Vitamin D After Pregnancy
. 2019 Jul 26;7(7):CD008873.
doi: 10.1002/14651858.CD008873.pub4.
Vitamin D supplementation for women during pregnancy
Affiliations
- PMID: 31348529
- PMCID: PMC6659840
- DOI: 10.1002/14651858.CD008873.pub4
Free PMC article
Vitamin D supplementation for women during pregnancy
Cristina Palacios et al. Cochrane Database Syst Rev. .
Free PMC article
Abstract
Background: Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012 and then in 2016.
Objectives: 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 maternal and neonatal outcomes.
Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2018), contacted relevant organisations (15 May 2018), reference lists of retrieved trials and registries at clinicaltrials.gov and WHO International Clinical Trials Registry Platform (12 July 2018). Abstracts were included if they had enough information to extract the data.
Selection criteria: 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.
Data collection and analysis: Two review authors independently i) assessed the eligibility of trials against the inclusion criteria, ii) extracted data from included trials, and iii) assessed the risk of bias of the included trials. The certainty of the evidence was assessed using the GRADE approach.
Main results: We included 30 trials (7033 women), excluded 60 trials, identified six as ongoing/unpublished trials and two trials are awaiting assessments.Supplementation with vitamin D alone versus placebo/no interventionA total of 22 trials involving 3725 pregnant women were included in this comparison; 19 trials were assessed as having low-to-moderate risk of bias for most domains and three trials were assessed as having high risk of bias for most domains. Supplementation with vitamin D alone during pregnancy probably reduces the risk of pre-eclampsia (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.30 to 0.79; 4 trials, 499 women, moderate-certainty evidence) and gestational diabetes (RR 0.51, 95% CI 0.27 to 0.97; 4 trials, 446 women, moderate-certainty evidence); and probably reduces the risk of having a baby with low birthweight (less than 2500 g) (RR 0.55, 95% CI 0.35 to 0.87; 5 trials, 697 women, moderate-certainty evidence) compared to women who received placebo or no intervention. Vitamin D supplementation may make little or no difference in the risk of having a preterm birth < 37 weeks compared to no intervention or placebo (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women, low-certainty evidence). In terms of maternal adverse events, vitamin D supplementation may reduce the risk of severe postpartum haemorrhage (RR 0.68, 95% CI 0.51 to 0.91; 1 trial, 1134 women, low-certainty evidence). There were no cases of hypercalcaemia (1 trial, 1134 women, low-certainty evidence), and we are very uncertain as to whether vitamin D increases or decreases the risk of nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 trial, 135 women, very low-certainty evidence). However, given the scarcity of data in general for maternal adverse events, no firm conclusions can be drawn.Supplementation with vitamin D and calcium versus placebo/no interventionNine trials involving 1916 pregnant women were included in this comparison; three trials were assessed as having low risk of bias for allocation and blinding, four trials were assessed as having high risk of bias and two had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium during pregnancy probably reduces the risk of pre-eclampsia (RR 0.50, 95% CI 0.32 to 0.78; 4 trials, 1174 women, moderate-certainty evidence). The effect of the intervention is uncertain on gestational diabetes (RR 0.33,% CI 0.01 to 7.84; 1 trial, 54 women, very low-certainty evidence); and low birthweight (less than 2500 g) (RR 0.68, 95% CI 0.10 to 4.55; 2 trials, 110 women, very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D and calcium during pregnancy may increase the risk of preterm birth < 37 weeks in comparison to women who received placebo or no intervention (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women, low-certainty evidence). No trial in this comparison reported on maternal adverse events.Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)One trial in 1300 participants was included in this comparison; it was assessed as having low risk of bias. Pre-eclampsia was not assessed. Supplementation with vitamin D + other nutrients may make little or no difference in the risk of preterm birth < 37 weeks (RR 1.04, 95% CI 0.68 to 1.59; 1 trial, 1298 women, low-certainty evidence); or low birthweight (less than 2500 g) (RR 1.12, 95% CI 0.82 to 1.51; 1 trial, 1298 women, low-certainty evidence). It is unclear whether it makes any difference to the risk of gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73) or maternal adverse events (hypercalcaemia no events; hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; 1 trial, 1298 women,) because the certainty of the evidence for both outcomes was found to be very low.
Authors' conclusions: We included 30 trials (7033 women) across three separate comparisons. Our GRADE assessments ranged from moderate to very low, with downgrading decisions based on limitations in study design, imprecision and indirectness.Supplementing pregnant women with vitamin D alone probably reduces the risk of pre-eclampsia, gestational diabetes, low birthweight and may reduce the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre-eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth < 37 weeks' gestation or low birthweight (less than 2500 g). 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.
Conflict of interest statement
The other authors have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).
Cristina Palacios received funds from the World Health Organization (WHO) to pay for travel expenses to present and meet with co‐authors and to write the review.
Lia Kostiuk ‐ received partial financial support from the WHO for this commissioned work.
