Kimberly O. O'Brien

Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir Space Station

Bone loss is a current limitation for long‐term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4–6 months were evaluated. Spaceflight‐induced bone loss was associated with increased bone resorption and decreased calcium absorption.

Serum hepcidin is significantly associated with iron absorption from food and supplemental sources in healthy young women

BACKGROUND Hepcidin is a key regulator of iron homeostasis, but to date no studies have examined the effect of hepcidin on iron absorption in humans. OBJECTIVE Our objective was to assess relations between both serum hepcidin and serum prohepcidin with nonheme-iron absorption in the presence and absence of food with the use of dual stable-iron-isotope techniques. DESIGN The study group included 18 healthy nonpregnant women. Women received in random order a supplemental iron source (7.6 mg FeSO4 providing 0.9 mg 58Fe as FeSO4) and 6.8 mg 57Fe ferrous sulfate tracer administered with a nonheme food source [orange-fleshed sweet potato (OFSP): 1.4 mg native Fe]. Iron absorption was determined by analyzing blood samples taken 14 d after dosing with the use of magnetic sector thermal ionization mass spectrometry. Serum hepcidin was assessed by a new competitive serum enzyme-linked immunosorbent assay (ELISA) specific for the refolded, mature 25-amino acid form, and serum prohepcidin was assessed by an ELISA specific for amino acids 28-47 of the hepcidin prohormone. RESULTS In these women, iron absorption averaged 14.71 +/- 10.7% from the supplemental iron compared with 3.63 +/- 6.5% from the OFSP. Absorption of nonheme iron assessed in the presence (P = 0.038) and absence (P = 0.0296) of food was significantly associated with serum hepcidin but was not significantly related to serum prohepcidin. CONCLUSION Serum hepcidin, but not prohepcidin, was inversely associated with iron absorption from supplemental and food-based nonheme-iron sources in iron-replete healthy women.

Characteristics and risk factors for adverse birth outcomes in pregnant black adolescents

OBJECTIVES To describe maternal characteristics and birth outcomes in a group of pregnant minority adolescents and to characterize the impact of maternal age (<15 years versus 15-17 years) on birth outcomes. STUDY DESIGN A 10-year retrospective chart review was conducted in 1120 pregnant black adolescents (< or =17 years of age) who had received prenatal care at an inner-city maternity clinic in Baltimore, Md. RESULTS Pregnant black adolescents had a higher incidence of low birth weight infants, preterm delivery, and fetal death compared with normative data from the United States. Younger adolescents were more likely to have inadequate utilization of prenatal care (P<.01). Older adolescents had a higher incidence of gonorrhea infections (P=.046), greater rates of self-reported substance abuse (P=.063), and a higher history of cigarette smoking (P<.01). Low prepregnancy body mass index (BMI), inadequate weight gain, and poor prenatal care utilization were strong independent predictors of preterm birth (P<.05). Low prepregnancy BMI, inadequate weight gain, female infant, and self-reported cigarette smoking history were significantly associated with decreased infant birth weight (P<.05). CONCLUSIONS Pregnant black adolescents had increased risks of adverse pregnancy outcomes. This population should be studied further to develop age-appropriate and population-specific interventions to improve birth outcomes.

Pregnancy and iron homeostasis: an update

It has been nearly 15 years since the first review on pregnancy and iron deficiency was published in Nutrition Reviews. Many unresolved issues raised in that seminal review have been addressed. New proteins involved in nonheme and heme iron transport have been identified in the enterocyte, and information on the roles of these proteins in the placenta is evolving. The systemic iron regulatory hormone, hepcidin, has since been identified as a key regulator of iron homeostasis. Additional data on the efficacy and consequences of prenatal iron supplementation are available. Emerging data on developmental changes in iron absorption across early infancy have further emphasized the need to ensure that the iron endowment of the neonate at birth is optimal. This is especially important, given growing evidence linking neonatal iron status with subsequent cognitive and neurobehavioral outcomes. Along with the many advances, new questions and gaps in knowledge have been identified. This review summarizes new data on maternal iron utilization across pregnancy as it impacts the pregnant woman and the iron status of the neonate at birth.

Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial.

Proton pump inhibitors (PPIs) are the most potent gastric acid suppressing drugs available, and their use is widespread. An emerging concern about chronic PPI therapy is whether these drugs impair intestinal calcium absorption, resulting in a negative calcium balance and thereby potentially causing bone loss. The objective of this study was to evaluate the acute effect of the PPI esomeprazole or placebo on intestinal calcium absorption in healthy adults. Twelve young adults participated in a placebo‐controlled, double‐blind, crossover study. There were two 3‐week interventions that included a 14‐day adjustment period (designed to stabilize calcium homeostasis) followed by 6 days of a diet containing 800 mg of calcium and 2.1 g/kg of protein (intervention). During the last 3 days of the adjustment period and throughout the intervention period, subjects consumed esomeprazole or placebo. Half the subjects underwent 24‐hour continuous gastric acid pH monitoring. Intestinal calcium absorption was measured using dual‐stable calcium isotopes at the end of each intervention. Treatment with esomprazole significantly increased gastric pH (mean pH on PPI 5.38 ± 0.13, mean pH on placebo 2.70 ± 0.44, p = .005). Neither calcium absorption (PPI 34.2% ± 2.4%, placebo 31.5% ± 2.1%, p = .24) nor urinary calcium (PPI 321 ± 38 mg/34 hours, placebo 355 ± 37 mg/34 hours, p = .07) differed between the PPI and placebo groups. It is concluded that short‐term gastric acid suppression by PPIs does not attenuate intestinal calcium absorption in healthy young adults.

