Selenium and the risk of pre-eclampsia

There is a clear relationship between a pregnant woman’s selenium status and her risk of pre-eclampsia.   Observational studies show that low selenium status is associated with a greater risk of pre-eclampsia.  Studies of selenium supplementation have shown reduced incidence of pre-eclampsia [Xu].

What is pre-eclampsia?
Pre-eclampsia is a complex condition characterized by the onset, around week 20 of the pregnancy, of the following symptoms:

• abnormally high protein levels in the urine (indicating possible damage to the kidneys)
• systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg when measured twice with an interval of at least 4–6 hours and not more than 7 days apart [Uzan]
• severe headaches
• blurred vision
• decreased platelet levels in the blood [Mayo Clinic]

Pre-eclampsia seems to be caused by an abnormal development of the new blood vessels that are needed to carry blood to the placenta.  The new blood vessels are narrower than they should be, and they respond differently to hormonal signaling [Mayo Clinic].

Pre-eclampsia is a serious disorder in pregnancy; it can cause premature birth, death of the mother, or death of the child at and around the time of birth [Uzan].

Selenium supplementation and the risk of pre-eclampsia: a meta-analysis
In 2016, Dr. Xu and his colleagues reported the results of a meta-analysis of 13 observational studies with 1515 participants and 3 randomized controlled trials with 439 participants.

The combined results of the 3 randomized controlled studies showed a relative risk of 0.28 (confidence interval: 0.09 to 0.84) for pre-eclampsia in the selenium supplementation group.

Relative risk is the ratio of the risk in the selenium treatment group to the risk in the placebo group.  The 0.28 relative risk shows a strong protective effect for the selenium supplementation.  The confidence interval shows that the researchers were 95% confident that the population relative risk lies somewhere between 0.09 and 0.84.

Subtracting 0.28 from 1.0, we get 0.72, a relative risk reduction of 72% resulting from the use of selenium supplements as compared with placebo.  The true relative risk reduction most probably lies somewhere between 16% and 91%.  The point is, there was a significant reduction of the risk in the selenium supplementation groups in these three studies.

If the relative risk calculated for the 3 studies had been greater than 1.0, then we would have suspected that the selenium supplementation was harmful.  But the results of the meta-analysis show that selenium supplementation is significantly beneficial in reducing the risk of pre-eclampsia [Xu].  This is good news.

Individual studies of selenium supplementation and risk of pre-eclampsia
Let’s look at some of the interesting randomized, double-blind, placebo-controlled trials of supplementation with selenium and its effect on the risk of pre-eclampsia.

The Rayman study of selenium supplementation and risk of pre-eclampsia
In 2014, Professor Margaret P. Rayman and her colleagues reported the results of a study in which 230 first-time-pregnant women were randomly assigned to one of two study groups:

• a selenium treatment group receiving a 60-microgram selenium-enriched yeast tablet daily
• a placebo group receiving a matching placebo yeast tablet daily

The treatment began at 12 to 14 weeks of pregnancy and continued until the women gave birth.

The researchers measured the women’s whole-blood selenium concentrations at baseline and at 35 weeks.  They also measured the women’s plasma selenoprotein P concentrations at 35 weeks.

The whole-blood selenium concentrations of the pregnant women rose significantly in the selenium treatment group, and  the whole-blood selenium concentrations of the pregnant women in the placebo group declined significantly.  By week 35, the whole-blood selenium concentrations and the selenoprotein P concentrations in the women in the treatment group were significantly higher than the corresponding concentrations in the women in the placebo group [Rayman 2014].

The primary outcome in the study involved comparisons of the levels of a sFlt-1 protein in the blood that is known to disable the proteins that promote the growth and development of blood vessels.  Increased concentrations of the sFlt-1  protein are a bio-marker for the increased risk of pre-eclampsia.

At week 35, measurements of the concentrations of the sFlt-1 protein showed that the concentrations were significantly lower in the selenium treatment group than in the placebo group, connoting a reduced risk of pre-eclampsia [Rayman 2014].

