title: Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring.
abstract: 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 during pregnancy.
  
  
  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.
  
  
  CONCLUSIONS
  Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia.
authors.affiliation: National Centre for Register-based Research, Aarhus University, Fuglesangs Allé 4, 8210, Aarhus V, Denmark; Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Fuglesangs Allé 4, Aarhus V, Denmark. Electronic address: prn@econ.au.dk.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Nielsen
authors.affiliation: Physiology and Behavior Laboratory, ETH Zurich, Switzerland; Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
authors.affiliation: National Centre for Register-based Research, Aarhus University, Fuglesangs Allé 4, 8210, Aarhus V, Denmark; Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Fuglesangs Allé 4, Aarhus V, Denmark; Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Fuglesangs Allé 4, Aarhus V, Denmark.
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
mesh_terms: D000740:Anemia / Q000150:complications / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000209:etiology*
keywords: Anemia; Cohort study; Denmark; Infection; Schizophrenia