Table 1.
Summary of the randomized clinical trials (RCTs)
| First author, year | Design | Participants, n | Place | Health condition | Gestational age (wk) | Duration (wk) | Treatment | Control | Explored variables | Outcome | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| treatment | control | ||||||||||
| Rodrigues Amorim Adegboye, 2021 [35] | RCT | 13 | 9 | Rio de Janeiro, Brazil | Healthy | 16.2 ± 2.4 | < 20 to 30–38 wk | fortified sachet with vitamin D (500 IU) and calcium (500 mg) twice a day | placebo sachet | 25(OH)D, CRP | CRP levels had no significant differences between supplemented and placebo groups |
| Khatiwada, 2021 [9, 33] | RCT | 110 | 107 | South Carolina, USA | Healthy | 10–14 | > 20 | 4400 IU vitamin D3/day | 400 vitamin D3/day | 25(OH)D, TGF-β, IFN-γ, CRP, IL-2, IL-4, IL-5, IL-10, VEGF, | Immune-mediators in the late pregnancy did not change in response to vitamin D supplementation during pregnancy |
| Gunasegaran, 2021 [36] | RCT | 34 | 36 | Tamil Nadu, India | GDM | 24–28 | 6 | vitamin D 1000 IU and calcium 1000 mg | itamin D 250 IU and calcium 500 mg | 25(OH)D, GSH | Supplementation with 1000 IU vitamin D and 1000 mg Calcium, had a positive effect on oxidative stress in women with GDM |
| Motamed, 2020 [23] | RCT | 37 | 37 | Tehran, Iran | Healthy | 8–12 | 28.7 |
2000 IU/d vitamin D3 + current supplementation during pregnancy |
1000 IU/d vitamin D3 + current supplementation during pregnancy | MDA, TAC in the serum of mothers and offsprings’ cord blood | No significant within & between group differences in serum and cord blood concentration of MDA and TAC |
| Motamed, 2019 [24, 37] | RCT | 37 | 37 | Tehran, Iran | Healthy | 8–12 | 28.7 |
2000 IU/d vitamin D3 + current supplementation during pregnancya |
1000 IU/d vitamin D3 + current supplementation during pregnancy | 25(OH)D, hs-CRP, and cell-culture supernatant concentrations of IL-1 beta, IL-6, and TNF-α in mothers and offsprings’ cord blood | A significant decrease of TNF-α in maternal PBMCs of 2000 IU/d vitamin D group & lower concentration of cord blood IL-6 in 2000 IU/d compared to 1000 IU/d vit D group |
| Jamilian, 2019 [10] | RCT | 30 | 30 | Kashan, Iran | Healthy | 24–28 | 6 | 200 IU/d vitamin D3 + 100 mg/d magnesium + 4 mg/d zinc + 400 mg calcium/d | Placebo | 25(OH)D, hs-CRP, MDA, TAC in the maternal serum | Intervention caused a significant decrease in serum hs-CRP & plasma MDA & an increment in TAC levels compared to placebo group |
| Braithwaite, 2019 [34, 39] | RCT | 93 | 102 | UK | Healthy | 10–17 | 20.5 | 1000 IU/d vitamin D3 | Placebo | 25(OH)D, CRP in the maternal plasma | Vitamin D 3 supplementation had no effect on CRP status |
| Hornsby, 2018 [32] | RCT | 26 | 25 | Boston, USA | Healthy | 10–18 | 25 | 4400 IU/d vitamin D3 | 400 IU/d vitamin D3 | 25(OH)D, IFN- γ, IL-1 β, IL-6, and IL-8 in the supernant of cultured CBMCs | The levels of IFN-γ, IL-1β, IL-6, and IL-8 in CBMCs of 4400 IU/d vitamin D group increased |
| Razavi, 2017 [11, 38] | RCT | 30 | 30 | Tabriz, Iran | GDM | 24–28 | 6 |
T1: 50,000 IU vitamin D3 every 2 week T2: 50,000 IU vitamin D3 every 2 week + 1000 mg/d omega-3 |
Placebo | serum levels of 25(OH)D, hs_CRP and plasma concentration of MDA, TAC, GSH in mothers | vitamin D + Omega3 (T1) decreased the concentration of hs-CRP, MDA & increased TAC & GSH compared to other groups |
