Vitamin D supplementation for women during pregnancy

Vitamin D is produced by the human body from exposure to sunlight and can also be consumed from foods such as fish-liver oils, fatty fish, mushrooms, egg yolks, and liver. Vitamin D has many functions in the body; it helps maintain bone integrity and calcium homeostasis.

During pregnancy, vitamin D deficiency or insufficiency may develop. Vitamin D supplementation during pregnancy has been suggested to safely improve pregnancy and infant outcomes. This review included six randomised controlled trials. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation or a placebo and one trial with 400 women compared the effects of vitamin D and calcium with no supplementation.

The results show that the provision of vitamin D supplements during pregnancy improves the women’s vitamin D levels, as measured by 25-hydroxyvitamin D levels, at term. However, the clinical significance of this finding is yet to be determined as there is no evidence that vitamin D supplementation prevents pre-eclampsia, gestational diabetes, impaired glucose tolerance, caesarean section, gestational hypertension, or death in the mothers; or preterm birth, stillbirth, neonatal death, neonatal admission to intensive care unit, newborns with low Apgar score or neonatal infection.

Data from three trials involving 463 women show a trend for women who receive vitamin D supplementation during pregnancy to less frequently have a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo, although the statistical significance was borderline.

The number of trials and outcomes reported are too limited, and in general are of low quality, to draw conclusions on the usefulness and safety of this intervention as a part of routine antenatal care. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.

Authors' conclusions: 

Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.

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Background: 

Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes.

Objectives: 

To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011).

Selection criteria: 

Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy.

Data collection and analysis: 

Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy.

Main results: 

The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation.

Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous.

Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01).

In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores.