{"doi":"10.1093/humrep/deac172","title":"Prospectively assessed perceived stress associated with early pregnancy losses among women with history of pregnancy loss","abstract":"STUDY QUESTION: What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss? SUMMARY ANSWER: Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss. WHAT IS KNOWN ALREADY?: Women who have experienced a pregnancy loss may be more vulnerable to stress while trying to become pregnant again. While prior research has indicated a link between psychological stress and clinically confirmed miscarriages, research is lacking among a pre-conceptional cohort followed prospectively for the effects of perceived stress during early critical windows of pregnancy establishment on risk of both hCG-detected pregnancy losses and confirmed losses, while considering important time-varying confounders. STUDY DESIGN, SIZE, DURATION: Secondary data analysis of the EAGeR trial (2007-2011) among women with an hCG-detected pregnancy (n = 797 women). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women from four US clinical centers enrolled pre-conceptionally and were followed ≤6 cycles while attempting pregnancy and, as applicable, throughout pregnancy. Perceived stress was captured via daily diaries and end-of-month questionnaires. Main outcome measures include hCG-detected and clinically recognized pregnancy losses. MAIN RESULTS AND THE ROLE OF CHANCE: Among women who had an hCG-confirmed pregnancy, 188 pregnancies (23.6%) ended in loss. Women with high (>50th percentile) versus low (≤50th percentile) peri-implantation or early pregnancy weekly perceived stress had an elevated risk of experiencing any pregnancy loss (hazard ratio (HR): 1.69, 95% CI: 1.13, 2.54) or clinical loss (HR: 1.58, 95% CI: 0.96, 2.60), with higher risks observed for women experiencing an hCG-detected loss (HR: 2.16, 95% CI: 1.04, 4.46). Models accounted for women's age, BMI, employment, marital status, income, education, race, parity, prior losses, exercise and time-varying nausea/vomiting, caffeine, alcohol and smoking. LIMITATIONS, REASONS FOR CAUTION: We were limited in our ability to clearly identify the mechanisms of stress on pregnancy loss due to our sole reliance on self-reported perceived stress, and the lack of biomarkers of different pathways of stress. WIDER IMPLICATIONS OF THE FINDINGS: This study provides new insight on early pregnancy perceived stress and risk of pregnancy loss, most notably hCG-detected losses, among women with a history of a prior loss. Our study is an improvement over past studies in its ability to account for time-varying early pregnancy symptoms, such as nausea/vomiting, and lifestyle factors, such as caffeine, alcohol and smoking, which are also risk factors for psychological stress and pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Additionally, K.C.S. was supported by the National Institute on Aging of the National Institutes of Health under Award Number K01AG058781. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: #NCT00467363.","journal":"Human Reproduction","year":2022,"id":258944,"datarank":0.7994500927177299,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.36589432903330515,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.36589432903330515,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":17,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00467363"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308445,"name":"Stefanie N. Hinkle","orcid":"0000-0003-4312-708X","position":1,"is_corresponding":false},{"id":311702,"name":"Keewan Kim","orcid":"0000-0002-1892-6739","position":2,"is_corresponding":false},{"id":311705,"name":"Lindsey A. Sjaarda","orcid":"0000-0003-0539-8110","position":3,"is_corresponding":false},{"id":257473,"name":"Robert M. Silver","orcid":"0000-0002-5794-3152","position":4,"is_corresponding":false},{"id":495874,"name":"Joseph B. Stanford","orcid":"0000-0002-9932-3947","position":5,"is_corresponding":false},{"id":320648,"name":"Alexandra Purdue‐Smithe","orcid":"0000-0002-7356-3651","position":6,"is_corresponding":false},{"id":436083,"name":"Torie C. Plowden","orcid":"0000-0001-9086-2947","position":7,"is_corresponding":false},{"id":311707,"name":"Enrique F. Schisterman","orcid":"0000-0003-3757-641X","position":8,"is_corresponding":false},{"id":311701,"name":"Sunni L. Mumford","orcid":"0000-0003-0133-3176","position":9,"is_corresponding":false},{"id":400024,"name":"Karen C. Schliep","orcid":"0000-0003-1771-3157","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:25:47.305414Z","pmid":"35972454","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}