NEW HAVEN, Conn. (Ivanhoe Newswire) -- Here’s a frightening statistic: One in every fifty school children in the US will be diagnosed with autism. Unfortunately, it can take doctors years to identify the disorder, delaying much needed treatment, but a new research may help doctors predict a child’s risk of developing autism – at birth!
Skiing alongside 12-year-old Jaya Dominici, you wouldn’t know that she’s severely autistic, unless, you try to talk to her. Maria suspected her daughter was autistic at 18-months, but she wasn’t diagnosed until three. “It was really like a baseball bat right to the head, because you know it’s going to be forever," Maria Dominici, Jaya's Mother, told Ivanhoe.
Early detection is critical, because “the brain is completely unformed at birth. We can change behaviors very early,” Doctor Harvey J. Kliman, MD, PhD, a Research Scientist in the Department of Obstetrics and Gynecology at the Yale University School of Medicine, told Ivanhoe.
A new study examining the placenta, the organ that provides nutrients to the baby from the mother, may help doctors diagnose autism shortly after birth. Researchers analyzed placentas from 217 births and found that in families at high genetic risk for having an autistic child, there were more of these abnormal folds and creases.
Researchers won’t know how many children, whose placentas were studied, will have autism for at least another year, but for Maria, it would have helped me to get earlier intervention,” Dominici said.
The study is a joint effort by researchers at Yale University’s School Of Medicine and the University Of California at Davis. Doctor Kliman says the test will be available in the next few months. You may also be interested in learning that boys are four- to-five times more likely to have autism than girls.
Harvey J. Kliman, MD, PhD, Department of Obstetrics and Gynecology at the Yale University School of Medicine, talks about using the placenta to help predict autism.
How did you get into working with placentas?
Dr. Kliman: Well, you would never plan on something like this. The only way to do something like this is by accident; that is what happened with me. I have been working on the placenta since the early 1980s when I was a resident and a research fellow at the University of Pennsylvania. I started working on the placenta and amazingly as soon as I started working on the placenta, all of the people in pathology said, ‘well you are interested in the placenta, you can look at all of these placentas then’ and they literally started giving me all of the placentas in the whole department. While I was in that lab, I figured out some basic cell biology of how the placenta is actually put together; how the cells grow; what makes a normal shaped placenta and an abnormal placenta. So, that is the basic science.
How did you come to Yale?
Dr. Kliman: I was recruited to Yale by the Chairman of Obstetrics and Gynecology. I have been here for about 22 years now. When I first came, my responsibility was to look at pregnancy loss cases and pregnancy complications and what I had noticed is that many of the cases that were pregnancy losses or complications had an abnormal feature; an abnormal folding of the way the placenta grew. Typically, what the textbook said is that when you see that, it is a specific genetic diagnosis of one egg and two sperm going into the egg and that is called triploidy. The reason you have to make that diagnosis is that a small percent of those women go onto have something called choriocarcinoma, which is a cancer of their pregnancy. So, you have to make sure that you do not have that.
What did you discover when you started looking specifically at these types of cases?
Dr. Kliman: When I started looking at those cases, I found that about half of them were these abnormal pregnancies with the one egg and two sperm. However, the other half were not triploid and I went to the genetics lab and I said, ‘what gives with these cases? They have the abnormal folding pattern, but they are not these triploid pregnancies’ and they said, ‘well Harvey, in that case, it was Trisomy 21 or it was Trisomy 13 or it was Trisomy 18. These are different genetic complications that can lead to a pregnancy loss.’ So, I thought in my head, the textbooks say that these abnormal folds are specific to one condition. I think it is a much more general marker for abnormal genetic pregnancies and that went on for many years. I did not really think too much of it. I used it in my clinical practice, so when patients came to me I would look at the placentas and I would say that is what I think it is. Then, one day, I was given two cases to look at; two placentas from children who had Asperger’s syndrome, which is a form of autism. This was about 10 to 12 years ago and unfortunately about 10 to 12 years ago, Wakefield in England published in the Lancet that the MMR vaccine caused autism. The problem with that is it has been proven to be completely wrong.
Could you tell us about the amazing study you are doing with placentas that is helping to predict autism?
