Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment).
A Cochrane review [Abstract] 1 included 30 studies with a total of 7033 subjects.
Supplementation with vitamin D alone vs placebo/no intervention: A total of 22 trials involving 3725 subjects were included. 19 trials were assessed as having low-to-moderate risk of bias. Supplementation with vitamin D alone during pregnancy reduced the risk of pre-eclampsia, gestational diabetes, low birthweight (less than 2500 g), and severe postpartum haemorrhage (table T1). There was little or no difference in the risk of preterm birth< 37 weeks.
Supplementation with vitamin D plus calcium vs placebo/no intervention: A total of 9 trials involving 1916 subjects were included. 3 trials were assessed as having low risk of bias for allocation and blinding, 4 trials were assessed as having high risk of bias and 2 had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium reduced the risk of pre-eclampsia (table T2). The effect of the intervention was uncertain on gestational diabetes and low birthweight (less than 2500 g), and increased the risk of preterm birth < 37 weeks. No trial in this comparison reported on maternal adverse events.
| Outcome | Relative effect (95% CI) | Risk with placebo/control | Risk with intervention - vitamin D supplementation (95% CI) | №of participants (studies) Certainty of the evidence |
|---|---|---|---|---|
| Pre-eclampsia | RR 0.48 (0.30, 0.79) | 168 per 1000 | 79 per 1000 (49 to 131) | 499 (4) Moderate |
| Gestational diabetes | RR 0.51 (0.27 to 0.97) | 127 per 1000 | 65 per 1000 (34 to 123) | 446 (4) Moderate |
| Low birthweight (less than 2500 g) | RR 0.55 (0.35 to 0.87) | 136 per 1000 | 75 per 1000 (48 to 118) | 697 (5) Moderate |
| Preterm birth (less than 37 weeks' gestation) | RR 0.66 (0.34 to 1.30) | 87 per 1000 | 57 per 1000 (29 to 113) | 1640 (7) |
| Maternal adverse events: severe postpartum haemorrhage | RR 0.68 (0.51 to 0.91) | 158 per 1000 | 106 per 1000 (79 to 142) | 1134 (1) Low |
| Outcome | Relative effect (95% CI) | Risk with placebo/control | Risk with intervention - vitamin D supplementation (95% CI) | №of participants (studies) Certainty of the evidence |
|---|---|---|---|---|
| Pre-eclampsia | RR 0.50 (0.32 to 0.78) | 94 per 1000 | 47 per 1000 (30 to 73) | 1174 (4) Moderate |
| Gestational diabetes | RR 0.33 (0.01 to 7.84) | 37 per 1000 | 12 per 1000 (0 to 290) | 54 (1) Very low |
| Low birthweight (less than 2500 g) | RR 0.68 (0.10 to 4.55) | 59 per 1000 | 40 per 1000 (6 to 268) | 110 (2) Very low |
| Preterm birth (less than 37 weeks' gestation) | RR 1.52 (1.01 to 2.28) | 72 per 1000 | 110 per 1000 (73 to 165) | 942 (5) Low |
Another Cochrane review 2 included 30 trials involving 7289 women.
601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; n=5 214)Supplementation with 601 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia (RR 0.96, 95% CI 0.65 to 1.42; 5 trials; n=1553), may reduce the risk of gestational diabetes (RR 0.54, 95% CI 0.34 to 0.86; 5 trials; n=1846), may make little or no difference to the risk of preterm birth (RR 1.25, 95% CI 0.92 to 1.69; 4 trials; n=2294); and may make little or no difference to the risk of low birthweight (RR 0.90, 95% CI 0.66 to 1.24; 4 trials; n=1550) compared to women receiving 600 IU/d or less.
4000 IU or more versus 3999 IU or less of vitamin D alone (15 trials; n=4763)Supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of: pre-eclampsia (RR 0.87, 95% CI 0.62 to 1.22; 4 trials, n=1903); gestational diabetes (RR 0.89, 95% CI 0.56 to 1.42; 5 trials, n=2276); preterm birth (RR 0.85, 95% CI 0.64 to 1.12; 6 trials, n=2948); and low birthweight (RR 0.92, 95% CI 0.49 to 1.70; 2 trials; n=1099) compared to women receiving 3999 IU/d or less.Adverse events (such as hypercalcaemia, hypocalcaemia, hypercalciuria, and hypovitaminosis D) were reported differently in most trials; however, in general, there was little to no side effects reported or similar cases between groups.
Date of latest search:2019-08-21
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