{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:00:45Z","timestamp":1793127645240,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gansu Province Science and Technology Key R&D Special Plan","award":["17YF1FA108"],"award-info":[{"award-number":["17YF1FA108"]}]},{"DOI":"10.13039\/501100007764","name":"Lanzhou Science and Technology Bureau","doi-asserted-by":"publisher","award":["2019-RC-60"],"award-info":[{"award-number":["2019-RC-60"]}],"id":[{"id":"10.13039\/501100007764","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Health Qual Life Outcomes"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To evaluate the interaction of depression and anxiety with the development of recurrent pregnancy loss (RPL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A nested case\u2013control study involving 2558 participants was conducted with data from the prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, self-rating anxiety scale and self-rating depression scale were collected after each participant\u2019s first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent 2\u00a0years. All patients diagosed RPL were recruited as cases whilst a randomly selected group of women with only one miscarriage in the past were recruited as controls. The logistic regression and the interaction effects between anxiety and depression and RPL were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The prevalence of anxiety (n\u2009=\u2009325, 28.7% vs. n\u2009=\u2009278, 19.5%) and depression symptoms (n\u2009=\u2009550, 48.6% vs. n\u2009=\u2009589, 41.3%) for the 1132 RPL cases were higher than 1426 non-RPL controls (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). After adjusting for possible confounding variables, the odds ratio (OR) value, reflecting the multiplicative interaction, was 1.91 (95% CI 1.50\u20132.44,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) for cases with both anxiety and depression symptoms compared with the non-RPL group. The relative excess risk of interaction value, reflecting the additive interaction between anxiety and depression to RPL was 1.15 (95% CI 0.32\u20134.21). Moreover, the adjusted OR for RPL cases with mild anxiety and severe depression was 2.77 (95% CI 1.07\u201344.14,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), for RPL cases with severe anxiety and mild depression was 4.23 (95% CI 1.01\u201322.21,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), for RPL cases with severe anxiety and moderate depression was 4.34 (95% CI 1.03\u201321.28,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and for RPL cases with severe anxiety and severe depression was 5.95 (95% CI 1.09\u201345.09,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Either depression or anxiety alone could increase the risk of subsequent RPL. Anxiety and depression had a synergistic effect after the first miscarriage which increased the development of subsequent RPL disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12955-021-01703-1","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T06:03:50Z","timestamp":1615183430000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Anxiety and depression are risk factors for recurrent pregnancy loss: a nested case\u2013control study"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1476-5237","authenticated-orcid":false,"given":"Yanxia","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyin","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"1703_CR1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0140-6736(06)69204-0","volume":"368","author":"R Rai","year":"2006","unstructured":"Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601\u201311.","journal-title":"Lancet"},{"key":"1703_CR2","unstructured":"Embryology TESoHRa: recurrent pregnancy loss; 2017."},{"issue":"2","key":"1703_CR3","doi-asserted-by":"publisher","first-page":"hoy004","DOI":"10.1093\/hropen\/hoy004","volume":"2018","author":"R BenderAtik","year":"2018","unstructured":"ESHRE Guideline Group on RPL, BenderAtik R, Christiansen OB, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018;2018(2):hoy004.","journal-title":"Hum Reprod Open"},{"key":"1703_CR4","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12955-018-0982-z","volume":"16","author":"Z Tavoli","year":"2018","unstructured":"Tavoli Z, Mohammadi M, Tavoli A, Moini A, Effatpanah M, Khedmat L, Montazeri A. Quality of life and psychological distress in women with recurrent miscarriage: a comparative study. Health Qual Life Outcomes. 2018;16:150.","journal-title":"Health Qual Life Outcomes"},{"key":"1703_CR5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.psychres.2012.08.029","volume":"205","author":"E Toffol","year":"2013","unstructured":"Toffol E, Koponen P, Partonen T. Miscarriage and mental health: results of two population-based studies. Psychiatry Res. 2013;205:151\u20138.","journal-title":"Psychiatry Res"},{"key":"1703_CR6","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.4088\/JCP.v67n0819","volume":"67","author":"R Neugebauer","year":"2006","unstructured":"Neugebauer R, Kline J, Markowitz JC, Bleiberg KL, Baxi L, Rosing MA, Levin B, Keith J. Pilot randomized controlled trial of interpersonal counseling for subsyndromal depression following miscarriage. J Clin Psychiatry. 