Dr. Kliman: I do lots of medical legal consultations and I was asked by some lawyers to look at specific cases and I looked at them and I saw, the same abnormal folding pattern that I had been seeing for many years in genetic cases and I said, ‘wow, I do not know much about autism,’ in fact, let me rephrase it, I know nothing about autism. I know that the press now thinks it is due to this vaccine problem, but I am looking at the placentas and I think it is actually a genetic problem. There is something wrong with the genetics of the pregnancy. So I thought that was unusual, but what am I going to do about it. How will I prove that? I happened to be at a dinner party and sitting next to me was a man, a doctor with a PhD here at Yale, George Anderson who works at the Yale Child Study Center and he told me what he did and I told him what I did and I said, ‘could you get me some placentas from children with autism?’ And he said, ‘well I don’t know, but we do have a lot of children who have autism that we have seen; maybe we can go back and see which of those cases we can find the placenta.’ So, it took about four years to do the study, but we actually found 13 cases of children with proven autism; we had their placentas and we compared them to controls and we found that the children with autism had a much higher frequency of these abnormal folds. So that was encouraging.
You were right, correct?
Dr. Kliman: It sort of suggested that my initial observation was true. However, 13 cases is not enough to really go out to the public and say, hey I have a test for autism now. So, things were very quiet for a number of years. That was published in 2006. Finally on November 1, 2010 on the front page of the New York Times in the upper left hand corner was an article about the group from the University of California in Davis and they were doing a study of families who already had one child with autism and they thought that the cause of autism was environmental exposure; some toxin in the environment. That has some logic because there are more toxins in the environment, the incidence of autism by some people seems to be going up, and so maybe there is a connection. So their idea was to collect everything they could about the pregnancy, the environment and the placentas from these children who were born in families who already had one child with autism. We call those families the at risk families. In other words, they are at risk for having another child with autism. So, I called them up and I ended up talking with Cheryl Walker. She is an MD and obstetrician and she was responsible for collecting all of the placentas for the study.
How long did it take her to get back with you?
Dr. Kliman: It took her a couple of months. She sent me pieces of placenta and they came to my lab here at Yale and with the help of my technician and some students, we cut up the pieces into four different pieces. We ended up with 868 slides of pieces of placenta.
After you cut them; what did you do next?
Dr. Kliman: We mixed them all up so they were random and it took about 2 to 3 months to look through all those slides. And, when I was done, I said, ‘Cheryl, here are the results, call me in a couple of years when you know what happens to these kids.’ And she said, ‘well Harvey, I have a little something to tell you which I did not tell you before. I sort of tricked you. I was not sure that what you were talking about was real, and I did not want to do something without having the right controls, so I actually only gave you only 117 cases from the at-risk families and 100 placentas from normal controls’.
Why did she do that?
Dr. Kliman: She did it because she did not really think that I could figure out the difference between the two groups. For me, I was really excited because this now gave me the opportunity to compare the at risk placentas to the controls and see if they are different. And what we found when we actually looked at the data, there is a tremendous difference between those groups. The at-risk placentas have many of these abnormal folds and the controls have almost none. And it is very easy to tell the difference.
I bet they were shocked?
Dr. Kliman: They were shocked at UC Davis; I was shocked. This has now turned a very powerful test that we can use this test, at birth, for families that do not know if they are at-risk. Now we have something where the at-risk has a lot of these inclusions and abnormal folds and the controls don’t, so just by looking at the placenta, at birth, we can tell which group a family is in. If they are in the positive group, my goal is to be able to do things for these children, not myself personally, because I do not do this, but to have them go to specialists who will be able to observe the children, teach the parents to watch for certain milestones, and then actually intervene with newborn behavioral intervention, very early intervention, that can improve the outcomes of these children.
How significant is this in helping with the early detection of autism?
Dr. Kliman: Before this test, the PlacentASD test, as we call it, there is no method at birth to know this at all. There is zero method, so parents would normally, if they do not have a child with autism already, not notice this until the child is two or three years of age. The CDC, the Centers for Disease Control, who looks at the frequency of autism and the prevalence; how many families have it, they recently came out in March of this year with an estimate of 2%; 1 out of 50 children now born in this country are diagnosed with autism. They have actually shown that sometimes families do not know until their child goes to school in kindergarten.
Why don’t parents know?
Dr. Kliman: Parents do not know all of the different milestones that their child should be reaching, but a teacher who sees lots of children says, Johnnie is not quite the same as the rest of the kids and I would like you to take your child to a specialist to maybe look to see if something is going on. In the past, they would have to wait a long time if they had no hint that there was any autism risk in the family. Having this test be positive at birth gives us a really special opportunity to do something.
Why is that?
Dr. Kliman: The brain is completely unformed at birth. It is basically a clean slate, so you are able to do things with a young child that you cannot do later. It gets to the point where the brain is so wired and formed that it is hard to change behaviors. For example, people know that young children can learn multiple languages. If you have a family that has a French speaker and an English speaker, and they teach both languages to a young child, the child can actually learn both languages. I can tell you, at this point, I could never do that. My brain is too set, and the older you get the more difficult it is to make changes. So knowing at birth really gives us a golden opportunity to have the best positive potential outcome for these children.
