link Abnormal placental folds signal autism risk at birth.
Researchers at the Yale School of Medicine have figured out how to measure an infant’s risk of developing autism by looking for abnormalities in his/her placenta at birth, allowing for earlier diagnosis and treatment for the developmental disorder. The findings are reported in the April 25 online issue of Biological Psychiatry.
One out of 50 children are diagnosed with an autism spectrum disorder in the United States each year, according to the Centers for Disease Control and Prevention (CDC), but the diagnosis is usually made when these children are 3 to 4 years of age or older. By then the best opportunities for intervention have been lost because the brain is most responsive to treatment in the first year of life.
Senior author Dr. Harvey Kliman, research scientist in the Department of Obstetrics, Gynecology & Reproductive Sciences at the Yale School of Medicine, and research collaborators at the MIND Institute at the University of California, Davis, have found that abnormal placental folds and abnormal cell growths called trophoblast inclusions are key markers to identify newborns who are at risk for autism.
Kliman and his team examined 117 placentas from infants of at-risk families, those with one or more previous children with autism. These families were participating in a study called Markers of Autism Risk in Babies – Learning Early Signs. Kliman compared these at-risk placentas to 100 control placentas collected by the UC Davis researchers from the same geographic area.
The at-risk placentas had as many as 15 trophoblast inclusions, while none of the control placentas had more than two trophoblast inclusions. Kliman said a placenta with four or more trophoblast inclusions conservatively predicts an infant with a 96.7% probability of being at risk for autism.
Currently, the best early marker of autism risk is family history. Couples with a child with autism are nine times more likely to have another child with autism. Kliman said that when these at-risk families have subsequent children they could employ early intervention strategies to improve outcomes. “Regrettably couples without known genetic susceptibility must rely on identification of early signs or indicators that may not overtly manifest until the child’s second or third year of life,” said Kliman.
“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 will have early interventions and an improved quality of life as a result of this test,” Kliman added.
Other authors on the study include Kaitlin Anderson, Kristin Milano, and Saier Ye of Yale University; and Cheryl Walker, Daniel Tancredi, Isaac Pessah, and Irva Hertz-Picciotto of UC Davis.
The at-risk placentas had as many as 15 trophoblast inclusions, while none of the control placentas had more than two trophoblast inclusions. Kliman said a placenta with four or more trophoblast inclusions conservatively predicts an infant with a 96.7% probability of being at risk for autism.
Interesting. Can someone help me understand the 96.7% number above though? Maybe it's too early in the morning or something for me. It's not ~97% chance the child will be autistic but rather ~97% chance they will be at risk?
Fascinating. I really hope we can make some breakthroughs in autism soon so that mothers can stop blaming themselves for things they may or may not have done.
rbp as one of our local scientists, can you come decipher the stats?
Ha, I was just reading this and trying to make sense of it. I've got nothing so far. (I am entirely self-taught in statistics, so some studies go over my head.)
The at-risk placentas had as many as 15 trophoblast inclusions, while none of the control placentas had more than two trophoblast inclusions. Kliman said a placenta with four or more trophoblast inclusions conservatively predicts an infant with a 96.7% probability of being at risk for autism.
Interesting. Can someone help me understand the 96.7% number above though? Maybe it's too early in the morning or something for me. It's not ~97% chance the child will be autistic but rather ~97% chance they will be at risk?
I think it means that if you randomly looked at a placenta and tried to predict whether that placenta came from a mother of a previous child with autism (i.e. a baby at high risk) or a mother of a previous child without autism (lower risk) if the placenta had 4 or more trophoblast inclusions there would be a ~97% chance it came from a mother of a previous child with autism.
but are OBs going to be trained and take the time to actually look at the placenta after birth??
The study is interesting, and they might someday if other findings continue to corroborate this one, but the study was published over 2 years ago and obviously there hasn't been a big revolution in this area.
Interesting. Can someone help me understand the 96.7% number above though? Maybe it's too early in the morning or something for me. It's not ~97% chance the child will be autistic but rather ~97% chance they will be at risk?
