ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02434380
Recruitment Status : Active, not recruiting
First Posted : May 5, 2015
Last Update Posted : October 4, 2018
Sponsor:
Collaborators:
University of Southampton
Bahman Hospital Beirut Lebanon
Information provided by (Responsible Party):
Dr. Ghada El-Hajj Fuleihan, American University of Beirut Medical Center

Brief Summary:
The optimal vitamin D replacement dose during pregnancy remains undefined. Therefore, the aim of this study is to test the hypothesis that a daily equivalent dose of vitamin D of 3,000 IU/day is needed for Middle Eastern women, to optimize maternal vitamin D level and neonatal musculoskeletal parameters, specifically knee-heel length at birth and bone mineral content at one month of age.

Condition or disease Intervention/treatment Phase
Hypovitaminosis D Pregnancy Complications Infant, Newborn, Diseases Dietary Supplement: Euro D Phase 3

Detailed Description:

Hypovitaminosis D is prevalent worldwide across the lifecycle, including pregnant women, and particularly in the Middle East. It has been associated with adverse maternal and neonatal outcomes. While the Institute of Medicine (IOM) recommends 600 IU of vitamin D per day to reach a 25-Hydroxyvitamin D (25(OH)D) level ≥ 20 ng/ml, the Endocrine Society (ES) recommends 1,500-2,000 IU/day to reach a level ≥ 30 ng/ml, and the WHO guidelines do not recommend any supplementation as part of routine prenatal care. They do however underscore the fact that subjects with the lowest levels may be the ones to benefit most from vitamin D replacement. The benefits of such an approach and the doses needed to reach desirable levels have not been tested. This randomized trial proposes to do so, testing the effect of two vitamin D doses, a low dose of 600 IU daily and a high dose of 3,000 IU daily.

330 pregnant women, with 25(OH)D level 10-30 ng/ml during the early second trimester will be recruited form the American University of Beirut-Medical Center (AUB-MC), and Bahman Hospital. They will be randomized, in a double blinded fashion, to receive daily equivalent doses of cholecalciferol, 600 IU or 3,000 IU until delivery. Maternal clinical information and a food frequency questionnaire will be obtained at each visit until delivery. Maternal 25(OH)D and chemistries, including Calcium, creatinine, lipid profile, glucose and Insulin will be assessed at study entry, during third trimester and at delivery. Fetal measurements will be collected at study entry and during the second trimester. Neonatal anthropometric variables and venous umbilical cord 25(OH)D level will be measured at birth and infants will also undergo dual-energy x-ray absorptiometry (DEXA) scan assessment, for bone and fat mass, at one to 6 weeks. Maternal and neonatal genetic studies for vitamin D genes polymorphism, and other modules of placnetal calcium transport will be also performed.

Throughout the study, adverse events will be collected systematically and an independent Data and Safety Monitoring Board will be asked to review serious adverse events.

The percent of women achieving 25(OH)D ≥ 20ng/ml in the low dose will be compared to that in the high dose using Chi-Square. Independent t-test will be used to compare mean neonatal bone mineral content at one month of age between the 2 arms. For other outcomes, t-test will be used for continuous outcomes and Chi-square will be used for binary outcomes to compare means and proportions, respectively. The primary analysis is an intention-to-treat analysis (ITT) of unadjusted results. For the primary outcomes, p- values will be considered statistically significant if ≤ 0.025.

The investigators study would be the only randomized controlled trial in the Middle East, to investigate the recommended daily allowance for vitamin D, and the desirable dose to optimize neonatal musculoskeletal health, in women with low 25(OH)D levels, levels that are reflective of those in most countries from the Middle East.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes: a Randomized Controlled Trial in Pregnant Women With Hypovitaminosis D
Study Start Date : July 2015
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Minerals Vitamin D
Drug Information available for: Vitamin D

Arm Intervention/treatment
Active Comparator: Low dose vitamin D
Vitamin D3 Euro D 10,000 IU (1 tablet) plus Euro D Placebo (1 tablet) weekly, alternating with Euro D Placebo (2 tablets) weekly, starting at the second trimester and continued until delivery.
Dietary Supplement: Euro D
Vitamin D3 Euro D 10,000 IU (1 tablet) plus Euro D Placebo (1 tablet) weekly, alternating with Euro D Placebo (2 tablets) weekly, starting at the second trimester and continued until delivery.
Other Name: Europharm

Active Comparator: High dose vitamin D
Vitamin D3 Euro D 10,000 IU (2 tablets, equivalent to 20,000 IU) weekly, starting at the second trimester and continued until delivery.
Dietary Supplement: Euro D
Vitamin D3 Euro D 10,000 IU (2 tablets, equivalent to 20,000 IU) weekly, starting at the second trimester and continued until delivery.
Other Name: Europharm




Primary Outcome Measures :
  1. The proportions of women who will reach the IOM defined desirable 25(OH)D level ≥20ng/ml. [ Time Frame: At delivery ]
  2. Infant bone mineral content (BMC) [ Time Frame: one to six weeks ]
    We will assess Infant bone mineral content (BMC) by whole body dual-energy x-ray absorptiometry (DEXA) scan


