title: Vitamin D replacement in children, adolescents and pregnant women in the Middle East and North Africa: A systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Hypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region.
  
  
  OBJECTIVE
  To evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes.
  
  
  METHODS
  This is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (<800IU), intermediate (800-2000IU) or high (>2000IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3.
  
  
  RESULTS
  We identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women. In children and adolescents, an intermediate vitamin D dose (1901IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% confidence interval (CI) 8.1-18.8) ng/ml, compared to placebo, favoring the intermediate dose (p<0.001). The proportion of children and adolescents reaching a 25(OH)D level≥ 20ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12-16weeks of gestation and continued until delivery, and six trials started supplementation at 20-28weeks' gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3-11.9) ng/ml (p<0.001) comparing the high dose (3662IU/d) to the intermediate dose (1836IU/d), and 12.3 (95% CI 6.4-18.2) ng/ml (p<0.001), comparing the high dose (3399IU/d) to the low dose (375IU/d). Comparing the intermediate (1832IU/d) to the low dose (301IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5-10.8) ng/ml (p<0.001). The proportion of pregnant women reaching a 25(OH)D level≥20ng/ml was 80%-90%, 73% and 27%-43% in the high, intermediate, and low dose groups, respectively. The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high across all doamins.
  
  
  CONCLUSIONS
  In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1000-2000IU daily may be necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes.
authors.affiliation: Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon; Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address: mc39@aub.edu.lb.
authors.forename: Marlene
authors.initials: M
authors.lastname: Chakhtoura
authors.affiliation: Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Sara
authors.initials: S
authors.lastname: El Ghandour
authors.affiliation: Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Khaled
authors.initials: K
authors.lastname: Shawwa
authors.affiliation: Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Health Research Methods, Evidence, and Impact (HE&I), McMaster University, Hamilton, Canada.
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.affiliation: Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon; Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Asma
authors.initials: A
authors.lastname: Arabi
authors.affiliation: Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Global and Public Health Weill Cornell Medical College, Doha, Qatar.
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Mahfoud
authors.affiliation: Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Robert
authors.initials: R
authors.lastname: Habib
authors.affiliation: Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Hassan
authors.initials: H
authors.lastname: Hoballah
authors.affiliation: Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon; Scholars in HeAlth Research Program (SHARP), American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Ghada
authors.initials: G
authors.lastname: El Hajj Fuleihan
mesh_terms: D000293:Adolescent; D000328:Adult; D000352:Africa, Northern; D002648:Child; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D008877:Middle East; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Children and adolescents; Meta-analysis; Middle East and North Africa; Pregnant women; Vitamin D