Flu in pregnancy may raise schizophrenia risk in offspring

Aug 6, 2004 (CIDRAP News) – An analyis of decades-old serum samples from pregnant women suggests that a mother's influenza illness early in pregnancy may increase the risk of schizophrenia for her child years later.

The study, published Aug 2 in the Archives of General Psychiatry, showed that the risk of schizophrenia in adult offspring increased threefold for influenza exposure during the first half of pregnancy. However, this finding fell just short of being statistically significant (P=.052). Flu in the first trimester of pregnancy was associated with a sevenfold increase in risk of schizophrenia in the offspring, but this finding also failed to achieve significance (P=.08). There was no increased risk associated with flu exposure during the second or third trimester.

The report says that many other studies have investigated a possible link between a mother's bout with the flu and her adult child's eventual development of schizophrenia, a serious brain disorder that makes it difficult for a person to grasp reality, think logically, or behave normally.

But these findings are the first serologic evidence of a link, and the data suggest the possibility that up to 14% of schizophrenia cases would not have occurred if influenza in early to mid pregnancy had been prevented, the authors state.

The study evaluated sera from pregnant women who were part of a large birth cohort called the Child Health and Development Study (CHDS) from 1959 through 1966. During that time, the CHDS recruited nearly every pregnant woman who received obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, Calif.

The study was conducted by researchers at the New York State Psychiatric Institute and the Mailman School of Public Health at Columbia University, in collaboration with Kaiser Permanente Medical Care Plan, Northern California Region, and the Public Health Institute in Berkeley, Calif. Its findings are part of the broader Prenatal Determinants of Schizophrenia (PDS) study.

The researchers identified 64 people in the birth cohort who had schizophrenia as adults, plus 125 people in the cohort who had no mental illness and matched the case-patients by sex and date of birth. The investigators then measured influenza antibodies in archived serum samples taken from the mothers of the case-patients and controls during pregnancy.

Although the sample was small and the findings did not achieve significance, the authors wrote, "Prospective acquisition of the serum samples in a well-characterized, continuously monitored birth cohort and the use of a face-to-face psychiatric diagnosis lend credence to this result."

"These findings represent the strongest evidence thus far that prenatal exposure to influenza plays a role in schizophrenia," Ezra Susser, MD, DPH, senior investigator of the PDS study and chairman of the Department of Epidemiology at the Mailman School of Public Health, said in a press release. "Although the findings may ultimately have implications for prevention, we strongly caution against making any public health policy recommendations until these links have been confirmed through further study."

The study was funded by the National Institute of Mental Health, the National Alliance for Research on Schizophrenia and Depression, and the Lieber Center for Schizophrenia Research.

Brown AS, Begg MD, Gravenstein S, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004;61(8):774-80 [Abstract]

See also:

Mailman School of Public Health news release

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