{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:57:55Z","timestamp":1775159875240,"version":"3.50.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0166892","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T19:40:09Z","timestamp":1480362009000},"page":"e0166892","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["No Association between TNF-\u03b1 -308G\/A Polymorphism and Idiopathic Recurrent Miscarriage: A Systematic Review with Meta-Analysis and Trial Sequential Analysis"],"prefix":"10.1371","volume":"11","author":[{"given":"Jiashu","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gechen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengzhang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolan","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengming","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,11,28]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198807283190401","article-title":"Incidence of early loss of pregnancy","volume":"319","author":"AJ Wilcox","year":"1988","journal-title":"New England Journal of Medicine"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0140-6736(80)91991-1","article-title":"Fetal loss after implantation: a prospective study","volume":"316","author":"J Miller","year":"1980","journal-title":"The Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1136\/bmj.320.7251.1708","article-title":"Maternal age and fetal loss: population based register linkage study","volume":"320","author":"MN Andersen A-","year":"2000","journal-title":"Bmj"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1093\/humrep\/17.6.1649","article-title":"Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study","volume":"17","author":"E de La Rochebrochard","year":"2002","journal-title":"Human Reproduction"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1192\/bjp.155.6.810","article-title":"The psychiatric consequences of spontaneous abortion","volume":"155","author":"T Friedman","year":"1989","journal-title":"The British Journal of Psychiatry"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/01.gco.0000194112.86051.26","article-title":"Recurrent miscarriage: pathophysiology and outcome","volume":"17","author":"B Carrington","year":"2005","journal-title":"Current Opinion in Obstetrics and Gynecology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0140-6736(90)92159-F","article-title":"Recurrent miscarriage I: definition and epidemiology","volume":"336","author":"GM Stirrat","year":"1990","journal-title":"The Lancet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0140-6736(06)69204-0","article-title":"Recurrent miscarriage","volume":"368","author":"R Rai","year":"2006","journal-title":"The Lancet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1093\/humrep\/14.11.2868","article-title":"A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage","volume":"14","author":"S Brigham","year":"1999","journal-title":"Human Reproduction"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/00001648-199009000-00008","article-title":"Risk factors for early pregnancy loss","volume":"1","author":"AJ Wilcox","year":"1990","journal-title":"Epidemiology"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2741\/2737","article-title":"Cytokine imbalance in pregnancy complications and its modulation","volume":"13","author":"R Raghupathy","year":"2008","journal-title":"Front Biosci"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1093\/humrep\/16.10.2219","article-title":"Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions","volume":"16","author":"M Makhseed","year":"2001","journal-title":"Human Reproduction"},{"key":"ref13","first-page":"219","author":"R Raghupathy","year":"2001"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0165-0378(00)00060-7","article-title":"Cytokine network at the feto-maternal interface","volume":"47","author":"S Saito","year":"2000","journal-title":"Journal of reproductive immunology"},{"key":"ref15","first-page":"64","article-title":"Immunology of Gametes and Embryo Implantation","author":"J Kwak-Kim","year":"2005"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ejogrb.2005.03.008","article-title":"Th1\/Th2 cytokines balance\u2014yin and yang of reproductive immunology. European Journal of Obstetrics &amp;","volume":"122","author":"JR Wilczy\u0144ski","year":"2005","journal-title":"Gynecology and Reproductive Biology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0092-8674(01)00237-9","article-title":"The TNF and TNF receptor superfamilies: integrating mammalian biology","volume":"104","author":"RM Locksley","year":"2001","journal-title":"Cell"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF02390365","article-title":"Determination of tumor necrosis factor alpha (TNF\u03b1) and Interleukin 2 (IL2) in women with idiopathic recurrent miscarriage","volume":"249","author":"P Mallmann","year":"1991","journal-title":"Archives of gynecology and obstetrics"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"485","DOI":"10.4049\/jimmunol.174.1.485","article-title":"TNF-\u03b1 is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss","volume":"174","author":"J Berman","year":"2005","journal-title":"The Journal of Immunology"},{"key":"ref20","doi-asserted-by":"crossref","DOI":"10.1155\/MI\/2006\/30485","article-title":"Elevated