Allison McIntyre

Maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents.

BACKGROUND Maternal calcium intake and vitamin D status may affect fetal bone development. OBJECTIVE This study was designed to examine relations between maternal calcium intake, 25-hydroxyvitamin D [25(OH)D] status, and fetal bone growth across pregnancy. DESIGN This was a prospective longitudinal design. Maternal 25(OH)D, parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were determined at midgestation (∼26 wk) and at delivery in 171 adolescents (≤ 18 y). Dietary recalls and fetal sonograms were performed up to 3 times across gestation, and fetal femur and humerus z scores were generated. RESULTS Fetal femur and humerus z scores and neonatal birth length were significantly greater (P < 0.03) in adolescents consuming ≥ 1050 mg than in those consuming <1050 mg Ca/d. Maternal 25(OH)D > 50 nmol/L was significantly positively associated with fetal femur and humerus z scores (P < 0.01). When maternal smoking, height, race, weight gain, and gestational age were controlled for, these relations remained significant. Interactions between calcium intake and 25(OH)D were evident. Calcium intake was associated with fetal femur z scores and birth length only when maternal 25(OH)D was ≤ 50 nmol/L (P < 0.05). Similarly, maternal 25(OH)D was associated with fetal femur and humerus z scores only when maternal calcium intake was <1050 mg/d (P < 0.03). CONCLUSIONS Optimal calcium intake and adequate maternal vitamin D status are both needed to maximize fetal bone growth. Interactions between these nutrients were evident when either calcium or vitamin D status was limited. Improving maternal calcium intake and/or vitamin D status during pregnancy may have a positive effect on fetal skeletal development in pregnant adolescents.

Maternal Hepcidin Is Associated with Placental Transfer of Iron Derived from Dietary Heme and Nonheme Sources

The determinants of placental transport of dietary iron remain largely uncharacterized. The objective of this research was to elucidate determinants of fetal Fe transfer from maternally ingested dietary heme and non-heme Fe. The study was undertaken in 19 pregnant females (16-32 y) who ingested intrinsically labeled (58)Fe-heme and a nonheme Fe source ((57)FeSO(4)) during the third trimester of pregnancy. At delivery, maternal and cord blood was obtained to assess neonatal (57)Fe and (58)Fe enrichment as a function of maternal/neonatal Fe status [serum ferritin (SF), transferrin receptor, hemoglobin (Hb), total body Fe, and hepcidin]. There was a greater percentage of maternally absorbed (58)Fe tracer present in the neonates compared to the (57)Fe tracer (5.4 ± 2.4 vs. 4.0 ± 1.6; P < 0.0001). Net dietary nonheme Fe (mg) and heme Fe (mg) transferred to the fetus were both inversely correlated with measures of maternal serum hepcidin (P = 0.002, r(2) = 0.43; P = 0.004, r(2) = 0.39) and SF (P = 0.0008, r(2) = 0.49; P = 0.003, r(2) = 0.41) and directly associated with neonatal Hb (P = 0.004, r(2) = 0.39; P = 0.008, r(2) = 0.35). The results of this study suggest that during pregnancy there appears to be preferential fetal use of maternally ingested Fe derived from a dietary, animal-based heme source compared to Fe ingested as ferrous sulfate. Maternal serum hepcidin and maternal/neonatal Fe status may play a role in placental uptake of dietary heme and nonheme Fe.

Vitamin D insufficiency is prevalent and vitamin D is inversely associated with parathyroid hormone and calcitriol in pregnant adolescents