I think it means that if you randomly looked at a placenta and tried to predict whether that placenta came from a mother of a previous child with autism (i.e. a baby at high risk) or a mother of a previous child without autism (lower risk) if the placenta had 4 or more trophoblast inclusions there would be a ~97% chance it came from a mother of a previous child with autism.
Thanks kershnic. After reading the study, this is also what I got out of it. It appears that the authors did a blind analysis of placentas from high-risk parents and a control group (i.e., the research analyzing the placentas didn't know which group the placentas had come from). But they hadn't yet followed the kids from these groups to see if they were ultimately diagnosed with autism. So as of publication, all they can report is a strong correlation between this unusual feature on placentas (the TIs) and familial risk of developing autism.
Sort of weird that no one has replicated this study, which was published over 2 years ago. On the surface, it could support the notion of prenatal maternal infection or autoimmune disorders being associated with an increased risk of ASD. Or if the folds are somehow associated with premature delivery which seems to be associated with a greater risk of ASD.
Points that strike me about this-
The concept of developing autism. Many parents I know feel their child had autism from birth rather than "became autistic" at some point in time. There are parents who can pinpoint a line in the sand. I suspect this difference, supports my next point.
The notion that ASD is a single condition. I suspect that, in time, ASD will be proven to be a collection of condition with a similar set of behaviors and deficits. It could explain differences in IQ, atypicality, comorbids, and outcome.
The stated 9x greater risk seems high. Most studies from that point in time put the risk at 7 fold in general. The risk is lower for girls (~10% of younger female sibs vs ~25% of boys) and higher if the child has 2+ older sibs with ASD (~33%).
The notion of Early Intervention being "critical" and "Improving quality of life" is sort of vague. What improvements have been documented.
There was an article on BBC recently which said that children (not sure of age off the top of my head) who are autistic will sniff unpleasant odors as long as they will sniff pleasant odors. Children who are not autistic spend less time sniffing unpleasant odors.
The hope is that autism could be diagnosed, or at least screened for, earlier than it is currently.
but are OBs going to be trained and take the time to actually look at the placenta after birth??
Both of my OBs who delivered my kids took the time to show my the placentas and explain them a little. I had asked in advance though, so they knew I wanted this. I have no idea what a trophoblast is, or if they were present or not.
I read an interesting article last year about placentas in general, and how the health of the placenta can influence the health of children in a host of ways. I'm assuming this is one arm of the research going on.
Interesting stuff, but it will have to be validated big time before it's put into practice.
You don't really need to know to understand the study, as long as you're not the one who needs to examine placentas. I believe it just means a specific type of abnormal cells in a specific area of the placenta. The trophoblast is the outer layer of cells from the embryo I believe, but that continues developing with the fetus and placenta.
EDIT: Apparently these trophoblast inclusions are previously known to be associated with several genetic issues.
You don't really need to know to understand the study, as long as you're not the one who needs to examine placentas. I believe it just means a specific type of abnormal cells in a specific area of the placenta. The trophoblast is the outer layer of cells from the embryo I believe, but that continues developing with the fetus and placenta.
I wonder if this can be seen with the naked eye, or does it need to be examined microscopically?
I didn't click on the link, so sorry if this was addressed
You don't really need to know to understand the study, as long as you're not the one who needs to examine placentas. I believe it just means a specific type of abnormal cells in a specific area of the placenta. The trophoblast is the outer layer of cells from the embryo I believe, but that continues developing with the fetus and placenta.
I wonder if this can be seen with the naked eye, or does it need to be examined microscopically?
I didn't click on the link, so sorry if this was addressed
It's not just a naked eye thing, it's an involved process requiring equipment and training.
From the article:
Placentas were obtained shortly after birth, chilled, and maintained until processing, with a time interval between birth and fixation of 1–24 hours. Randomly selected 3 × 3 cm full-thickness samples were taken, de-identified, and placed in 10% phosphate-buffered formalin for between a few days to 3 years before they were batched and sent for histopathologic evaluation at the Yale Reproductive and Placental Research Unit.
