Vitamin D replacement in children, adolescents and pregnant women in the Middle East and North Africa

Abstract

Introduction 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 (< 800 IU), intermediate (800–2,000 IU) or high (> 2,000 IU) 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 (1,901 IU/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 ≥ 20 ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12–16 weeks of gestation and continued until delivery, and six trials started supplementation at 20–28 weeks 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 (3,662 IU/d) to the intermediate dose (1,836 IU/d), and 12.3 (95% CI 6.4–18.2) ng/ml (p <0.001), comparing the high dose (3,399 IU/d) to the low dose (375 IU/d). Comparing the intermediate (1,832 IU/d) to the low dose (301 IU/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 ≥ 20 ng/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. Conclusion In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1,000–2,000 IU seems necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20 ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes.

Effect of vitamin A, calcium and vitamin D fortification and supplementation on nutritional status of women: an overview of systematic reviews

“…low-income settings in India, Bangladesh, Indonesia, Tanzania, Gambia, Zimbabwe, Kenya, Ghana, Peru, and Brazil (Oliveira et al [ 21 ]) Pregnant and puerperal women (Neves et al [ 20 ]) Lactating women (Caminha et al [ 19 ]) Pregnant women (Thorne-Lyman and Fawzi [ 25 ]; McCauley et al [ 24 ]) Pregnant women (Christesen et al [ 22 ]; De-Regil et al [ 17 ]; Roth et al [ 9 ]) Adult women of age > 18 years (Reid et al [ 27 ]) Pregnant women, children, and adolescents (Chakhtoura et al [ 26 ]) Children, adolescents, pre-pregnant women, women of reproductive age group, and post-menopausal women (Das et al [ 28 ]) Adult women of age > 18 years (Trowman et al [ 29 ]; Cumming [ 30 ]) Pregnant women (Buppasiri et al [ 31 ]). Obese/ overweight participants (Onakpoya et al [ 32 ]) Pregnant and puerperal women (Arthur et al [ 18 ]) Pre-pregnant women, women of reproductive age group, and post-menopausal women (Das et al [ 28 ]) included Intervention Supplementation of vitamin A alone or in combination with other micronutrients (Oliveira et al [ 21 ]; McCauley et al [ 24 ]; Neves et al [ 20 ]) Supplementation of vitamin A/beta carotene (Thorne-Lyman and Fawzi [ 25 ]; Caminha et al [ 19 ]) Supplementation of vitamin D (Chakhtoura et al [ 26 ]; Christesen et al [ 22 ]; Reid et al [ 27 ]; De-Regil et al [ 17 ]; Roth et al [ 9 ]) Fortified food with vitamin D along with other micronutrients (Das et al [ 28 ]) Calcium supplementation with or without dairy products or combined calcium supplementation (Trowman et al [ 29 ]; Cumming [31]; Buppasiri et al [ 31 ]; Onakpoya et al [ 32 ]; Arthur et al [ 18 ]) Alkaline phosphatase and s...…”

“…Supplementation of vitamin D (Chakhtoura et al [ 26 ]; Christesen et al [ 22 ]; Reid et al [ 27 ]; De-Regil et al [ 17 ]; Roth et al [ 9 ])…”

“…Vitamin D supplementation: 25(OH)D levels at term/delivery (De-Regil et al [ 17 ]; Roth et al [ 9 ]; Chakhtoura et al [ 26 ]), vitamin D symptoms (Christesen et al [ 22 ]), bone mineral density (Reid et al [ 27 ]), serum calcium levels (Chakhtoura et al [ 26 ]), weight gain (Christesen et al [ 22 ]); side effects of vitamin D (De-Regil et al [ 17 ]), and hypercalcemia, hypocalcemia, hypercalciuria (Roth et al [ 9 ])…”

Impact of three different daily doses of vitamin D3supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial

“…This observation was consistent with what was reported by Rajakumar et al (35) who showed that 2098 IU of vitamin D/d were needed to maintain serum 25(OH)D levels at 50 nmol/l in 97•5 % of US children. A systematic review and meta-analysis from Middle East and North Africa (NENA region) also suggested that a daily dose of 1000-2000 IU of vitamin D will be required to obtain serum 25(OH)D levels of >50 nmol/l in the majority of the paediatric population (27) . These observations raise doubts about the adequacy of current recommendations of 400 IU/d by ICMR or 600 IU/d by IAP and IOM for Indian children and adolescents.…”

Vitamin D supplemental therapy can explore the interplay circuit between hypovitaminosis D, high serum IL-6 and pregnancy-associated morbidities

“…Similarly, Cooper et al 39 found supplementation of women with cholecalciferol 1000IU/day during pregnancy is safe and sufficient to ensure repletion of VD stores in pregnant women and Yilmaz et al 40 documented that VD-ST with 1200IU/day from the 12 th GW can prevent neonatal VD deficiency. Also, Chakhtoura et al 41 reported that in pregnant women VD dose of 1000-2000IU daily may be necessary to allow for the majority of this population to have serum VD level of 50nmol/L.…”