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

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

Journal: BMJ global health 2021;6(9):e005856

PMID: 34518202

Abstract

BACKGROUND

Selenium (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.

METHODS

Gestational 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.

FINDINGS

In 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.

INTERPRETATION

While 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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Address: Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA [email protected] [email protected].; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.; Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Karachi, Sindh, Pakistan.; Center for Public Health Kinetics, New Delhi, India.; Research Division, Public Health Laboratory, Center for Public Health Kinetics, Chake Chake, Tanzania.; Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Dhaka District, Bangladesh.; Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; INTERBIO-21st Study Consortium, Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.; Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Dhaka District, Bangladesh.; Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Pirkanmaa, Finland.; Benh Vien Tu Du, Ho Chi Minh City, Viet Nam.; Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.; Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA.; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Medford, Massachusetts, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Grand Forks Human Nutrition Research Center, USDA ARS, Grand Forks, North Dakota, USA.; Projahnmo Research Foundation, Dhaka, Bangladesh.; Center for Public Health Kinetics, New Delhi, India.; Research Division, Public Health Laboratory, Center for Public Health Kinetics, Chake Chake, Tanzania.; Nutritional and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Dhaka District, Bangladesh.; School of Medicine, University of Zambia, Lusaka, Zambia.; School of Public Health, University of Zambia, Lusaka, Zambia.; Cardiology, ICDDR,B, Dhaka, Bangladesh.; Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh.; University of Tampere, Tampere, Pirkanmaa, Finland.; School of Public Health, University of Malawi College of Medicine, Blantyre, Malawi.; Medical Research Centre Oulu, PEDEGO Research Unit, University of Oulu, Oulu, Pohjois-Pohjanmaa, Finland.; Department of Women's and Children's Health, University of Liverpool, Liverpool, Merseyside, UK.; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA.; Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA.; Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.; Department of Medicine, World Health Organization, Geneva, Switzerland.; Global Alliance to Prevent Prematurity and Stillbirth, Lynnwood, Washington, USA.; Division of Perinatal Medicine, University of Liverpool, Liverpool, UK.; Center for Child Health Research, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Pirkanmaa, Finland.; Department of Pediatrics, Tampere University Hospital, Tampere, Finland.; International Center for Maternal and Newborn Health, Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.; Department of Biological Sciences and Center for Human Health and the Enivironment, North Carolina State University, Raleigh, North Carolina, USA.; Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, USA [email protected] [email protected].; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Burroughs Wellcome Fund, Research Triangle Park, North Carolina, USA.
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