There was no consistent evidence tying vitamin D levels to pregnancy-related hypertensive disorders, researchers found. A Mendelian randomization analysis did not provide strong evidence of a linear effect between 25-hydroxyvitamin D levels and risk of gestational hypertension or preeclampsia in pregnant women, reported Maria C. Magnus, PhD, of the University of Bristol in England, and colleagues, writing in The BMJ. They noted that prior meta-analyses of observational studies in The BMJ and BMC Pregnancy and Childbirth suggested an inverse association between vitamin D and preeclampsia, but that a recent meta-analysis found "no strong evidence of a protective effect" on either gestational hypertension or preeclampsia. Since these studies all had different designs and analytical approaches, however, Magnus and colleagues then decided to use Mendelian randomization analysis, which examines "the association of genetically determined levels of the exposure in relation to the outcomes of interest." The team performed both a one-sample mendelian randomization analysis, which "provides researchers with greater control of the analysis," and a two-sample analysis, which "takes advantage of published summary estimates from large-scale genome-wide association studies." The data came from two European pregnancy cohorts (the Avon Longitudinal Study of Parents and Children and the Generation R study), as well as two case-control studies -- one subgroup nested within the Norwegian Mother and Child Cohort Study, and the U.K. Genetics of Pre-eclampsia study. Overall, there were 7,389 women in the one-sample analysis -- 715 with gestational hypertension and 135 with preeclampsia. In the two-sample analysis, the authors also used published estimates of links between "genetic instruments" and vitamin D levels from 21 European cohorts (n=42,024), as well as 3,388 pre-eclampsia cases, and 6,059 controls. Gestational hypertension and pre-eclampsia were defined by the International Society for the Study of Hypertension in Pregnancy. A multivariate analysis found no "strong evidence" of a link between vitamin D levels and gestational hypertension, and "weak evidence" of a linear association (pooled adjusted RR 1.03, 95% CI 1.00-1.07) per 10% decrease in vitamin D level. The authors did note that a vitamin D level of <25 nmol/L was linked with an increased risk of preeclampsia compared with vitamin D levels of ≥75 nmol/L (pooled adjusted RR 2.04, 95% CI 1.02-4.07). But the mendelian randomization analyses found similar results, with both the one-sample and the two-sample analyses finding "no consistent evidence" of a causal effect of vitamin D levels on the risk of preeclampsia or gestational hypertension. Putting the findings into context, Magnus and colleagues wrote that the findings support those of the World Health Organization, which currently states that evidence for recommending vitamin D supplementation to reduce adverse pregnancy outcomes is insufficient. In addition, the team recommended both large, well-conducted trials of vitamin D supplementation or further mendelian randomization studies with a larger number of women with preeclampsia or additional genetic instruments to help "finally establish whether vitamin D status has a role in pregnancy-related hypertensive disorders." This study was supported by grants from the European Union and the Norwegian government. Magnus reported from the U.K. government, as did other co-authors, along with support from the National Institutes of Health, the European Research Council, Roche Diagnostics, Medtronic, the European Commission, the government of the Netherlands, and the European Research Council.