2006;67:1299\u2013304.","journal-title":"J Clin Psychiatry"},{"key":"1703_CR7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S0022-3999(03)00042-4","volume":"56","author":"PA Geller","year":"2004","unstructured":"Geller PA, Kerns D, Klier CM. Anxiety following miscarriage and the subsequentpregnancy: a review of the literature and future directions. J Psychosom Res. 2004;56:35\u201345.","journal-title":"J Psychosom Res"},{"issue":"3","key":"1703_CR8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1471-0528.2009.02427.x","volume":"117","author":"L Saraswat","year":"2010","unstructured":"Saraswat L, Bhattacharya S, Maheshwari A, Bhattacharya S. Maternal and perinatal outcome in women with threatened miscarriage in the first trimester: a systematic review. BJOG. 2010;117(3):245\u201357.","journal-title":"BJOG"},{"key":"1703_CR9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.12891\/ceog2070.2016","volume":"43","author":"XL Qu","year":"2016","unstructured":"Qu XL, Zhu WJ, Chen WQ, et al. Effect of pregnancy-specific stress on spontaneous preterm birth among Chinese people. Clin Exp Obstet Gynecol. 2016;43:103\u20138.","journal-title":"Clin Exp Obstet Gynecol"},{"key":"1703_CR10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1089\/jwh.2007.0505","volume":"17","author":"N Brier","year":"2008","unstructured":"Brier N. Grief following miscarriage: a comprehensive review of the literature. J Womens Health (Larchmt). 2008;17:451\u201364.","journal-title":"J Womens Health (Larchmt)"},{"issue":"3","key":"1703_CR11","first-page":"CD008679","volume":"3","author":"FA Murphy","year":"2012","unstructured":"Murphy FA, Lipp A, Powles DL. Follow-up for improving psychological well being for women after a miscarriage. Cochrane Database Syst Rev. 2012;3(3):CD008679.","journal-title":"Cochrane Database Syst Rev"},{"key":"1703_CR12","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1176\/ajp.143.11.1471","volume":"143","author":"WW Zung","year":"1986","unstructured":"Zung WW. Prevalence of clinically significant anxiety in a family practice setting. Am J Psychiatry. 1986;143:1471\u20132.","journal-title":"Am J Psychiatry"},{"key":"1703_CR13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1001\/archpsyc.1965.01720310065008","volume":"12","author":"WW Zung","year":"1965","unstructured":"Zung WW. A self-rating depression scale. Arch Gen Psychiatry. 1965;12:63\u201370.","journal-title":"Arch Gen Psychiatry"},{"key":"1703_CR14","unstructured":"\u6c6a\u5411\u4e1c: \u5fc3\u7406\u536b\u751f\u8bc4\u5b9a\u91cf\u8868\u624b\u518c. \u4e2d\u56fd\u5fc3\u7406\u536b\u751f\u6742\u5fd7\u793e; 1999."},{"key":"1703_CR15","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12978-016-0188-y","volume":"13","author":"YX Zhang","year":"2016","unstructured":"Zhang YX, Zhang XQ, Wang QR, Yuan YQ, Yang JG, Zhang XW, Li Q. Psychological burden, sexual satisfaction and erectile function in men whose partners experience recurrent pregnancy loss in China: a cross-sectional study. Reprod Health. 2016;13:73.","journal-title":"Reprod Health"},{"key":"1703_CR16","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s10654-005-7835-x","volume":"20","author":"T Andersson","year":"2005","unstructured":"Andersson T, Alfredsson L, Kallberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol. 2005;20:575\u20139.","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"1703_CR17","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.rbmo.2019.04.008","volume":"39","author":"A Youssef","year":"2019","unstructured":"Youssef A, Vermeulen N, Lashley EELO, Goddijn M, van der Hoorn MLP. Comparison and appraisal of (inter)national recurrent pregnancy loss guidelines. Reprod Biomed Online. 2019;39(3):497\u2013503.","journal-title":"Reprod Biomed Online."},{"key":"1703_CR18","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1016\/j.fertnstert.2008.12.048","volume":"93","author":"IH Lok","year":"2010","unstructured":"Lok IH, Yip AS, Lee DT, Sahota D, Chung TK. A 1-year longitudinal study of psychological morbidity after miscarriage. Fertil Steril. 2010;93:1966\u201375.","journal-title":"Fertil Steril"},{"key":"1703_CR19","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jpsychores.2007.04.004","volume":"63","author":"AV Nikcevic","year":"2007","unstructured":"Nikcevic AV, Kuczmierczyk AR, Nicolaides KH. The influence of medical and psychological interventions on women\u2019s distress after miscarriage. J Psychosom Res. 2007;63:283\u201390.","journal-title":"J Psychosom Res"},{"key":"1703_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0165-0327(99)00126-3","volume":"59","author":"CM Klier","year":"2000","unstructured":"Klier CM, Geller PA, Neugebauer R. Minor depressive disorder in the context of miscarriage. J Affect Disord. 