Pregnancies helped by Vitamin D – recommendations and trials underway – review

Created January 2018

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials

the bmj | BM/2017;359:j5237 | doi: 10.1136/bmj.j5237

Daniel E Roth,1,2,3 Michael Leung,2 Elnathan Mesfin,2 Huma Qamar,2,3 Jessica Watterworth,2,3 Eszter Papp2

1 department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

2 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

Correspondence to: D E Roth daniel.roth@sickkids.ca

* Yet another review/meta-analysis which ignores the dose size used * The same importance is given to 400 IU daily as 6,000 IU daily * So, since most of the studies give only 400 IU, the great benefits of studies giving >4,000 IU remain hidden * Surprisingly the vast majority of all studies (even with small doses) found an increase in birth weight - see chart below) --- * Preeclampsia risk reduced 60 percent if supplement with Vitamin D (they ignored dose size) – meta-analysis Sept 2017 * Low Vitamin D results in adverse pregnancy and birth outcomes – Wagner meta-analysis March 2017 * Preterm birth rate reduced by 43 percent with adequate Vitamin D supplementation – meta-analysis Feb 2017 * Review on this page found no preterm benefit when dignoring vitamin D dose size * Gates funding Vitamin D studies during pregnancy to improve growth– Dec 2012 * Roth (an author of review) got a contract 5 years before from Gates Foundation, but did not mention this is the review 1. Based on good studies ignored by this review VitaminDWiki recommends a minimum of 4,000 IU during pregnancy Healthy pregnancies need lots of vitamin D > 4,000 IU {include} 1. Pregnancy category starts with {include}

WHAT IS ALREADY KNOWN ON THIS TOPIC

Numerous randomised trials and systematic reviews of vitamin D supplementation during pregnancy have been published, with conflicting results and conclusions
Recommendations regarding vitamin D supplementation vary widely among medical and professional organisations, and WHO currently recommends against routine prenatal vitamin D supplementation

WHAT THIS STUDY ADDS
Systematic review and meta-analyses of 43 trials including 8406 participants showed that prenatal vitamin D supplementation was associated with increased maternal and cord serum 25-hydroxyvitamin D concentrations, increased mean birth weight, reduced the risk of small for gestational age, reduced the risk of wheeze in offspring, and increased infant length at one year of age There was a lack of evidence of benefits of prenatal vitamin D supplementation for maternal health conditions related to pregnancy, no effect on other birth outcomes of public health importance such as preterm birth, and scant evidence on safety outcomes
Few of the trials were designed to test the effect of vitamin D on clinical or functional outcomes, and most trials were small and at overall high or uncertain risk of bias
Thirty five planned or ongoing prenatal vitamin D trials could contribute an additional 12 530 participants to future systematic reviews

Increasing number of studies and participating mothers

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

📄 Download the main PDF from VitaminDWiki

Vitamin D recommendations for pregnancies

**
Canadian Paediatric Society	2000 IU
Indian – govt	400 IU – if have little access to sunlight
Canada – Health	Drink milk, and 600 IU (IoM)
US Institute of Medicine	600 IU
US American College of Obstetricians and Gynecologists	1,000-2,000 IU
US Endocrine Society	1500 IU only if at risk for Vitamin D deficiency
Australia	200 IU if have minimal access to sunlight
European Food Safety Authority	600 IU
UK Scientific Advisory Committee on Nutrition (SCAN)	400 IU
World Health Organization	0 – is not recommended	**