Prenatal Programming: Christopher Coe
1. How did you become interested in the relationship between the prenatal environment and lifespan development?
> I wish I could say I had a crystal ball at the beginning to actually know where my career would go. It wasn't quite that well planned out. I was interested in, as an undergrad, in the human condition, broadly. Why do we behave the way we do? How come our physiology is the way it is? What is the relationship between the brain and behavior? And so it was through those interests that I became interested in the origins of those relationships, the explanations for why we behave the way we do. And that led me naturally to look at the development of those systems and that behavior. And so it wasn't so much that I made a conscious decision at the beginning to become someone who studies infant development in humans and in animals, but that in the process of trying to figure out those other answers to the big questions, as I saw it as an undergrad, it became evident to me that we had to seelearn more about how they they come to be. And what that means for me today is not just studying it in a developing child or a young infant animal, but actually going back even further into prenatal life and studying fetal development and the relationship between moms and their babies even before the moment of birth.
2. What is your current area of research?
> For many years, I studied the relationship between biology and behavior. And that typically meant in the post-natal life, after the moment of birth, meaning that there was a living animal or a living child that I studied. And that was interesting, and I don't feel bad at all about having spent maybe 10 to 15 years of my career on that topic, which are, "What are the implications of the early rearing environment?" "What affect does stress have, or parenting have, on the development of a child or a young animal?"
But as I continued that work, I became increasingly interested in what happens even before the moment of birth and the degree to which prenatal events, fetal events, fetal experiences, the relationship between a mother and her baby... before the moment of birth start us on a certain path -- a path towards health or a path towards illness -- creating temperament, determining the kind of brain we would have.
And so today, much of my research is focused on that question: "How pre-formed are we already by the time we come out of our mothers?" If I were to pose it as a question, I would say -- if I were to ask somebody, what were the most important nine months of their life, if they had done research of the sort I do, I think they would include the most important nine months of their life for setting them on a certain path, either towards health or towards illness, was before the moment of birth. And then the question I would follow that up with would be, "How much do you actually know about those nine months? Have you ever asked your mother, was she sick? Did she have morning sickness? Was it a stressful or an easy pregnancy? Were you a term baby? How much did you weigh? Did your mother drink? Did she smoke? Did she eat allergenic foods?" Most of us know very little about what I would say are the most important nine months of our life.
3. What is “prenatal programming”?
> I wish I could claim that the term "pre-natal programming" was mine. The person who probably deserves the most credit, it's not that there were no other researchers, but the one who deserves the most credit is an epidemiologist named David Barker. And he has documented at the population level, society level for humans that when there have been adverse circumstances during pregnancy and usually he focuses on under nutrition or malnutrition, that it changes the growth rate of babies, not surprisingly. But what is surprising is that they then come out with a very different physiology such that if they now are exposed to a good world, a world with high nutrition, high calorie foods, that those same babies are pre-disposed to obesity. He describes it as having developed a "thrifty phenotype." Having experienced in utero that it might be an adverse world where there wouldn't be enough food, the regulatory aspects of their metabolism shift to be, if you will, greedy, a bit avarice with calories and food such now, such that if they come out into a world, let's say they're adopted from a third-world country into an industrialized one, they are predisposed to obesity and with that predisposition comes a greater risk for cardiovascular disease and a greater risk for diabetes. So the notion of pre-natal programming began with that, with this idea that under nutrition, poor growth could change you. But it has been broadened considerably beyond that to include the programming of the brain, the programming of the immune system and the degree to which all aspects of our being maybe even our temperament and behavior, our stress reactivity may be, if you will, preset or programmed by events that happen in utero.
4. How might illness during pregnancy affect prenatal programming?
> A kind of study that I do now is to ask the question, "Suppose there was a viral infection, suppose a woman had a very serious flu during her pregnancy. Is that the kind of event that could change the baby's developmental course such that after birth it is now different." In the psychiatric literature, there has been a long concerned suspicion that one of the risks for developing schizophrenia is that your mother was sick during pregnancy and specifically the focus has been on flu, although most of us think of flu as benign, just a disease you have for a week and get over. That's true for most of us, but it's not necessarily the case, if you're pregnant. It turns out that 1 in every 10 women, during their pregnancy, has the flu so we're not talking about a small number of women or their babies and so what we're studying now is whether a flu infection during pregnancy could create the brain phenotype of schizophrenia. So schizophrenics have a different brain than psychiatrically normal people. The brain tends to be a little bit smaller. The brain has less grey and white matter and the ventricles are enlarged and so what we're studying is, "Is it possible that a flu infection could create the brain phenotype that one sees associated with schizophrenia?" And in our current studies, the answer is yes, that it is, that it is possible that a viral infection can do that. Which is not to say flu causes schizophrenia, but it counts as a risk factor or a pre-programming bias and then of course, it would depend on the kind of rearing environment you had and whether you had a good or a bad rearing environment. But if you had this predisposition and then on top of that you now were raised in an environment which pushed you further towards psychopathology, it would be hand in glove. You'd have the risk and the rearing environment which pushed you over the edge. It's not to say that it's irreversible, that it's destiny, that at the moment of birth you have to go down a certain path. It's just like a little marble falling down through one of those maze games and which path does the marble take? It's just been kicked over one a few or a few nails over and, or pegs over, and it's coming down the peg board.
