Little is known about the expression of heme transporters in human placenta and possible associations between these transporters and maternal or neonatal iron status. To address this area of research, relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein (BCRP), was assessed using Western-blot analysis in human placental tissue in relation to maternal/neonatal iron status and placental iron concentration. Placental FLVCR1 (n = 71) and BCRP (n = 83) expression were assessed at term (36.6-41.7 wk gestation) in a cohort of pregnant adolescents (13-18 y of age) at high-risk of iron deficiency. Both FLVCR1 and BCRP were detected in all placental samples assayed. Placental FLVCR1 expression was positively related to placental BCRP expression (n = 69; R(2) = 0.104; P < 0.05). Adolescents that were anemic at delivery had lower placental FLVCR1 expression (n = 49; P < 0.05). Placental FLVCR1 expression was positively associated with placental iron concentration at delivery (n = 61; R(2) = 0.064; P < 0.05). In contrast, placental BCRP expression was not significantly associated with maternal iron status or placental iron content. Both FLVCR1 and BCRP are highly expressed in human placental tissue, but only FLVCR1 was significantly inversely associated with maternal iron status and placental iron concentration. Further analysis is needed to explore potential functional roles of FLVCR1 in human placental iron transport.

Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13–18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 ± 3.4 weeks) to delivery (39.3 ± 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid-gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy.

Pregnant adolescents may be at risk for suboptimal vitamin D status and bone loss across pregnancy. RANK/RANK‐L/OPG interactions are integral to osteoclast activity and alterations in RANK‐L expression may be associated with the critical balance between maternal bone loss and fetal bone growth during pregnancy. To assess these issues, vitamin D status (25‐hydroxyvitamin D) was monitored in pregnant adolescents (<18 years old) and their neonates in relation to longitudinal measures of fetal femur and humerus growth, and placental expression of RANK‐L. Fetal femur and humerus length was obtained by sonogram three times across gestation to assess fetal bone growth. Blood samples were collected from each adolescent mid‐gestation and at parturition when cord blood and placental tissue were also obtained. In 25 adolescents studied to date, expression of soluble RANK‐L in the placenta approached significance as a predictor of fetal bone growth (p=.066). At delivery, 71% (n=17) of teens had elevated PTH (>46 pg/mL). 41% (n=43) of teens and 63% of neonates (n=38), had suboptimal vitamin D levels (<20 ng/mL). Recruitment and analyses are on‐going and additional relationships between serum osteoprotegerin (OPG), maternal bone loss, and fetal bone accrual across pregnancy will be explored.Grant Funding SourceUSDA Grant No: 2008‐01857

Mechanisms of placental heme iron transport are largely unknown. To address this, expression of the heme transporter Feline Leukemia Virus, Subgroup C, Receptor (FLVCR) was measured in placental tissue from 84 pregnant teens (13–18 y). Iron (Fe) status indicators, serum ferritin (SF) and serum transferrin receptor (sTfR), were measured at mid‐gestation (25.1±3.5 wks) and in maternal/cord blood at delivery (39.8±1.1 wks). At delivery, 33% (18/54) of teens were anemic (Hb<11 g/dL); hemoglobin (Hb) averaged 11.6±1.5 g/dL (n=54). Maternal SF at delivery was 21.8±13.3 μg/L (n=67); 52% (35/67) had depleted Fe stores (SF<20 μg/L). Neonatal SF averaged 140.8±79.9 μg/L (n=65). At delivery, maternal and neonatal sTfR averaged 5.8±3.7 mg/L (n=66) and 8.0±2.4 mg/L (n=65), respectively. A significant relationship was observed between maternal mid‐gestation SF and neonatal SF (p<0.05, n=52) and between placental FLVCR expression and the maternal delivery: neonatal SF ratio (p<0.01, n=43). Although FLVCR expression was regulated in response to maternal and neonatal Fe status, up‐regulation of this protein was not sufficient to normalize ferritin stores in neonates born to teens with depleted Fe stores. Funded by: NRI Grants 2008‐01857 & 2005‐35200, USDA HATCH (2006‐07‐160), and HHMI.

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