet understand, which play a role in causing neural tube defects.  Neural tube defects can be quite devastating; they affect the brain, the spinal cord. So, depending on how severe they are, they can have quite an effect on the individual. Research a number of years ago showed that folic acid supplementation might prevent this specific birth defect, neural tube defects, and the fact, based upon that research, the U.S. some years ago began to fortify grain products to include extra folic acid or folate, and because of this supplementation, the prevalence of neural tube defects in the U.S. decreased by more than 25%-- simply by adding this important vitamin to food that we take in normally, particularly bread.  This is a great success story. We'd like to have other such success stories so we could lessen the burden to individuals and to society in terms of birth defects.

Dr. Guttmacher on camera

Dr. Guttmacher: One way to do that is to use model systems to study development . . .


Model Systems to Study Development

  • Animal models help researchers study normal development and understand how things can go wrong.


Pictures of worms, mice, frog, bee, zebrafish

Dr. Guttmacher: . . . by model systems-- of course, I mean organisms other than humans. It's hard to study human embryology. We do it but it has its own difficulties. And there are other kinds of model organisms that can help us understand development . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . .  in a way that is a certainly applicable to humans but allows us to really get much more understanding of the way that organs form.  One very useful model organism is the zebrafish. The zebrafish is a great model for figuring out how things develop embryologically.


Video of a zebrafish swimming in a tank.

Dr. Guttmacher:  Like humans Zebrafish are vertebrates, so they have central nervous systems much like ours, et cetera. But they mature much more quickly-- the embryos-- than is true for humans, so that there's much less time involved in doing any kind of research. Zebrafish lay hundreds of eggs at weekly intervals, . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . .  so that makes them very amenable to large scale chemical and genetic screens to understand embryology, and they're transparent so that you can actually look directly at the developing organs.


Video of zebrafish embryo developing

Dr. Guttmacher:  And in this video that you see now you can see obviously since they speed it up somewhat but you can see the zebrafish embryo developing and this is, in fact, what scientists can see by looking through their own microscopes. They can look at multiple zebrafishes developing. We can do various things to perturb the development of the zebrafish, whether it be to introduce some kind of chemical into the water in which they're swimming or to manipulate the genes of the zebrafish . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . . in ways that allow us to understand exactly what's happening— because we're able to observe it happening.


Systems Biology

  • Other research focuses on relationships among genes
  • Gene regulatory networks are the intricate sequences of genetic switches that control embryo formation.
  • Understanding these networks may reveal new ways to treat or prevent birth defects.


Picture of gene regulatory network by Eric Davidson, et al. BioTapestry

Dr. Guttmacher: Systems biology is another tool for understanding the formation of organs in the embryo, and therefore, to really let us understand much better than we do today exactly how birth defects come to be. The systems biology approach allows us to look at gene regulatory networks. They are really quite intricate but very important in terms of controlling the switches that turn on and off certain parts of embryo formation, in a certain timed manner that's very important. So systems biology, by integrating these entire networks of genes involved, . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . . allows us to look at the complexity of organ development, whether it be in model organisms or in the human. We know that it's (the) interplay of multiple systems that is really important to understand the complexity of development.


Chemical Genomics

  • High-throughput screening of small molecules (like folate) may yield new therapies to ameliorate birth defects:
    • Losartan for Marfan/Loeys-Dietz syndromes
    • mGluR5 antagonists for Fragile X syndrome
    • GalK inhibitor for galactosemia

Dr. Guttmacher: Chemical genomics is another tool which is very useful, particularly in terms of developing new drug targets and new effective drugs for birth defects.  Chemical genomics allows us to use high throughput screening techniques of small molecules such as folate, and that can yield new therapies to really lessen the impact of birth defects. There are already several examples that are in development or actually have already been developed besides folate. One of them is the use of losartan for Marfan syndrome, a fairly common kind of birth defect that affects the structure of many parts of the body. There's also the development of an mGluR5 antagonist for Fragile X syndrome, which is an inherited condition that leads both to intellectual and developmental disability and certain structural changes in people who are born with it. As well as that there are also galK inhibitors for galactosemia, . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . . which is not something that causes a structural birth defect, so much as it causes significant developmental problems which are present at birth in that it's an inborn error of metabolism, as we call it.  Something that is present at birth in the way we metabolize things and that's another very useful approach that again has come out of this chemical genomics approach.