5. Explain the importance of prenatal care, including the relationship between maternal nutrition during pregnancy and children’s health.
> The social policy, societal implications of this area, of this type of research is obviously that the prenatal environment matters. And then as a society, one would have to ask the question, "Are we doing enough for women? Are we providing enough support? Are we encouraging family values in the sense of the real meaning of the word? Are we encouraging the right kind of nurturing, supportive environment for women when they're pregnant to enable them to have not a stress free pregnancy, that would be hard to imagine, but one which is... a kind of a pregnancy which facilitates fetal development and enables the baby to start life out appropriately. And it goes beyond just sort of the obvious issues like giving women classes so they're less anxious about delivery. That's important. I'm not, but it also includes discussions about nutrition. I didn't give as an example that we're now becoming increasingly aware that allergies and asthma actually start prenatally. So even though asthma typically emerges at three to four years of age, it actually has its antecedents back in fetal life, and I can give as a personal example, I have a kid with nut allergies. Well, he's not a kid, he's a grown up now, but he was a kid once with nut allergies. Had I known that he had a genetic risk for allergies, my wife should have avoided nuts during pregnancy. I have two children, one with nut allergies, one without. So we would have needed a crystal ball; she ate nuts during both pregnancies. We would have needed a crystal ball to know which of our babies was predisposed towards allergies. But if you had that foresight, one would then want to avoid peanuts and cashews and other allergenic foods because we, we're now aware that the foods that women eat, some of the proteins will cross the placenta and so within two hours of a woman drinking a glass of milk or eating an egg both milk proteins and egg proteins will cross the placenta. And those are just two of many examples of this important relationship that I'm talking about between the mother and her developing baby and so when you ask, "What are the implications for society? The implications for medicine?" I would say it is a very important message.
6. What is the good news and the bad news about prenatal adversity, and how do mothers’ coping strategies promote resilience in their unborn babies?
> So in my answers to your prior questions I have always said "animals and humans," because these kinds of relationships and influences precede us, and so the good news is -- in, amongst the bad news -- the good news is mother nature has been dealing with this vulnerability for a long time, in a sense, as long as there has been in-utero development, as long as there have been mammals, and as a consequence, the good news for us is that we are remarkably resilient. Even as little babies we can withstand quite a hit and keep on going. And so while prenatal events do change us, a good pregnancy will probably last 'til the end and will go to term, and your baby will be healthy and normal, despite a certain amount of adversity. That doesn't mean there won't be an influence, but not necessarily a life-threatening one. There have been studies on the women who unfortunately lost husbands during 9-11, because of the age range of the men in the building at the time. Sadly, there were a lot of families, not only did they lose the breadwinner, but the women were pregnant at the time, and the studies of their babies indicate that the overwhelming majority went to term just fine, did not have a marked increase in pregnancy complications, delivery complications. So I guess the good news is we're pretty tough as a species. Women are, as they sometimes kiddingly say, the stronger sex. You were made that way because you have this extra job to do, which is to, at some point if you decide to, carry a baby. And so it's, at the same time, with one hand, I'm emphasizing the potential, the importance of prenatal influences, I think with the other hand, I have to equally say that our babies are remarkably resilient and can withstand quite a bit of buffer, buffeting and -- because they are in a sense buffered. The placenta buffers them some, and probably the greatest buffer is the mother's psychological state. I teach a class on stress and coping, and I talk about the importance of coping abilities. What, one of the things that distinguishes us from the animals is our incredible ability to rethink, reappraise situations, and to the extent to which women are able to do that, to accommodate, cope with the stresses in their lives, to the extent to which they get support from their husbands, family, society, that will enable them to withstand quite a bit of adversity without any bad outcome for their baby.
