University of Oulu

Monangi N, Xu H, Khanam R, et al. Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis. BMJ Global Health 2021;6:e005856

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

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Author: Monangi, Nagendra1,2,3,4; Xu, Huan2,3,5; Khanam, Rasheda6;
Organizations: 1Cincinnati Childrens Hosp Med Ctr, Div Neonatol, Cincinnati, OH 45229 USA.
2Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Ctr Prevent Preterm Birth, Cincinnati, OH 45229 USA.
3March Dimes Prematur Res Ctr Ohio Collaborat, Cincinnati, OH 45229 USA.
4Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA.
5Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.
6Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Int Hlth, Baltimore, MD USA.
7Aga Khan Univ, Dept Pediat & Child Hlth, Fac Hlth Sci, Biorepository & Omics Res Grp,Med Coll, Karachi, Sindh, Pakistan.
8Ctr Publ Hlth Kinet, New Delhi, India.
9Ctr Publ Hlth Kinet, Publ Hlth Lab, Div Res, Chake Chake, Tanzania.
10Int Ctr Diarrhoeal Dis Res, Maternal & Child Hlth Div, Dhaka, Bangladesh.
11Univ N Carolina, Obstet & Gynecol, Chapel Hill, NC 27515 USA.
12Univ Oxford, Nuffield Dept Womens & Reprod Hlth, INTERBIO 21st Study Consortium, Oxford, England.
13Int Ctr Diarrhoeal Dis Res, Nutr & Clin Serv Div, Dhaka, Bangladesh.
14Tampere Univ, Fac Med & Hlth Technol, Ctr Child Hlth Res, Tampere, Pirkanmaa, Finland.
15Benh Vien Tu Du, Ho Chi Minh City, Vietnam.
16Univ Liverpool, Dept Womens & Childrens Hlth, Liverpool, Merseyside, England.
17Univ Cincinnati, Dept Chem, Cincinnati, OH USA.
18Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Medford, MA 02155 USA.
19Hosp Sick Children, Dept Paediat, Toronto, ON, Canada.
20USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
21Projahnmo Res Fdn, Dhaka, Bangladesh.
22Univ Zambia, Sch Med, Lusaka, Zambia.
23Univ Zambia, Sch Publ Hlth, Lusaka, Zambia.
24ICDDR, Cardiol, Dhaka, Bangladesh.
25Univ Tampere, Tampere, Pirkanmaa, Finland.
26Univ Malawi, Coll Med, Sch Publ Hlth, Blantyre, Malawi.
27Univ Oulu, PEDEGO Res Unit, Med Res Ctr Oulu, Oulu, Pohjois Pohjanm, Finland.
28Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
29Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
30Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
31Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
32WHO, Dept Med, Geneva, Switzerland.
33Global Alliance Prevent Prematur & Stillbirth, Lynnwood, WA USA.
34Univ Liverpool, Div Perinatal Med, Liverpool, Merseyside, England.
35Univ Tampere, Fac Med & Hlth Technol, Ctr Child Hlth Res, Tampere, Pirkanmaa, Finland.
36Tampere Univ Hosp, Dept Pediat, Tampere, Finland.
37Johns Hopkins Univ, Int Ctr Maternal & Newborn Hlth, Dept Int Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
38Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England.
39North Carolina State Univ, Dept Biol Sci, Raleigh, NC USA.
40North Carolina State Univ, Ctr Human Hlth & Enivironm, Raleigh, NC USA.
41Aga Khan Univ, Dept Pediat & Child Hlth, Karachi, Pakistan.
42Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA.
43Burroughs Wellcome Fund, Res Triangle Pk, NC USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.1 MB)
Persistent link:
Language: English
Published: BMJ, 2021
Publish Date: 2021-10-05


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.

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Series: BMJ global health
ISSN: 2059-7908
ISSN-E: 2059-7908
ISSN-L: 2059-7908
Volume: 6
Issue: 9
Article number: e005856
DOI: 10.1136/bmjgh-2021-005856
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: This work was supported by the Bill & Melinda Gates Foundation. The funders did not have any role in study design, data analysis, data interpretation, writing of the report or submission for publication. The findings and conclusions of this article are solely the responsibility of the authors. Bill & Melinda Gates Foundation (OPP1175128, OPP1152451). Funders: GZ is supported by the March of Dimes Prematurity Research Center Ohio Collaborative and by the Burroughs Wellcome Fund Outcomes of Pregnancy (CPPOP): UCSF California Preterm Birth Initiative. NEST: National Institute of Environmental Health Sciences (R21ES014947, R01ES016772, P30ES025128 and P01ES022831), the US Environmental Protection Agency (RD-83543701), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK085173) and the Duke Cancer Institute. iLiNS-DYAD-M trial is funded by a grant to the University of California, Davis from the Bill & Melinda Gates Foundation (OPP49817). A grant to the University of California, Davis from the Office of Health, Infectious Diseases and Nutrition, Bureau for Global Health, US Agency for International Development (USAID) under terms of Cooperative Agreement No. AID-OAA-A-12-00005 through the Food and Nutrition Technical Assistance III Project (FANTA), managed by FHI 360. The Global Alliance to Prevention of Prematurity and Stillbirth (GAPPS) Biorepository Programme funded by the Preventing Preterm Birth Initiative grant from the Bill & Melinda Gates Foundation (OPP1033514). MDIG trial funded by The Bill & Melinda Gates Foundation (OPP1066764).
Copyright information: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: