Research aims and hypotheses. Adverse in-utero and perinatal events may contribute to an increased risk of suicidal behavior (i.e., suicide death and suicide attempt) throughout the lifespan due to impaired neurodevelopment, in line with the Developmental Origins of Health and Diseases hypothesis. However, current evidence is limited. While prior studies have focused on broad indicators of impaired neurodevelopment (e.g., low birth weight), it is necessary to identify specific and modifiable in-utero/perinatal events to target with early interventions to promote effective suicide prevention. Therefore, our first aim is to investigate the association of a) exposure to infections during pregnancy, b) exposure to psychotropic medications during pregnancy, and c) obstetric complications during delivery with suicidal behavior. We hypothesize an increased risk of suicidal behavior for individuals exposed to these in-utero/perinatal events. Our second aim is to determine whether the associations between in-utero/perinatal events and suicidal behavior differ with respect to individual vulnerability to mental disorders. In line with a stress-diathesis model of suicide, we hypothesize a synergistic association (i.e., interaction) between in-utero/perinatal events and family history of mental disorders (a proxy for individual vulnerability to mental disorders) in increasing offspring suicidal behavior. Our third aim is to determine whether the associations between the investigated in-utero/perinatal events and suicidal behavior are mediated by mental disorders preceding suicide attempt. We hypothesize that mental disorders, specifically depressive, psychotic, and neurodevelopmental disorders, partially mediate these associations.
Sample, measures, and procedures. We will rely on individual-level data from administrative registers covering the entire Danish population. All persons born in 1953 or later and living in Denmark between 1980 and 2020 will be included (N=4,472,970). Both suicidal behavior and in-utero/perinatal exposure, as well as all study variables, will be ascertained using official inpatient and outpatient data from administrative registers. We will use Poisson regression models to test our hypotheses, adjusting for confounding variables (first aim). Co-sibling comparison models will be used to further account for unmeasured confounding. Moderation analyses will be used to test whether in-utero/perinatal events are associated with suicidal behavior uniquely or more strongly among individuals with family history of mental disorders (second aim). Mediation analyses will be used to investigate the extent to which mental disorders preceding suicide attempt account for the observed associations between in-utero/perinatal events and suicidal behavior (third aim).
Potential impact and next steps. This project will contribute to our understanding of the role that specific in-utero/perinatal factors with a biological influence on neurodevelopment play in the pathway leading to suicidal behavior. This will be a further step towards optimizing intervention efforts focusing on early maternal and infant care for population-based prevention of suicide. The project will also contribute to the theoretical knowledge on suicide etiology by testing a stress-diathesis model and disentangling mediation pathways to suicidal behavior for individuals exposed to adverse in-utero/perinatal events. Finally, findings may inform future studies to further clarify the associations between in-utero/perinatal events and suicidal behavior at the biological and molecular levels.
