This study is a Phase III, randomized controlled, superiority trial, with two parallel groups, conducted in 2 centers. Participants, health care providers, data collectors, outcome adjudicator and biostatistician will be blinded to treatment allocation. Randomization will be performed as permuted block randomization with a 1:1 allocation
This trial will be done in the Lebanese and other Middle Eastern populations, countries where vitamin D levels are reflective of the levels in the region. Recruitment will be done at the American University of Beirut-Medical center and RHUH Hospital, involving private clinics and Outpatient Department (OPD), allowing to include participants representing different regions and different socio-economic status.
Pregnant women who consent to participate in the study will have a baseline blood test , at 11-13 weeks (during the routine nuchal translucency US visit). Recruitment:
Screened participants, fulfilling the inclusion criteria, will be called back and enrolled at 15-17 weeks.
Participants with 25(OH)D < 10 ng/ml will be referred for vitamin D replacement.
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,
For pregnant women with 25(OH)D below 10 ng/ml, it would be unethical to give low doses of vitamin D supplementation.
For pregnant women with 25(OH)D above 30ng/ml, vitamin D replacement with 600 IU daily are enough.
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 OB-GYN.
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 > 600IU daily
Fetal physical anomalies on the initial US
Renal stones
Hyperparathyroidism
Uncontrolled thyroid dysfunction
Diagnosis of cancer in the last 10 years (other than basal cell carcinoma)
Serum calcium >10mg/dl
Diabetes mellitus type 1 or type 2
Previous gestational diabetes mellitus.
Allergy to any component of vitamin D formulation