BACKGROUND AND PURPOSE: 

• Vitamin D, 1,25-dihydroxyvitamin D3 (Vitamin D) can suppress renin biosynthesis and regulate implantation
  • Therefore, may impact gestational hypertension and/or preeclampsia   
• Previous literature on the relationship between low Vitamin D concentration and gestational hypertension/preeclampsia is inconclusive 
•  ‘Mendelian randomization’ is a technique that assesses genetic variants that impact pathways  
  • Genetic variants are random events at the time of conception, not likely to be impacted by bias
• Magnus et al. (BMJ 2018) sought to determine whether low Vitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia using knowledge of genetic variants that impact Vitamin D pathways

METHODS: 

• One and two sample mendelian randomization analysis  
  • Such analyses can be used to determine possible causal relationships  
• ‘One Sample’ mendelian randomization analysis  
  • Assesses the genetic variants along the vitamin D pathway and outcomes (gestational hypertension and preeclampsia) in the same individual 
• ‘Two Sample’ mendelian randomization analysis 
  • Results from genome studies are used to determine how the variants impact Vitamin D levels and assess whether variants that result in lower Vitamin D levels are associated with higher risk for gestational hypertension or preeclampsia  
• Vitamin D levels were measured in serum and plasma, and adjusted based on seasons and categorized based on Endocrine Society recommendations  
  • < 25 nmol/L | 25-49.9 nmol/L | 50-74.9 nmol/L | ≥75 nmol/L 
• Primary outcomes  
  • Gestational hypertension  
  • Preeclampsia  
• Definitions of preeclampsia and gestational hypertension were based on International Society for the Study of Hypertension in Pregnancy criteria

RESULTS: 

• One sample analysis 
  • 7389 women were included  
    • 751 with gestational hypertension  
    • 135 with pre-eclampsia 
• Two sample analysis  
  • 3388 preeclampsia cases 
  • 6059 controls  

In the conventional multivariable analysis comparing Vit D levels to outcomes  

• Pre-eclampsia 
  • Vitamin D levels <25 nmol/L compared with ≥75 nmol/L  
    • RR 2.04 (95% CI, 1.02 to 4.07)  
  • Gestational hypertension: No association  

One sample mendelian randomization analysis (using total genetic risk score) 

• There was no strong evidence for a linear effect (increase or decrease) of Vitamin D on the risk of gestational hypertension or pre-eclampsia 

Two sample mendelian randomization analysis 

• Preeclampsia: Odds ratio (OR) 0.98 (95% CI, 0.89 to 1.07) per 10% decrease in Vitamin D level 
• Nor was there evidence of a causal linear effect

CONCLUSION: 

• The authors did not “find any appreciable evidence of a causal effect of Vitamin D levels less than 75 nmol/L or less than 50 nmol/L on the risk of pre-eclampsia” 
• These results support the WHO guidance that currently, there is insufficient evidence to warrant vitamin D supplementation to prevent adverse pregnancy outcomes  
• Future studies are needed with larger number of women and more genetic instruments 
  • RCTs can assess the effect of supplements at particularly critical periods in time (e.g. around conception)

Learn More – Primary Sources: 

Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study

Related ObG Topics:

Does Vitamin D Intake Decrease the Risk for Gestational Diabetes Mellitus?

Vitamin D Levels: Is There an Association with Livebirth and/or Miscarriage

Are Vitamin D Levels Linked to Preeclampsia and Preterm Birth?

(Cochrane 2016) Vitamin D During Pregnancy and Adverse Pregnancy Outcomes

Does Vitamin D Decrease Risk of Respiratory Infections?