Key messages
Vitamin D supplementation during pregnancy may help improve certain health outcomes in mothers and their babies and reduce the risk of adverse (harmful) pregnancy outcomes.
Public health implications
Vitamin D deficiency during pregnancy has been associated with health complications in mothers and their babies. It is thought that additional vitamin D through supplementation during pregnancy might be needed to protect against these complications.
What did we want to find out?
To determine if vitamin D supplementation during pregnancy can safely improve certain health outcomes in the mothers and their babies (such as fewer preterm births and low birthweight babies) and reduce the risk of adverse pregnancy outcomes (such as excessive bleeding).
What did we do?
This is an update of a review that was first published in 2012 and subsequently updated in 2016 and 2019. We searched for clinical trials (December 2022) that looked at vitamin D supplementation, alone or in combination with calcium or other vitamins and minerals, during pregnancy, in comparison to placebo or no intervention. We reviewed each study using a tool to assess their trustworthiness. We compared and summarised the results of the studies and rated our confidence in the information, based on factors such as study methods and sizes.
What did we find?
The previous version of this review included 30 studies. In this update, we have removed 20 of these studies to 'awaiting classification' and excluded one study due to low trustworthiness. We have added one new study. This current review includes a total of 10 studies, 117 excluded studies, 34 studies in awaiting assessment, and seven ongoing studies.
Overall, we are not sure if supplementation with vitamin D alone compared to no intervention or a placebo (eight studies, 2313 women) prevents pregnancy-associated hypertension, diabetes during pregnancy, babies born earlier than expected, and kidney disease in this setting. It may prevent severe excessive bleeding at birth (although this was based on a single study) and it may reduce the risk of having a baby with a low birthweight, but an increase in this risk cannot be ruled out at this stage. Also, we are not sure if supplementation with vitamin D and calcium versus placebo or no intervention (one study, 84 women) prevents babies being born earlier than expected and low birthweight. No other outcomes were reported in the only study included. Lastly, we are not sure if supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) (one study, 1298 women) prevents diabetes during pregnancy, maternal adverse events, babies born earlier than expected, or low birthweight. Other outcomes were not reported.
What are the limitations of the evidence?
The quality and small to medium size of most studies were limitations in this review. Not all the studies provided data about the outcomes we were interested in. More well-conducted research is needed so that we can be more certain of the effects of vitamin D supplementation in pregnancy on these outcomes. This includes research into possible adverse events, which is lacking in the current evidence.
How up-to-date is this evidence?
The evidence is up-to-date as of December 2022.
This updated review using the trustworthy assessment tool removed 21 studies from the previous update and added one new study for a total of 10 included studies. In this setting, supplementation with vitamin D alone compared to no intervention or a placebo resulted in very uncertain evidence on pre-eclampsia, gestational diabetes, preterm birth, or nephritic syndrome. It may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome. It may also reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out. Supplementation with vitamin D and calcium versus placebo or no intervention resulted in very uncertain evidence on preterm birth and low birthweight. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported in the only study included in this comparison. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) resulted in very uncertain evidence on gestational diabetes and maternal adverse events (hypercalciuria) and uncertain evidence on preterm birth and low birthweight. Pre-eclampsia was not reported in the only study included in this comparison.
All findings warrant further research. Additional rigorous, high-quality, and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.
Vitamin D supplementation during pregnancy may help improve maternal and neonatal health outcomes (such as fewer preterm birth and low birthweight babies) and reduce the risk of adverse pregnancy outcomes (such as severe postpartum haemorrhage).
To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve certain maternal and neonatal outcomes.
We searched the Cochrane Pregnancy and Childbirth Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and relevant conference proceedings) (3 December 2022). We also searched the reference lists of retrieved studies.
Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention.
Two review authors independently i) assessed the eligibility of studies against the inclusion criteria, ii) assessed trustworthiness based on pre-defined criteria of scientific integrity, iii) extracted data from included studies, and iv) assessed the risk of bias of the included studies. We assessed the certainty of the evidence using the GRADE approach.
The previous version of this review included 30 studies; in this update, we have removed 20 of these studies to 'awaiting classification' following assessments of trustworthiness, one study has been excluded, and one new study included. This current review has a total of 10 included studies, 117 excluded studies, 34 studies in awaiting assessment, and seven ongoing studies. We used the GRADE approach to assess the certainty of the evidence. This removal of the studies resulted in evidence that was downgraded to low-certainty or very low-certainty due to study design limitations, inconsistency between studies, and imprecision.
Supplementation with vitamin D compared to no intervention or a placebo
A total of eight studies involving 2313 pregnant women were included in this comparison. We assessed four studies as having a low risk of bias for most domains and four studies as having high risk or unclear risk of bias for most domains. The evidence is very uncertain about the effect of supplementation with vitamin D during pregnancy compared to placebo or no intervention on pre-eclampsia (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.21 to 1.33; 1 study, 165 women), gestational diabetes (RR 0.53, 95% CI 0.03 to 8.28; 1 study, 165 women), preterm birth (< 37 weeks) (RR 0.76, 95% CI 0.25 to 2.33; 3 studies, 1368 women), nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 study, 135 women), or hypercalcaemia (1 study; no cases reported). Supplementation with vitamin D during pregnancy may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome (RR 0.68, 95% CI 0.51 to 0.91; 1 study, 1134 women; low-certainty evidence) and may reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out (RR 0.69, 95% CI 0.44 to 1.08; 3 studies, 371 infants; low-certainty evidence).
Supplementation with vitamin D + calcium compared to no intervention or a placebo
One study involving 84 pregnant women was included in this comparison. Overall, this study was at moderate to high risk of bias. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported. The evidence is very uncertain about the effect of supplementation with vitamin D and calcium on preterm birth (RR not estimable; very low-certainty evidence) or for low birthweight (RR 1.45, 95% CI 0.14 to 14.94; very low-certainty evidence) compared to women who received placebo or no intervention.
Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)
One study involving 1298 pregnant women was included in this comparison. We assessed this study as having a low risk of bias in all domains. Pre-eclampsia was not reported. The evidence is very uncertain about the effect of supplementation with vitamin D, calcium, and other vitamins and minerals during pregnancy compared to no vitamin D on gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73; very low-certainty evidence), maternal adverse events (hypercalcaemia no events and hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; very low-certainty evidence), preterm birth (RR 1.04, 95% CI 0.68 to 1.59; low-certainty evidence), or low birthweight (RR 1.12, 95% CI 0.82 to 1.51; low-certainty evidence).