Maternal selenium levels and whole genome screen in recurrent spontaneous preterm birth population: A nested case control study

Angharad G Care,Juhi K Gupta,Laura Goodfellow,Ge Zhang,Nagendra Monangi,Elizabeth Belling,Julio Landero,Joanne Chappell,Andrew Sharp,Ana Alfirevic,Bertram Müller-Myhsok,Louis J Muglia,Zarko Alfirevic

doi:10.1016/j.ejogrb.2021.08.015

Abstract

ObjectiveTo establish if low maternal selenium (Se) was associated with sPTB in women with recurrent sPTB and identify genetic link with maternal Se levels. DesignNested case-control study. SettingTertiary Maternity Hospital. PopulationPlasma and whole blood from pregnant women with history of early sPTB/PPROM < 34+0 and European ancestry were obtained at 20 weeks (range 15–24 weeks). ‘Cases’ were recurrent PTB/PPROM < 34+0 weeks and term (≥37+0) deliveries were classified as ‘high-risk controls.’ Women with previous term births and index birth ≥ 39 weeks were ‘low-risk controls’. MethodsMaternal plasma Se measured by ICP-MS was used as a continuous phenotype in a GWAS analysis. Se was added to a logistic regression model using PTB predictor variables. Main outcome measuresMaternal Se concentration, recurrent early sPTB/PPROM. Results53/177 high-risk women had a recurrent sPTB/PPROM < 34+0weeks and were 2.7 times more likely to have a Se level < 83.3 ppm at 20weeks of pregnancy compared with low-risk term controls (n = 179), (RR 2.7, 95%CI 1.5–4.8; p = .001). One SNP from a non-coding region (FOXN3 intron variant, rs55793422) reached genome-wide significance level (p = 3.73E−08). Targeted analysis of Se gene variant did not show difference between preterm and term births. (χ2 test, OR = 0.95; 95%CI = 0.59–1.56; p = 0.82). When Se levels were added to a clinical prediction model, only an additional 5% of cases (n = 3) and 0.6% (n = 1) of controls were correctly identified. ConclusionsLow plasma Se is associated with sPTB risk but is not sufficiently predictive at individual patient level. We did not find a genetic association between maternal Se levels and Se-related genes.

Highlights

Selenium (Se) is of importance to human wellbeing through its incorporation into numerous selenoproteins involved in antioxidant, anti-inflammatory and anti-apoptotic functions [1]
Women with early spon-taneous preterm birth (sPTB)/prelabour rupture of membranes (PPROM) had a lower median Se level (73 ppm) than either the high-risk control group (78.7 ppm) or the low-risk controls (83.3 ppm). (Fig. 2) Participants with recurrent sPTB were 2.7 times more likely to have a Se level below median at 20 weeks of pregnancy (RR 2.7, 95% confidence intervals (CI) 1.5–4.8; p = .001)
This is the first genome wide association study (GWAS) study that used maternal Se levels as continuous data linked with PTB and investigates a recurrent sPTB population

Summary

Objective

To establish if low maternal selenium (Se) was associated with sPTB in women with recurrent sPTB and identify genetic link with maternal Se levels. ‘Cases’ were recurrent PTB/ PPROM < 34+0 weeks and term (!37+0) deliveries were classified as ‘high-risk controls.’. Results: 53/177 high-risk women had a recurrent sPTB/PPROM < 34+0weeks and were 2.7 times more likely to have a Se level < 83.3 ppm at 20weeks of pregnancy compared with low-risk term controls (n = 179), (RR 2.7, 95%CI 1.5–4.8; p = .001). When Se levels were added to a clinical prediction model, only an additional 5% of cases (n = 3) and 0.6% (n = 1) of controls were correctly identified. Conclusions: Low plasma Se is associated with sPTB risk but is not sufficiently predictive at individual patient level.

Introduction

Methods

Study participants

Strengths and limitations

Results in context

Conclusions