Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial

Margaret P Rayman,Christopher W G Redman,Katherine Bodman-Smith,Sigurd Johnsen,Elizabeth Searle,Sarah C Bath,Lynne Kelly,Jinyuan Mao

doi:10.1017/s0007114514000531

Margaret P Rayman, Christopher W G Redman + Show 6 more

Open Access

https://doi.org/10.1017/s0007114514000531

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Abstract

Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 μg/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.

Highlights

Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality
The oxidatively stressed syncytiotrophoblast responds by the increased release of two anti-angiogenic factors – soluble vascular endothelial growth factor receptor-1 and soluble endoglin – into the maternal circulation that oppose the actions of vascular endothelial growth factor and placental
When the two outcomes were combined on the basis that there may be some continuity between the conditions(60 – 63), and when the analyses were adjusted for baseline Se concentration and haematocrit, Se treatment significantly reduced the odds of having either pre-eclampsia or pregnancy-induced hypertension (PIH) in all participants and with near significance in those in the bottom third of Se status at baseline (Table 6), with large treatment effects

Summary

Ethics statement

The present study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects were approved by the Milton Keynes Research Ethics Committee (REC reference no. 08/ H0603/46).

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