circulating IL-1\u03b2 and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome","volume":"2006","author":"N Vitoratos","year":"2006","journal-title":"Mediators of inflammation"},{"issue":"9","key":"ref21","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.cca.2011.01.002","article-title":"Cytokines in recurrent pregnancy loss","volume":"412","author":"V Saini","year":"2011","journal-title":"Clinica chimica acta"},{"issue":"8","key":"ref22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0143-4004(05)80184-5","article-title":"Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts","volume":"15","author":"J Yui","year":"1994","journal-title":"Placenta"},{"issue":"2","key":"ref23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.placenta.2008.10.012","article-title":"Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium","volume":"30","author":"S Haider","year":"2009","journal-title":"Placenta"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1073\/pnas.94.7.3195","article-title":"Effects of a polymorphism in the human tumor necrosis factor \u03b1 promoter on transcriptional activation","volume":"94","author":"AG Wilson","year":"1997","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"ref25","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/1097-0029(20000801)50:3<216::AID-JEMT5>3.0.CO;2-Q","article-title":"TNF-\u03b1 gene polymorphism: clinical and biological implications","volume":"50","author":"AH Hajeer","year":"2000","journal-title":"Microscopy research and technique"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1600-0897.2008.00602.x","article-title":"Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review","volume":"60","author":"YK Choi","year":"2008","journal-title":"Am J Reprod Immunol"},{"issue":"1\/2","key":"ref27","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/09723757.2008.11886033","article-title":"Immuno-molecular etiology of recurrent pregnancy loss and the anthropological perspective","volume":"8","author":"GK Walia","year":"2008","journal-title":"International Journal of Human Genetics"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0165-0378(01)00069-9","article-title":"Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss","volume":"51","author":"SJ Babbage","year":"2001","journal-title":"J Reprod Immunol"},{"issue":"1","key":"ref29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.8755-8920.2001.450106.x","article-title":"The carriage of pro-inflammatory cytokine gene polymorphisms in recurrent pregnancy loss","volume":"45","author":"JG Reid","year":"2001","journal-title":"Am J Reprod Immunol"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jri.2003.12.001","article-title":"Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women","volume":"61","author":"D Pietrowski","year":"2004","journal-title":"J Reprod Immunol"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jri.2005.01.008","article-title":"Cytokine gene polymorphisms and susceptibility to recurrent pregnancy loss in Iranian women","volume":"65","author":"E Kamali-Sarvestani","year":"2005","journal-title":"J Reprod Immunol"},{"issue":"2","key":"ref32","first-page":"95","article-title":"Assessment of five thrombophilic genetic polymorphisms among couples with habitual abortion","volume":"142","author":"A Quintero-Ramos","year":"2006","journal-title":"Gac Med Mex"},{"issue":"5","key":"ref33","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.fertnstert.2008.01.090","article-title":"Tumor necrosis factor alpha and lymphotoxin alpha haplotypes in idiopathic recurrent pregnancy loss","volume":"91","author":"W Zammiti","year":"2009","journal-title":"Fertil Steril"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1477-7827-8-114","article-title":"Association between -238 but not -308 polymorphism of Tumor necrosis factor alpha (TNF-alpha)v and unexplained recurrent spontaneous abortion (URSA) in Chinese population","volume":"8","author":"C Liu","year":"2010","journal-title":"Reprod Biol Endocrinol"},{"issue":"7","key":"ref35","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/1933719110366603","article-title":"TNFA gene promoter polymorphisms and susceptibility to recurrent pregnancy loss in Italian women","volume":"17","author":"R Palmirotta","year":"2010","journal-title":"Reprod Sci"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cyto.2012.05.018","article-title":"Association of CTLA-4 and TNF-alpha polymorphism with recurrent miscarriage among North Indian women","volume":"60","author":"R Gupta","year":"2012","journal-title":"Cytokine"},{"issue":"5","key":"ref37","first-page":"484","article-title":"The relationship between cytokine gene polymorphism and unexplained recurrent spontaneous abortion in Saudi females","volume":"34","author":"AF Alkhuriji","year":"2013","journal-title":"Saudi Med J"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1177\/1933719112459237","article-title":"Tumor necrosis factor-alpha gene polymorphisms in Korean patients with recurrent spontaneous abortion","volume":"20","author":"BE Lee","year":"2013","journal-title":"Reprod Sci"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jri.2009.12.005","article-title":"Tumor necrosis factor-alpha polymorphisms in women with idiopathic recurrent miscarriage","volume":"84","author":"RR