The Clinical Iron Supplement Fer-In-Sol Improves Fetal Iron Status and Brain Weight in Rats Prenatally Exposed to Alcohol

Abstract

Abstract Objectives Prenatal alcohol exposure (PAE) causes iron deficiency in fetal rats, even when their mothers consume enough iron. Increasing maternal dietary iron improves fetal outcomes, including blood status, brain iron, and proinflammatory cytokines. Clinically, gestational iron deficiency is widespread, with a great need for effective iron interventions in alcohol-exposed pregnancies. Here, we test the ability of a popular clinical iron supplement, Fer-In-Sol (ferrous sulfate), to mitigate PAE's effects when co-administered with alcohol during pregnancy. We hypothesized that the prenatal iron supplement would normalize fetal iron status and have minimal adverse effects on the PAE dams and fetuses. Methods Pregnant Long-Evans rats consumed an iron-adequate diet (AIN-76A, 100 ppm iron) and received 5 g/kg alcohol or isocaloric maltodextrin (MD) by gavage on gestational days (GD) 13.5–19.5. Some dams received 6 mg/kg oral iron as ferrous sulfate from GD12.5–19.5, generating a 2 × 2 design. At GD20.5, we used an ANOVA to analyze mothers and fetuses, with litter as the experimental unit. Results Iron had no effect on PAE-induced reductions in maternal gestational weight gain (P = 0.7818) or maternal food intake (P = 0.7299). Iron did not mitigate a PAE-induced 17% reduction in fetal weight (P = 0.4803). Although iron failed to improve a 10% reduction in placental efficiency (P = 0.0589) or 10% elevation in relative heart weight (P = 0.2958) due to PAE, iron did elevate PAE fetal brain weight by 5%, and it no longer differed from MD-controls (P = 0.5255). Furthermore, iron normalized fetal hematology values in PAE, and improved fetal red blood cell numbers (P = 0.0458) and hematocrit (P = 0.0439) and trended to normalize hemoglobin (P = 0.0585). Iron did not significantly alter maternal blood, suggesting that this iron dose was not excessive. As expected, PAE increased malondialdehyde (MDA) levels in maternal (+10%, P = 0.0224) and fetal livers (+44%, P < 0.0001). Iron supplementation caused an additional, modest rise in maternal (+15%, P = 0.0042) and fetal (+22%, P = 0.0093) livers. Conclusions These data show that maternal iron supplementation improves select fetal outcomes in PAE, including brain weight and blood values, and suggests that this may be a clinically feasible approach to improve prenatal iron status and fetal outcomes in PAE pregnancies. Funding Sources NIAAA NIDDK.