## 5 Vitamin D and GDM: An Overview of Randomised Controlled Trials
### Efficacy of Vitamin D Supplementation for Reducing Incident GDM  
Regarding the effects of vitamin D supplementation on risk of incident GDM, results from the included RCTs were highly disparate. Of the 12 RCTs conducted in healthy women without GDM, only seven reported on incident GDM as an outcome [40; 41; 42; 44; 77; 80; 83]. Among these seven trials, five reported no change in the risk of GDM after supplementation with 1600 [44], 4000 [77], or 5000 IU [42] of cholecalciferod daily from \(\leq\)20 weeks gestation or after receiving bolus doses of 50,000 IU biweekly from 14-16 weeks gestation [80] or 60,000 to 120,000 IU once, twice or four times from 20 weeks gestation [41]. Of note, two of these studies were open-label trials [41; 77], one was single-blind [44] and all five were conducted in different geographical regions (Iran, India, Australia, Pakistan, Europe). All the trials also had different comparators including placebo, no supplements, iron and calcium, or low dose vitamin D. Hence, directly comparing these results or drawing conclusions as to the reasons for the lack of findings is challenging given the substantial heterogeneity between the study settings, designs and participants. In the two remaining trials [40; 83], both of which were conducted in Iran, a reduced risk of GDM following vitamin D supplementation was reported. One of these trials was a double-blind RCT of 90 women which supplemented 5000 IU of vitamin D daily (type not reported) from 12 to 26 weeks gestation [83]. Here, [PERSON] et al. [83] found a reduction in the proportion of abnormal glucose tolerance tests at 26 weeks gestation in the supplemented group compared with placebo. Participating women were at risk of GDM and given the small sample size, the generalisability of these results is questionable. The second trial was an open-label RCT and the largest trial to date as it included 500 women [40]. This trial found that women receiving biweekly supplementation with 50,000 IU of cholecalciferod from 12 weeks gestation had a significantly reduced risk of GDM, compared with a control group receiving the standard prenatal daily dose of 400 IU [40]. These findings suggest that perhaps commencing supplementation at higher doses earlier in pregnancy may be more effective in preventing GDM. However, given the overall divergent results and null findings in most of the studies, there is a clear need for further well-designed trials using larger cohorts and a range of time points to clarify the benefits of vitamin D supplementation in reducing the risk of incident GDM, should any benefit exist. Efficacy of Vitamin D Supplementation for Improving Glycaemic Control in Pregnant Women with and without GDM  
Twelve studies reported the effects of vitamin D supplementation on glycaemic parameters, of which six were in women with GDM [39; 45; 46; 76; 78; 84; 85] and six were in healthy (or at risk) populations [37; 38; 43; 79; 81; 82]. The six studies in women with GDM were conducted in Iran [45; 46; 78; 84; 85] and China [39; 76]. All studies reported a reduction in fasting glucose, with the exception of one study by [PERSON] et al. [76] which reported no effect in 133 women receiving cholecalciferol at doses of 200 IU daily, 50,000 IU monthly or 50,000 IU biweekly compared with placebo. Similarly, all studies reported a reduction in insulin levels and insulin resistance measured by the homeostatic model assessment of insulin resistance (HOMA-IR), except for one study by [PERSON] et al. [85] which found no effect on these measures in 76 women receiving 50,000 IU biweekly from 24-28 weeks gestation for two months. However, [PERSON] et al. [85] did note a significant increase in HbA1c in the placebo group (compared with HbA1c remaining stable in the vitamin D group), whereas HbA1c was not assessed in the remaining studies.