Vitamin D and Gestational Hypertension, Preeclampsia Risk: Is There a Connection?

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Serum and  plasma 25-hydroxyvitamin D levels were obtained during pregnancy.
Serum and plasma 25-hydroxyvitamin D levels were obtained during pregnancy.

No causal effect was identified between vitamin D level and risk of developing gestational diabetes or preeclampsia, according to a study in BMJ.

Maria C Magnus, PhD, from the Medical Research Council Integrative Epidemiology Unit at the University of Bristol in the United Kingdom, and colleagues sought to investigate the causal effect of 25-hydroxyvitamin D level on pregnancy-related hypertensive disorders. Patient information included in the analysis — such as antenatal 25-hydroxyvitamin D levels, pre-eclampsia, and gestational hypertension — was elicited from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n= 4066) and the Generation R Study (n=3323). Women were excluded if they had multiple births, were of non-European ethnicity, and had a diagnosis of hypertension before pregnancy.

Serum (ALSPAC) and plasma (Generation R) levels of 25-hydroxyvitamin D were assessed during pregnancy using liquid chromatography-tandem mass spectrometry. The researchers categorized 25-hydroxyvitamin D levels by 10% decrease as well as by level (<25 nmol/L, 25-49.9 nmol/L, 50-74.9 nmol/L, and ≥75 nmol/L).

The researchers also conducted a 2-sample mendelian randomization analysis of preeclampsia using estimates of the associations between the genetic instruments and 25-hydroxyvitamin D l levels, and the associations between the genetic instruments and preeclampsia from 2 independent samples. The sample size included 3388 pre-eclampsia cases and 6059 control.

Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg on at least 2 separate readings first occurring after 20 week' gestation was indicative of a diagnosis of gestational hypertension; proteinuria (≥0.3 g/d) in the presence of gestational hypertension was indicative of pre-eclampsia.

Preeclampsia was associated with a relative risk of 1.03 (95% CI, 1.00-1.07) per 10% decrease in 25-hydroxyvitamin D level and 2.04 (95% CI, 1.02-4.07) for 25-hydroxyvitamin D levels <25 nmol/L vs ≥75 nmol/L.  There was no association identified between 25-hydroxyvitamin D level and risk for gestational hypertension.

The 1-sample analysis did not support a linear effect of a 10% decrease in 25-hydroxyvitamin D level and risk of gestational hypertension (odds ratio [OR], 0.90; 95% CI, 0.78-1.03) or preeclampsia (OR, 1.19; 95% CI, 0.92-1.52), respectively. The 2-sample mendelian randomization revealed pre-eclampsia to be associated with an OR of 0.98 (95% CI, 0.89-1.07) per 10% decrease in 25-hydroxyvitamin D level, an OR of 0.96 (95% CI, 0.80-1.15) per unit increase in the log(odds) of a 25-hydroxyvitamin D level <75 nmol/L, and an OR of 0.93 (95% CI, 0.72-1.19) per unit increase in the log(odds) of a 25-hydroxyvitamin D level <50 nmol/L.

“A lower 25-hydroxyvitamin D level was weakly associated with a lower risk of gestational hypertension and higher risk of pre-eclampsia in the one sample mendelian randomisation analysis … [which] could indicate that the null association between 25-hydroxyvitamin D level and gestational hypertension in the multivariable analysis was influenced by unobserved confounding,” the researchers concluded. “No evidence was found of an association between 25-hydroxyvitamin D level and pre-eclampsia in the larger two sample mendelian randomization.”

Reference

Magnus MC, Miliku K, Bauer A, et al. Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study [published online June 20, 2018]. BMJ. doi: 10.1136/bmj.k2167

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