Mednick et al and O'Callaghan et al have recently reported that individuals exposed to the 1957 A2 influenza pandemic during their second trimester in utero are at risk for later schizophrenia. In this study, we determined whether their findings could be reproducible in a Japanese sample. In Japan, there were two waves of the 1957 A2 influenza pandemic; the first occurred from June to July, and the second from November to December. In addition, an epidemic of influenza A/B mixed type prevailed from January to February 1957. We obtained information on all dates of birth of 1187 individuals born between June 1955 and May 1960, who were treated for schizophrenia during the study period. November 1991 to September 1992, at 18 mental hospitals around Tokyo metropolitan areas. Hospital clinical diagnosis was used. We defined the index year from June 1957, beginning the first wave of the pandemic, to May 1958. We compared the number of schizophrenic births in each month of the index year with the average number of births in the corresponding month of the two years before, and following, the index year. The observed number of births in June 1957 and April 1958 were found to be significantly high compared with the average number of births for the corresponding month in the four control years. The 63% excess of schizophrenic births in June 1957 ensued about 5 months after the peak of influenza A/B mixed type epidemic; there was also 49% increase in births about 5 months after the second wave of the pandemic. Given that full term delivery occurred in our sample (ie, 9 months pregnancy), our results support the view of Mednick et al and O'Callaghan et al that maternal exposure to influenza in the mid-pregnancy increases the risk of developing schizophrenia.

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