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Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.
BMJ. 2017 Nov 29; 359:j5237.BMJ

Abstract

Objectives To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials.Design Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials.Data sources Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials.Eligibility criteria for study selection Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal.Results 43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews.Conclusions Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes.Systematic review registration PROSPERO CRD42016051292.

Authors+Show Affiliations

Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada. Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada.Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada.Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.Centre for Global Child Health and SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

29187358

Citation

Roth, Daniel E., et al. "Vitamin D Supplementation During Pregnancy: State of the Evidence From a Systematic Review of Randomised Trials." BMJ (Clinical Research Ed.), vol. 359, 2017, pp. j5237.
Roth DE, Leung M, Mesfin E, et al. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237.
Roth, D. E., Leung, M., Mesfin, E., Qamar, H., Watterworth, J., & Papp, E. (2017). Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ (Clinical Research Ed.), 359, j5237. https://doi.org/10.1136/bmj.j5237
Roth DE, et al. Vitamin D Supplementation During Pregnancy: State of the Evidence From a Systematic Review of Randomised Trials. BMJ. 2017 Nov 29;359:j5237. PubMed PMID: 29187358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. AU - Roth,Daniel E, AU - Leung,Michael, AU - Mesfin,Elnathan, AU - Qamar,Huma, AU - Watterworth,Jessica, AU - Papp,Eszter, Y1 - 2017/11/29/ PY - 2017/12/1/entrez PY - 2017/12/1/pubmed PY - 2017/12/5/medline SP - j5237 EP - j5237 JF - BMJ (Clinical research ed.) JO - BMJ VL - 359 N2 - Objectives To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials.Design Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials.Data sources Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials.Eligibility criteria for study selection Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal.Results 43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews.Conclusions Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes.Systematic review registration PROSPERO CRD42016051292. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/29187358/Vitamin_D_supplementation_during_pregnancy:_state_of_the_evidence_from_a_systematic_review_of_randomised_trials_ DB - PRIME DP - Unbound Medicine ER -