Monday, 29 April 2013

Autism and the folding placenta

Men don't generally talk about placentas it has to be said. But today, in the name of blogging, I'm going to.

I'm going to start by telling you how the placenta really is a marvel of biological engineering. An absolutely vital part of our existence in-utero that nourishes us and protects us during our earliest days living in the amniotic sac. Little wonder that whole nations have come to revere the placenta as mother, sibling even doubles of ourselves (see here). Although I have to say I do draw the line at placenta pate.
 Folding time @ Wikipedia  

The reason for all this appreciation of the placenta follows the publication of a paper by Cheryl Walker and colleagues* who, as part of the MARBLES initiative (don't you just love these acronyms), reported that looking for trophoblast inclusions (TIs) in the placenta "could serve as a predictor for children at elevated risk for autism spectrum disorder (ASD)".

Trophoblasts by the way, are a specialised group of cells which play an important role in processes like embryo implantation. Trophoblast inclusions are abnormal cell cluster which form, "a distinctive microscopic placental morphological abnormality" linked to tissue folding described by some of the same authors in earlier work in this area**.

In the most recent paper, the authors detail the blinded examination of 117 placentas (used of course) from "at-risk" siblings of children already diagnosed with an autism spectrum disorder (ASD) compared with 100 control specimens for the frequency of TIs. Whereas control placentas had no more than 4 TIs, the at-risk sibling placentas "had an eight-fold increased odds of having two or more TIs" according to accompanying press.

Prediction values, as in blinded prediction of those at-risk siblings compared to controls were reported according to the number of TIs identified. In other accompanying press literature on this study, a figure of 90%+ accuracy is reported "to identify without prior knowledge which of the placentas came from the younger sibling of a child with autism, and which from another study participant who did not have autism in the family".  This however was offset by corresponding issues with sensitivity. The implication for this work being that examining placentas might yield either important information about the subsequent risk of a child developing autism or an ASD and/or lead to new clues about the prenatal environment linked to cases of autism.

I highlighted the previous paper by some of the authors in this area and note how in that study they were actually looking at archived placental tissue from those who were subsequently diagnosed with ASD (n=13). Indeed in that study, TIs were reported as present in 5 of the 13 samples from participants with ASD (38%) compared with 8 of 61 controls (13%). You can perhaps see from these figures that we are probably not talking about an all-or-nothing relationship when it comes to TIs 'predicting' autism or not.

There's no doubt that the Walker results are interesting and potentially informative if reproducible bearing in mind I'm still a little unclear on the hows and whys of TIs and autism risk. Sure, the authors speculate that this might be part and parcel of some of the genetic landscape of autism, given the link between TIs and chromosomal disorders***, but that might not be the whole story**** (thanks Natasa) and with some interesting knock-on effects***** (open-access). Please note I am not making links between any specific infection, autism and TIs at this point.

I'm very interested in this whole area of pregnancy and gestation as perhaps being critical times for autism, sorry the autisms; recognising that this area of investigation might not cover every case of autism - think regression for example. I'm minded also to take you back to the Barker hypothesis (see this post) and think whether or not one might extrapolate some of the work on placental functioning****** to overlap with autism risk? Just thinking out loud as others eminently more qualified than I already have.


* Walker CK. et al. Trophoblast inclusions are significantly increased in the placentas of children in families at risk for autism. Biol Psychiatry. April 2013.

** Anderson GM. et al. Placental trophoblast inclusions in autism spectrum disorder. Biol Psychiatry. 2007; 61: 487-491.

*** Kliman HJ. Structural abnormalities in the placenta. BMC Pregnancy and Childbirth. 2012; 12(Suppl 1): A3.

**** Banks J. et al. Chlamydia trachomatis infection of mouse trophoblasts. Infection & Immunity. 1982; 38: 368-370.

***** de la Torre E. et al. Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J Immunol. 2009; 182: 3735–3745.

****** Henrikson T. & Clausen T. The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstetricia et Gynecologica Scandinavica. 2008; 81: 112–114.

---------- Walker, C., Anderson, K., Milano, K., Ye, S., Tancredi, D., Pessah, I., Hertz-Picciotto, I., & Kliman, H. (2013). Trophoblast Inclusions Are Significantly Increased in the Placentas of Children in Families at Risk for Autism Biological Psychiatry DOI: 10.1016/j.biopsych.2013.03.006