Infants who have been exposed to influenza in the womb during the first half of pregnancy appear to have an increased risk of schizophrenia, according to results of a new study. Simply vaccinating women of reproductive age against influenza may reduce the rate of schizophrenia in the population, Dr. Alan S. Brown and colleagues suggest.

While other studies have suggested such a link, influenza exposures in the populations studied were not rigorously determined, Brown, of New York State Psychiatric Institute, and his group point out in their report in the Archives of General Psychiatry.

The investigators therefore evaluated blood samples from women who participated in the Prenatal Determinants of Schizophrenia study to look for evidence of influenza exposure. The study group included nearly every pregnant woman who received obstetric care from the Kaiser Foundation Health Plan in Alameda County, California, between 1959 and 1966.

Among 12,094 children born, 64 were diagnosed with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified or schizotypal personality disorder between 1981 and 1997. The study also included 125 children who were matched to the cases for gender, date of birth, and timing of maternal blood draws.

The investigators found a three-fold increased risk of schizophrenia spectrum disorder for those exposed to influenza during the first half of pregnancy. The risk was even higher for those exposed during the first trimester.

Brown’s group theorizes that antibodies elicited by the virus in the pregnant woman can cross the placenta, disturb fetal brain development and increase vulnerability to schizophrenia. Other possible mechanisms include fever in the mother, use of over-the-counter medications or reduced oxygen levels in the fetus.

The researchers suggest that up to 14 percent of schizophrenia cases would not have occurred if influenza exposure during early to midpregnancy had been prevented.

If confirmed by other studies, these findings may have implications for reducing or preventing a significant portion of schizophrenia cases, the investigators conclude.

Archives General Psychiatry, August 2004.