Low Iron Intake in Pregnancy May Boost Autism Risk

Megan Brooks

September 24, 2014

A new study has for the first time found a link between maternal iron intake and risk for autism.

Dr. Rebecca Schmidt

The study shows a 5-fold greater risk for autism spectrum disorder (ASD) in children whose mothers had low supplemental iron intake and other risk factors, including age older than 35 years and metabolic conditions such as diabetes, hypertension, and obesity.

"Our findings suggest that there may be another reason to follow recommendations for iron supplementation during pregnancy and while breastfeeding, especially for women who are over 35 years of age and/or obese or diabetic," study investigator Rebecca J. Schmidt, PhD, of the University of California (UC), Davis, MIND Institute, in Sacramento, told Medscape Medical News.

The study was published online September 22 in the American Journal of Epidemiology.

CHARGE Study

In a prior study (http://ajcn.nutrition.org/content/96/1/80), the researchers found that children whose mothers took folic acid supplements early in pregnancy had a reduced risk for autism or Asperger syndrome, a finding that has since been replicated.

Their latest study, they say, is the first to examine the relationship between maternal iron intake and ASD risk. Participants included 520 children with ASD and 346 typically developing children from the Northern California–based Childhood Autism Risks from Genetics and the Environment (CHARGE) study. The children were between 1 and 5 years old.

Average daily iron intake was quantified on the basis of self-reported frequency, dose, and brands of supplements and cereals consumed each month from 3 months before pregnancy through the end of pregnancy and during breastfeeding (index period).

The researchers found that mothers of children with ASD were less apt to report taking iron-specific supplements during the index period (adjusted odds ratio [aOR], 0.63; 95% confidence interval [CI], 0.44 - 0.91).

Mothers of children with ASD also had lower mean daily iron intake than mothers of typically developing children (51.7 vs 57.1 mg/day, P = .03).

The association between lower maternal iron intake and increased ASD risk was strongest during breastfeeding, after adjustment for folic acid intake.

The researchers also observed a significant interaction between low iron intake and advanced maternal age and metabolic conditions, with combined exposures associated with a 5-fold increased risk of having a child with ASD.

More Study Needed

Iron deficiency affects as many as 50% of pregnancies. Iron is critical to early brain development, contributing to neurotransmitter production, myelination, and immune function. All 3 of these pathways have been associated with autism.

"Because this is the first study, the findings definitely need to be replicated before we can have confidence in the association," Dr. Schmidt told Medscape Medical News. "In addition, in this study, we asked moms to remember their supplement use up to several years earlier, so it is possible they did not remember accurately and that mothers of children with autism remembered differently than mothers of children who are developing typically.

"Finally, there could be differences in women who took iron compared to those who did not that we were unable to account for in our study," she said.

Reached for comment on the study, Max Wiznitzer, MD, associate professor of pediatrics and neurology at Case Western Reserve University and pediatric neurologist at Rainbow Babies and Children's Hospital in Cleveland, Ohio, said it is an interesting study but that he too felt that having mothers recall their iron intake after many years is a weakness.

"I can't remember what I had for breakfast 6 months ago, let alone years ago," Dr. Wiznitzer said. "There was no determination of maternal iron status by lab tests ― just an inference. [We] need a prospective study," he added.

Dr. Schmidt and colleagues plan to follow up this study in several ways. "One is to examine tests for anemia in medical records that we have for these CHARGE women to see if there were differences," Dr. Schmidt explained.

Another is to examine the association of iron intake and ASD risk in the prospective Markers of Autism Risk in Babies – Learning Early Signs (MARBLES) study at UC Davis to see whether they can replicate the CHARGE findings.

The CHARGE study is supported by grants from the National Institutes of Health, the US Environmental Protection Agency Science to Achieve Results (STAR) program, and the UC Davis MIND Institute. The authors have reported no relevant financial relationships.

Am J Epidemiol. Published online September 22, 2014. Abstract

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