Vitamin D in Pregnancy (GRAVITD)
Vitamin D Deficiency in Pregnancy - Identifying Associations and Mechanisms Linking Maternal Vitamin D Deficiency to Placental Dysfunction and Adverse Pregnancy Outcomes
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Anticipated)
Enrollment
Phase
Phase
- Not Applicable
Contacts and Locations
Study Contact
Study Contact
- Name: Anna Louise Vestergaard, MD
- Phone Number: +45 28951794
- Email: alv@clin.au.dk
Study Locations
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-
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Aarhus, Denmark, DK-8000
- Active, not recruiting
- Department of Biomedicine, University of Aarhus
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Randers, Denmark, DK-8930
- Recruiting
- Randers Regional Hospital
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Contact:
- Pinar Bor, MD, PhD
- Email: isipinbo@rm.dk
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Contact:
- Anna Louise Vestergaard, MD
- Email: annavt@rm.dk
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- All pregnant women attending the nuchal translucency scan in week 11-13 of gestation as part of the national prenatal screening program
Exclusion Criteria:
- Age< 18 years
- Women with calcium metabolism disorders,
- Women who gets doctor prescribed vitamin D treatment
- Women with chronic kidney disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
PLACEBO_COMPARATOR: Current recommended dose of vitamin D
Women in this study arm receive 10 µg of vitamin D3 per day, which is the dose in a standard prenatal multivitamin and the dose currently recommended by the Danish Health Authorities to all pregnant women.
They will receive a prenatal vitamin containing 10µg of vitamin D + a placebo supplement.
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This intervention serves as a control as they get the current recommended vitamin D dose
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EXPERIMENTAL: Higher dose of vitamin D
Women in this arm receive 90µg of vitamin D3 per day: 10 µg from a standard prenatal multivitamin + an additional supplement containing 80µg of vitamin D3.
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The intervention is a higher dose of vitamin D than what is currently recommended to Danish pregnant women
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The prevalence of pre-eclampsia (PE)
Time Frame: From 20 weeks of gestation to delivery
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The effect of 90 μg on the prevalence of PE
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From 20 weeks of gestation to delivery
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The prevalence of fetal growth retardation (FGR)
Time Frame: From 20 weeks of gestation to delivery
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The effect of 90 μg on the prevalence of FGR
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From 20 weeks of gestation to delivery
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The prevalence of gestational diabetes (GDM)
Time Frame: From 20 weeks of gestation to delivery
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The effect of 90 μg on the prevalence of GDM
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From 20 weeks of gestation to delivery
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes in the placental expression of genes- and proteins related to vitamin D, evaluated using Next Generation Sequencing (NGS), quantitative Polymerase Chain Reaction (qPCR), methylation (Bisulfite conversion) and western blotting.
Time Frame: At delivery
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Characterization of the changes in the placenta as a result of vitamin D deficiency in healthy women including evaluation of the effect of BMI on placental function and vitamin D metabolism. NGS will be used to obtain a pathway analysis of differences between groups. Important findings from NGS will be verified on genetic and protein levels by qPCR and Western blotting respectively. Findings from NGS, qPCR and western blotting will be combined to characterize the changes in placentas from vitamin D deficient women compared to vitamin D sufficient women stratified by BMI. Further, changes in the expression of pivotal genes/proteins related to vitamin D metabolism (CYP2R1, CYP27B1, CYP24A1, Vitamin D receptor) will be investigated using qPCR, methylation analysis and western blotting. Findings from qPCR (gene level) methylation (gene level) and western blotting (protein level) are combined to characterize changes in placentas. Analyses will be done in subgroups of participants |
At delivery
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|
Changes in the placental expression of genes- and proteins related to vitamin D and the pathogenesis of PE, FGR and GDM in placental tissue from complicated pregnancies compared to uncomplicated pregnancies, evaluated using NGS, qPCR and western blotting
Time Frame: At delivery
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Identification of changes in placental expression of genes and proteins related to the pathogenesis of PE, FGR and GDM and their relationship to vitamin D sensitive placental functions in complicated pregnancies (PE, FGR, GDM) compared to healthy uncomplicated pregnancies. NGS will be used to obtain a pathway analysis of differences in the gene expression between complicated pregnancies (PE, FGR, GDM) and healthy uncomplicated pregnancies. Important findings from the NGS studies will be verified on genetic and protein levels by qPCR and Western blotting. Findings from the NGS and the verifying results from qPCR (gene level) and western blotting (protein level) will be combined to characterize the changes in placentas from complicated pregnancies (PE, FGR, GDM) compared to healthy uncomplicated pregnancies. Analyses will be done in subgroups of participants |
At delivery
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Birthweight
Time Frame: At delivery
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The effect of 90 μg vitamin D on birthweight.
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At delivery
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Size related to gestational age
Time Frame: At delivery
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The effect of 90 μg vitamin D on size related to gestational age (Small for Gestational Age;SGA, Appropriate for Gestational Age; AGA, Large for Gestational Age;LGA)
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At delivery
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The prevalence of preterm birth
Time Frame: At delivery
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The effect of 90 μg vitamin D on the prevalence of preterm birth (birth < 37 weeks of gestation).
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At delivery
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The prevalence of postterm birth
Time Frame: At delivery
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The effect of 90 μg vitamin D on the prevalence of postterm birth (birth > 40 weeks of gestation)
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At delivery
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The prevalence of gestational hypertension
Time Frame: From 20 weeks of gestation to delivery
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The effect of 90 μg vitamin D on the prevalence of gestational hypertension (>140/90)
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From 20 weeks of gestation to delivery
|
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Mode of delivery
Time Frame: At delivery
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Mode of delivery
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At delivery
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The prevalence of infection during delivery
Time Frame: At delivery
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Infection during delivery (incl.
use of antibiotics)
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At delivery
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Admission to the neonatal ward
Time Frame: The first two weeks after birth
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Admission of the new born child to the neonatal ward
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The first two weeks after birth
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Prevalence of post partum hemorrhage > 500 ml
Time Frame: The first 24 hours after delivery
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The effect of 90 μg vitamin D on the prevalence of post partum hemorrhage > 500 ml
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The first 24 hours after delivery
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Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Study Start
Primary Completion (ANTICIPATED)
Primary Completion
Study Completion (ANTICIPATED)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (ACTUAL)
First Posted
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Nutrition Disorders
- Avitaminosis
- Deficiency Diseases
- Malnutrition
- Fetal Diseases
- Pregnancy Complications
- Hypertension, Pregnancy-Induced
- Growth Disorders
- Vitamin D Deficiency
- Eclampsia
- Pre-Eclampsia
- Fetal Growth Retardation
- Diabetes, Gestational
- Physiological Effects of Drugs
- Micronutrients
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Vitamin D
- Cholecalciferol
- Vitamins
- Ergocalciferols
Other Study ID Numbers
Other Study ID Numbers
- GRAVITD
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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