MIND Institute, Yale study finds abnormalities in the placentas of children at risk for autism
A study by researchers at the UC Davis MIND Institute and the Yale University School of Medicine has found that more than 95 percent of the placentas of infants who are among those at the greatest risk of developing autism contained abnormal cells, called trophoblast inclusions, suggesting that the abnormality may hold promise as a very early marker for autism risk.
The researchers cautioned that the study found an association between trophoblast inclusions and autism risk, rather than a direct correlation with autism itself. The study is published online today in Biological Psychiatry.
“There's no evidence that the trophoblast inclusions themselves have any direct impact on neurodevelopment,” said Cheryl Walker, assistant professor in the UC Davis Department of Obstetrics and Gynecology and lead author for the study. “Rather, they are likely a symptom of altered physiology or a genetic predisposition, particularly given their association with other genetic abnormalities, and are almost certain to be triggered by environmental exposures.
“Given that they appear to result from dysregulation in cell proliferation, candidate exposures that we may explore in the future include physiologic states that can promote growth excess, including maternal obesity, excess gestational weight gain, diabetes, nutritional factors, and exposure to endocrine disrupting chemicals — all of which may influence growth in fetal tissues like the placenta and brain.”
Trophoblasts are specialized cells present as the earliest fetal tissue that are critical in embryo implantation and form the conduit for interaction between mother and fetus. Trophoblast inclusions are unusual microscopic findings marked by cell clusters that appear to represent abnormal tissue-folding within the placenta. They have been associated with a wide range of chromosomal abnormalities.
The research was conducted in participants in the Markers for Autism Risk in Babies — Learning Early Signs (MARBLES) Study, a collaboration of the MIND Institute and the UC Davis Center for Children’s Environmental Health.
MARBLES is conducted in families with the greatest risk for having a child who develops autism: those who already have at least one child with the condition. The study’s participants are followed before, during and after their pregnancies. Researchers obtain information about the pre- and post-natal environment to which the baby is exposed. The study obtains biological and environmental samples from study participants, including samples of their placentas following delivery.
For the current study, 117 placentas were obtained from women in the MARBLES Study and 100 from a random sampling of women who had at least one previous pregnancy, provided by the UC Davis Department of Obstetrics and Gynecology. The research found that the placentas of the at-risk mothers of children with autism contained as many as 15 trophoblast inclusions, while the placentas from the control pregnancies had at the most two.
“It will be exciting to learn sometime next year, when our MARBLES Study participants are old enough to have confirmation of their developmental status, whether trophoblast inclusions are associated with autism or other forms of developmental delay,” Walker said. “Whatever that research yields, we also want to learn what genetic and environmental influences are involved in the creation of these abnormalities in placental architecture.
“The depth and breadth of data that the MARBLES Study collects on environmental exposures leading up to conception, through pregnancy, breastfeeding, infancy and childhood, will allow us to explore these hypotheses and many more in the years to come.”
“This research provides what might turn out to be the first indication of a non-genetic biological marker of autism as early as birth,” said Irva Hertz-Picciotto, professor of public health sciences and principal investigator of the MARBLES Study. “Further work will determine what types of maternal/prenatal exposures and conditions, as well as genetics variants, might predict these trophoblast inclusions.”
Senior study author Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine, suggests that risk of autism may be diagnosed through examining the placenta at birth.
“I hope that diagnosing the risk of developing autism by examining the placenta at birth will become routine, and that the children who are shown to have increased numbers of trophoblast inclusions [in their placentas] will have the early interventions and an improved quality-of-life as a result of this test,” Kliman said.
Other study authors include Daniel Tancredi and Isaac Pessah of UC Davis and Kaitlin Anderson, Kristin Milano and Saier Ye of Yale University.
The study was funded by the National Institutes of Health Grants 1 PO1 ES11269 and R01 ES 015359, the U.S. Environmental Protection Agency Science to Achieve Results (STAR) program R829388 and R833292 and the MIND Institute and the Yale University Reproductive and Placental Research Unit.