Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis
Authors: Monangi Nagendra , Xu Huan , Khanam Rasheda , Khan Waqasuddin , Deb Saikat , Pervin Jesmin , Price Joan T ,   INTERBIO-21st Study Consortium, Kennedy Stephen H , Al Mahmud Abdullah , Fan Yuemei , Le Thanh Q , Care Angharad , Landero Julio A , Combs Gerald F , Belling Elizabeth , Chappell Joanne , Kong Fansheng , Lacher Criag , Ahmed Salahuddin , Chowdhury Nabidul Haque , Rahman Sayedur , Kabir Furqan , Nisar Imran , Hotwani Aneeta , Mehmood Usma , Nizar Ambreen , Khalid Javairia , Dhingra Usha , Dutta Arup , Ali Said , Aftab Fahad , Juma Mohammed Hamad , Rahman Monjur , Vwalika Bellington , Musonda Patrick , Ahmed Tahmeed , Islam Md Munirul , Ashorn Ulla , Maleta Kenneth , Hallman Mikko , Goodfellow Laura , Gupta Juhi K , Alfirevic Ana , Murphy Susan , Rand Larry , Ryckman Kelli K , Murray Jeffrey C , Bahl Rajiv , Litch James A , Baruch-Gravett Courtney , Alfirevic Zarko , Ashorn Per , Baqui Abdullah , Hirst Jane , Hoyo Cathrine , Jehan Fyezah , Jelliffe-Pawlowski Laura L , Rahman Anisur , Roth Daniel E , Sazawal Sunil , Stringer Jeffrey , Zhang Ge , Muglia Louis 
Published: September 2021

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.