Each placental sample was cut into five equal slices, four of which were placed into 25 × 30 mm cassettes, processed in the Yale Dermatopathology Histology laboratory, embedded in paraffin, microtomed at 5 μm, placed on routine glass slides, and stained with hematoxylin and eosin. The final observable cross-sectional area averaged 315 ± 90 mm2. The 868 resulting slides were randomized (http://randomizer.org) and read in numeric order by an experienced placental pathologist
Well, that makes so much sense rbp I will just stick to my lawyering lol.
No! I didn't mean to be snippy!
I have lots of stupid questions about the law LOL. I would be crucified on CEP.
OH, I didn't mean you were being snippy. I just still have no clue what I was looking at lol. I just meant I will stick to lawyering because at least I understand that...sometimes anyway
I have lots of stupid questions about the law LOL. I would be crucified on CEP.
OH, I didn't mean you were being snippy. I just still have no clue what I was looking at lol. I just meant I will stick to lawyering because at least I understand that...sometimes anyway
The figure I posted is a little much; it shows a bunch of different types of TIs. I just wanted to give you an idea of what the researchers were looking at. I'm not sure if there's any indication of TIs to the naked eye.
The TIs at the bottom of the figure are calcified, which means they're older. (This is not a topic I know much about, so I'm just trying to interpret the paper as I go.)
I wonder if this can be seen with the naked eye, or does it need to be examined microscopically?
I didn't click on the link, so sorry if this was addressed
It's not just a naked eye thing, it's an involved process requiring equipment and training.
From the article:
Placentas were obtained shortly after birth, chilled, and maintained until processing, with a time interval between birth and fixation of 1–24 hours. Randomly selected 3 × 3 cm full-thickness samples were taken, de-identified, and placed in 10% phosphate-buffered formalin for between a few days to 3 years before they were batched and sent for histopathologic evaluation at the Yale Reproductive and Placental Research Unit.
Each placental sample was cut into five equal slices, four of which were placed into 25 × 30 mm cassettes, processed in the Yale Dermatopathology Histology laboratory, embedded in paraffin, microtomed at 5 μm, placed on routine glass slides, and stained with hematoxylin and eosin. The final observable cross-sectional area averaged 315 ± 90 mm2. The 868 resulting slides were randomized (http://randomizer.org) and read in numeric order by an experienced placental pathologist
Thanks. Yeah I don't see this ever being routine, but it's an interesting study!
It's not just a naked eye thing, it's an involved process requiring equipment and training.
From the article:
Placentas were obtained shortly after birth, chilled, and maintained until processing, with a time interval between birth and fixation of 1–24 hours. Randomly selected 3 × 3 cm full-thickness samples were taken, de-identified, and placed in 10% phosphate-buffered formalin for between a few days to 3 years before they were batched and sent for histopathologic evaluation at the Yale Reproductive and Placental Research Unit.
Each placental sample was cut into five equal slices, four of which were placed into 25 × 30 mm cassettes, processed in the Yale Dermatopathology Histology laboratory, embedded in paraffin, microtomed at 5 μm, placed on routine glass slides, and stained with hematoxylin and eosin. The final observable cross-sectional area averaged 315 ± 90 mm2. The 868 resulting slides were randomized (http://randomizer.org) and read in numeric order by an experienced placental pathologist
Thanks. Yeah I don't see this ever being routine, but it's an interesting study!
I guess that if a link between TIs and autism risk can be confirmed, then maybe this analysis will be recommended for couples with other risk factors? It definitely doesn't sound like an analysis that would become standard for all births.
OH, I didn't mean you were being snippy. I just still have no clue what I was looking at lol. I just meant I will stick to lawyering because at least I understand that...sometimes anyway
The figure I posted is a little much; it shows a bunch of different types of TIs. I just wanted to give you an idea of what the researchers were looking at. I'm not sure if there's any indication of TIs to the naked eye.
The TIs at the bottom of the figure are calcified, which means they're older. (This is not a topic I know much about, so I'm just trying to interpret the paper as I go.)
Interesting. My placenta had calcifications even though DS was born a little early 39 weeks.