Maternal iron deficiency and the risk of schizophrenia in offspring

Arch Gen Psychiatry. 2008 Oct;65(10):1136-44. doi: 10.1001/archpsyc.65.10.1136.


Context: Iron is essential for brain development and functioning. Emerging evidence suggests that iron deficiency in early life leads to long-lasting neural and behavioral deficits in infants and children. Adopting a life course perspective, we examined the effects of early iron deficiency on the risk of schizophrenia in adulthood.

Objective: To determine whether maternal iron deficiency, assessed by maternal hemoglobin concentration during pregnancy, increases the susceptibility to schizophrenia spectrum disorders (SSDs) among offspring.

Design: Data were drawn from a population-based cohort born from 1959 through 1967 and followed up for development of SSD from 1981 through 1997.

Participants: Of 6872 offspring for whom maternal hemoglobin concentration was available, 57 had SSDs (0.8%) and 6815 did not (99.2%).

Main outcome measure: Prospectively assayed, the mean value of maternal hemoglobin concentration was the primary exposure. Hemoglobin concentration was analyzed as a continuous and a categorical variable.

Results: A mean maternal hemoglobin concentration of 10.0 g/dL or less was associated with a nearly 4-fold statistically significant increased rate of SSDs (adjusted rate ratio, 3.73; 95% confidence interval, 1.41-9.81; P = .008) compared with a mean maternal hemoglobin concentration of 12.0 g/dL or higher, adjusting for maternal education and ethnicity. For every 1-g/dL increase in mean maternal hemoglobin concentration, a 27% decrease in the rate of SSDs was observed (95% confidence interval, 0.55-0.96; P = .02).

Conclusions: The findings suggest that maternal iron deficiency may be a risk factor for SSDs among offspring. Given that this hypothesis offers the potential for reducing the risk for SSDs, further investigation in independent samples is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / epidemiology*
  • Body Mass Index
  • Cohort Studies
  • Comorbidity
  • Cross-Sectional Studies
  • Female
  • Hemoglobinometry
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature, Diseases / blood
  • Infant, Premature, Diseases / epidemiology
  • Infant, Small for Gestational Age
  • Male
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / epidemiology*
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Proportional Hazards Models
  • Prospective Studies
  • Retrospective Studies
  • Risk Factors
  • Schizophrenia / blood
  • Schizophrenia / epidemiology*