Secondary Outcome Measures :
  1. Maternal 25(OH)D level [ Time Frame: At delivery ]
    We will assess mean maternal 25(OH)D level

  2. Neonatal 25(OH)D level, at delivery [ Time Frame: At birth ]
    We will assess mean neonatal 25(OH)D level

  3. Mean infant fat mass [ Time Frame: At one month of age ]
    We will assess Infant fat mass by whole body dual-energy x-ray absorptiometry (DEXA) scan

  4. Neonatal Knee to heel length at birth [ Time Frame: At birth ]
    We will assess neonatal Knee to heel length at birth using simple vernier calipers

  5. Maternal Parathyroid Hormone (PTH) Level [ Time Frame: At delivery ]
    We will assess mean maternal PTH level

  6. Neonatal Parathyroid Hormone (PTH) Level [ Time Frame: At birth ]
    We will assess mean neonatal PTH level

  7. Mean change in maternal urine calcium [ Time Frame: Change between baseline and 3 months following intervention ]
    We will assess the change in urine calcium level after 3 months of vitamin D supplementation.


Other Outcome Measures:
  1. Composite outcome (incidence of C-section and gestational diabetes mellitus (GDM)) [ Time Frame: At delivery ]
    We will assess the incidence of a composite outcome (C-section and gestational diabetes mellitus (GDM)) in a subgroup of women who has no previous C-section.

  2. Maternal weight [ Time Frame: At delivery ]
  3. Maternal Blood Pressure (BP) [ Time Frame: At delivery ]
  4. Number of ill days [ Time Frame: At 28-32 weeks Gestational Age (GA) and at delivery ]
  5. Intrauterine fetal skeletal measures [ Time Frame: At 11-13 weeks and at 20 weeks ]
    We will collect intrauterine fetal skeletal measures including crown-rump, femur length, abdominal circumference, head circumference, biparietal diameter

  6. APGAR score [ Time Frame: At delivery ]
    Proportion of neonates with low APGAR (<7) score at 1 and 5 minutes, at delivery

  7. Neonatal weight [ Time Frame: At birth ]
  8. Neonatal length [ Time Frame: At birth ]
  9. Placental weight [ Time Frame: At delivery ]
  10. Placental 1α hydroxylase activity [ Time Frame: At delivery ]
  11. Sub-group analysis: The proportions of women who will reach the IOM defined desirable 25(OH)D level ≥20ng/ml. [ Time Frame: At delivery ]
    Subgroup analysis based on baseline 25(OH)D, less than 20 ng/ml versus less than 30 ng/ml and season of birth will be performed

  12. Sub-group analysis:Infant bone mineral content (BMC) [ Time Frame: One month of age ]
    Subgroup analysis based on baseline 25(OH)D, less than 20 ng/ml versus less than 30 ng/ml and season of birth will be performed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Pregnant women gestational age (GA)< 14 weeks at screening visit. Middle Eastern woman (Middle East countries defined by WHO: Bahrain, Egypt, Iran, Iraq, Palestine, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syria, , United Arab Emirates, Yemen)
  • 25(OH)D level between 10ng/ml and 30ng/ml
  • Age > 18 years
  • Vitamin D supplementation ≤ 200 IU daily (If daily vitamin D supplementation > 200 IU daily, at enrollment, the pregnant women will be advised to adjust prenatal multivitamin doses in such a way that total vitamin D supplementation per week doesn't exceed 1400 IU per week, in consultation with primary Obstetric and Gynecology (OB-GYN) physician.)

Exclusion Criteria:

  • 25(OH)D level < 10 ng/ml or > 30 ng/ml.
  • Known metabolic bone disease
  • Current medications likely to interfere with vitamin D metabolism (enzyme inducing anticonvulsants, anti -TB)
  • Vitamin D supplementation > 600 IU daily
  • Pregnant women with twins

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02434380


Locations
Lebanon
American University of Beirut
Hamra, Lebanon
Sponsors and Collaborators
American University of Beirut Medical Center
University of Southampton
Bahman Hospital Beirut Lebanon
Investigators
Principal Investigator: Ghada El Hajj Fuleihan, Professor of Medicine American University of Beirut Medical Center

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Ghada El-Hajj Fuleihan, Professor of Medicine, American University of Beirut Medical Center
ClinicalTrials.gov Identifier: NCT02434380     History of Changes
Other Study ID Numbers: AUBMC-GE-HF-2
AUBMC-IM-GE-HF-22 ( Other Grant/Funding Number: American University of Beirut )
First Posted: May 5, 2015    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018

Keywords provided by Dr. Ghada El-Hajj Fuleihan, American University of Beirut Medical Center:
Vitamin D
Bone mineral content
Knee-heel length
Middle East

Additional relevant MeSH terms:
Pregnancy Complications
Avitaminosis
Rickets
Vitamin D Deficiency
Infant, Newborn, Diseases
Deficiency Diseases
Malnutrition
Nutrition Disorders
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Calcium Metabolism Disorders
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents