Maternal intake of supplemental iron and risk of autism spectrum disorder

Abstract

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.

Keywords: autism; case-control studies; child development; dietary supplements; iron; pregnancy; primary prevention; risk factors.

Figure 1.

Percentages of mothers of children with autism spectrum disorder and mothers of children with typical development who took iron supplements during the index period (from 3 months before pregnancy through the end of pregnancy and during breastfeeding), Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, California, 2003–2009. A trend towards a significant difference between groups was found during the breastfeeding (BF) period (P = 0.06).

Figure 2.

Adjusted odds ratios for associations between reported maternal iron supplement intake during the index period (from 3 months before pregnancy through the end of pregnancy and during breastfeeding) and autism spectrum disorder, Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, California, 2003–2009. Odds ratios were adjusted for maternal folic acid intake during the first month of pregnancy, child's year of birth, and home ownership. Vertical bars represent 95% confidence intervals. Frequencies and P values are presented in Web Table 2. There was a significant association with autism spectrum disorder during the breastfeeding (BF) period (P < 0.05) and a borderline-significant association during months 4, 5, 6, and 9 of pregnancy (P < 0.10).

Figure 3.

Mean iron intakes of mothers of children with autism spectrum disorder and mothers of children with typical development during the index period (from 3 months before pregnancy through the end of pregnancy and during breastfeeding), Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, California, 2003–2009. Vertical bars represent 95% confidence intervals. Dietary Reference Intakes for iron in females aged 19–50 years are 18 mg/day for all women, 27 mg/day during pregnancy, and 9 mg/day during lactation (39). Significant differences between mothers of children with autism spectrum disorder and mothers of children with typical development were found for the 3 months before and the first month of pregnancy (P < 0.01) and for the second month of pregnancy (P < 0.05). A borderline-significant association was observed for months 3, 4, and 6 of pregnancy and during the breastfeeding (BF) period (P < 0.10).

Figure 4.

Adjusted odds ratios for associations between mean maternal iron intake during the index period (from 3 months before pregnancy through the end of pregnancy and during breastfeeding) and autism spectrum disorder, Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, California, 2003–2009. Odds ratios were adjusted for maternal folic acid intake during the first month of pregnancy, child's year of birth, and home ownership. Vertical bars represent 95% confidence intervals. Frequencies and P values are presented in Web Table 3. There was a significant inverse association with autism spectrum disorder for the highest iron quintile (P = 0.02) during the breastfeeding (BF) period; a significant positive association for the fourth quintile (P = 0.04) and a borderline-significant association for the third quintile (P = 0.10) during the second month of pregnancy; and a borderline-significant association for the fourth quintile (P = 0.06) during breastfeeding.