Maternal iron intake and offspring autism risk

Much like the discussions around the paper by Rogers and colleagues (see here) on treating autism in the first year of life, the media scrum around the findings from Rebecca Schmidt and colleagues [1] talking about maternal iron supplements and offspring autism spectrum disorder (ASD) risk preceded the publication of the paper by a few days. It's getting to be a pet-hate of mine that big headlines are being generated sometimes days before your average Jane or Joe can see the data upon which they're based...

Grumbling aside, here are a few factoids from the now published Schmidt paper:

• CHARGE was the source initiative for participants, as it has been for various studies, and following on from other research on nutrition during pregnancy potentially affecting offspring autism risk from this group (see here), the idea was to look at pre- and pregnancy maternal iron intake in relation to autism risk.
• Data for mothers of children with autism (n=520) were compared against mothers with children who did not have autism (n=346) and "maternal daily iron intake was quantified on the basis of frequency, dose, and brands of supplements and cereals consumed each month from 3 months before pregnancy through the end of pregnancy and during breastfeeding (the index period), as reported in parental interviews". You'll note the words 'parental interviews' there.
• Results: well, the mothers of children with autism were less likely to report taking 'iron-specific supplements' than control mothers and overall, a "lower mean daily iron intake" in the order of 5-6 mg/day less than controls was observed.
• "Low iron intake significantly interacted with advanced maternal age and metabolic conditions; combined exposures were associated with a 5-fold increased ASD risk". Advanced maternal age by the way, refers to women who were 35 or older at the time of their child's birth, and metabolic conditions means obesity, diabetes or hypertension (in line with other evidence).

These are interesting findings which add to the growing literature on how maternal nutrition before and during the nine months that made us potentially impacts on offspring development and outcome. Certainly, there are hints of the foetal programming hypothesis in there, for which the late David Barker receives quite a bit of credit. I was also wondering whether other issues potentially affecting foetal nutrition such as the inter-pregnancy interval (see here) might also tie into these findings too?

But there are some obvious cautions to take on board when it comes to these findings. First is the continued reliance on self-report, which even under the most controlled of situations, is always going to be an estimate at best. Next, and I might be completely wrong about this, but even with the report of a mean daily intake of ~51 mg/day, the mothers with children with autism group were still quite a bit above the daily recommendations in the United States (see here) for pregnant or lactating women. Finally, I'm wondering whether the idea of "combined exposures" when it comes to maternal age and the presence of metabolic syndrome might actually be the more important issue raised in this paper...

Iron and autism is a topic which has been discussed a few times on this blog (see here). The data is slightly mixed when it comes to looking at iron levels in children with autism as per my discussions on the Reynolds paper [2] versus the Hergüner findings [3]. Dr Schmidt and colleagues did not directly assay for iron or ferritin levels in their current paper so we can't really say much more at this point on how actual maternal iron levels translated into offspring iron levels and what effect(s) this may have had on offspring autism or other risks. That and whether other factors might also have played some role as per the rodent findings from Harvey & Boksa [4] talking about an additive effect from iron deficiency and prenatal immune activation (a topic that has cropped up a few times with autism in mind). These are perhaps the next studies that need to be done alongside what biological effects supplementation may have [5].

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[1] Schmidt RJ. et al. Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder. Am J Epidemiol. 2014. 22 September.

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

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

[4] Harvey L. & Boksa P. Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring. Brain Behav Immun. 2014 Aug;40:27-37.

[5] Dosman CF. et al. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 2007 Mar;36(3):152-8.

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Rebecca J. Schmidt, Daniel J. Tancredi, Paula Krakowiak, Robin L. Hansen, & Sally Ozonoff (2014). Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder American Journal of Epidemiology : doi: 10.1093/aje/kwu208