So, just help me here, how significant is that because there is no cure for autism. People, who are diagnosed, if that is the correct term with autism, live with that for their life and there are obviously therapies, etc. to try and help them. So, what is the significance of this?
Dr. Kliman: That is a great question and while it is true that the genetic basis for what causes autism is in these people, if we have early intervention, we can help these children become socialized, so they can fit in to the point where we cannot even tell that they have any condition. Let me also point something out, people have said to me, ‘can this test be used for prenatal diagnosis, diagnosis before delivery, because maybe a family would want to terminate a pregnancy.’ And I am completely against that. The reason is, is that these children are exceptional. Many of them are very smart. There are many professors with autism at MIT right now. When we look at Google and Facebook and Microsoft, and maybe even Apple computer, we are talking about people who are brilliant; who are very creative, but they are not quite adapted to social interactions. They are not as empathetic as a normal person might be for example. If we can train children early to respond to someone being upset, or someone being hurt, we can take someone who is exceptional, and actually very smart, with spatial recognition and mathematics, and things like that, and have them be happier. That is why I think it is so important to make this diagnosis early to give these children, and then adults, the best chance possible to be productive members of our society.
What about the gender difference, because autism affects one gender more than the other, doesn’t it?
Dr. Kliman: Well that is a very interesting question. Boys are much more commonly affected by autism than girls. I think it is 4 to 5 times the frequency. We do not quite understand that. Early on in my studies, I wanted to know is there a difference in the folding pattern between the girls and the boys in the at-risk group and they are the same. So, basically, once you are in the at-risk group, boys and girls seem to be about the same in those families, but why particular families are affected and why boys have it more often, we are really not sure at this point.
Where does the research go from here because like anything, it often is a springboard into something else, so where do you go from here doctor?
Dr. Kliman: There are two aspects that I am interested in. First of all, we need to see the outcomes of all the children in the at-risk group that we looked at from the University of California at Davis. Their study is called the MARBLES Study and that is where these patients came from. We have another year or two or maybe even three before we get all the final diagnoses. However, the early indications are that these children from these at-risk families do not just have autism, but they have other neurodevelopmental conditions for example, obsessive compulsive disorder, ADHD, attention deficit disorder hyperactivity; so it is probably going to be a broader umbrella of what these children have besides just autism, so one thing is to see what happens to the children.
And the second?
Dr. Kliman: The second avenue that I am interested in is trying to understand the basic biology. We still have these specimens and the nice thing is that we can actually look at them and ask simple questions of why are the placentas in the at-risk group different than the controls and we have some markers that we are looking at. Maybe by studying those, we will understand what the basis is for this. The third avenue is what we talked about before a little bit, what can we do to change the lives of these children and I have now engaged with a number of Centers both locally and nationally and I am going to meet with some in London, when I go there in a few weeks, to see what we can do about early intervention. Nobody has created a framework for dealing with newborns in terms of this diagnosis. So this is a completely uncharted area. I think that is an exciting avenue too; to help the people who do therapy for older children; showing them how they can apply it to younger ages.
Is the test available now? Can parents, who just had a baby able to participate?
Dr. Kliman: The ideal time to do the PlacentASD test is at the time of delivery. The plan is, is that when a family is pregnant; they will actually sign up for this test. We will send them a box, where they can send the placenta back to us here at our lab at Yale, and at the time of delivery, the placenta will be put in a container, snapped closed, sealed, and shipped to our laboratory. Once there we will cut it up, process it, and look to see if it is abnormal or normal. However, there are families that already have a child, maybe the child is 3 or 4 or 10 and they might be interested to know if their child has the same marker; in that case, we can go backwards if the placenta was sent to the local pathology department; if the slides exist in drawers in those pathology labs, we can also look at them.
What is the main thing you deal with parents with an autistic child?
Dr. Kliman: One of the things I deal with a lot with families is guilt; and one thing I need to make clear is it is nobody’s fault that your child has autism. This is not caused by anything a mother does during her pregnancy. It is not caused by vaccines. It is not caused by the diet or anything else that someone might do; most likely the major component is genetic with a potential small component of the environment. I think the main component is genetic and given that, there is really nothing that the parents could have done to prevent it. So sometimes simply doing this test to help them deal with the guilt, they may have, is a useful way to approach it.
How exciting is all of this, not only for you as part of the research team, but for people in general?
Dr. Kliman: I am very excited. I mean, I have been working as an MD/PhD for 35 years now doing various aspects of research. I have been happy and proud of many of my contributions, but this one feels very special to me, because I think this one has the potential to affect many, many children to improve their life outcomes and I hope improve society.
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