Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes

March 17, 2023 updated by: Dr. Ghada El-Hajj Fuleihan, American University of Beirut Medical Center

Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes: a Randomized Controlled Trial in Pregnant Women With Hypovitaminosis D

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

330

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Lebanon
      • Hamra, Lebanon
        • American University of Beirut

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • Europharm
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 Names:
  • 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 (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 Names:
  • Europharm
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 Names:
  • Europharm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportions of women who will reach the IOM defined desirable 25(OH)D level ≥20ng/ml.
Time Frame: At delivery
At delivery
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
one to six weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal 25(OH)D level
Time Frame: At delivery
We will assess mean maternal 25(OH)D level
At delivery
Neonatal 25(OH)D level, at delivery
Time Frame: At birth
We will assess mean neonatal 25(OH)D level
At birth
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
At one month of age
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
At birth
Maternal Parathyroid Hormone (PTH) Level
Time Frame: At delivery
We will assess mean maternal PTH level
At delivery
Neonatal Parathyroid Hormone (PTH) Level
Time Frame: At birth
We will assess mean neonatal PTH level
At birth
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.
Change between baseline and 3 months following intervention

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At delivery
Maternal weight
Time Frame: At delivery
At delivery
Maternal Blood Pressure (BP)
Time Frame: At delivery
At delivery
Number of ill days
Time Frame: At 28-32 weeks Gestational Age (GA) and at delivery
At 28-32 weeks Gestational Age (GA) and at delivery
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
At 11-13 weeks and at 20 weeks
APGAR score
Time Frame: At delivery
Proportion of neonates with low APGAR (<7) score at 1 and 5 minutes, at delivery
At delivery
Neonatal weight
Time Frame: At birth
At birth
Neonatal length
Time Frame: At birth
At birth
Placental weight
Time Frame: At delivery
At delivery
Placental 1α hydroxylase activity
Time Frame: At delivery
At delivery
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
At delivery
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.
One month of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

American University of Beirut Medical Center

Collaborators

University of Southampton
Bahman Hospital Beirut Lebanon

Investigators

  • Principal Investigator: Ghada El Hajj Fuleihan, Professor of Medicine, American University of Beirut Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

October 1, 2018

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

April 27, 2015

First Submitted That Met QC Criteria

May 4, 2015

First Posted (Estimate)

May 5, 2015

Study Record Updates

Last Update Posted (Actual)

March 20, 2023

Last Update Submitted That Met QC Criteria

March 17, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AUBMC-GE-HF-2
  • AUBMC-IM-GE-HF-22 (Other Grant/Funding Number: American University of Beirut)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infant, Newborn, Diseases

Clinical Trials on Euro D

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Costa Rica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe