Background: Maternal iron deficiency and infection during pregnancy have individually been associated with increased
risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus
far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and
prepartum anemia on schizophrenia risk in the offspring.
Methods: We conducted a population-based study with individual record linkage of the Danish Civil Registration
System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton
births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort
members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia
at any time during the pregnancy.Maternal infection was defined based on infections requiring hospital admission
Results: Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted
analyses (1.45-fold increase for anemia, 95% CI: 1.14–1.82; 1.32-fold increase for infection, 95% CI: 1.17–1.48).
The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03–1.31) after adjustment
for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a
2.49-fold increased schizophrenia risk (95% CI: 1.29–4.27). The interaction analysis, however, failed to provide
evidence for multiplicative interactions between the two factors.
Conclusion: Our findings indicate thatmaternal anemia and infection have additive but not interactive effects, and
therefore, they may represent two independent risk factors of schizophrenia.