Umbilical Cord Coiling in High-risk Pregnancies: Associations With Determinants of Adverse Birth Outcomes and Iron Status.

Abnormal umbilical cord coiling has been associated with adverse neonatal outcomes, but the etiology of these findings remains poorly characterized. This study was undertaken to examine associations between cord coiling and maternal iron (Fe) status and to identify potential determinants of hypo- and hypercoiling in 2 higher risk obstetric groups: pregnant adolescents (≤18 years, n = 92) and adult women carrying twins (n = 49), triplets (n = 11), or quadruplets (n = 1). Umbilical cords were classified as hypo-, normo-, or hypercoiled using digital photographs to assess gross appearance. Hypocoiling and hypercoiling were observed in 44% (n = 86/195) and 13% (n = 26/195) of the combined study population. The prevalence of hypocoiling among women carrying multiples was over 3-fold higher than the prevalence in singleton pregnancies based on the published data. Within the entire study population, hypocoiling was associated with a lower gestational age at birth when compared to normocoiling and hypercoiling (36.3 ± 3.6 weeks [n = 86] vs 37.8 ± 2.7 [n = 83], P < .01, and 38.2 ± 2.6 [n = 26], P < .01, respectively), whereas hypercoiling was associated with significantly lower serum ferritin when compared to normocoiling ( P < .01) and hypocoiling ( P < .001). In the multiples cohort only, hypercoiling was significantly associated with multiparity ( P < .01) and lower birth weight ( P < .05). Further studies are needed to identify the determinants and consequences of cord coiling.

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.

Placental vitamin D receptor (VDR) expression is related to neonatal vitamin D status, placental calcium transfer, and fetal bone length in pregnant adolescents.

The purpose of the study was to identify determinants of placental vitamin D receptor (VDR) expression and placental calcium (Ca) transfer among pregnant adolescents. Placental tissue was obtained in 94 adolescents (≤18 yr) at term. In 12 of these teens, stable Ca isotopes were given intravenously ((42)Ca) and orally ((44)Ca) early in labor. Placental VDR expression was assessed via Western blot and validated by RT-PCR. Maternal-to-fetal Ca transfer was calculated as the enrichment in cord blood at delivery relative to maternal serum enrichment 2 h postdosing. Isotopic study outcomes were examined in relation to fetal long bone length, placental VDR, serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and parathyroid hormone (PTH) in maternal circulation and cord blood at delivery. Placental VDR expression was inversely associated with neonatal 25(OH)D (P=0.012) and positively with neonatal 1,25(OH)2D (P=0.006). Placental VDR was a positive predictor of fetal femur length Z score (P=0.018; R(2)=0.06) and was positively correlated with maternal-to-fetal transfer of intravenous (42)Ca (P=0.004; R(2)=0.62). The fetus may regulate placental VDR expression given the significant associations with neonatal vitamin D metabolites. The association between placental VDR and fetal long bone length may indicate a role for VDR in fetal bone development, potentially by mediating transplacental Ca transfer.

Placental heme receptor LRP1 correlates with the heme exporter FLVCR1 and neonatal iron status.

LDL receptor-related protein 1 (LRP1) is a transmembrane receptor highly expressed in human placenta. It was recently found to be the receptor for heme and its plasma-binding protein hemopexin (Hx) and is integral to systemic heme clearance. Little is known about systemic concentrations of Hx during pregnancy and whether maternal Hx and placental LRP1 contributes to fetal iron (Fe) homeostasis during pregnancy. We hypothesized that placental LRP1 would be upregulated in maternal/neonatal Fe insufficiency and would be related to maternal circulating Hx. Placental LRP1 expression was assessed in 57 pregnant adolescents (14-18 years) in relationship with maternal and cord blood Fe status indicators (hemoglobin (Hb), serum ferritin, transferrin receptor), the Fe regulatory hormone hepcidin and serum Hx. Hx at mid-gestation correlated positively with Hb at mid-gestation (r=0.35, P=0.02) and Hx at delivery correlated positively with cord hepcidin (r=0.37, P=0.005). Placental LRP1 protein expression was significantly higher in women who exhibited greater decreases in serum Hx from mid-gestation to term (r=0.28, P=0.04). Significant associations were also found between placental LRP1 protein with cord hepcidin (r=-0.29, P=0.03) and placental heme exporter feline leukemia virus C receptor 1 (r=0.34, P=0.03). Our data are consistent with a role for placental heme Fe utilization in supporting fetal Fe demands.

