{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:27:11Z","timestamp":1789032431821,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01-HD086742"],"award-info":[{"award-number":["R01-HD086742"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01-HD105863"],"award-info":[{"award-number":["R01-HD105863"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n To what extent is perceived stress during preconception and pregnancy associated with miscarriage incidence?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n Perceived stress during early pregnancy, but not preconception, was associated with higher miscarriage incidence.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n Some studies have found that higher stress levels are associated with miscarriage risk. However, many of these studies were retrospective, focused on occupational stress only, and\/or suffered from under-ascertainment of miscarriage.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n Pregnancy Study Online (PRESTO) is an ongoing prospective preconception cohort study that recruited participants during 2013\u20132025. Eligible participants were females aged 21\u201345\u2009years, who resided in the USA or Canada and were trying to conceive without fertility treatments. Eligible partners were males aged \u226521\u2009years.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n We collected data on perceived stress using the 10-item version of the Perceived Stress Scale (PSS-10) during preconception (every 8\u2009weeks) and early pregnancy for female participants and during preconception only for male participants. We identified pregnancies and miscarriages on bimonthly follow-up questionnaires during preconception and additional questionnaires during early and late pregnancy and postpartum. We fit Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% CIs for the effect of preconception PSS-10 scores (n\u2009=\u200911\u00a0189 female and 2656 male participants) and early pregnancy PSS-10 scores (n\u2009=\u20098319 female participants) on miscarriage incidence, adjusting for potential confounders.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n About 20% of the pregnancies ended in miscarriage, with the loss occurring at a median of six gestational weeks. Preconception PSS-10 scores in the female or male partner were not appreciably associated with miscarriage incidence. Female PSS-10 scores during gestational weeks 5\u20138 were strongly associated with higher miscarriage incidence: adjusted HRs for PSS-10 scores of 10\u201314, 15\u201319, 20\u201324, and \u226525 vs &lt;10 in gestational weeks 5\u20138 were 1.38 (95% CI: 1.07, 1.77), 1.17 (95% CI: 0.89, 1.52), 1.35 (95% CI: 1.00, 1.83), and 2.05 (95% CI: 1.40, 2.99), respectively. In week-specific analyses, an association existed during weeks 4\u20138 and peaked at week 7.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n Our results may be susceptible to reverse causation, unmeasured confounding by nausea and vomiting in pregnancy, and exposure misclassification.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n Interventions aimed at decreasing stress during early pregnancy may be effective at reducing miscarriage incidence, but confirmation of our results in randomized studies is warranted.<\/jats:p>\n <\/jats:sec>\n \n STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD086742, R01-HD105863). Lauren Wise has received in-kind donations for primary data collection in PRESTO from ChartNeo.com. The other authors have no conflicts to report.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/deaf243","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:32:27Z","timestamp":1770726747000},"page":"606-615","source":"Crossref","is-referenced-by-count":1,"title":["A prospective study of periconceptional perceived stress and rate of miscarriage"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3929-4451","authenticated-orcid":false,"given":"Amelia K","family":"Wesselink","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-0761","authenticated-orcid":false,"given":"Ruth J","family":"Geller","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-6404","authenticated-orcid":false,"given":"Sharonda M","family":"Lovett","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael I","family":"Nillni","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Boston University Chobanian and Avedisian School of Medicine , Boston, MA,","place":["USA"]},{"name":"National Center for PTSD, Women\u2019s Health Sciences Division, Veteran\u2019s Administration Boston Healthcare System , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Savitz","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Brown University School of Public Health , Providence, RI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J","family":"Rothman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-3752","authenticated-orcid":false,"given":"Lauren A","family":"Wise","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"2026040814593386900_deaf243-B1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3389\/fpsyg.2020.00787","article-title":"Effect of psychotherapy on reduction of fear of childbirth and pregnancy stress: a randomized controlled trial","volume":"11","author":"Abdollahi","year":"2020","journal-title":"Front Psychol"},{"key":"2026040814593386900_deaf243-B2","first-page":"e110","article-title":"ACOG Practice Bulletin No. 10: management of stillbirth","volume":"135","author":"American College of Obstetricians and Gynecologists","year":"2020","journal-title":"Obstet Gynecol"},{"key":"2026040814593386900_deaf243-B3","doi-asserted-by":"crossref","first-page":"e0166133","DOI":"10.1371\/journal.pone.0166133","article-title":"Associations between nausea, vomiting, fatigue and health-related quality of life of women in early