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.

The Effect of Vitamin D2 and Vitamin D3 on Intestinal Calcium Absorption in Nigerian Children with Rickets

CONTEXT Children with calcium-deficiency rickets have high 1,25-dihydroxyvitamin D values. OBJECTIVE The objective of the study was to determine whether vitamin D increased calcium absorption. DESIGN This was an experimental study. SETTING The study was conducted at a teaching hospital. PARTICIPANTS Participants included 17 children with nutritional rickets. INTERVENTION The participants were randomized to 1.25 mg oral vitamin D(3) (n = 8) or vitamin D(2) (n = 9). MAIN OUTCOME MEASURE Fractional calcium absorption 3 da after vitamin D administration was measured. RESULTS Mean baseline 25-hydroxyvitamin D concentrations were 20 ng/ml (range 5-31 ng/ml). The increase in 25-hydroxyvitamin D was equivalent after vitamin D(3) (29 +/- 10 ng/ml) or vitamin D(2) (29 +/- 17 ng/ml). Mean 1,25-dihydroxyvitamin D values increased from 143 +/- 76 pg/ml to 243 +/- 102 pg/ml (P = 0.001), and the increase in 1,25-dihydroxyvitamin D did not differ between vitamin D(2) and vitamin D(3) (107 +/- 110 and 91 +/- 102 ng/ml, respectively). The increment in 1,25-dihydroxyvitamin D was explained almost entirely by the baseline 25-hydroxyvitamin D concentration (r(2) = 0.72; P < 0.001). Mean fractional calcium absorption did not differ before (52.6 +/- 21.4%) or after (53.2 +/- 23.5%) vitamin D, and effects of vitamin D(2) and vitamin D(3) on calcium absorption were not significantly different. Fractional calcium absorption was not closely related to concentrations of 25-hydroxyvitamin D (r = 0.01, P = 0.93) or 1,25-dihydroxyvitamin D (r = 0.21, P = 0.24). The effect of vitamin D on calcium absorption did not vary with baseline 25-hydroxyvitamin D values or with the absolute increase in 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D values. CONCLUSIONS Despite similar increases in 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with vitamin D(2) or vitamin D(3), fractional calcium absorption did not increase, indicating that rickets in Nigerian children is not primarily due to vitamin D-deficient calcium malabsorption.

Vitamin D Insufficiency Is Prevalent among Pregnant African American Adolescents

STUDY OBJECTIVE Recent attention has focused on vitamin D insufficiency but few data exist on vitamin D status among pregnant minority youth. DESIGN A screening study was undertaken in adolescents having prenatal blood samples drawn for other routine tests obtained during the second trimester (18+/-1.8 week gestation, n=44) or third trimester of pregnancy (28.4+/-2.1 week gestation, n=36). Serum 25- hydroxyvitamin D (25(OH)D) was measured and significant determinants of vitamin D insufficiency in this cohort were identified. SETTING Urban prenatal clinic. PARTICIPANTS Eighty pregnant African American adolescents (< or = 18 y of age). MAIN OUTCOME MEASURE(S) Vitamin D status, STDs, hemoglobin, season, birth weight RESULTS Serum 25(OH)D in this group averaged 21.6+/-8 ng/mL (age 16.5+/-1.1 y, n=80), and did not significantly differ between the second (20.95+/-8.2 ng/mL, n=44) and third trimester cohorts (22.5+/-7.9 ng/mL, n=36). Vitamin D insufficiency (< 20 ng/mL) was evident in 46.25% and vitamin D deficiency (<15 ng/mL) was evident in 21.25% of those studied. Significant predictors of suboptimal vitamin D status included sampling during the winter months (P=0.004), lower hemoglobin concentration (P=0.019), and higher second trimester leptin levels (P=0.018). Inverse associations between 25(OH)D and bacterial vaginosis were evident when controlled for season of sampling (P=0.02, n=80). CONCLUSIONS Vitamin D insufficiency was prevalent among urban pregnant minority adolescents. Further studies are needed to address the impact of this finding on maternal and neonatal calcium homeostasis and bone health.

Absorption by 1-year-old children of an iron supplement given with cow's milk or juice

A paucity of data are available on toddlers for the evaluation of optimal strategies of Fe supplementation. In this study, we used a two-tracer stable isotope technique to determine Fe absorption from a 5-mg dose of stable isotopically enriched (57Fe or 58Fe) ferrous sulfate given with cows milk (CM) compared with the same dose given with apple juice. Ten children (age 13 ± 1 mo, weight 10.8 ± 1.1 kg) who had recently discontinued formula feeding and begun on CM were studied. Red blood cell(RBC) iron incorporation of the isotope was determined 14 d after dosing with57 Fe and 58Fe. Fe absorption was calculated based on the assumption that 90% of absorbed Fe is incorporated into RBC. Absorption of Fe was significantly greater (13.7 ± 6.4%) when given with juice than with milk (5.7 ± 4.0%), p < 0.01 by paired t tests. Fe absorption from the dose given with juice was significantly negatively correlated with serum ferritin (n = 9, r = -0.70,p < 0.05). These results indicate that 1) a small supplement of Fe is better absorbed when given with juice than with CM, and 2) a large variability in Fe absorption exists in healthy 1-y-old infants, which is related to their existing Fe stores.

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.