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Evidence summaries

Vitamin D Supplementation for Women during Pregnancy

Vitamin D supplementation in pregnancy appears to reduce the risk of pre-eclampsia, gestational diabetes, and low birthweight compared with placebo or no treatment. Level of evidence: "B"

Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment).

Summary

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.

Vitamin D supplementation compared to placebo/control

OutcomeRelative effect (95% CI)Risk with placebo/controlRisk with intervention - vitamin D supplementation (95% CI)of participants (studies) Certainty of the evidence
Pre-eclampsiaRR 0.48 (0.30, 0.79)168 per 100079 per 1000 (49 to 131)499 (4) Moderate
Gestational diabetesRR 0.51 (0.27 to 0.97)127 per 100065 per 1000 (34 to 123)446 (4) Moderate
Low birthweight (less than 2500 g)RR 0.55 (0.35 to 0.87)136 per 100075 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 100057 per 1000 (29 to 113)1640 (7)
Maternal adverse events: severe postpartum haemorrhageRR 0.68 (0.51 to 0.91)158 per 1000106 per 1000 (79 to 142)1134 (1) Low

Vitamin D plus calcium supplementation compared to placebo/control

OutcomeRelative effect (95% CI)Risk with placebo/controlRisk with intervention - vitamin D supplementation (95% CI)of participants (studies) Certainty of the evidence
Pre-eclampsiaRR 0.50 (0.32 to 0.78)94 per 100047 per 1000 (30 to 73)1174 (4) Moderate
Gestational diabetesRR 0.33 (0.01 to 7.84)37 per 100012 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 100040 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 1000110 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.

Clinical comments

Note

Date of latest search:2019-08-21

    References

    • Palacios C, Kostiuk LK, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev 2019;(7):CD008873.[PubMed]
    • Palacios C, Trak-Fellermeier MA, Martinez RX et al. Regimens of vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev 2019;(10):CD013446. [PubMed]

Primary/Secondary Keywords