Skip to main content
Log in

Review of the Plausibility of Iron Deficiency Hypothesis of Autism

  • Review Paper
  • Published:
Review Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Iron consumption among mothers has recently been found to decrease the risk of autism in offspring. However, epidemiological evidence of an increasing iron deficiency among mothers or infants is lacking, and evidence within an individual-level framework of iron deficiency confers doubt upon iron’s role as a direct cause of autism. We attempt to review the evidence that challenges a direct causal explanation of in utero or infancy iron deficiency leading to autism and, instead, reveal iron to be more likely an effect modifier for another, yet unknown, cause of autism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • American Academy of Pediatrics Committee on Nutrition. (1992). The use of whole cow’s milk in infancy. Pediatrics, 89, 1105–1109.

    Google Scholar 

  • Balarajan, Y., Subramanian, S. V., & Fawzi, W. W. (2013). Maternal iron and folic acid supplementation is associated with lower risk of low birth weight in India. The Journal of Nutrition, 143, 1309–1315.

    Article  PubMed  Google Scholar 

  • Burke, R. M., Leon, J. S., & Suchdev, P. S. (2014). Identification, prevention and treatment of iron deficiency during the first 1000 days. Nutrients, 6, 4093–4114.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheslack-Postava, K., Jokiranta, E., Suominen, A., et al. (2014). Variation by diagnostic subtype in risk for autism spectrum disorders associated with maternal parity among Finnish births. Paediatric and Perinatal Epidemiology, 28, 58–66.

    Article  PubMed  Google Scholar 

  • Darshan, D., & Anderson, G. J. (2007). Liver-gut axis in the regulation of iron homeostasis. World Journal of Gastroenterology, 13, 4737–4745.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dewey, K. G., & Chaparro, C. M. (2007). Session 4: mineral metabolism and body composition iron status of breast-fed infants. The Proceedings of the Nutrition Society, 66, 412–422.

    Article  PubMed  Google Scholar 

  • Donahue, S. M., Kleinman, K. P., Gillman, M. W., et al. (2010). Trends in birth weight and gestational length among singleton term births in the United States: 1990-2005. Obstetrics and Gynecology, 115, 357–364.

    Article  PubMed  PubMed Central  Google Scholar 

  • Doom, J. R., Georgieff, M. K., & Gunnar, M. R. (2015). Institutional care and iron deficiency increase ADHD symptomology and lower IQ 2.5-5 years post-adoption. Developmental Science, 18, 484–494.

    Article  PubMed  Google Scholar 

  • Finkelstein, J. L., O'Brien, K. O., Abrams, S. A., et al. (2013). Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 mo of age. The American Journal of Clinical Nutrition, 98, 1475–1484.

    Article  PubMed  Google Scholar 

  • Georgieff, M. K. (2008). The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus. Biochemical Society Transactions, 36, 1267–1271.

    Article  PubMed  PubMed Central  Google Scholar 

  • Haider, B. A., Olofin, I., Wang, M., et al. (2013). Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ, 346, f3443.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hallberg, L. (1995). Results of surveys to assess iron status in Europe. Nutrition Reviews, 53, 314–322.

    Article  PubMed  Google Scholar 

  • Jakobsson, M., Gissler, M., Paavonen, J., et al. (2008). The incidence of preterm deliveries decreases in Finland. BJOG, 115, 38–43.

    Article  PubMed  Google Scholar 

  • Johnson, S., Hollis, C., Kochhar, P., et al. (2010). Autism spectrum disorders in extremely preterm children. The Journal of Pediatrics, 156, 525–531 e522.

    Article  PubMed  Google Scholar 

  • Khambalia, A. Z., Collins, C. E., Roberts, C. L., et al. (2015). High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth. The British Journal of Nutrition, 114, 455–461.

    Article  PubMed  Google Scholar 

  • Kumar, A., Rai, A. K., Basu, S., et al. (2008). Cord blood and breast milk iron status in maternal anemia. Pediatrics, 121, e673–e677.

    Article  PubMed  Google Scholar 

  • Lampi, K. M., Lehtonen, L., Tran, P. L., et al. (2012). Risk of autism spectrum disorders in low birth weight and small for gestational age infants. The Journal of Pediatrics, 161, 830–836.

    Article  PubMed  PubMed Central  Google Scholar 

  • Looker, A. C., Dallman, P. R., Carroll, M. D., et al. (1997). Prevalence of iron deficiency in the United States. JAMA, 277, 973–976.

    Article  PubMed  Google Scholar 

  • Male, C., Persson, L. A., Freeman, V., et al. (2001). Prevalence of iron deficiency in 12-mo-old infants from 11 European areas and influence of dietary factors on iron status (euro-growth study). Acta Paediatrica, 90, 492–498.

    Article  PubMed  Google Scholar 

  • Martin JA, Hamilton BE and Osterman MJ. (2015) Births in the United States, 2014. NCHS Data Brief: 1–8.

  • McArdle, H. J., Gambling, L., & Kennedy, C. (2014). Iron deficiency during pregnancy: the consequences for placental function and fetal outcome. The Proceedings of the Nutrition Society, 73, 9–15.

    Article  PubMed  Google Scholar 

  • McDonald, S. J., Middleton, P., Dowswell, T., et al. (2013). Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews, 7, CD004074.

    Google Scholar 

  • Mei, Z., Cogswell, M. E., Looker, A. C., et al. (2011). Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. The American Journal of Clinical Nutrition, 93, 1312–1320.