The Tara study of selenium supplementation and risk of pre-eclampsia
In 2010, Dr. Tara, Dr. Rayman, and members of their research team reported the results of a study in which 166 first-time-pregnant women in their first trimester of pregnancy were assigned randomly to one of two study groups:

• a selenium treatment group taking 100 micrograms of a selenium-enriched yeast preparation daily
• a control group taking a matching placebo yeast tablet daily

The study continued until the women gave birth.  The researchers’ measurements showed that the serum selenium concentrations in the women in the treatment group increased significantly; the serum selenium concentrations in the women in the placebo group remained unchanged during the study.  The supplementation with selenium was not associated with any major side effects [Tara].

There were no cases of pre-eclampsia in the selenium treatment group; there were 3 cases of pre-eclampsia in the placebo group, suggesting that there may be an association between selenium supplementation and a lower frequency of pre-eclampsia.  Although the difference did not reach the level of statistical significance, it may be clinically significant [Tara].

The high-selenium yeast tablets and the matching placebo yeast tablets used in the Rayman and Tara studies were provided by the Danish pharmaceutical firm Pharma Nord.

The Han study of selenium supplementation and risk of pre-eclampsia
Dr. Han and a team of researchers studied the effect of selenium supplementation on 100 pregnant women with high-risk factors of pregnancy-induced high blood pressure.  The at-risk pregnant women were randomly assigned to one of two groups:

• a treatment group taking 100 micrograms of a natural dietetic selenium liquid daily
• a control group taking a similar placebo liquid daily

The pregnant women took their assigned supplements for 6 to 8 weeks during late pregnancy.  Their pre-natal care was the same regardless of the study group to which they had been assigned.

The study results showed that the selenium supplement increased significantly the blood selenium levels in the pregnant women in the treatment group while the blood selenium levels in the pregnant women in the control group decreased significantly during the period of pregnancy.

The selenium supplement prevented and decreased the incidence of pregnancy-induced high blood pressure and the incidence of pregnancy-associated edema [Han].

Summary: selenium supplementation and pre-eclampsia
In a review article, Professor Rayman, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK, has documented the following relevant relationships:

• Women who have first-trimester and/or recurrent miscarriages have significantly lower selenium status than do pregnant women who do not miscarry.
• Selenium intake and selenium status have both been linked to risk of pre-eclampsia.
• Pre-eclamptic women have significantly lower plasma and toenail selenium concentrations than do matched healthy pregnant women.
• Expanded plasma volume during pregnancy may account for some of the decline in selenium status, but systemic inflammation – associated with both miscarriage and with pre-eclampsia – is also likely to be a factor decreasing blood selenium levels [Rayman 2012].

The above-described randomized controlled trials of selenium supplementation and risk of pre-eclampsia show a beneficial health effect for pregnant women who have low selenium status.

Sources

Han, L., & Zhou, S. M. (1994). Selenium supplement in the prevention of pregnancy induced hypertension. Chinese Medical Journal, 107(11), 870-871.

Mayo Clinic. (2017). Preeclampsia.  Symptoms and Causes.  Retrieved from
http://www.mayoclinic.org/diseases-conditions/preeclampsia/symptoms-causes/dxc-20316143.

Rayman, M. P., Searle, E., Kelly, L., Johnsen, S., Bodman-Smith, K., Bath, S. C., & … Redman, C. G. (2014). Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial. The British Journal of Nutrition, 112(1), 99-111.

Rayman, M. P. (2012). Selenium and human health. Lancet (London, England), 379(9822), 1256-1268.

Tara, F., Maamouri, G., Rayman, M. P., Ghayour-Mobarhan, M., Sahebkar, A., Yazarlu, O., & Ferns, G. (2010). Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwanese Journal of Obstetrics & Gynecology, 49(2), 181-187.

Uzan, J., Carbonnel, M., Piconne, O., Asmar, R., & Ayoubi, J. (2011). Pre-eclampsia: pathophysiology, diagnosis, and management. Vascular Health and Risk Management, 7467-474.

Xu, M., Guo, D., Gu, H., Zhang, L., & Lv, S. (2016). Selenium and Preeclampsia: a Systematic Review and Meta-analysis. Biological Trace Element Research, 171(2), 283-292. doi:10.1007/s12011-015-0545-7.

Disclaimer: The information presented in this article is not intended as medical advice and should not be used as such.