Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes
Condition: Hypovitaminosis D; Pregnancy Complications; Infant, Newborn, Diseases
MeSH terms: Rickets; Pregnancy Complications; Infant, Newborn, Diseases; Avitaminosis; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Euro D; Euro D
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 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.; 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 intervention name(s): Europharm; Europharm
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vitamin D; Bone mineral content; Knee-heel length; Middle East