7. Why are pregnant women a unique population, and why is prenatal research so important?
> I'll answer that in an indirect way. I was sitting on a plane at one point and making sort of small talk conversation that one does with whoever is next to you in the plane seat, and this particular person happened to be with the World Health Organization and was on his way to Geneva and was instrumental in coming with disaster plans for countries where there are civil wars, environmental crises; and I asked him given my perspective, "Do you have anything special in place for pregnant women? So that when there are these horrible events that happen--wars, tsunamis, earthquakes, do you have anything in place that would give special attention to pregnant women? Not that everybody doesn't deserve help but that if what I've said so far is true we might have a greater concern about the well-being of fetuses during this kind of adversity." And he was surprised to hear me describe pregnant women as a unique population that would warrant our special attention. So during Katrina in New Orleans did we hear in the newspapers, did we have government agencies going out of their way to consider this the answer I would say is no. They're considered like other people and just normal in the sense and they are normal and they are regular people; but there may be some special needs which just even having this word. I think it's having the notion of prenatal program and for the most part I think we tend to view the nature nurture story beginning at the moment of birth. And so we mostly focus on our babies when they're born. Once you just open up your mind to thinking about fetal experience and we now know you can teach babies to learn; you can teach them food preferences. I have a friend, a colleague, who taught baby rats to like, or not like apple juice; so he injected apple juice into the amniotic fluid of rats and they rink the amniotic fluid as do all babies and he was able to teach a baby rate to either like or not like apple juice before it was born. And then after it was born it kept that preference. We now know babies can hear music. There's always that discussion about would it help to play Mozart during your pregnancy. Would that make your baby smarter or change his temperament. Well the answer is that they don't hear very well but they do hear and there's some evidence that their predilection towards one language or not. So whether a baby is going to come out and speak French or Chinese or English obviously it doesn't speak yet at birth but it hears language and we don't even fully know the ramifications of that kind of bigger perspective; and so I would say yes there are a lot of implications of these kinds of observations in animals and people.
8. Where do you see your research heading in the future?
> I have been doing research now for 35 years, and so one could think that after 35 years, I must be coming to the end, but I guess I would repeat the common statement that people make about research. That's that for every questions you answer you open up new questions to study. So that's sort of the case for me. And this may be the most exciting time to be in science of my 35 year career. The technologies, the techniques available to us today are just breathtaking. They're nothing shy of revolutionary in terms of the way they've opened up new avenues to answer these older questions. It wasn't that we never thought about prenatal influence, but today I can take a picture of a child's brain or an animal's brain without having to harm it in any way. So I use neuroimaging in my research, MRI. I study the development of immunity. We know much more about the immune system today than we ever did 20 years ago. I can literally count every white blood cell, the last single one. We have the machines where we beam 10,000 white blood cells down in a line, with a laser, bounce them off each one. I can count and tell you exactly what type of white blood cell it is. So if one's interested in studying the development of allergies and asthma, if one's interested in evaluating the status of the brain, this is an incredible time to be in science. A study that I was a part of last summer, we used a new techniques called proteomics, where you can, with a given fluid, whether it be blood or urine or cerebrospinal fluid, you can measure every single protein in it. So as opposed to measuring the way I used to, one hormone, one protein at a time, you now get a printout of every single protein in it, and so in this particular experiment, we were comparing infants who were normal, healthy, to ones that were iron-deficient, and we were comparing fluids from these two infants, and I could literally scan down hundreds, thousands of proteins simultaneously. And we found in this case that there were 12 that were different. So that kind of new technique, metabolomics, proteomics, insights into hte immune system, the ability to measure the immune system, neuroimaging, this is a very exciting time to be in science. And it's a particularly exciting time for psychologists, at least psychologists who are willing to take the time to learn this kind of biology, because it will require a new generation of psychologists who are comfortable both with thinking like a psychologist on the one hand, and thinking like a geneticist or molecular biologist on the other. To do that, in part, many of us, at least in my generation, do it through collaborations, through teamwork. And so that too is changing the nature of science itself, whereas when I first started in this area, you worked in your own lab, in a Mom and Pop shop, just by yourself, or maybe with one colleague and a few students, now my projects involve these incredible collaborations, where I work with nutritionists, neuroimaging folks, geneticists, it's literally changed the nature of how we work. And it's just assumed that this kind of research will be interdisciplinary. Today we do it mostly through collaborations, but I would expect the next generation will come up with people who are able to think themselves in all these different fields simultaneously. The old-fashioned psychologist who sat there with a clipboard and a questionnaire, well, there are sill things to be learned from self-report. But that's what I would say -- it's so 90s. The next generation is definitely high-tech psychology. We always have this discussion with the deans of my university, because they still think of us as a social sciences profession or department, and we're not. Psychology today utilizes all the tools of medicine, even molecular biology. So my lab is fully equipped to do every immune assay that a card-carrying immunologist would do, which is not something you might think a psychologist would have as a part of his or her repertoire.