Adverse Pregnancy Outcomes Following the Assassination of John F. Kennedy in 1963

Introduction Women exposed to stressful events during pregnancy are thought to be at increased risk of adverse birth outcomes. However, studies investigating stressful events are often unable to control for important confounders, such as behavioral and genetic characteristics, or to isolate the impact of the stressor from other secondary effects. We used a discordant-sibling design, which provides stronger inferences about causality, to examine whether a widespread stressor with limited impact on day-to-day life (John F. Kennedy assassination) resulted in an increased risk of adverse birth outcomes. Methods Data were obtained from the Collaborative Perinatal Project, a prospective, multi-site cohort study conducted in the US from 1959 to 1965. Our analysis was restricted to singleton live births >= 24 weeks born before the assassination (n = 24,406) or in utero at the time (n = 5833). We also evaluated associations within siblings discordant for exposure (n = 1144). We used survival analysis to evaluate associations between exposure and preterm birth and marginal models to evaluate associations with birthweight and placental pathology. Results First trimester exposure was associated with preterm birth (hazard ratio (HR): 1.17; 95% CI: 1.05, 1.31). In the discordant-sibling model, the point estimate was similar (HR: 1.22; 95% CI: 0.36, 4.06). Third trimester exposure was associated with increased odds of fetal acute inflammation in the placenta (odds ratio (OR): 1.34, 95% CI: 1.05, 1.71). Conclusions for Practice First trimester exposure to an acute stressor was associated with preterm birth. We did not observe increased odds of placental pathology with first trimester exposure; however, stress may increase preterm birth risk through chronic placental inflammation, which was not evaluated in this sample.