Maternal influenza has been associated previously with schizophrenia in offspring in a number of studies.
1,2 In the present investigation, we examined the relationship between this infection during pregnancy and the occurrence of bipolar disorder (BD). This hypothesis was based on several observations in the literature. First, some evidence suggests that patients with BD are more likely to be born during the winter and early spring.
3 Second, in the British Perinatal Mortality Survey,
4 influenza and pyrexia were reported more frequently during pregnancy by mothers of patients with affective psychosis compared with control subjects, although limitations of that study included diagnoses based on case notes, no differentiation of the manic depressive phenotype from depressive psychosis, and a small sample size. Third, subjects who were in utero during the second trimester at the time of the 1957 A2/Singapore influenza pandemic manifested a significant increase in the prevalence of major affective disorder, with a similar although nonsignificant (
P > .05 as reported by the authors) elevation in BD prevalence.
5 That study was limited, however, by exposure misclassification, given that the exposure was defined by ecologic data rather than by infection in individual pregnancies. Another study, which used maternal recall of gestational influenza after diagnosis of BD in offspring, reported a numerical although nonsignificant increase in the risk of BD (
P = .09).
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