Are prenatal vitamin D levels tied to adverse pregnancy outcomes?
Women with low levels of 25-hydroxyvitamin D (vitamin D) are not at increased risk of gestational hypertension or preeclampsia, according to the results of a study published in The British Medical Journal. The findings are from an analysis by European researchers.
Using a technique called Mendelian randomization, the authors examined whether genetic variants associated with variable vitamin D production and metabolism also influenced the risk of pregnancy-induced hypertension and preeclampsia among 7,389 women (751 had gestational hypertension and 135 preeclampsia). Data were extracted from two large European studies (Avon Longitudinal Study of Parents and Children and Generation R Study). They also performed another (two sample) Mendelian randomization analysis of 3,388 preeclampsia cases and 6,059 controls.
Analyzing genetic information as proxies for the exposure of interest in this way avoids some of the problems that afflict traditional observational studies, making the results less prone to confounding. An association observed using Mendelian randomization would therefore strengthen inference of a causal relationship. In this study, the genes assessed in relation to vitamin D synthesis were CYP2R1 DHCR7/NADSYN1 and in relation to metabolism were CYP24A1 and GC.
A marginally significant relative risk (RR) for preeclampsia of 1.03 (95% confidence interval [CI] 1.00 to 1.07) per 10% decrease in vitamin D level was observed. A RR of 2.04 (1.02 to 4.07) was noted for vitamin D levels < 25 nmol/L compared with levels ≥75 nmol/L. No association was found for gestational hypertension. No strong evidence of a linear effect of vitamin D on risk of either gestational hypertension or preeclampsia was found in the one-sample Mendelian randomization: odds ratio (OR) 0.90 (95% CI 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. In the two-sample Mendelian randomization, the OR for preeclampsia was also not significant at 0.98 (0.89 to 1.07) per 10% decrease in vitamin D level, 0.96 (0.80 to 1.15) per unit increased in the log(odds) of vitamin D level < 75 nmol/L and OR of 0.93 (0.78 to 1.19) per unit increased in the log(odds) of vitamin D levels < 50 nmol/L. No consistent evidence was seen of any associations between four single-nucleotide polymorphisms (SNPs) with gestational hypertension or preeclampsia in the two cohorts. Evaluation of those four genetic variants showed weak evidence of an association between one of the SNPs and preeclampsia.
The authors said that vitamin D levels in the one-sample Mendelian randomization in both cohorts were positively associated with age (difference 1 to 2 years) and education (7% to 9% difference in proportion with high education). An inverse association was seen with smoking (13% to 20% difference in proportion of women who smoked during pregnancy) and body mass index (BMI) (6% to 38% difference in proportion with normal BMI.
The authors concluded that a lower vitamin D level was weakly associated with lower risk of gestational risk of hypertension and higher risk of preeclampsia in the one-sample mendelian analysis. “Further evidence from larger studies is needed to provide conclusive evidence,” they said. No evidence was found of an association between vitamin D level and preeclampsia in the two-sample mendelian randomization analysis. The strengths of the study, the authors noted, were use of genetic variants to reduce confounding and the inclusion of multiple cohorts.
The findings, the authors said, support the current World Health Organization position on vitamin D which is that evidence is insufficient on which to base a recommendation for vitamin D supplementation by women during pregnancy. The National Academy of Medicine (formerly the Institute of Medicine) recommends a dietary allowance of 600 IU daily of vitamin D during pregnancy and lactation.