Vitamin D Status and Metabolism in Human Pregnancy

Pregnancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03051867
• Other study ID #: OSP 74161
• Status: Completed
• Phase: N/A
• First received: February 7, 2017
• Last updated: February 9, 2017
• Start date: January 15, 2009
• Est. completion date: December 18, 2011

Study information

• Verified date: February 2017
• Source: Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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:

1. Blood biomarkers of vitamin D metabolism at week 0 (study-baseline) and week 10 (representing study-end)

2. Placental biomarkers of vitamin D metabolism at delivery

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: December 18, 2011
• Est. primary completion date: December 18, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pregnancy

Locations

Country	Name	City	State
United States	Human Metabolic Research Unit, Cornell University	Ithaca	New York

Sponsors (1)

Lead Sponsor	Collaborator
Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O'Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013 Mar 26;346:f1169. doi: 10.1136/bmj.f1169. Review. — View Citation

Hashemipour S, Lalooha F, Zahir Mirdamadi S, Ziaee A, Dabaghi Ghaleh T. Effect of vitamin D administration in vitamin D-deficient pregnant women on maternal and neonatal serum calcium and vitamin D concentrations: a randomised clinical trial. Br J Nutr. 2013 Nov 14;110(9):1611-6. doi: 10.1017/S0007114513001244. — View Citation

Kalra P, Das V, Agarwal A, Kumar M, Ramesh V, Bhatia E, Gupta S, Singh S, Saxena P, Bhatia V. Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant. Br J Nutr. 2012 Sep 28;108(6):1052-8. doi: 10.1017/S0007114511006246. — View Citation

Liu NQ, Hewison M. Vitamin D, the placenta and pregnancy. Arch Biochem Biophys. 2012 Jul 1;523(1):37-47. doi: 10.1016/j.abb.2011.11.018. Review. — View Citation

Ma R, Gu Y, Zhao S, Sun J, Groome LJ, Wang Y. Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E928-35. doi: 10.1152/ajpendo.00279.2012. — View Citation

Olausson H, Goldberg GR, Laskey MA, Schoenmakers I, Jarjou LM, Prentice A. Calcium economy in human pregnancy and lactation. Nutr Res Rev. 2012 Jun;25(1):40-67. doi: 10.1017/S0954422411000187. Review. — View Citation

Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of vitamin D in pregnancy and lactation: emerging concepts. Womens Health (Lond). 2012 May;8(3):323-40. doi: 10.2217/whe.12.17. Review. — View Citation

Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Stabler SP, Allen RH, Caudill MA. Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr. 2012 May;95(5):1060-71. doi: 10.3945/ajcn.111.022772. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maternal circulating concentrations of 25-hydroxyvitamin D	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.	Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)
Primary	Maternal circulating concentrations of 1,25-dihydroxyvitamin D	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.	Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)
Primary	Maternal circulating concentrations 24,25-dihydroxyvitamin D	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.	Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)
Primary	Placental mRNA abundance of 25-hydroxylase	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.	Delivery
Primary	Placental mRNA abundance of 24-hydroxylase	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.	Delivery
Primary	Placental 25-hydroxyvitamin D	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.	Delivery
Primary	Placental 24,25-dihydroxyvitamin D	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.	Delivery
Secondary	Maternal circulating intact parathyroid hormone	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.	Baseline (week 0; 26-29 wk gestation) and study-end (week 10; 36-39 wk gestation)
Secondary	Maternal circulating carboxy-terminal cross-linking telopeptide of type 1 collagen	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.	Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation), and delivery
Secondary	Maternal urinary deoxypyridinoline/creatinine	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.	Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation)
Secondary	Maternal circulating osteocalcin	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.	Baseline (week 0; 26-29 wk gestation), study-end (week 10; 36-39 wk gestation), and delivery