Funding outcome

Introduction: Iron deficiency (ID) is the most common nutritional deficiency worldwide putting 40% of pregnant women at risk. Additionally, anemia is identified as a modifiable risk factor of hypertensive disorder in pregnancy (HDP). Pregnancy often being the first-time hypertension is identified by obstetricians, and therefore the likelihood of these morbidities co-existing is high. During pregnancy, the mother undergoes anatomical and physiological changes, including expansion of blood volume and a decrease in vascular resistance. However, these changes are blunted in HDP, impairing oxygen delivery to the fetus. Interestingly, anemia has been shown to cause systemic vasorelaxation accompanied by an increase in cardiac output. Experiments using hypertensive models have shown that dietary ID anemia reduces blood pressure and confers cardiovascular protection. Whereas ID anemia has classically been seen as a pregnancy complication, we hypothesize that dietary ID anemia can confer protection during pregnancy in spontaneously hypertensive rats (SHR). Methods: Female SHR and normotensive control Wistar Kyoto rats (WKY) were fed either an iron-replete (37mg/kg) or an iron-restricted (3mg/kg) diet prior to and during pregnancy (n=12-16). Blood pressure measurements were performed using tail-cuff plethysmography at gestational day (GD) 0, 7, 14 and 21. Pregnant rats were then euthanized at GD21 and tissues were collected for gene expression assessments by RT-qPCR (n=5). Data were analyzed using 2-way ANOVA and the student t-test. Results: Dietary iron restriction reduced maternal hemoglobin (Hb) levels compared to control SHR/WKY counterparts (p<0.0001). Maternal ID reduced mean arterial pressure throughout gestation in ID-treated SHR compared to control SHR (p=0.005); no differences were evident in WKY dams (p=0.1). ID treatment in SHR and WKY resulted in a 10% and 15% decrease in fetal body weight compared to controls, respectively (p=0.001 for both). Fetal Hb levels in ID SHR were reduced by 41% (p<0.0001) compared to respective controls, while ID WKY were reduced by 53% (p<0.0001). Maternal ID caused an increase in placental weights in WKY (+22%, p=0.0002), but not in SHR (p=0.94). ID affected gene expression profiles in SHR maternal hearts; Bax, Bad, and Caspase 3 gene expression were increased 1.5, 1.4, and 1.8-fold (p=0.03, p=0.03, and p=0.01 respectively). These changes were accompanied by the upregulation of antioxidant genes Sod1 (1.5-fold, p=0.01) and Catalase (1.8-fold, p=0.01), altogether suggesting an elevation of intrinsic apoptotic pathways and oxidative stress in ID hearts. Conclusion: These results suggest that while ID may positively impact pregnancies with pre-existing hypertension, there are also deleterious outcomes. Altogether these results can influence how clinicians treat ID in individuals with HDP.