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 |
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 |
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 |
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 |
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 |
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 | 400Â 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 |