Carrie Thomas

Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy

BACKGROUND Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations. OBJECTIVE We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status. DESIGN The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum. RESULTS Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin. CONCLUSIONS In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens.

Duodenal Absorption and Tissue Utilization of Dietary Heme and Nonheme Iron Differ in Rats

BACKGROUND Dietary heme contributes to iron intake, yet regulation of heme absorption and tissue utilization of absorbed heme remains undefined. OBJECTIVES In a rat model of iron overload, we used stable iron isotopes to examine heme- and nonheme-iron absorption in relation to liver hepcidin and to compare relative utilization of absorbed heme and nonheme iron by erythroid (RBC) and iron storage tissues (liver and spleen). METHODS Twelve male Sprague-Dawley rats were randomly assigned to groups for injections of either saline or iron dextran (16 or 48 mg Fe over 2 wk). After iron loading, rats were administered oral stable iron in the forms of (57)Fe-ferrous sulfate and (58)Fe-labeled hemoglobin. Expression of liver hepcidin and duodenal iron transporters and tissue stable iron enrichment was determined 10 d postdosing. RESULTS High iron loading increased hepatic hepcidin by 3-fold and reduced duodenal expression of divalent metal transporter 1 (DMT1) by 76%. Nonheme-iron absorption was 2.5 times higher than heme-iron absorption (P = 0.0008). Absorption of both forms of iron was inversely correlated with hepatic hepcidin expression (heme-iron absorption: r = -0.77, P = 0.003; nonheme-iron absorption: r = -0.80, P = 0.002), but hepcidin had a stronger impact on nonheme-iron absorption (P = 0.04). Significantly more (57)Fe was recovered in RBCs (P = 0.02), and more (58)Fe was recovered in the spleen (P = 0.01). CONCLUSIONS Elevated hepcidin significantly decreased heme- and nonheme-iron absorption but had a greater impact on nonheme-iron absorption. Differential tissue utilization of heme vs. nonheme iron was evident between erythroid and iron storage tissues, suggesting that some heme may be exported into the circulation in a form different from that of nonheme iron.

Iron Requirements and Adverse Pregnancy Outcomes

Optimal iron (Fe) status across pregnancy is recognized for its benefits on maternal pregnancy outcomes and is increasingly linked to neonatal Fe stores at birth and subsequent health outcomes in the offspring. In spite of the importance of this nutrient, many unresolved questions exist on the basic science of Fe regulation at this key life stage. Increased attention has been placed on identification of optimal biomarkers of maternal Fe status across gestation, and on the challenge of evaluating Fe status indicators as a function of variable plasma volume expansion and maternal inflammatory status. While maternal consequences of anemia are well appreciated, elevated hemoglobin concentrations have also been linked to increased risk of adverse pregnancy outcomes. Discussion of maternal Fe status during gestation is incomplete without concurrent consideration of how maternal stores influence placental Fe transfer and the adequacy of neonatal Fe stores at birth. This is especially important when considering data that finds associations between neonatal Fe status and subsequent cognitive and neurobehavioral outcomes. This review summarizes new data on maternal Fe utilization across pregnancy as it impacts the pregnant woman and her neonate at birth.

Vitamin D mediates the relationship between placental cathelicidin and group B streptococcus colonization during pregnancy

Vitamin D is thought to modulate innate immune responses, and recent studies have highlighted the autocrine and paracrine functions of vitamin D in the placenta. Our objective was to determine the relationship between maternal vitamin D status and placental antimicrobial peptide (AMP) expression in a group of racially and ethnically diverse pregnant adolescents. In this study, 158 pregnant adolescents were recruited from the Rochester Adolescent Maternity Program (RAMP) in Rochester, NY. Maternal serum concentrations of the vitamin D biomarkers, 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D), were measured at mid-gestation (∼26 weeks) and at delivery. At the placental level, vitamin D regulatory proteins (cubilin, megalin, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), vitamin D receptor (VDR)) and AMPs (cathelicidin and hepcidin) were analyzed using quantitative PCR and western blot techniques. Placental CYP27B1 mRNA expression was significantly positively associated with both placental cathelicidin mRNA expression (P<0.0001) and placental hepcidin mRNA expression (P=0.002). In teens with positive recto-vaginal group B streptococcus (GBS) colonization, placental mRNA expression of cathelicidin (P=0.007), cubilin (P=0.03), and CYP27B1 (P=0.04) were significantly lower compared to those who tested negative for this infection. A mediation analysis showed that the indirect relationship between GBS colonization and placental cathelicidin mRNA expression was mediated by the placental mRNA expression of the vitamin D proteins cubilin and CYP27B1 (P=0.02). Additional research is needed to identify the role and relative contributions of placental and systemic vitamin D metabolites in relation to potentially pathogenic microorganisms which may be present during pregnancy.