    Article  PubMed  Google Scholar 

  • Mei, Z., Pfeiffer, C. M., Looker, A. C., et al. (2012). Serum soluble transferrin receptor concentrations in US preschool children and non-pregnant women of childbearing age from the National Health and Nutrition Examination Survey 2003-2010. Clinica Chimica Acta, 413, 1479–1484.

    Article  Google Scholar 

  • Meltzer, H. M., Brantsaeter, A. L., Borch-Iohnsen, B., et al. (2010). Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study. Environmental Research, 110, 497–504.

    Article  PubMed  Google Scholar 

  • Milman, N., Byg, K. E., Ovesen, L., et al. (2003). Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload. European Journal of Haematology, 71, 51–61.

    Article  PubMed  Google Scholar 

  • Morisaki, N., Esplin, M. S., Varner, M. W., et al. (2013). Declines in birth weight and fetal growth independent of gestational length. Obstetrics and Gynecology, 121, 51–58.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mujica-Coopman, M. F., Borja, A., Pizarro, F., et al. (2014). Prevalence of deficiency and dietary intake of iron, zinc and copper in Chilean childbearing age women. Archivos Latinoamericanos de Nutrición, 64, 9–15.

    PubMed  Google Scholar 

  • Oliveira Fde, C., Assis, K. F., Martins, M. C., et al. (2014). Timing of clamping and factors associated with iron stores in full-term newborns. Revista de Saúde Pública, 48, 10–18.

    Article  PubMed  Google Scholar 

  • Papadopoulou, E., Stratakis, N., Roumeliotaki, T., et al. (2013). The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother-child cohort study in Crete, Greece (Rhea study). European Journal of Nutrition, 52, 327–336.

    Article  PubMed  Google Scholar 

  • Pena-Rosas, J. P., De-Regil, L. M., Garcia-Casal, M. N., et al. (2015). Daily oral iron supplementation during pregnancy. Cochrane Database of Systematic Reviews, 7, CD004736.

    Google Scholar 

  • Preziosi, P., Prual, A., Galan, P., et al. (1997). Effect of iron supplementation on the iron status of pregnant women: consequences for newborns. The American Journal of Clinical Nutrition, 66, 1178–1182.

    PubMed  Google Scholar 

  • Rios-Castillo, I., Brito, A., Olivares, M., et al. (2013). Low prevalence of iron deficiency anemia between 1981 and 2010 in Chilean women of childbearing age. Salud Pública de México, 55, 478–483.

    Article  PubMed  Google Scholar 

  • Scanlon, K. S., Yip, R., Schieve, L. A., et al. (2000). High and low hemoglobin levels during pregnancy: differential risks for preterm birth and small for gestational age. Obstetrics and Gynecology, 96, 741–748.

    PubMed  Google Scholar 

  • Schaaf, J. M., Mol, B. W., Abu-Hanna, A., et al. (2011). Trends in preterm birth: singleton and multiple pregnancies in the Netherlands, 2000-2007. BJOG, 118, 1196–1204.

    Article  PubMed  Google Scholar 

  • Schmidt, R. J., Tancredi, D. J., Krakowiak, P., et al. (2014). Maternal intake of supplemental iron and risk of autism spectrum disorder. American Journal of Epidemiology, 180, 890–900.

    Article  PubMed  PubMed Central  Google Scholar 

  • Scholl, T. O. (2011). Maternal iron status: relation to fetal growth, length of gestation, and iron endowment of the neonate. Nutrition Reviews, 69(Suppl 1), S23–S29.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shao, J., Lou, J., Rao, R., et al. (2012). Maternal serum ferritin concentration is positively associated with newborn iron stores in women with low ferritin status in late pregnancy. The Journal of Nutrition, 142, 2004–2009.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shastri, L., Mishra, P. E., Dwarkanath, P., et al. (2015). Association of oral iron supplementation with birth outcomes in non-anaemic south Indian pregnant women. European Journal of Clinical Nutrition, 69, 609–613.

    Article  PubMed  Google Scholar 

  • Silvestre, D., Martinez-Costa, C., Lagarda, M. J., et al. (2001). Copper, iron, and zinc contents in human milk during the first three months of lactation: a longitudinal study. Biological Trace Element Research, 80, 1–11.

    Article  PubMed  Google Scholar 

  • Walsh, T., O'Broin, S. D., Cooley, S., et al. (2011). Laboratory assessment of iron status in pregnancy. Clinical Chemistry and Laboratory Medicine, 49, 1225–1230.

    Article  PubMed  Google Scholar 

  • Yip, R. (1997). The challenge of improving iron nutrition: limitations and potentials of major intervention approaches. European Journal of Clinical Nutrition, 51(Suppl 4), S16–S24.

    PubMed  Google Scholar 

  • Zhao, G., Xu, G., Zhou, M., et al. (2015). Prenatal iron supplementation reduces maternal anemia, iron deficiency, and iron deficiency anemia in a randomized clinical trial in rural China, but iron deficiency remains widespread in mothers and neonates. The Journal of Nutrition, 145, 1916–1923.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ziaei, S., Norrozi, M., Faghihzadeh, S., et al. (2007). A randomised placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin > or = 13.2 g/dl. BJOG, 114, 684–688.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aaron Grossman.

Ethics declarations

Inform Consent

For this type of study, formal consent is not required.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of Interest

The author declares no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grossman, A. Review of the Plausibility of Iron Deficiency Hypothesis of Autism. Rev J Autism Dev Disord 4, 205–208 (2017). https://doi.org/10.1007/s40489-017-0108-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40489-017-0108-2

Keywords

Navigation