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Key to early diagnosis of autism may be in the placenta

Researchers at Yale School of Medicine have discovered in the placenta what may be the earliest marker for autism, possibly helping physicians diagnose the condition at birth, rather than the standard age of two or older.

The findings are reported in the June 26 online issue of Biological Psychiatry. Autism is a developmental disorder that has a profound effect on socialization, communication, learning and other behaviors. In most cases, onset is early in infancy. Information on the earliest development aspects of autism in children has been limited even though approximately one in every 200 children is diagnosed with an Autism Spectrum Disorder (ASD). The earlier the diagnosis is made, the greater the treatment impact.

Current studies are searching for characteristics in children at risk for ASD so that the diagnosis can be made prior to age one. The ideal time for diagnosis would be at birth, according to senior author on the study Harvey J. Kliman, M.D., research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at the Yale School of Medicine.

In previous work, Kliman had observed an unusual pathologic finding in the placentas from children with Asperger Syndrome, an ASD condition which, like autism, impairs the ability to relate to others.

"By serendipity, at a dinner party I happened to sit next to George M. Anderson, a research scientist in the Yale Child Study Center who had access to many cases of children with ASD," said Kliman. "We realized that by working together we might be able to determine if this placental abnormality could be a useful clinical marker."

With the help of Andrea Jacobs-Stannard, a student in Kliman's laboratory, and Katarzyna Chawarska and Fred R. Volkmar of the Yale Child Study Center, the group designed a study to see if the placental abnormality, specifically the presence of trophoblast inclusions, was a marker for ASD. The multidisciplinary team of Yale researchers compared placentas from 13 children with ASD to those from 61 unaffected children for the presence of trophoblast inclusions.

They found that the placentas from ASD children were three times more likely to have the inclusions. Kliman and the team identified trophoblast inclusions by performing microscopic examinations of placental tissues.

"We knew that trophoblast inclusions were increased in cases of chromosome abnormalities and genetic diseases, but we had no idea whether they would be significantly increased in cases of ASD," said Kliman. "These results are consistent with studies by others who have shown that ASD has a clear genetic basis."

Trophoblast inclusions reflect abnormal folding of microscopic layers in the placenta and appear to result from altered cell growth. Kliman likened the presence of trophoblast inclusions to an automobile check-engine-light. "When the light goes on it simply means that something is not right," said Kliman. "If the light is on and there is, for example, steam coming from under the hood, then it is likely that the radiator is leaking. However, if the check engine light is on and there is nothing obviously wrong, then the car should be carefully checked."

The Yale team plans to replicate the evaluation with larger multi-center and prospective studies. They will examine the placentas of the children in the study in greater detail to gain insight into the biological basis of the inclusions in ASD.

Volkmar said, "If the work is confirmed by the next series of studies, then the finding of trophoblast inclusions at the time of birth in the absence of any obvious genetic abnormalities would be an indication to have a child examined by a specialist to determine the presence of ASD."

Karen N. Peart | EurekAlert!
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