2000;59:13\u201321.","journal-title":"J Affect Disord"},{"key":"1703_CR21","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1093\/humrep\/der441","volume":"27","author":"M Kagami","year":"2012","unstructured":"Kagami M, Maruyama T, Koizumi T, Miyazaki K, Nishikawa-Uchida S, Oda H, Uchida H, Fujisawa D, Ozawa N, Schmidt L, Yoshimura Y. Psychological adjustment and psychosocial stress among Japanese couples with a history of recurrent pregnancy loss. Hum Reprod. 2012;27:787\u201394.","journal-title":"Hum Reprod"},{"key":"1703_CR22","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1515\/jpm-2011-0313","volume":"40","author":"N Mevorach-Zussman","year":"2012","unstructured":"Mevorach-Zussman N, Bolotin A, Shalev H, Bilenko N, Mazor M, Bashiri A. Anxiety and deterioration of quality of life factors associated with recurrent miscarriage in an observational study. J Perinat Med. 2012;40:495\u2013501.","journal-title":"J Perinat Med"},{"key":"1703_CR23","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/humrep\/dev014","volume":"30","author":"AM Kolte","year":"2015","unstructured":"Kolte AM, Olsen LR, Mikkelsen EM, Christiansen OB, Nielsen HS. Depression and emotional stress is highly prevalent among women with recurrent pregnancy loss. Hum Reprod. 2015;30:777\u201382.","journal-title":"Hum Reprod"},{"key":"1703_CR24","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1093\/humrep\/dey362","volume":"34","author":"E Koert","year":"2019","unstructured":"Koert E, Malling GMH, Sylvest R, Krog MC, Kolte AM, Schmidt L, Nielsen HS. Recurrent pregnancy loss: couples\u2019 perspectives on their need for treatment, support and follow up. Hum Reprod. 2019;34:291\u20136.","journal-title":"Hum Reprod"},{"issue":"5","key":"1703_CR25","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1080\/02646838.2019.1578870","volume":"37","author":"S Ramakrishna","year":"2019","unstructured":"Ramakrishna S, Cooklin AR, Leach LS. Comorbid anxiety and depression: a community-based study examining symptomology and correlates during the postpartum period. J Reprod Infant Psychol. 2019;37(5):468\u201379.","journal-title":"J Reprod Infant Psychol."},{"issue":"Suppl1","key":"1703_CR26","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.1016\/S0049-3848(15)50446-5","volume":"135","author":"S Hoirisch-Clapauch","year":"2015","unstructured":"Hoirisch-Clapauch S, et al. Adverse obstetric and neonatal outcomes in women with mental disorders. Thromb Res. 2015;135(Suppl1):S60\u20133.","journal-title":"Thromb Res"},{"issue":"10","key":"1703_CR27","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1093\/humrep\/17.10.2580","volume":"17","author":"M Sugiura-Ogasawara","year":"2002","unstructured":"Sugiura-Ogasawara M, Furukawa TA, Nakano Y, Hori S, Aoki K, Kitamura T. Depression as a potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. Hum Reprod. 2002;17(10):2580\u20134.","journal-title":"Hum Reprod"},{"issue":"8","key":"1703_CR28","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1055\/s-0033-1357487","volume":"39","author":"AW Austin","year":"2013","unstructured":"Austin AW, Wissmann T, von K\u00e4nel R. Stress and hemostasis: an update. Semin Thromb Hemost. 2013;39(8):902\u201312.","journal-title":"Semin Thromb Hemost"}],"container-title":["Health and Quality of Life Outcomes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12955-021-01703-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12955-021-01703-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12955-021-01703-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T11:28:00Z","timestamp":1671535680000},"score":1,"resource":{"primary":{"URL":"https:\/\/hqlo.biomedcentral.com\/articles\/10.1186\/s12955-021-01703-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1703"],"URL":"https:\/\/doi.org\/10.1186\/s12955-021-01703-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-59392\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-59392\/v2","asserted-by":"object"}]},"ISSN":["1477-7525"],"issn-type":[{"value":"1477-7525","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]},"assertion":[{"value":"13 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval for this prospective cohort study was obtained from the Gansu Provincial Maternity and Child-care Hospital\u2019s Ethics Committee (File NO.:[2017] GSFY (16). The standard informed consent form and the confidentiality agreement for all participants were signed and preserved after they had been introduced to the purpose of the study and informed about their right to interrupt the interview at any time or decline to be interviewed without any future prejudice. The collected data were anonymous and could not be linked to any particular respondent. No payments were made for participation in the studies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}