Ironing out iron and autism

I'm a little bit puzzled when it comes to iron and autism.  In one of my earliest posts on this blog I talked about iron deficiency and autism, and how at that point there was some suggestion that there may be issues with iron availability in cases of autism and what remedial measures might be indicated.

Opposites attract? @ Wikipedia  

As with just about everything in autism research, things are never so straight forward though. With the recent paper from Reynolds and colleagues* (open-access) published as part of the Pediatrics special on autism we are advised that their data "do not support previous reports that children with ASD are at greater risk for ID [iron deficiency] than the general population".

A few details about the Reynolds study:

• Iron status and intake data were collected for 222 participants of the Autism Treatment Network Diet and Nutrition Study. Coincidentally, this initiative might also be reporting on vitamin D status in autism quite soon, so one to watch there also in light of other sunshine vitamin interest with autism in mind.
• Low iron stores indicated by serum ferritin levels <12mcg/L were present in 8% of their study cohort (18/218). Low transferrin saturation (TS) (defined as <10%) was present in 6% (12/199) bearing in mind some gaps in the testing regime in some important individual participants. Anaemia (UK spelling) was present in 7 participants (3%).
• The authors discuss some limitations of their findings including the possibility that accompanying inflammation might influence results, and the fact that they did not look at measures such as C-reactive protein (CRP) in their cohort (see this previous post). 

The message from Reynolds et al is that iron is a vital part of biochemical functioning - they mention tyrosine hydroxylase but I would be minded to also point out its role in a related enzyme tryptophan hydroxylase - and with autism in mind, how we need to be quite careful how we interpret any iron results.

I wouldn't argue with that but just before you start muttering to yourself that iron might be another research dead-end for autism, have a peek at the quite recent study from Hergüner and colleagues** whose estimates of iron deficiency (24%) and anaemia (15%) in their cohort of children with autism were a little bit different from Reynolds.

Again, a few points to mention about the Hergüner et al research:

• Sorry that I can't link to the full-text paper but this was a study of 116 children diagnosed with DSM-IV autism (aged 3-16 years). 
• As per the authorship group, participants were all Turkish in residency (and I assume origin), and various serum levels of iron and related measures were analysed.
• The figures for iron deficiency and anaemia were quite different from those reported by Reynolds; indeed when participants were divided up into under-6s (n=37) and 6 and overs (n=79), iron deficiency was more prevalent in the younger aged group.
• The authors conclude: "results of this study suggest that serum ferritin levels should be measured in every case with autism as a part of routine investigation".

I was intrigued at the disparity between these data (and others***) bearing in mind the different geographic and ethnic populations studied and the various interfering variables affecting results including sample size. Reynolds and colleagues are very forthcoming in mentioning how their results show so much difference from the other studies mentioned but are not altogether clear as to why there is such difference aside from noting that iron deficiency seems to be generally on the decrease in countries such as the United States and indeed worldwide. Factors such as fortification, guidance on not introducing cows milk too early and even delayed cord clamping**** probably all contributing to the decline.

I don't have anything further to add to this explanation by the way, aside from always being rather interested in results which don't follow the majority trend, and indeed whether this could imply some specific population/ethnic differences in risk among autism worldwide. It would be rather useful to have more up-to-date information from non-US parts of the world to work with including food diaries as per what Reynolds used to establish dietary iron intake. That and whether issues such as those pertaining to things like malabsorption may show some effect which might lead down some interesting paths...

----------

* Reynolds A. et al. Iron status in children with autism spectrum disorder. Pediatrics. 2012; 130 Suppl 2:S154-S159.

** Hergüner S. et al. Ferritin and iron levels in children with autistic disorder. Eur J Pediatr. 2012; 171: 143-146.

*** Latif A. et al. Iron deficiency in autism and Asperger syndrome. Autism. 2002; 6: 103-114.

**** Andersson O. et al. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. BMJ. 2011; 343: d7157.

----------

Reynolds A, Krebs NF, Stewart PA, Austin H, Johnson SL, Withrow N, Molloy C, James SJ, Johnson C, Clemons T, Schmidt B, & Hyman SL (2012). Iron status in children with autism spectrum disorder. Pediatrics, 130 Suppl 2 PMID: 23118246