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Completed

NCT Number: NCT03051867

Vitamin D Status and Metabolism in Human Pregnancy

The purpose of the present study is to understand the effect of pregnancy on vitamin D metabolism and requirements as well as the modulatory role of the placenta in vitamin D metabolism during pregnancy. In addition, a human placental cell culture model will be employed to examine vitamin D metabolic flux in human trophoblast cells. The impact of maternal vitamin D status on maternal and fetal bone health during gestation will also be examined.

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Key information

Conditions

Age range

21 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Human Metabolic Research Unit, Cornell University

Ithaca, New York, 14853, United States

About this study

Rationale

Despite mounting evidence that maternal vitamin D status is linked to pregnancy outcomes [1,2], the impact of pregnancy on vitamin D metabolism and requirement has yet to be clearly defined. In addition, although the placenta is known to express all components of the vitamin D metabolic pathway [3,4], very little is known about placental vitamin D metabolism. Moreover, although vitamin D is known to affect bone health in the nonpregnant state, the effect of maternal vitamin D status on maternal and fetal bone health in human pregnancy is unclear [5-7]. Therefore, the present study seeks to advance current understanding of vitamin D metabolism and requirements during pregnancy.

Objective and Research Questions

This study aims to examine: 1) the effect of pregnancy on a comprehensive panel of blood biomarkers of vitamin D status and metabolism; 2) the role of the placenta in modulating circulating vitamin D metabolites; and 3) the impact of maternal vitamin D status on maternal and fetal markers of bone metabolism.

Study Population, Design, and Exposure

As a secondary analysis, this study uses biological samples obtained from pregnant and nonpregnant control women who participated in a 12-wk randomized controlled trial in 2009-2010 which featured two doses of choline (i.e., 480 or 930 mg choline/d) (NCT01127022) [8]. Throughout the controlled feeding period, 26 third-trimester pregnant women and 21 nonpregnant women (both reproductive groups aged > 21 y) in a good health status consumed equivalent intakes of vitamin D (511 IU/d), calcium (1.6 g/d) and phosphorus (1.9 g/d) from the study diet and prenatal multivitamin supplement (Pregnancy Plus; Fairhaven Health LLC) for ≥ 10 weeks.

Dependent variables:

  • Blood biomarkers of vitamin D metabolism at week 0 (study-baseline) and week 10 (representing study-end)
  • Placental biomarkers of vitamin D metabolism at delivery
  • Markers of bone metabolism in maternal and fetal cord blood as well as maternal urine

Ethical considerations

The study protocol of the original RCT was approved by the Institutional Review Board for Human Study Participant Use at Cornell University and the Cayuga Medical Center where pregnant women delivered their babies. Informed consent was obtained from all participants before study entry, and the original study was registered at clinicaltrials.gov as NCT01127022. For this secondary analysis, deidentified data will be used.

Dissemination Findings

Findings from the present study will be reported in manuscripts that will be submitted for publication to a leading medical/nutrition journal in an appropriate field (i.e. nutrition, bone, placenta, and reproductive physiology). In addition, findings will be presented as abstracts, posters, and presentations at research conferences.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age of 21-40 y
  • Healthiness as assessed by health-related questionnaire, a blood chemistry profile, and a complete blood count
  • Normal liver and kidney function
  • Willingness to comply with the study protocol
  • Singleton pregnancy (pregnant women only)

Exclusion criteria

  • Use of tobacco, drug, or alcohol
  • Use of prescription medications known to affect liver function
  • Pregnancy associated complications

Treatment and study plan

Primary outcomes

  1. Maternal circulating concentrations of 25-hydroxyvitamin D

    Time frame: Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)

    Serum 25-hydroxyvitamin D [25(OH)D] will be measured using an isotope dilution LC-MS/MS methodology, and the effect of reproductive state on serum 25(OH)D will be examined using a linear mixed model which considers confounding factors.

  2. Maternal circulating concentrations of 1,25-dihydroxyvitamin D

    Time frame: Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)

    Plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] will be measured using an EIA kit, and the effect of reproductive state on circulating 1,25(OH)2D will be examined using a linear mixed model which considers confounding factors.

  3. Maternal circulating concentrations 24,25-dihydroxyvitamin D

    Time frame: Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)

    Plasma 24,25-dihydroxyvitamin D [24,25(OH)2D] will be measured using an isotope dilution LC-MS/MS methodology, and the effect of reproductive state on circulating 24,25(OH)2D will be examined using a linear mixed model which considers potential confounders.

  4. Placental mRNA abundance of 25-hydroxylase

    Time frame: Delivery

    Placental mRNA abundance of 25-hydroxylase [CYP2R1] will be measured using a qPCR, and the associations of placental CYP2R1 mRNA abundance with serum 25(OH)D will be examined using a linear mixed model which considers potential confounders.

  5. Placental mRNA abundance of 24-hydroxylase

    Time frame: Delivery

    Placental mRNA abundance of 24-hydroxylase [CYP24A1] will be measured using a qPCR, and the associations of placental CYP24A1 mRNA abundance with circulating 24,25(OH)2D will be examined using a linear mixed model which considers potential confounders.

  6. Placental 25-hydroxyvitamin D

    Time frame: Delivery

    25(OH)D will be measured from placental tissue using an isotope dilution LC-MS/MS methodology, and the associations of placental 25(OH)D with serum 25(OH)D as well as placental CYP2R1 mRNA abundance will be examined using a Pearson correlation test and a linear mixed model which considers potential confounders.

  7. Placental 24,25-dihydroxyvitamin D

    Time frame: Delivery

    24,25(OH)2D will be measured from placental tissue using an isotope dilution LC-MS/MS methodology, and the associations of placental 24,25(OH)2D with circulating 25(OH)D and 24,25(OH)2D as well as placental CYP24A1 mRNA abundance will be examined using a Pearson correlation test and a linear mixed model which adjusts for potential confounders.

Secondary outcomes

  1. Maternal circulating intact parathyroid hormone

    Time frame: Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)

    Plasma intact parathyroid hormone [iPTH] will be measured using an automated immunoassay, and the relationship of maternal serum 25(OH)D with maternal iPTH will be assessed using a linear mixed model which considers potential confounders.

  2. Maternal circulating carboxy-terminal cross-linking telopeptide of type 1 collagen

    Time frame: Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation), and delivery

    Plasma carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx] will be measured using an ELISA kit, and the relationships of maternal serum 25(OH)D with maternal CTx will be assessed using a linear mixed model which considers potential confounders.

  3. Maternal urinary deoxypyridinoline/creatinine

    Time frame: Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation)

    Urinary deoxypyridinoline/creatinine [DPD/Cr] will be measured using an ELISA kit, and the relationships of maternal serum 25(OH)D with maternal DPD/Cr will be assessed using a linear mixed model which considers potential confounders.

  4. Maternal circulating osteocalcin

    Time frame: Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation), and delivery

    Plasma osteocalcin [OC] will be measured using an ELISA kit, and the relationships of maternal serum 25(OH)D with maternal OC will be assessed using a linear mixed model which considers potential confounders.

Sponsors and collaborators

Lead sponsor

Cornell University

Other

Registry information

Official study title

Vitamin D Status and Metabolism in Pregnant and Nonpregnant Control Women Consuming Controlled and Equivalent Intakes of Vitamin D

Important dates

Study start
2009
Primary completion
2010
Study completion
2011
First posted
Feb 14, 2017
Registry last updated
Feb 14, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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