Fetal Exposure to Preeclampsia and Later Risk of Cardiometabolic Disorders: A Population-Based Cohort Study

Abstract

BACKGROUND: Fetal preeclampsia exposure has been associated with later cardiometabolic disease. However, this association has been investigated in few large population-wide studies, and it is unknown whether the association represents a causal relationship or is the result of shared etiological factors. METHODS: To further investigate the relationship between preeclampsia exposure and later cardiometabolic disease, we identified 1 692 944 singleton infants born in Norway during 1967 to 1997, where 44 299 were exposed to preeclampsia in utero. The individuals were followed for hypertension, diabetes, and dyslipidemia as defined by dispensed medication. We used Cox regression models to calculate the association between preeclampsia exposure and cardiometabolic outcomes adjusting for measured confounders. We also used full sibling comparisons and stratified Cox regression to control for unmeasured familial confounders. RESULTS: On the population level, exposed individuals had increased risk of hypertension (adjusted hazard ratio [aHR] 1.51 [95% CI, 1.41–1.63]), diabetes (aHR 1.33 [95% CI, 1.24-1.43], and dyslipidemia (aHR 1.28 [95% CI, 1.13–1.45]) compared with unexposed individuals. In sibling data, individuals not exposed to preeclampsia, but with an exposed sibling, had higher risk of hypertension and diabetes than individuals where no siblings were exposed to preeclampsia. Moreover, when comparing siblings discordant on preeclampsia exposure, there were no associations between preeclampsia and hypertension (aHR 1.05 [95% CI, 0.88–1.26]), diabetes (aHR 0.96 [95% CI, 0.80–1.14]), and dyslipidemia (aHR 0.86 [95% CI, 0.62–1.20]). CONCLUSIONS: Fetal preeclampsia exposure was associated with adult life hypertension, diabetes, and dyslipidemia, but these associations were likely due to shared etiological factors, rather than exposure to the preeclamptic condition itself.