Schizophrenia and 1957 pandemic of influenza: meta-analysis

Abstract

Maternal influenza during pregnancy is a controversial risk factor for schizophrenia in the child. We conducted a meta-analysis to examine whether birth during the 9-month period after the pandemic of 1957 was a risk factor for schizophrenia. Studies that compared the risk of schizophrenia among subjects born after the pandemic with that among those born in corresponding time periods in surrounding years were divided into those conducted in the United States, Europe, or Australia (type A studies, n = 8) and those from Japan, where the epidemic came in 2 waves (type B studies, n = 3). Other studies examined the risk among subjects born to mothers who were pregnant during the pandemic and reported having had influenza (type C studies, n = 2). Relative risks (RRs) were extracted or calculated for each month and/or trimester of possible exposure by 2 independent authors. All analyses were performed using a fixed-effects model. The weighted results of the type A studies did not indicate a significantly increased risk of schizophrenia among children exposed during any trimester or month of prenatal life. Not a single study found a significant first- or second-trimester effect. The mean weighted RR for subjects who were in their first, second, or third trimester of prenatal life during the pandemic (8 effect sizes) was 0.91 (95% confidence interval [CI]: 0.85-0.98), 1.00 (95% CI: 0.93-1.07), and 1.05 (95% CI: 0.98-1.12), respectively. The pooled results of the type B and type C studies were also negative. Given high infection rates during the pandemic (about 50%), these results do not support the maternal influenza hypothesis.

Fig. 1.

Natural Logarithm of Relative Risks (and 95% Confidence Intervals) for Subjects Included in Eight Ecological Studies from Europe, America, and Australia (Type A Studies) of Risk for Schizophrenia Associated with Exposure to 1957 Influenza Pandemic During Second Trimester of Prenatal Life. Studies are identified by first author and year of publication. Figure shows natural logarithm of all effect sizes and natural logarithm of grand mean.