Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis

Abstract

BackgroundSelenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.MethodsGestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis.FindingsIn all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi.InterpretationWhile our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.

Genetics, epigenetics, and transcriptomics of preterm birth

“…132 In a worldwide study of 9946 singleton live births from 17 geographically diverse locations, statistically significant associations between maternal Se concentration and sPTB at some sites were observed. 133 However, this finding was not generalizable across the whole cohort and might lower the enthusiasm for the broad use of Se supplements as a general strategy to prevent sPTB. However, these results suggest there could be a potential benefit for certain high-risk, low-income geographic regions.…”

“…Though low plasma Se has been associated with sPTB risk, it was not found to be sufficiently predictive at individual patient level 132 . In a worldwide study of 9946 singleton live births from 17 geographically diverse locations, statistically significant associations between maternal Se concentration and sPTB at some sites were observed 133 . However, this finding was not generalizable across the whole cohort and might lower the enthusiasm for the broad use of Se supplements as a general strategy to prevent sPTB.…”

The Placental Epigenome as a Molecular Link Between Prenatal Exposures and Fetal Health Outcomes Through the DOHaD Hypothesis

“…Selenium is an essential metalloid element that humans are primarily exposed to through diet or occupational hazards. Se is an essential element and deficiencies have been linked to numerous adverse health outcomes including preterm birth and infant neurobehavior [ 33 , 54 ]. In both the New Hampshire Birth Cohort Study (NHBCS, N = 343) and Rhode Island Child Health Study (RICHS) ( N = 141), 8 differentially methylated CpG sites (FDR < 0.05) were associated with placental Se concentration.…”

The Role of Selenoprotein Tissue Homeostasis in MetS Programming: Energy Balance and Cardiometabolic Implications

“…An increase in gestational duration and a reduction in PTD were found associated with a higher Se intake during gestation, but not after Se supplementation, probably due to the fact that about half of the women had an optimal dietary Se intake. Monnagi et al (2021), in samples collected from different populations (17 international birth cohorts with diverse ethnic backgrounds and geographic distributions), analyzed the relationship among maternal Se concentrations during pregnancy with PTD risk and gestational duration [ 108 ]. In this study, the hypothesized mechanisms to link Se and PTD risk were attributed to the selenoproteins GPx3, SelP, and TXNRD, for their antioxidant and anti-inflammatory action.…”