Video of robots in chemical genomics facility.

Dr. Guttmacher: You can see on the screen now robots in the chemical genomics facility using this very high throughput approach whereby one can screen potentially tens of thousands, if not hundreds of thousands, of small molecular compounds in a very short interval to see whether they have actually— there was an antagonist or an agonist involved in the pathways that you're particularly interested in for a given birth defect.

Dr. Guttmacher on camera

Dr. Guttmacher: There are many other research opportunities on the horizon, we think that will allow us to again better understand birth defects and be able to prevent and treat them more effectively.


Other Future Research Opportunities

  • Develop a complete genetic map of common and rare structural and functional birth defects
  • Delineate environmental (e.g., teratogens, radiation) interactions with the genome – of both the mother and fetus
  • Develop new, non-invasive tools to assess development in utero


Pictures of DNA double helix and embryo

Dr. Guttmacher: One of our goals is to develop a complete genetic map of common and rare structural and functional birth defects, if we have that complete genetic map that gives us many more possible drug targets to intervene with. Another idea is to delineate the environmental interactions with the genome. That is, things that cause birth defects: whether they be radiation exposure, chemicals, drugs, other kinds of things, to understand exactly how they interact with the genome of both the mother and of the fetus, because we think genomes are important. And again, the interaction between these environmental factors and these two genomes that leads to birth defects in certain situations. Another approach is to develop new, noninvasive, tools to assess the development of the human in utero.

Dr. Guttmacher on camera

Dr. Guttmacher: It would be wonderful if we could somehow observe human development the way we can the zebrafish. We'll never be able to do quite that, but it would be very useful to have better tools for noticing what's going on in human development actually as its happening rather than having to rely completely on other kinds of models.


Future Research Opportunities

  • Study all drugs (including over-the-counter medicines) in pregnant women.


Picture of a man and a pregnant  woman

Dr. Guttmacher: Another important research opportunity comes from the fact that the vast majority of drugs used by pregnant women have never been studied in pregnancy; these can be drugs which a woman is using because of some complication of pregnancy.

Dr. Guttmacher on camera

Dr. Guttmacher: Maybe a woman develops high blood pressure during pregnancy and needs to be given a drug to control her blood pressure both for her own health and for the health of the fetus or it can simply be a drug, maybe even an over-the-counter drug, that the woman was using before she became pregnant because of some underlying medical condition or some health concern and she continues to use during pregnancy.  Whichever category of drug, the chances are it's never been studied in pregnancy so we don't truly know the effects on the fetus. This is a huge— not only research opportunity— I would say, but a huge responsibility. We need to do a better job of studying these drugs when they're used in pregnancy when both women can be vulnerable and certainly the fetus is particularly vulnerable.



  • Research has yielded important understanding to help prevent and treat some birth defects.
  • We must take advantage of scientific advances and new tools to learn more about the causes of birth defects, and translate those findings into effective therapies and prevention strategies.

Dr. Guttmacher: So, in summary, I hope that I've shared with you pretty convincing evidence that research has already yielded an important understanding that really does help us prevent and treat birth defects. But that we're at the beginning of an era where we have new scientific tools, new kinds of approaches, . . .

Dr. Guttmacher on camera

Dr. Guttmacher: . . . having the human genome in hand, having the power of chemical genomics, these kinds of approaches that are recent tools for us. That we are at the beginning of an era where we believe we can harness these kinds of new tools to have a completely new, and much more in-depth, understanding of exactly how birth defects come to be and, based upon that understanding, have much more effect with strategies for treating and for preventing birth defects.


For more information, visit:

Picture of kids playing

Dr. Guttmacher: If you'd like more information about this and related topics you should visit the NICHD-- that is the National Institute of Child Health and Human Development website.

Dr. Guttmacher on camera

Dr. Guttmacher: Thanks very much for your attention to this and we welcome your interest again in treating and in preventing birth defects.


Eunice Kennedy Shriver
National Institute of Child Health & Human Development

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