Maternal inflammation at delivery affects assessment of maternal iron status.

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.

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.

Impact of an urban community hypertension screening program on participating high school students.

BACKGROUND: Hypertension is increasingly being recognized as a major health problem in adolescents, particularly those of minority ethnicity. We assessed elevated blood pressure (BP) prevalence and predictors, as well as the impact of participating in a community hypertension screening program among high school students in an urban school district. METHODS: In 2008, 603 predominantly Hispanic students from nine Los Angeles high schools in predominantly Hispanic communities were recruited and trained to screen for high BP (> or = 140/90 mm Hg) in their communities. As part of the program, students measured one another's blood pressure and completed a pre- and post-assessment (2 weeks later), which measured hypertension risk factors, knowledge, interest in health careers, and empowerment. A multivariable analysis using logistic regression evaluated the association between several factors and presence of elevated BP. RESULTS: Eighty-two (14%) of students had BP readings in the hypertensive range, with 78 (95%) of whom had no prior diagnosis of hypertension. Being overweight (OR 2.85, 95% CI = 1.31-6.20) or obese (OR 8.90, 95% CI = 3.83-20.69) were the only factors independently associated with elevated BP. Significant increases were observed in student knowledge regarding hypertension and interest pursuing three of five health professions (P < .05), but no significant change in student empowerment was noted. CONCLUSIONS: One in six urban district high school students screened in this study had presence of elevated BP, the overwhelming majority of whom had no prior hypertension diagnosis. Program participation slightly boosted health career interest and hypertension knowledge. Involvement of urban high school students in self-screening hypertension programs may be of benefit.

Patterns and Correlates of Self-Reported Physical Activity in a Cohort of Racially Diverse Pregnant Adolescents.

STUDY OBJECTIVE: Regular physical activity (PA) during pregnancy decreases the risk of gestational hypertension and preeclampsia. Currently, little is known about the PA of pregnant adolescents. Our intent was to characterize the PA behaviors of a group of racially diverse, low-income pregnant teens and to identify potential determinants of PA. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A cohort of 157 racially diverse pregnant adolescents (13-18 years of age) completed up to 3 previous day PA recalls as part of a larger prospective longitudinal study on determinants of maternal and fetal bone health. Subjects self-reported activities from 7 AM to 11:30 PM, choosing from a list of 37 activities including a category for "other." Subjects recorded activities in 30-minute intervals. MAIN OUTCOME MEASURES: Estimated metabolic equivalent task (MET) values were assigned to each activity and summed for a measure of total daily PA in MET min/d. Determinants of PA were evaluated using a stepwise linear mixed effect model. RESULTS: The average calculated MET min/d was 1478 ± 130. Significant determinants of MET min/d included race (P = .007), maternal age at conception (P = .042), gestational age (P = .002), and attending school (P < .001). Black teens were less physically active than white teens, and older teens were more active than younger teens; activity decreased throughout gestation, and teens currently attending school were more active. CONCLUSION: PA is low across gestation and pregnant teens spent more than half of their monitored time in sedentary activities. Targeted interventions are needed to achieve current PA goals in this pediatric obstetric population.

A social media intervention to improve nutrition knowledge and behaviors of low income, pregnant adolescents and adult women.

Pregnant adolescents are at increased risk of adverse pregnancy outcomes compared to adult women, necessitating a need for early and comprehensive health care. This study aimed to evaluate the effectiveness of a social media intervention (i.e. weekly prenatal health messages) on improving diet quality, and health beliefs and knowledge. Participants (10 adolescents and 12 adults) completed pre-post intervention interviews, nutrition knowledge and health belief questionnaires, and 24-hour diet recalls. Participants entering pregnancy as overweight or obese were more likely to experience excessive GWG during the intervention. The adults had greater participation during the study despite high levels of social media access among both groups. Participants were able to identify sugar-sweetened foods and acknowledged the benefits of whole grains; however, overall knowledge of MyPlate Guidelines was limited. Social media-based education was well received by participants but did not result in large changes in dietary intake and knowledge. Although larger studies are needed, social media appears to have the potential to reach high-risk women.

