Association between maternal infections during pregnancy and offspring suicide risk: A national cohort study

Maternal infections during pregnancy may impact offspring brain development and increase the risk of mental disorders, but their impact on suicidal behavior remains unclear. In this study, we investigated associations between maternal infections before, during, and after pregnancy and offspring suicide attempt later in life to understand the mechanisms explaining these associations. Furthermore, paternal infections during these same periods were examined to pinpoint the possible specific role of intra-uterine exposure vs. genetic and socioeconomic confounding factors. A cohort design was applied to individual-level register-based data including all persons aged 10+ years and living in Denmark in 1987-2021. Information on maternal infection (bacterial, viral, and other, as well as at different body sites) was obtained from the Medical Birth Register based of diagnoses received during hospital contacts. The main outcome was hospital presentations for suicide attempt in the offspring. Adjusted Incidence Rate Ratios (IRR) were estimated to quantify the association between exposure to maternal infections and offspring suicide attempt. Of 2,157,641 individuals (35,047,803 person-years), 38,840 (1.8%), 26,158 (1.2%), and 34,853 (1.6%), had been exposed to maternal infection during, before, and after pregnancy, respectively, while 32,275 attempted suicide. Rates among those exposed to maternal infection during pregnancy and those non-exposed were 141.2 and 90.0 per 100,000 person-years, respectively. After adjustment, individuals exposed to maternal infections during pregnancy had higher risk of suicide attempt when compared to non-exposed (IRR 1.46 [1.36-1.56]), particularly those exposed in the second and third trimesters. Elevated risks were also observed among individuals whose mothers with infections prior (incidence rate: 144.3 per 100,000; IRR 1.45 [1.33-1.57]) and after pregnancy (incidence rate: 128.3 per 100,000; IRR 1.31 [1.21-1.42]). However, no associations were found for paternal infections during, before, or after pregnancy and offspring suicide attempt. These findings show that maternal, but not paternal, infections were associated with later risk of suicide attempt in the offspring, pointing out to a possible role of the intra-uterine environment. The similar estimates obtained for exposure to maternal infections before and after pregnancy suggests that part of this risk may stem from an underlying susceptibility to infections or socioeconomic confounding factors, as well as to possible measurement errors in the onset of infections.