Monday, 28 July 2014

Prenatal and neonatal blood mercury levels and autism

Acknowledging that some topics have the ability to furrow brows when it comes to autism research, mercury and autism is becoming something of a frequent talking point on this blog as a function of a whole slew of articles appearing in the peer-reviewed domain. If I were to [very tentatively] summarise the collected literature so far, it would be to say something like:

Mosaic of mercury @ Wikipedia 
(i) there is quite a bit more research to be done on some sources of mercury being 'linked' to cases of autism i.e. air pollution, fish consumption (see here),
and
(ii) the body burden of mercury for some on the autism spectrum is elevated (see here) compared to other groups and potentially linked to "a decreased ability to excrete mercury due to a combination of lowered reduced glutathione, emergence of oxidative stress, and excessive use of oral antibiotics" according to the review by Francesca Gorini and colleagues [1] (open-access).

I know some people may not like hearing that summary but that's my interpretation of the various reviews and meta-analyses conducted so far. I should add that I'm not though passing any specific comment on whether mercury 'causes' autism bearing in mind what we know about the developmental consequences of exposure.

The paper by Vincent Yau and colleagues [2] looking at maternal serum and infant newborn bloodspot levels of mercury adds to that literature with their conclusion: "levels of total mercury in serum collected from mothers during mid-pregnancy and from newborn bloodspots were not significantly associated with risk of ASD [autism spectrum disorder]". I believe we had seen this data presented before at the 2011 IMFAR conference too (see here).

A few details first:

  • Based on data obtained from the EMA (Early Markers of Autism) study, a cohort "identified from the California Department of Developmental Services (DDS)" records, mid-pregnancy maternal serum samples and the wonderful resource that is the neonatal bloodspots related to some 84 children diagnosed with an ASD were analysed for total mercury content (inorganic and organic mercury). Blinded results were compared with 159 population controls (asymptomatic) and 49 children diagnosed with a learning (intellectual) disability or developmental delay.
  • ICP mass spectrometry was the name of the analytical game, which as I've talked about before, is one of the methods of choice when it comes to the analysis of the metallome. Archived blood spot samples were subject to laser ablation as a function of their mounting. 
  • Results: "Maternal serum and infant blood mercury levels were significantly correlated among all study groups". In other words, maternal mercury burden seemed to be associated with neonatal offspring burden (albeit with a correlation coefficient ~0.4 which is OK but not exactly great).
  • Further: "Results for mercury levels in newborn blood samples were similar" across the groups. Ergo, at birth, levels of total mercury from neonatal bloodspots "were not significantly associated with risk of ASD". That's not to say that there weren't some differences in average levels of blood mercury levels across the groups, just that such differences were not deemed to elevate the risk of ASD overall.

Like quite a lot of the science in this area, there are several ways you could interpret these results. You could, for example say that the maternal burden of mercury during pregnancy was not associated with offspring risk of autism. You could also say that 'at or shortly after birth' (remember those words), blood mercury levels do not seem to correlate with the risk of autism. Therefore mercury is not a factor in relation to autism as per other results in this area [3]. You could say those things, as you might for several other variables supposedly related to autism... vitamin D for example? (see here and then see here).

But you might also consider the bank of research which has reported elevated levels of mercury in various biofluids and tissues particularly focused on slightly older infants and children with autism as illustrative of something potentially important: increasing exposure to mercury with age. Take for example the paper by Majewska and colleagues [4] and their findings reporting: "Autistic children significantly differed from healthy peers in the concentrations of mercury in hair: younger autistics had lower levels, while older - higher levels than their respective controls". The results from Hertz-Picciotto and colleagues [4] (open-access here) also implied that behaviour might play a role in blood mercury levels: "Interestingly, although few children had Hg amalgams, those who did and who also either chewed gum or had bruxism appeared to have experienced sufficient release of inorganic Hg to be measurable in blood". I say this noting that not every child with autism has mercury amalgams, as neither do they all partake in teeth grinding.

The Yau results make an important contribution to the issue of mercury and autism in terms of maternal contribution and mercury load at birth. As part of some further investigations, and bearing in mind that participants in the EMA initiative might also be involved in other State initiatives (beincharge!), I would like to see further follow-up of participants and if and how their mercury load might have changed as they matured. Analysis of other parameters mentioned in that Gorini review paper - such as glutathione measures for example - might also offer some important accompanying data on whether excretion factors are part of the issue here and what might be done to help relieve any excess burden of the troublesome heavy metal that is mercury. Oh, and given that genetic factors might also play some role in mercury accumulation as per the findings by Llop and colleagues [5] (open-access), there may also be more research to do here too...

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[1] Gorini F. et al. The Role of Heavy Metal Pollution in Neurobehavioral Disorders: a Focus on Autism. Review Journal of Autism and Developmental Disorders. 2014. June 27.

[2] Yau VM. et al. Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders. Environ Res. 2014 Jun 27;133C:294-303. 

[3] van Wijngaarden E. et al. Autism spectrum disorder phenotypes and prenatal exposure to methylmercury. Epidemiology. 2013 Sep;24(5):651-9. 

[4] Hertz-Picciotto I. et al. Blood mercury concentrations in CHARGE Study children with and without autism. Environ Health Perspect. 2010 Jan;118(1):161-6.

[5] Llop S. et al. Polymorphisms in ABC transporter genes and concentrations of mercury in newborns--evidence from two Mediterranean birth cohorts. PLoS One. 2014 May 15;9(5):e97172. 

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ResearchBlogging.org Yau VM, Green PG, Alaimo CP, Yoshida CK, Lutsky M, Windham GC, Delorenze G, Kharrazi M, Grether JK, & Croen LA (2014). Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders. Environmental research, 133C, 294-303 PMID: 24981828