Juan Pablo Peña‐Rosas ‐ the WHO receives partial financial support from the Bill & Melinda Gates Foundation, US Agency for International Development and Nutrition International to support its work in the area of nutrition, including the commissioning of systematic reviews of interventions for health throughout the life course. Donors do not fund specific guidelines and do not participate in any decision related to the guideline development process, including the composition of research questions, membership of the guideline groups, conduct and interpretation of systematic reviews, or formulation of recommendations.
Figures
Study flow diagram for this update
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Funnel plot of comparison: 1 Vitamin D alone versus no treatment/placebo (no vitamins or minerals), outcome: 1.15 Maternal vitamin D concentration at term (25‐hydroxyvitamin D) (nmol/L) (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 1 Pre‐eclampsia (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 2 Gestational diabetes (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 3 Maternal adverse events.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 4 Preterm birth (less than 37 weeks' gestation) (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 5 Low birthweight (less than 2500 g) (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 6 Pre‐eclampsia (by start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 7 Pre‐eclampsia (by pre‐gestational BMI).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 8 Pre‐eclampsia (by supplementation scheme/regimen).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 9 Pre‐eclampsia (by skin pigmentation based on Fitzpatrick skin tone chart).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 10 Pre‐eclampsia (by latitude).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 11 Pre‐eclampsia (by season at the start of pregnancy).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 12 Gestational diabetes (by start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 13 Gestational diabetes (by pre‐gestational BMI).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 14 Gestational diabetes (by supplementation scheme/regimen).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 15 Gestational diabetes (by skin pigmentation based on Fitzpatrick skin tone chart).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 16 Gestational diabetes (by latitude).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 17 Gestational diabetes (by season at the start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 18 Preterm birth (less than 37 weeks' gestation) (by start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 19 Preterm birth (less than 37 weeks' gestation) (by pre‐gestational BMI).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 20 Preterm birth (less than 37 weeks' gestation) (by supplementation scheme/regimen).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 21 Preterm birth (less than 37 weeks' gestation) (by skin pigmentation based on Fitzpatrick skin tone chart).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 22 Preterm birth (less than 37 weeks' gestation) (by latitude).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 23 Preterm birth (less than 37 weeks' gestation) (by season at the start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 24 Low birthweight (less than 2500 g) (by start of supplementation).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 25 Low birthweight (less than 2500 g) (by pre‐gestational BMI).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 26 Low birthweight (less than 2500 g) (by supplementation scheme/regimen).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 27 Low birthweight (less than 2500 g) (by skin pigmentation based on Fitzpatrick skin to.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 28 Low birthweight (less than 2500 g) (by latitude).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 29 Low birthweight (less than 2500 g) (by season at the start of pregnancy).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 30 Caesarean section.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 31 Gestational hypertension.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 32 Maternal death (death while pregnant or within 42 days of termination of pregnancy) (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 33 Maternal vitamin D concentration at term (25‐hydroxyvitamin D) (nmol/L) (ALL).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 34 Birth length (cm).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 35 Head circumference at birth (cm).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 36 Birthweight (g).
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 37 Stillbirth.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 38 Neonatal death.
Comparison 1 Supplementation with vitamin D alone versus placebo or no intervention (no vitamins or minerals), Outcome 39 Apgar score less than seven at five minutes.
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 1 Pre‐eclampsia (ALL).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 2 Gestational diabetes (ALL).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 3 Preterm birth (less than 37 weeks' gestation) (ALL).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 4 Low birthweight (less than 2500 g) (ALL).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 5 Caesarean section.
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 6 Gestational hypertension.
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 7 Maternal vitamin D concentration at term (25‐hydroxyvitamin D) (nmol/L) (ALL).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 8 Birth length (cm).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 9 Head circumference at birth (cm).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 10 Birthweight (g).
Comparison 2 Supplementation with vitamin D + calcium versus placebo or no intervention (no vitamin or minerals), Outcome 11 Neonatal death.
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 1 Gestational diabetes (ALL).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 2 Maternal adverse events.
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 3 Preterm birth (less than 37 weeks' gestation) (ALL).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 4 Low birthweight (less than 2500 g) (ALL).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 5 Caesarean section.
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 6 Gestational hypertension.
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 7 Maternal death (death while pregnant or within 42 days of termination of pregnancy).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 8 Maternal vitamin D concentration at term (25‐hydroxyvitamin D) (nmol/L) (ALL).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 9 Birth length (cm).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 10 Head circumference at birth (cm).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 11 Birthweight (g).
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 12 Stillbirth.
Comparison 3 Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D), Outcome 13 Neonatal death.
Update of
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Vitamin D supplementation for women during pregnancy.
De-Regil LM, Palacios C, Lombardo LK, Peña-Rosas JP. De-Regil LM, et al. Cochrane Database Syst Rev. 2016 Jan 14;(1):CD008873. doi: 10.1002/14651858.CD008873.pub3. Cochrane Database Syst Rev. 2016. PMID: 26765344 Updated. Review.
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