From the Journals

Prenatal vitamin D supplementation plagued by lack of evidence



Prenatal vitamin D supplementation may reduce the risk of small for gestational age and early wheeze in infants, but most of the evidence comes from small, low-quality trials, according to a systematic review and meta-analysis.

Researchers reported on a meta-analysis of 43 randomized controlled trials, involving 8,406 participants, which examined the effects of vitamin D supplementation during pregnancy (BMJ. 2017;359:j5237. doi: 10.1136/bmj.j5237).

The most commonly reported outcomes involved fetal growth and preterm birth. A pooling of 37 comparisons suggested that vitamin D supplementation increased mean birth weight by an average of 58 g, compared with low-dose vitamin D, no vitamin D, or placebo.

A smaller pooling of seven comparisons found a 40% reduction in the risk of small-for-gestational-age (SGA) infants (95% confidence interval, 0.40-0.90) but there were no significant effects on low birth weight, birth lengths, or birth head circumference. In addition, there was no apparent effect of vitamin D on gestational age at birth, or risk of preterm birth.

Two high-quality trials using a regular dose of vitamin D, which were conducted in high-income countries, found a 19% reduction in the risk of persistent/recurrent wheeze by age 3, which the authors said was consistent with other data suggesting a beneficial effect of vitamin D in adults with asthma. However, there were no other respiratory effects, such as on the risk of upper or lower respiratory tract infections.

There were few studies that reported on maternal clinical outcomes, and those that did showed no evidence of benefit.

“Though some observational studies have shown associations between maternal vitamin D deficiency and gestational diabetes and preeclampsia, we did not find robust corroborating evidence from randomised controlled trials,” wrote Daniel E. Roth, MD, and his colleagues at the Hospital for Sick Children, Toronto, and the University of Toronto.

They did report significantly higher maternal and cord blood concentrations of 25-hydroxyvitamin D in the intervention groups, compared with controls.

The median sample size of the studies was 133, and the researchers found that only 8 of the 43 trials had an overall low risk of bias. They also noted that there were wide variations in baseline maternal vitamin D levels.

“Though trials of prenatal vitamin D supplementation are being published at an accelerating pace, randomised controlled trials published up to 2017 were generally small, low quality, and rarely designed to examine clinical outcomes,” the researchers wrote.

The study was supported by the Hospital for Sick Children. No conflicts of interest were declared.

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