Risk of Schizophrenia Following Prenatal and Postnatal Exposure to Bereavement: a Nationwide Cohort Study in Denmark and Sweden

INTRODUCTION:  Schizophrenia is associated with socioeconomic consequences but its etiology is only partly known. The disease predisposition may be established early in life and prenatal stress may play a role. We aimed to examine whether prenatal maternal bereavement, as the indicator of prenatal stress, was associated with an increased risk of schizophrenia in offspring.

METHODS:  This population-based cohort study included all children born in Denmark (N=1 605 136) and Sweden (N=2 494 285) from 1973 to 1997. The exposure was maternal bereavement by the death of a close relative one year before or during pregnancy. Children were followed from 10 years of age until their death, migration, onset of schizophrenia, or December 31^st, 2007. The main outcome is hospitalization due to schizophrenia.

RESULTS:  A total of 102 045 children (2.49%) were born to mothers who had experienced bereavement one year before or during pregnancy. During up to 25 years of follow-up, 18 231 children were diagnosed with schizophrenia in 49.3 million person-years. The exposed children had a similar risk of hospitalization due to schizophrenia (adjusted incidence rate ratio (aIRR)=1.02, 95% CI: 0.91-1.13), compared to unexposed children. Children born to mothers who lost a spouse during pregnancy had a two-fold risk (aIRR=2.06, 95% CI: 1.20-3.55), and similar elevated risks were observed in children whose mothers lost a spouse during the 1st year (aIRR = 2.13, 95% CI: 1.44–3.15), the 2nd year (aIRR = 1.66, 95% CI: 1.13–2.43), the 3rd year (aIRR = 2.04, 95% CI: 1.47–2.85), and the 4-10^th year (aIRR = 1.50, 95% CI: 1.33–1.69) after childbirth.

CONCLUSIONS:  Our data do not support a programming role of prenatal stress following maternal bereavement on schizophrenia in later life. The increased risk in relation to spousal bereavement may mostly be explained by postpartum changes in familial environment.