Tera Kent

Placental CYP27B1 and CYP24A1 expression in human placental tissue and their association with maternal and neonatal calcitropic hormones.

CONTEXT Placental CYP27B1 may contribute to circulating maternal calcitriol concentrations across gestation, but determinants of CYP27B1 and CYP24A1 expression in term human placental tissue are not well established. OBJECTIVE We hypothesized that higher CYP27B1 protein expression would be associated with increased maternal calcitriol during gestation and that CYP27B1 expression would be impacted by substrate availability. DESIGN This was a prospective, longitudinal study. SETTING The study was completed in an urban, prenatal clinic located in Rochester, New York. PATIENTS The study was undertaken in a cohort of 70 pregnant adolescents (≤18 y of age) and their term neonates. INTERVENTION There was no intervention. MAIN OUTCOMES Protein and mRNA expressions of CYP27B1, CYP24A1, and vitamin D receptor were measured in term placental tissue and related to 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, PTH, serum total calcium, IL-6, leptin, and osteoprotegerin measured in maternal serum at midgestation and delivery and in umbilical cord serum at birth. RESULTS Placental CYP27B1 protein expression was significantly positively associated with maternal 25(OH)D at both midgestation (n = 68, P = .009) and delivery (n=67, P = .006). Maternal serum 1,25-dihydroxyvitamin D concentrations at midgestation were positively correlated with term placental CYP27B1 mRNA expression (n = 49, P = .002). Significant positive associations were evident between placental CYP27B1 and CYP24A1 protein expression (P = .001, n = 70). Maternal PTH concentrations at midgestation or delivery did not significantly impact placental protein or transcript level of either enzyme. Variability in placental CYP27B1 protein expression was best captured by a model that included maternal midgestation 25(OH)D concentration, placental vitamin D receptor protein expression, and maternal midgestation IL-6 concentrations (P = .002, n = 60, R(2) = 0.22). CONCLUSIONS Higher maternal 25(OH)D during pregnancy was associated with significantly higher placental protein expression of CYP27B1 at term supportive of a link between substrate availability and placental production of calcitriol.

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.

Prevalence of anemia and associations between neonatal iron status, hepcidin, and maternal iron status among neonates born to pregnant adolescents

Background:Little is known about anemia and iron status in US newborns because screening for anemia is typically not undertaken until 1 y of age. This study was undertaken to characterize and identify determinants of iron status in newborns born to pregnant adolescents.Methods:Pregnant adolescents (≤ 18 y, n = 193) were followed from ≥ 12 wk gestation until delivery. Hemoglobin, ferritin, soluble transferrin receptor, serum iron, hepcidin, erythropoietin (EPO), IL-6, and C-reactive protein were assessed in maternal and cord blood.Results:At birth, 21% of the neonates were anemic (Hb < 13.0 g/dl) and 25% had low iron stores (ferritin < 76 µg/l). Cord serum ferritin concentrations were not significantly associated with gestational age (GA) at birth across the range of 37–42 wk. Neonates born to mothers with ferritin < 12 µg/l had significantly lower ferritin (P = 0.003) compared to their counterparts. Hepcidin and IL-6 were significantly (P < 0.05) higher in neonates born to mothers with longer durations of active labor.Conclusion:Given the importance of the iron stores at birth on maintenance of iron homeostasis over early infancy, additional screening of iron status at birth is warranted among those born to this high risk obstetric population.

Vitamin D Status Affects Serum Metabolomic Profiles in Pregnant Adolescents.

Vitamin D is linked to a number of adverse pregnancy outcomes through largely unknown mechanisms. This study was conducted to examine the role of vitamin D status in metabolomic profiles in a group of 30 pregnant, African American adolescents (17.1 ± 1.1 years) at midgestation (26.8 ± 2.8 weeks), in 15 adolescents with 25-hydroxy vitamin D (25(OH)D) ≥20 ng/mL, and in 15 teens with 25(OH)D <20 ng/mL. Serum metabolomic profiles were examined using gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry. A novel hierarchical mixture model was used to evaluate differences in metabolite profiles between low and high groups. A total of 326 compounds were identified and included in subsequent statistical analyses. Eleven metabolites had significantly different means between the 2 vitamin D groups, after correcting for multiple hypothesis testing: pyridoxate, bilirubin, xylose, and cholate were higher, and leukotrienes, 1,2-propanediol, azelate, undecanedioate, sebacate, inflammation associated complement component 3 peptide (HWESASXX), and piperine were lower in serum from adolescents with 25(OH)D ≥20 ng/mL. Lower maternal vitamin D status at midgestation impacted serum metabolic profiles in pregnant adolescents.

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.

Elemental content of the placenta: A comparison between two high-risk obstetrical populations, adult women carrying multiples and adolescents carrying singletons

Background The placenta is responsible for the exchange of nutrients and for preventing harmful compounds from entering the fetal circulation. With increasing industrialization, exposures to commercial and toxic metals become a concern for both pregnant women and those planning a pregnancy. The understanding of transport mechanisms and pharmacokinetics for most inorganic elements is incomplete and limited to normal term deliveries. Objectives To obtain novel data on 46 inorganic elements in placentae from two high‐risk obstetric populations, women carrying multiples and adolescents carrying singletons, evaluating differences, if present, and identifying predictors of placental content. Methods Placental tissue was collected from adolescents carrying singletons and adults carrying multiples. Elemental content was analyzed using inductively coupled plasma‐mass spectrometry (ICP‐MS). Multivariate regression and factor analyses were used. Results With the exception of Au and Pt, almost all placentae contained quantifiable concentrations of each element analyzed. All placentae contained the essential elements Ca, Fe, Mg, Se and Zn, which clustered together onto the same factor. Most elements were higher in placentae from women carrying multiples. Differences in placental content disappeared after adjusting for maternal age. Rare earth elements (REEs) clustered together and remained higher in the multiples even after adjusting for maternal age. Conclusion Human placentae contain a wide range of elements, including REEs. Ranges differed considerably between cohorts. Elements with similar chemical properties, like REEs or nutritionally essential elements, clustered together. Maternal age, and therefore longer environmental exposure, was significantly associated with elevated element concentrations in the placenta. Placental concentrations of several metals that are known to be nutritionally essential (e.g., Fe, Ca, Mg, and Zn) did not differ significantly between cohorts, suggesting tight regulation, whereas concentrations of environmental contaminants differed significantly between groups, even after adjusting for maternal age. HighlightsLevels of 46 elements were measured in placentae from two high‐risk cohorts.Almost all placentae contained traces of the 46 elements, including REEs.Maternal age was significantly associated with concentrations in the placenta.Elements with similar properties and roles clustered together.