Educating and mobilizing youth to detect undiagnosed elevated blood pressure: searching for the silent killer.

BACKGROUND: Hispanic individuals with high blood pressure are less likely than other ethnic groups to be aware of their high blood pressure or to be on medication for the condition. We investigated the feasibility of using high school students in predominantly Hispanic neighborhoods to conduct a large-scale blood pressure screening and education outreach in their communities. METHODS: In 2005, 960 students from Los Angeles high schools in predominantly Hispanic communities were trained to conduct blood pressure screening and provide educational materials and referrals. A multivariable analysis using logistic regression was conducted to analyze the association between self-reported cardiovascular risk factors and elevated blood pressure. RESULTS: Students presented educational materials to 5395 persons and screened 5165 persons in their communities. Of 5395 individuals screened, 299 (6%) were found to have elevated blood pressure, of which only 77 (26%) were taking antihypertensive medication. Of those with elevated blood pressure on screening, 46% indicated they had a history of hypertension, and 3% of the entire screened community were identified as having elevated blood pressure for the first time. Older age, male sex, heavy alcohol consumption, and history of hypertension were all independently associated with elevated blood pressure. CONCLUSIONS: Training high school students to identify persons with elevated blood pressure is feasible and could reach large numbers of ethnic minorities unaware of their blood pressure status.

Medication Safety During Pregnancy: Improving Evidence-Based Practice.

Nearly 90% of women in the United States have taken medications during pregnancy. Medication exposures during pregnancy can result in adverse pregnancy and neonatal outcomes including birth defects, fetal loss, intrauterine growth restriction, prematurity, and longer-term neurodevelopmental outcomes. Advising pregnant women about the safety of medication use during pregnancy is complicated by a lack of data necessary to engage the woman in an informed discussion. Routinely, health care providers turn to the package insert, yet this information can be incomplete and can be based entirely on animal studies. Often, adequate safety data are not available. In a busy clinical setting, health care providers need to be able to quickly locate the most up-to-date information in order to counsel pregnant women concerned about medication exposure. Deciding where to locate the best available information is difficult, particularly when the needed information does not exist. Pregnancy registries are initiated to obtain more data about the safety of specific medication exposures during pregnancy; however, these studies are slow to produce meaningful information, and when they do, the information may not be readily available in a published form. Health care providers have valuable data in their everyday practice that can expand the knowledge base about medication safety during pregnancy. This review aims to discuss the limitations of the package insert regarding medication safety during pregnancy, highlight additional resources available to health care providers to inform practice, and communicate the importance of pregnancy registries for expanding knowledge about medication safety during pregnancy.

Prepregnancy Body Mass Index and Gestational Weight Gain Have No Negative Impact on Maternal or Neonatal Iron Status.

OBJECTIVE: To assess the impact of maternal obesity and excessive gestational weight gain (GWG) on maternal and neonatal iron status and to explore the possible mediating role of inflammation on hepcidin. METHODS: This analysis included 230 pregnant adolescents (13-18 years) enrolled in either a longitudinal or a cross-sectional study. Prepregnancy body mass index (ppBMI) and GWG were obtained from medical records. Maternal iron status (hemoglobin, serum iron, ferritin, transferrin receptor, total body iron, and hepcidin) and inflammation (interleukin-6 [IL-6] and leptin) were assessed at midgestation (26.2 ± 3.3 weeks) in the longitudinal cohort and at delivery (39.8 ± 1.3 weeks) in both study cohorts. Cord blood was collected in both studies and analyzed for iron indicators. RESULTS: Approximately 40% of the adolescents entered pregnancy overweight or obese. Multivariate analysis identified ppBMI as a negative predictor of serum iron at midgestation (P = .009) and a positive predictor of serum hepcidin at delivery (P = .02). None of the other maternal iron status indicators were significantly associated with ppBMI or GWG. Serum IL-6 was significantly positively associated with hepcidin at delivery (P = .0001) but not at midgestation. There was a positive relationship between ppBMI and cord hemoglobin (P = .03). CONCLUSION: These results suggest that adiposity-related inflammation does not override the iron-mediated signals that regulate hepcidin production during pregnancy, and in this adolescent cohort, there is no strong evidence for a detrimental effect of maternal obesity and excessive weight gain on iron status in the offspring at birth.