pregnancy: the Generation R Study","volume":"11","author":"Bai","year":"2016","journal-title":"PLoS One"},{"key":"2026040814593386900_deaf243-B4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.fertnstert.2016.03.009","article-title":"Lifestyle and pregnancy loss in a contemporary cohort of women recruited before conception: the LIFE study","volume":"106","author":"Buck Louis","year":"2016","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B5","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1093\/humrep\/deq260","article-title":"Severity and duration of nausea and vomiting symptoms in pregnancy and spontaneous abortion","volume":"25","author":"Chan","year":"2010","journal-title":"Hum Reprod"},{"key":"2026040814593386900_deaf243-B6","doi-asserted-by":"crossref","first-page":"229","DOI":"10.7326\/0003-4819-129-3-199808010-00012","article-title":"Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications","volume":"129","author":"Chrousos","year":"1998","journal-title":"Ann Intern Med"},{"key":"2026040814593386900_deaf243-B7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2307\/2136404","article-title":"A global measure of perceived stress","volume":"24","author":"Cohen","year":"1983","journal-title":"J Health Soc Behav"},{"key":"2026040814593386900_deaf243-B8","first-page":"31","volume-title":"The Social Psychology of Health: Claremont Symposium on Applied Social Psychology","author":"Cohen","year":"1988"},{"key":"2026040814593386900_deaf243-B9","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/humupd\/dmaa010","article-title":"Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis","volume":"26","author":"Du Fosse","year":"2020","journal-title":"Hum Reprod Update"},{"key":"2026040814593386900_deaf243-B10","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.fertnstert.2017.07.008","article-title":"Semen quality and pregnancy loss in a contemporary cohort of couples recruited before conception: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study","volume":"108","author":"Eisenberg","year":"2017","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B11","volume-title":"Pregnancy Loss (Before 20 Weeks of Pregnancy)","author":"Eunice K. Shriver National Institute of Child Health and Human Development","year":"2025"},{"key":"2026040814593386900_deaf243-B12","doi-asserted-by":"crossref","first-page":"367.e1","DOI":"10.1016\/j.ajog.2019.10.102","article-title":"Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study","volume":"222","author":"Farren","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"2026040814593386900_deaf243-B13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s12888-021-03283-2","article-title":"Effect of cognitive behavioral therapy-based counseling on perceived stress in pregnant women with history of primary infertility: a controlled randomized clinical trial","volume":"21","author":"Golshani","year":"2021","journal-title":"BMC Psychiatry"},{"key":"2026040814593386900_deaf243-B14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/EDE.0000000000001303","article-title":"Male preconception marijuana use and spontaneous abortion: a prospective cohort study","volume":"32","author":"Harlow","year":"2021","journal-title":"Epidemiology"},{"key":"2026040814593386900_deaf243-B15","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/aje\/kwh259","article-title":"Alcohol consumption at the time of conception and spontaneous abortion","volume":"160","author":"Henriksen","year":"2004","journal-title":"Am J Epidemiol"},{"key":"2026040814593386900_deaf243-B16","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1001\/jamainternmed.2016.5641","article-title":"Association of nausea and vomiting during pregnancy with pregnancy loss: a secondary analysis of a randomized clinical trial","volume":"176","author":"Hinkle","year":"2016","journal-title":"JAMA Intern Med"},{"key":"2026040814593386900_deaf243-B17","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.fertnstert.2014.04.021","article-title":"Effects of work and life stress on semen quality","volume":"102","author":"Janevic","year":"2014","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B18","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.rbmo.2021.04.018","article-title":"Meditation and mindfulness reduce perceived stress in women with recurrent pregnancy loss: a randomized controlled trial","volume":"43","author":"Jensen","year":"2021","journal-title":"Reprod Biomed Online"},{"key":"2026040814593386900_deaf243-B19","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.fertnstert.2010.05.048","article-title":"Human chorionic gonadotropin confers resistance to oxidative stress-induced apoptosis in decidualizing human endometrial stromal cells","volume":"95","author":"Kajihara","year":"2011","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0015-0282(16)59660-5","article-title":"Predictive value of abnormal sperm morphology in in vitro fertilization","volume":"49","author":"Kruger","year":"1988","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.anr.2012.08.004","article-title":"Review of the psychometric evidence of the perceived stress scale","volume":"6","author":"Lee","year":"2012","journal-title":"Asian Nurs Res"},{"key":"2026040814593386900_deaf243-B22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000430341","article-title":"Psychological stress-derived prolactin modulates occludin expression in vaginal epithelial cells to compromise barrier function","volume":"37","author":"Li","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"2026040814593386900_deaf243-B23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.fertnstert.2007.06.018","article-title":"Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates","volume":"90","author":"Lin","year":"2008","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B24","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/humrep\/dey030","article-title":"Biomarkers