Maternal Vitamin D Insufficiency Linked to Adverse Outcomes

Joe Barber Jr, PhD

March 27, 2013

Vitamin D insufficiency during pregnancy is associated with a number of adverse health outcomes for both mother and child, according to a systematic review and meta-analysis.

Fariba Aghajafari, MD, CCFP, and colleagues from the University of Calgary in Alberta, Canada, published their findings online March 26 in BMJ.

"Observational data suggest a link between low 25-hydroxyvitamin D (25-OHD) levels — the best measure of vitamin D status in humans — and an increased risk of adverse pregnancy outcomes," the authors write. "Despite these findings, the knowledge and understanding of the clinical importance and implications of these associations are limited."

Therefore, the authors searched MEDLINE, PubMed, Embase, CINAHL, the Cochrane Database of Systematic Reviews, and the Cochrane database of registered clinical trials to identify studies investigating an association between serum 25-OHD levels in pregnancy and several health outcomes. They identified 31 studies for inclusion in the systematic analysis.

The researchers included original studies that had an outcome of interest and that assessed serum 25-OHD levels. They excluded studies that used non-blood measures of 25-OHD, that measured other metabolites of vitamin D, that investigated biological mechanisms of vitamin D metabolites, or that included nonhuman subjects.

Low 25-OHD levels during pregnancy were associated with an increased risk for gestational diabetes (pooled odds ratio = 1.49; 95% confidence interval [CI], 1.18 - 1.89) with no evidence of heterogeneity (P = .58; I2 = 0%). The risk increased after the researchers adjusted for other factors, including ethnicity, skin color, and body mass index (pooled odds ratio = 1.98; 95% CI, 1.23 - 3.23).

The meta-analysis also identified an association between low 25-OHD levels in pregnancy and pre-eclampsia (pooled odds ratio = 1.79; 95% CI, 1.25 - 2.58) with no evidence of heterogeneity (P = .81; I2 = 0%); adjustment for confounders resulted in a lower, nonsignificant pooled odds ratio of 1.51 (95% CI, 0.89 - 2.57). Additionally, low 25-OHD levels in pregnancy increased the risk of small-for-gestational age infants (pooled odds ratio = 1.85; 95% CI, 1.52 - 2.26), and the association remained significant after adjusting for confounders (pooled risk ratio = 2.05; 95% CI, 1.54 - 2.74).

The limitations of the study included the inclusion of case-control studies in the meta-analysis and variation in the definition of 25-OHD insufficiency among the included studies.

"Our findings of a significant association between 25-OHD insufficiency and adverse pregnancy outcomes and birth variables are of concern," the authors write. "[T]here remains a need for large, well designed randomised controlled trials to determine whether strategies to optimise maternal 25-OHD levels are effective in improving pregnancy and neonatal outcomes."

In a linked commentary, Robyn Lucas, MBChB, MPH&TM, PhD, MHE, FAFPHM, from Australian National University in Canberra, and colleagues noted that the findings confirm the importance of vitamin D levels during pregnancy. "The findings of this meta-analysis support a goal of vitamin D sufficiency for all pregnant women," the commentators write. "Supplements, diet, and sunlight exposure all influence 25-OHD levels and should be used together, with care, because U shaped dose-response curves are reported for a range of health outcomes."

The study was supported by the University of Calgary Institute for Public Health, Alberta Innovates Health Solutions, the Canadian Institute of Health Research, and the Canadian Foundation for Healthcare Improvement. The authors and commentators have disclosed no relevant financial relationships.

BMJ. Published online March 26, 2013. Full article, Editorial