Association between short birth intervals and schizophrenia in the offspring

Pregnancy burdens maternal folate reserves. Postpartum restoration to normal folate values may take up to 1 year. Maternal folate deficiency during early pregnancy has been hypothesized as a cause of schizophrenia in the offspring. We investigated whether the risk of schizophrenia is increased in persons conceived shortly after another birth. A population-based cohort was established of 1.43 million persons born in Denmark between 1950 and 1983, yielding 17.6 million person-years of follow-up. Schizophrenia in cohort members (5095 cases) and their siblings and parents was identified by linkage with the Danish Psychiatric Case Register. Relative risks of schizophrenia were estimated by use of log-linear Poisson regression. As compared to intervals of 45 months and longer, the schizophrenia risk ratio was 1.14 (95% confidence interval [CI], 0.97 to 1.35) for interbirth intervals of up to 15 months, 1.32 (95% CI, 1.12 to 1.56) for intervals of 15 to 17 months, 1.38 (95% CI, 1.18 to 1.61), for intervals of 18 to 20 months and 1.13 (95% CI, 1.00 to 1.29) for intervals of 21 to 26 months. Relative risks did not essentially change after adjustment for age, sex, calendar year of diagnosis, maternal and paternal age, history of mental illness in a parent or sibling, sibship size, place of birth, and distance to younger sibling. These results show an association between short birth intervals and schizophrenia in the offspring. Although maternal folate depletion may play a role in this association, we cannot rule out other explanations such as maternal stress during pregnancy and childhood infections.