Few large studies have assessed changes in calcitropic hormones and maternal 25‐hydroxyvitamin D (25(OH)D) status across pregnancy, and how this may impact maternal bone turnover and neonatal hormone status. We aimed to identify determinants of 25(OH)D, parathyroid hormone (PTH), and calcitriol across pregnancy in a longitudinal study of 168 pregnant adolescents (≤18 years of age). Maternal 25(OH)D, PTH, and calcitriol were assessed at mid‐gestation (∼26 weeks), delivery, and in cord blood. Data were related to measures of maternal anthropometrics, dietary intake, physical activity, and bone turnover markers. Approximately 50% of teens and their infants had serum 25(OH)D ≤ 20 ng/mL; 25(OH)D was lower in African Americans versus whites (p < 0.001). PTH increased across gestation (p < 0.001). Elevated PTH (≥60 pg/mL) was detected in 25% of adolescents at delivery, and was associated with increased concentrations of serum N‐telopeptide (NTX) (p = 0.028). PTH and calcitriol did not significantly differ across the range of Ca intake consumed (257–3220 mg/d). In the group as a whole, PTH was inversely associated with 25(OH)D in maternal circulation at mid‐gestation (p = 0.023) and at delivery (p = 0.019). However, when the cohort was partitioned by 25(OH)D status, this relationship was only present in those with 25(OH)D ≤ 20 ng/mL, suggestive of a threshold below which 25(OH)D impacts PTH during pregnancy. Mid‐gestation 25(OH)D was inversely associated with calcitriol at delivery (p = 0.023), irrespective of Ca intake. Neonatal PTH and calcitriol were significantly lower than (p < 0.001), but unrelated to maternal concentrations. These findings indicate that maternal 25(OH)D status plays a role in calcitropic hormone regulation in pregnant adolescents.

Impact of maternal and neonatal iron status on placental transferrin receptor expression in pregnant adolescents.

OBJECTIVE To elucidate the role of maternal and neonatal iron status on placental transferrin receptor (TfR) expression. STUDY DESIGN AND OUTCOMES: Ninety-two healthy pregnant adolescents (ages 14-18 years) were followed across pregnancy. Maternal iron status (hemoglobin, hematocrit, serum ferritin, TfR, and total body iron) was assessed in mid-gestation (21-25 wks) and at delivery in the mother and neonate. Placental TfR protein expression was assessed by western blot in placental tissue collected at delivery. RESULTS Placental TfR expression was inversely associated with maternal iron status at mid-gestation (hemoglobin p = 0.046, R(2) = 0.1 and hematocrit p = 0.005, R(2) = 0.24) and at delivery (serum ferritin p = 0.02, R(2) = 0.08 and total body iron p = 0.02, R(2) = 0.07). Mothers with depleted body iron stores had significantly greater placental expression of TfR than mothers with body iron stores greater than zero (p = 0.003). Neonatal iron stores were also inversely associated with the expression of placental TfR (p = 0.04, R(2) = 0.06). Neonates with serum ferritin values ≤ 34 μg/L had significantly greater protein expression of placental TfR compared to neonates with cord serum ferritin values >34 μg/L (p = 0.01). CONCLUSIONS Expression of placental TfR is associated with both maternal and neonatal iron demands. Increased expression of placental TfR may be an important compensatory mechanism in response to iron deficiency in otherwise healthy pregnant women.

Utilization of Iron from an Animal-Based Iron Source Is Greater Than That of Ferrous Sulfate in Pregnant and Nonpregnant Women

Heme iron absorption during pregnancy and the role of hepcidin in regulating dietary heme iron absorption remains largely unexplored. The objective of this research was to examine relative differences in heme (animal based) and nonheme (ferrous sulfate) iron utilization. This study was undertaken in 18 pregnant (ages 16-32 y; wk 32-35 of gestation) and 11 nonpregnant women (ages 18-27 y). Women were randomly assigned to receive both an animal-based heme meal (intrinsically labeled (58)Fe pork) and labeled ferrous sulfate ((57)Fe) fed on alternate days. Blood samples obtained 2 wk postdosing were used to assess iron status indicators and serum hepcidin and iron utilization based on RBC incorporation of iron isotopes. Heme iron utilization was significantly greater than nonheme iron utilization in the pregnant (47.7 ± 14.4 vs. 40.4 ± 13.2%) and nonpregnant women (50.1 ± 14.8 vs. 15.3 ± 9.7%). Among pregnant women, utilization of nonheme iron was associated with iron status, as assessed by the serum transferrin receptor concentration (P = 0.003; r(2) = 0.43). In contrast, heme iron utilization was not influenced by maternal iron status. In the group as a whole, women with undetectable serum hepcidin had greater nonheme iron utilization compared with women with detectable serum hepcidin (P = 0.02; n = 29); however, there were no significant differences in heme iron utilization. Our study suggests that iron utilization from an animal-based food provides a highly bioavailable source of dietary iron for pregnant and nonpregnant women that is not as sensitive to hepcidin concentrations or iron stores compared with ferrous sulfate.

Placental Expression of the Heme Transporter, Feline Leukemia Virus Subgroup C Receptor, Is related to Maternal Iron Status in Pregnant Adolescents

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.