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Objective: In this birth cohort study, the authors examined the relation between prenatal exposure to maternal genital/reproductive (G/R) infections and schizophrenia in offspring. Method: The birth cohort consisted of 7,794 offspring of pregnancies with prospectively acquired data on maternal G/R infections from obstetric records. The authors diagnosed 71 cases of schizophrenia and other schizophrenia spectrum disorders in this cohort. The relationship between maternal G/R infections and schizophrenia risk was modeled. Results: Exposure to G/R infections during the periconceptional period was associated with a significantly increased risk of schizophrenia and other schizophrenia spectrum disorders, with adjustment for maternal race, education, age, and mental illness. Conclusions: Maternal G/R infection during periconception appears to increase the risk of schizophrenia in offspring.