Finan","year":"2010","journal-title":"J Reprod Immunol"},{"issue":"2","key":"ref40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4103\/0974-1208.86090","article-title":"Recurrent pregnancy loss: TNF-alpha and IL-10 polymorphisms","volume":"4","author":"A Kaur","year":"2011","journal-title":"J Hum Reprod Sci"},{"issue":"6","key":"ref41","first-page":"9786","article-title":"Relationship between cytokine gene polymorphisms and recurrent spontaneous abortion","volume":"8","author":"RX Liu","year":"2015","journal-title":"Int J Clin Exp Med"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4103\/0974-1208.183516","article-title":"Association of tumor necrosis factor-alpha 308G\/A polymorphism with recurrent miscarriages in women","volume":"9","author":"N Sudhir","year":"2016","journal-title":"Journal of Human Reproductive Sciences"},{"issue":"3","key":"ref43","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1530\/REP-07-0322","article-title":"Associations between tumor necrosis factor-alpha and lymphotoxin-alpha polymorphisms and idiopathic recurrent miscarriage","volume":"135","author":"W Zammiti","year":"2008","journal-title":"Reproduction"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1046\/j.1365-2249.2001.01663.x","article-title":"Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes","volume":"126","author":"N Baxter","year":"2001","journal-title":"Clin Exp Immunol"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0165-0378(02)00059-1","article-title":"Associations between cytokine gene polymorphisms and recurrent pregnancy loss","volume":"58","author":"S Daher","year":"2003","journal-title":"J Reprod Immunol"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1600-0897.2004.00179.x","article-title":"Cytokine gene polymorphisms in recurrent pregnancy loss of unknown cause","volume":"52","author":"N Prigoshin","year":"2004","journal-title":"Am J Reprod Immunol"},{"issue":"3","key":"ref47","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1744-313X.2012.01155.x","article-title":"HLA class II polymorphisms and recurrent spontaneous abortion in a Southern Brazilian cohort","volume":"40","author":"EP Bompeixe","year":"2013","journal-title":"Int J Immunogenet"},{"issue":"3","key":"ref48","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1472-6483(10)60176-9","article-title":"Association between genetic polymorphisms in cytokine genes and recurrent miscarriage\u2014a meta-analysis","volume":"19","author":"I Medica","year":"2009","journal-title":"Reprod Biomed Online"},{"issue":"5","key":"ref49","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.humimm.2012.01.008","article-title":"Association of tumor necrosis factor-\u03b1 gene promoter polymorphisms (-308G\/A,-238G\/A) with recurrent spontaneous abortion: a meta-analysis","volume":"73","author":"B Zhang","year":"2012","journal-title":"Human immunology"},{"issue":"1","key":"ref50","first-page":"1","article-title":"Association of TNF-\u03b1 genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis","volume":"14","author":"H-H Li","year":"2016","journal-title":"Reproductive Biology and Endocrinology"},{"issue":"2","key":"ref51","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/aji.12467","article-title":"Association of Interleukin-10-1082A\/G Polymorphism with Idiopathic Recurrent Miscarriage: A Systematic Review and Meta-Analysis","volume":"75","author":"Z Peng","year":"2016","journal-title":"Am J Reprod Immunol"},{"issue":"8","key":"ref52","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.jclinepi.2008.08.010","article-title":"Updating meta-analyses leads to larger type I errors than publication bias","volume":"62","author":"GF Borm","year":"2009","journal-title":"J Clin Epidemiol"},{"issue":"3","key":"ref53","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jrsm.1104","article-title":"Trial sequential methods for meta-analysis","volume":"5","author":"E Kulinskaya","year":"2014","journal-title":"Res Synth Methods"},{"issue":"2","key":"ref54","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1684\/ecn.2011.0285","article-title":"Functional study of TNF-\u03b1 promoter polymorphisms: literature review and meta-analysis","volume":"22","author":"A Mekinian","year":"2011","journal-title":"European cytokine network"},{"issue":"5","key":"ref55","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/sj.gene.6364055","article-title":"Is there a future for TNF promoter polymorphisms?","volume":"5","author":"J Bayley","year":"2004","journal-title":"Genes and immunity"},{"issue":"2","key":"ref56","first-page":"187","article-title":"The Essentiality of Reporting Hardy-Weinberg Equilibrium Calculations in Population-Based Genetic Association Studies","volume":"17","author":"A Namipashaki","year":"2015","journal-title":"Cell J"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0166892","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T15:17:44Z","timestamp":1601219864000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0166892"}},"subtitle":[],"editor":[{"given":"Jefferson","family":"Terry","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,11,28]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2016,11,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0166892","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,28]]}}}