Maternal vitamin D supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial

Abstract

We studied bone mineral content (BMC), bone mineral density (BMD), and body composition in offspring of women supplemented with vitamin D during pregnancy. Pregnant women were randomized to receive oral cholecalciferol 60,000 units 4 weekly (group 1), 8 weekly (group 2), or placebo (group 3). All received 1 g calcium daily (groups 1 and 2 without, and group 3 with 400 units vitamin D). Offspring at 12-16 months underwent dual-energy X-ray absorptiometry. Maternal hypovitaminosis D at recruitment was common (serum 25OHD <50 nmol/L in 88 %) and severe (25OHD <25 nmol/L in 46 %). Groups 1 and 2 (n = 23 and 13, median age 14 months) had higher cord blood 25OHD (47.8 ± 13.8 and 31.0 ± 14.0 nmol/L) versus group 3 (n = 16, median age 16 months, 17.8 ± 13.5 nmol/L, p < 0.001). Babies in group 3 had higher whole-body BMC (250.8 ± 42.5 gm) and BMD (0.335 ± 0.033 gm/cm) compared to group 1 (213.1 ± 46.2 gm and 0.295 ± 0.041 gm/cm) and group 2 (202.9 ± 29.9 gm and 0.287 ± 0.023 gm/cm) (p = 0.006 and 0.001, respectively). In multivariate analysis, age, weight z score, and lean body mass remained significant contributors to BMC. Parameters of body composition were comparable among the groups. Vitamin D supplementation to pregnant women with severe deficiency in doses that improved cord blood 25OHD did not result in improved bone health or body composition in offspring at 12-16 months, compared to a dose too small to improve 25OHD levels.

Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes

“…At 34 weeks of gestation, frequency of vitamin D sufficiency in the 2,000‐IU/d group was 1.8 times higher than in the 1,000‐IU/d group. This finding was similar to that of other trials that examined the effectiveness of the same doses of vitamin D supplementation (Cooper et al, ; De‐Regil, Palacios, Lombardo, & Pena‐Rosas, ; Grant et al, ; Hollis, Johnson, Hulsey, Ebeling, & Wagner, ; Roth et al, ; Sahoo, Katam, Das, Agarwal, & Bhatia, ; Zerofsky, Jacoby, Pedersen, & Stephensen, ). Pregnancy‐induced increased body fat mass and hemodilution may explain to some extent the increased vitamin D need of a pregnant woman.…”

Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality

“…After screening the titles and abstracts, we read 56 articles. Twenty-four RCTs 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 comprising 5405 participants met the inclusion criteria. Two of these trials are from the same RCT with different outcomes.…”

“…Vitamin D supplementation was in the form of cholecalciferol in 22 RCTs 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 and in the form of ergocalciferol in 3 RCTs. 12 , 17 , 25 For the intervention group, the daily doses were 800 IU in 1 RCT, 17 1000 IU in 6 RCTs, 12 , 14 , 16 , 18 , 25 , 26 1200 IU in 1 RCT, 34 2000 IU in 7 RCTs, 15 , 18 , 20 , 26 , 29 , 34 , 35 2800 IU in 1 RCT, 13 4000 IU in 4 RCTs, 15 , 20 , 21 , 29 4400 in 1 RCT, 24 or 5000 IU in 1 RCT 33 ; the weekly doses were 35 000 IU 30 or 50 000 IU 19 ; the fortnightly dose was 50 000 IU in 2 RCTs 23 , 28 ; the monthly dose was 60 000 IU 32 ; the bimonthly dose was 60 000 IU 32 ; and the bolus doses were 60 000 IU in 3 RCTs, 22 ...…”

“… 12 , 17 , 25 For the intervention group, the daily doses were 800 IU in 1 RCT, 17 1000 IU in 6 RCTs, 12 , 14 , 16 , 18 , 25 , 26 1200 IU in 1 RCT, 34 2000 IU in 7 RCTs, 15 , 18 , 20 , 26 , 29 , 34 , 35 2800 IU in 1 RCT, 13 4000 IU in 4 RCTs, 15 , 20 , 21 , 29 4400 in 1 RCT, 24 or 5000 IU in 1 RCT 33 ; the weekly doses were 35 000 IU 30 or 50 000 IU 19 ; the fortnightly dose was 50 000 IU in 2 RCTs 23 , 28 ; the monthly dose was 60 000 IU 32 ; the bimonthly dose was 60 000 IU 32 ; and the bolus doses were 60 000 IU in 3 RCTs, 22 , 27 , 31 120 000 IU in 2 RCTs, 22 , 31 or 200 000 IU in 2 RCTs. 17 , 25 In studies comprising 3 or more groups, as was the case in 9 RCTs, 15 , 17 , 18 , 20 , 22 , 25 , 26 , 32 , 34 the higher-dose groups were combined into 1 cohort as the intervention group and the lowest dose groups as the control cohort. There were no toxic effects on offspring in the included RCTs and no evidence of publication bias.…”

Vitamin D, and Maternal and Child Health

“…Only 160 women were followed up until delivery, and 52 children (17% of the original cohort) underwent DXA at 12-16 months of age. The children in the placebo group were significantly older at DXA scan and had higher measurements of whole-body BMC and BMD, but in multivariate analysis randomisation group was not a significant predictor of BMC or BMD [121]. Vaziri et al randomised 153 women to placebo or 2000 IU/ day cholecalciferol from 26 to 28 weeks until delivery, but only 25 infants (16% of the original cohort) had DXA assessment.…”