| Yazdchi, 2016 [25] | RCT | 38 | 38 | Tabriz, Iran | GDM | 24–28 | 8 | 50,000 IU twice a month vitamin D3 | Placebo | 25(OH)D, hs-CRP in the maternal serum | A significant increment of hs-CRP in placebo group, but no significant change in intervention group |
| Akhtar, 2016 [30] | RCT | 80 | 80 | Bangladesh | Healthy | 26–29 | 16.5 | 35,000 IU/wk vitamin D3 | Placebo |
25(OH)D, IL-10 TNF-alpha IFN- γ in the cultured CBMCs |
higher concentrations of IL-10 & TNF-α & IFN-γ in the vitamin D group compared to the placebo |
| Samimi, 2016 [12] | RCT | 30 | 30 | Kashan, Iran | at risk for pre-eclampsia | 20–32 | 12 | 50 000 IU vitamin D3 every 2 weeks + 1000 mg/ d calcium | Placebo | GSH in the maternal plasma | Plasma concentrations of GSH increased compared to placebo |
| Zhang, 2016 [29] | RCT |
38 38 37 |
20 | Shanghai, China | GDM | 24–28 | From 24–28 wk of gestation until delivery |
T1: 200 IU/d vitamin D3 T2: 2000 IU/d vitamin D3 T3: 4000 IU/d vitamin D3 |
Control | 25(OH)D in the serum and TAC and GSH in the plasma of mothers | TAC & GSH levels increased in response to T3 (50,000 IU every 2 weeks (4,000 IU daily for 12.5 days)) compared to other groups |
| Zerofsky, 2016 [31, 40] | RCT | 26 | 29 | California, USA | Healthy | 20 | 22 | 2000 IU/d vitamin D3 | 400 IU/d vitamin D3 | 25(OH)D, IL-10 in the maternal plasma | 2000-IU/d resulted in a significant increase in the percentage of CD4 + IL-10 + T cells compared to 400-IU/d that showed a 12% decrease in the same biomarker from the first to third visit |
| Asemi, 2014 [26] | RCT | 28 | 28 | Kashan, Iran | GDM | 24–28 | 6 | 1,000 mg/d Calcium + 50,000 IU vitamin D3 twice a month | Placebo | 25(OH)D in the serum and hs-CRP, MDA, GSH, TAC, NO in the plasma of mothers | Intervention caused a significant increase in GSH and prevented the increase of MDA levels compared to the placebo |
| Asemi, 2013 (a) [27] | RCT | 27 | 27 | Kashan, Iran | GDM | 24–28 | 6 | 50,000 IU vitamin D3 twice a month | Placebo | 25(OH)D, hs-CRP in the maternal serum | hs-CRP had a significant decrease in vitamin D group compared to the placebo group |
| Asemi, 2013 (b) [28] | RCT | 24 | 24 | Kashan, Iran | Healthy | 25 | 9 | 400 IU/d vitamin D3 | Placebo | 25(OH)D, calcium, hs-CRP in the serum MDA & GSH in the plasma of mothers | A significant decrease in serum hs-CRP in intervention group |
n Number, wk Week, GDM Gestational diabetes, 25(OH)D 25-hydroxyvitamin D3, hs-CRP High-sensitivity C-reactive protein, IL Interleukin, TNF-α Tumor Necrosis Factor-alpha, MDA Malondialdehyde, TAC Total antioxidant capacity, IFN-γ Interferon Gamma, GSH Glutathione, NO Nitric oxide, CRP C-reactive protein, TGF-β Transforming growth factor-beta, CBMCs Cord blood mononuclear cells
aCurrent supplementation during pregnancy: daily iron, folic acid and multivitamin supplementation
Overall risk-of-bias judgment: Low risk of bias: The study is judged to be at low risk of bias for all domains for this result; Some concerns: The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain; High risk of bias: The study is judged to be at high risk of bias in at least one domain for this result, or the study is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result