Effects of iron deficiency anemia on maternal hemodynamics and cardiac function in pregnant spontaneously hypertensive rats

Aim Hypertensive disorders of pregnancy (HDP) are characterized by adverse or inadequate maternal cardiovascular adaptations and are associated with poor perinatal outcomes. Iron deficiency (ID) is a common pregnancy complication that elicits numerous cardiovascular adaptations. Though generally considered deleterious in pregnancy, whether ID mitigates or exacerbates maternal cardiovascular dysfunction in HDP has not been investigated. Methods and Results Pregnant spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were fed either an iron-replete or an iron-restricted diet prior to and throughout pregnancy. Pregnant dams underwent tail-cuff plethysmography and echocardiography throughout pregnancy, as well as pressure-volume loop assessments and in-vivo blood pressure (BP) measurements on GD21 (term=GD22). Data were analyzed by 2-Way ANOVA with Holm-Šídák's post-hoc test. Dietary iron restriction caused progressive BP lowering throughout gestation that was most apparent in SHR dams. By GD21, all ID dams had moderate anemia, whereas ID fetuses of both strains exhibited signs of severe anemia, asymmetric growth restriction, and placentomegaly. Maternal ID was associated with left ventricular remodeling in both strains, albeit circulating NT-proBNP levels—a marker of pathological stretch—were reduced in ID-SHR dams. Maternal ID hearts exhibited enhanced ventricular performance reflected by increased stroke volume and cardiac output relative to their iron-replete counterparts. ID also improved cardiac efficiency and ventriculo-arterial coupling, and these latter effects were most pronounced in SHR dams. Conclusions ID in pregnancy was associated with greater BP lowering and improved cardiac performance in SHR dams compared to normotensive WKY dams, albeit ID fetuses from both strains exhibited growth restriction and placentomegaly. These findings highlight a complex interaction between ID anemia in pre-existing hypertension in pregnancy, and if translated to humans, could have important implications for the identification and management of both prevalent health conditions.