Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder

Rebecca J. Schmidt; Daniel J. Tancredi; Paula Krakowiak; Robin L. Hansen; Sally Ozonoff


Am J Epidemiol. 2014;180(9):890-900. 

In This Article

Abstract and Introduction


Iron deficiency affects 40%–50% of pregnancies. Iron is critical for early neurodevelopmental processes that are dysregulated in autism spectrum disorder (ASD). We examined maternal iron intake in relation to ASD risk in California-born children enrolled in a population-based case-control study (the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study) from 2003 to 2009 with a diagnosis of ASD (n = 520) or typical development (n = 346) that was clinically confirmed using standardized assessments. Mean 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. Mothers of cases were less likely to report taking iron-specific supplements during the index period (adjusted odds ratio = 0.63, 95% confidence interval: 0.44, 0.91), and they had a lower mean daily iron intake (51.7 (standard deviation, 34.0) mg/day) than mothers of controls (57.1 (standard deviation, 36.6) mg/day; P = 0.03). The highest quintile of iron intake during the index period was associated with reduced ASD risk compared with the lowest (adjusted odds ratio = 0.49, 95% confidence interval: 0.29, 0.82), especially during breastfeeding. Low iron intake significantly interacted with advanced maternal age and metabolic conditions; combined exposures were associated with a 5-fold increased ASD risk. Further studies of this link between maternal supplemental iron and ASD are needed to inform ASD prevention strategies.


Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by the presence of social deficits, language impairments, and stereotyped or repetitive behaviors and interests.[1–3] ASD affects 1 in every 68 children in the United States, and prevalence is increasing.[4] Combinations of multiple genetic and environmental factors likely play an etiological role in ASD. Evidence supports the hypothesis of prenatal origins for autism[5] and an influence of gestational nutrition.[6,7]

Iron deficiency, with its resultant anemia, is the most commonly measured nutrient deficiency, and it is especially common during pregnancy, affecting 40%–50% of women and their infants.[8–10] The fetus depends on maternal iron as his or her only source of iron,[11] and severe maternal iron deficiency can induce fetal and infant iron deficiency.[12,13] Iron is crucial to early neurodevelopment. In the brain, iron contributes to neurotransmitter production, myelination, and immune function;[14] dysregulation of all 3 of these pathways has been associated with ASD. Iron deficiency early in life has been shown to impair cognition, motor development, social orientation and engagement, and language development, with improvements being observed upon iron supplementation.[15–19] Poor iron status is more prevalent in children with ASD[20–24] and does not necessarily correlate with low iron intake,[22] suggesting that these children could absorb and/or metabolize iron less efficiently. However, to our knowledge, no study to date has examined gestational iron status in relation to development of ASD. We examined maternal intake of supplemental iron in relation to ASD risk.