of preconception stress and the incidence of pregnancy loss","volume":"33","author":"Lynch","year":"2018","journal-title":"Hum Reprod"},{"key":"2026040814593386900_deaf243-B25","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.fertnstert.2015.09.016","article-title":"Psychological stress and testicular function: a cross-sectional study of 1,215 Danish men","volume":"105","author":"Nordkap","year":"2016","journal-title":"Fertil Steril"},{"key":"2026040814593386900_deaf243-B26","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1111\/andr.12835","article-title":"Impact of psychological stress measured in three different scales on testis function: a cross-sectional study of 1362 young men","volume":"8","author":"Nordkap","year":"2020","journal-title":"Andrology"},{"key":"2026040814593386900_deaf243-B27","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":"Nybo Andersen","year":"2000","journal-title":"BMJ"},{"key":"2026040814593386900_deaf243-B28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jri.2009.10.011","article-title":"Stress in early pregnancy: maternal neuro-endocrine-immune responses and effects","volume":"85","author":"Parker","year":"2010","journal-title":"J Reprod Immunol"},{"key":"2026040814593386900_deaf243-B29","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/s41598-017-01792-3","article-title":"The association between psychological stress and miscarriage: a systematic review and meta-analysis","volume":"7","author":"Qu","year":"2017","journal-title":"Sci Rep"},{"key":"2026040814593386900_deaf243-B30","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss","volume":"397","author":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"2026040814593386900_deaf243-B31","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/humrep\/dew010","article-title":"Signs and symptoms associated with early pregnancy loss: findings from a population-based preconception cohort","volume":"31","author":"Sapra","year":"2016","journal-title":"Hum Reprod"},{"key":"2026040814593386900_deaf243-B32","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1093\/humrep\/deac172","article-title":"Prospectively assessed perceived stress associated with early pregnancy losses among women with history of pregnancy loss","volume":"37","author":"Schliep","year":"2022","journal-title":"Hum Reprod"},{"key":"2026040814593386900_deaf243-B33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000477707","article-title":"Overview of chromosome abnormalities in first trimester miscarriages: a series of 1,011 consecutive chorionic villi sample karyotypes","volume":"152","author":"Soler","year":"2017","journal-title":"Cytogenet Genome Res"},{"key":"2026040814593386900_deaf243-B34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jpsychires.2014.04.016","article-title":"Failure to replicate the association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants with risk of depression during pregnancy and post-partum reported by","volume":"56","author":"Stergiakouli","year":"2014","journal-title":"J Psychiatr Res"},{"key":"2026040814593386900_deaf243-B35","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1159\/000430178","article-title":"Human chorionic gonadotropin protects vascular endothelial cells from oxidative stress by apoptosis inhibition, cell survival signalling activation and mitochondrial function protection","volume":"36","author":"Surico","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"2026040814593386900_deaf243-B36","first-page":"258","article-title":"Successful pregnancy in a woman with ovarian failure associated with mutation in the beta-subunit of luteinizing hormone","volume":"55","author":"Takahashi","year":"2001","journal-title":"Horm Res"},{"key":"2026040814593386900_deaf243-B37","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/0962280206074463","article-title":"Multiple imputation of discrete and continuous data by fully conditional specification","volume":"16","author":"van Buuren","year":"2007","journal-title":"Stat Methods Med Res"},{"key":"2026040814593386900_deaf243-B38","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1093\/aje\/kwy186","article-title":"Perceived stress and fecundability: a preconception cohort study of North American couples","volume":"187","author":"Wesselink","year":"2018","journal-title":"Am J Epidemiol"},{"key":"2026040814593386900_deaf243-B39","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198807283190401","article-title":"Incidence of early loss of pregnancy","volume":"319","author":"Wilcox","year":"1988","journal-title":"N Engl J Med"},{"key":"2026040814593386900_deaf243-B40","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/ppe.12201","article-title":"Design and conduct of an internet-based preconception cohort study in North America: pregnancy study online","volume":"29","author":"Wise","year":"2015","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2026040814593386900_deaf243-B41","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1365-2605.2012.01276.x","article-title":"Sperm chromatin integrity may predict future fertility for unexplained recurrent spontaneous abortion patients","volume":"35","author":"Zhang","year":"2012","journal-title":"Int J Androl"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/4\/606\/66863568\/deaf243.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/4\/606\/66863568\/deaf243.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:59:45Z","timestamp":1775674785000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/41\/4\/606\/8475197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2,12]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deaf243","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,2,12]]}}}