Vitamin B12 and placental expression of transcobalamin in pregnant adolescents.

BACKGROUND: Transcobalamin is a key placental protein involved in transport of vitamin B12 to the fetus. However, few data currently exist on the ability of the placenta to modify vitamin B12 transporter expression, particularly in high-risk populations such as pregnant adolescents. OBJECTIVE: This study was conducted to determine the impact of maternal and neonatal serum vitamin B12 concentrations on placental transcobalamin (TC) expression in a cohort of healthy pregnant adolescents in the United States. DESIGN: Serum vitamin B12 concentrations were measured in maternal blood samples at mid-gestation (26.4 ± 2.8 weeks) and delivery (39.8 ± 1.4 weeks) and infant cord blood samples at birth. Placentas were collected at delivery and TC mRNA expression (ΔΔCt) and TC protein abundance (TC:α-actin) were evaluated. Linear and binomial regression models were used to examine the associations of maternal serum (mid-gestation, delivery) and cord blood vitamin B12 concentrations with placental TC mRNA expression and protein abundance (n = 63). RESULTS: Maternal serum vitamin B12 concentrations at mid-gestation or delivery were not significantly associated with placental TC mRNA expression or TC protein abundance (p > 0.05). Higher placental TC protein abundance was associated with increased cord blood vitamin B12 concentrations (p = 0.003). CONCLUSIONS: Higher placental TC protein abundance was associated with higher cord blood vitamin B12 concentrations, suggesting a potential role in vitamin B12 transport to the fetus.

Iron deficiency and anemia are prevalent in women with multiple gestations.

BACKGROUND: Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births. OBJECTIVE: We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia. DESIGN: A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6. RESULTS: The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 µg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery. CONCLUSIONS: ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802.

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 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.

Reductions in heel bone quality across gestation are attenuated in pregnant adolescents with higher prepregnancy weight and greater increases in PTH across gestation.

Few studies have examined the effect of maternal calcium intake and vitamin D status on bone health across gestation in pregnant adolescents. This study aimed to characterize maternal bone quality and determinants of bone-quality change across gestation in pregnant adolescents. Healthy pregnant adolescents (n = 156; aged 13 to 18 years) with singleton pregnancies and at 12 to 30 weeks gestation at enrollment were recruited from two urban maternity clinics in Baltimore, MD, and Rochester, NY, for this prospective longitudinal study. Maternal serum was collected at midgestation and at delivery for assessment of bone biomarkers and calcitropic hormones. Maternal bone quality (assessed by heel ultrasound) and sonographic fetal biometry were measured up to three times across pregnancy. Racially diverse teens (64.7% African American, 35.3% white) were followed from 21.0 (interquartile range [IQR] 17.3, 27.0) weeks of gestation until delivery at 40.0 (IQR 39.0, 40.7) weeks. Significant decreases in calcaneal speed of sound (SOS), broadband ultrasound attenuation (BUA), and quantitative ultrasound index (QUI) (-9.2 ± 16.1 m/s, -3.2 (-8.0, 2.1) dB/MHz and -5.3 ± 8.8, respectively) were evident across pregnancy. Multivariate analysis controlling for baseline measures and measurement intervals was used to identify independent predictors of normalized (per week) calcaneal bone loss. Weekly decreases in bone quality were not significantly associated with maternal calcium intake or 25(OH)D concentration. Greater weekly reductions in calcaneal bone quality were evident in teens with lower prepregnancy weight (BUA, p = 0.006 and QUI, p = 0.012) and among those with lower weekly increase in PTH (SOS, p = 0.046). Overall, significant decreases in calcaneal bone quality occurred across pregnancy in adolescents, but the magnitude of this loss was attenuated in those with greater prepregnancy weight and weekly increases in PTH. Further studies are needed to understand the role of elevated PTH and greater prepregnancy weight in preserving adolescent bone during pregnancy.

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.

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.