{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:07:36Z","timestamp":1788890856046,"version":"build-2803163510"},"reference-count":30,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"crossref","award":["50-53000-98-103"],"award-info":[{"award-number":["50-53000-98-103"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Health, Welfare and Sports to the Centre for Infectious Disease Control"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Sex Transm Infect"],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                      (chlamydia) infection has a variable course; most infections resolve but some lead to reproductive complications. Behavioural, immunological and host genetic factors likely influence risk. We aimed to identify predictors of complications in persons with and without chlamydia and develop prediction models for risk stratification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed data from a long-term cohort of Dutch individuals registered as female in municipal registries and previously screened for chlamydia, including demographic, behavioural, chlamydia-infection and serology variables, and 24 single nucleotide polymorphisms (SNPs). We constructed SNP sets capturing shared biological pathways. Using multivariable Cox regression, we developed and internally validated composite and outcome-specific models for reproductive complications (pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility) stratified by chlamydia status. Model performance was assessed. Point-based risk scores were derived from final models, estimating 15-year risks. Thresholds assessed the proportion classified as high risk and the proportion of outcomes captured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 5704 participants (35\u2009523 and 66\u2009511 person-years in chlamydia-positive and chlamydia-negative groups), 7.1% and 5.4%\u2009experienced reproductive complications, respectively. Across outcomes, predictors included behavioural, sociodemographic and immune-related genetic factors, with most identified SNPs known to be involved in immune pathways. Model discrimination was modest (area under the curve ~0.65). Using a \u226515% predicted risk threshold, 54% of chlamydia-positive individuals were classified as high risk of reproductive complications, capturing 75% of composite outcomes (positive predictive value (PPV) 9.7%). For PID, 27% were classified as high risk, capturing 39% of cases (PPV 6.9%), and for ectopic pregnancy, 1.7% were classified as high risk, capturing 10% of cases (PPV 11.8%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prediction models integrating behavioural, sociodemographic and host genetic factors showed modest performance, with better classification for chlamydia-positive individuals and PID than for ectopic pregnancy. Individual-level risk stratification is unlikely to be clinically useful, supporting population-level or group-level targeting of prevention and care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/sextrans-2025-056761","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:20:23Z","timestamp":1788888023000},"page":"sextrans-2025-056761","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Can we predict reproductive complications after\n                    <i>Chlamydia trachomatis<\/i>\n                    infection? A cohort study integrating demographic, behavioural, host genetic and infection-related factors"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-8904","authenticated-orcid":false,"given":"Zo\u00efe W","family":"Alexiou","sequence":"first","affiliation":[{"name":"Department of Genetics and Cell Biology, Research Institute for Oncology and Reproduction (GROW), Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands"},{"name":"Centre for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-6198","authenticated-orcid":false,"given":"Bernice M","family":"Hoenderboom","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4896-758X","authenticated-orcid":false,"given":"Nicole H T M","family":"Dukers-Muijrers","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health Mosa, Public Health Service South Limburg, Heerlen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-0002","authenticated-orcid":false,"given":"Sander","family":"Ouburg","sequence":"additional","affiliation":[{"name":"Microbe&Lab BV, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J P A","family":"Hoebe","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health Mosa, South Limburg Public Health Services, Heerlen, The Netherlands"},{"name":"Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Dutch Chlamydia trachomatis Reference Laboratory, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit H B","family":"van Benthem","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Servaas A","family":"Morr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, Research Institute for Oncology and Reproduction (GROW), Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Dutch Chlamydia trachomatis Reference Laboratory, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands"},{"name":"Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom Institute of Agriculture, Allahabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026090810201599000_sextrans-2025-056761v1.1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lanepe.2023.100743","article-title":"Management of asymptomatic sexually transmitted infections in Europe: towards a differentiated, evidence-based approach","volume":"34","author":"Kenyon","year":"2023","journal-title":"Lancet Reg Health Eur"},{"key":"2026090810201599000_sextrans-2025-056761v1.2","doi-asserted-by":"crossref","DOI":"10.1016\/j.lanepe.2024.101027","article-title":"Reproductive tract complication risks following Chlamydia trachomatis infections: a long-term prospective cohort study from 2008 to 2022","volume":"45","author":"Alexiou","year":"2024","journal-title":"Lancet Reg Health Eur"},{"key":"2026090810201599000_sextrans-2025-056761v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2021-054992"},{"key":"2026090810201599000_sextrans-2025-056761v1.4","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-078276","article-title":"Developing clinical prediction models: a step-by-step 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Association between serum Chlamydia trachomatis antibody levels and infertility among reproductive-aged women in the U.S. Front Public Health 2023;11. doi:10.3389\/fpubh.2023.1117245","DOI":"10.3389\/fpubh.2023.1117245"},{"key":"2026090810201599000_sextrans-2025-056761v1.13","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s10038-008-0307-x","article-title":"Two-stage designs to identify the effects of SNP combinations on complex diseases","volume":"53","author":"Kang","year":"2008","journal-title":"J Hum Genet"},{"key":"2026090810201599000_sextrans-2025-056761v1.14","doi-asserted-by":"crossref","unstructured":"Anyalechi GE , Hong J , Danavall DC , et al . High Plasmid Gene Protein 3 (Pgp3) Seropositivity, Pelvic Inflammatory Disease, and Infertility Among Women, National Health and Nutrition Examination Survey, United States, 2013-2016. Clinical Infectious Diseases 2013;73. doi:10.1093\/cid\/ciab506","DOI":"10.1093\/cid\/ciab506"},{"key":"2026090810201599000_sextrans-2025-056761v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab496"},{"key":"2026090810201599000_sextrans-2025-056761v1.16","doi-asserted-by":"crossref","unstructured":"Liu C , Mokashi NV , Darville T , et al . A Machine Learning-Based Analytic Pipeline Applied to Clinical and Serum IgG Immunoproteome Data To Predict Chlamydia trachomatis Genital Tract Ascension and Incident Infection in Women. Microbiol Spectr 2023;11. doi:10.1128\/spectrum.04689-22","DOI":"10.1128\/spectrum.04689-22"},{"key":"2026090810201599000_sextrans-2025-056761v1.17","doi-asserted-by":"crossref","DOI":"10.1111\/aji.70036","article-title":"Causal Relationship Between Antibody-Mediated Immune Responses of Chlamydia trachomatis Infection and Reproductive Tract Complications: A Bidirectional Mendelian Randomization Study","volume":"93","author":"Hong","year":"2025","journal-title":"Am J Reprod Immunol"},{"key":"2026090810201599000_sextrans-2025-056761v1.18","doi-asserted-by":"publisher","DOI":"10.1086\/597620"},{"key":"2026090810201599000_sextrans-2025-056761v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir822"},{"key":"2026090810201599000_sextrans-2025-056761v1.20","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1093\/infdis\/jiab149","article-title":"Host Genetic Risk Factors for Chlamydia trachomatis-Related Infertility in Women","volume":"224","author":"Zheng","year":"2021","journal-title":"J Infect Dis"},{"key":"2026090810201599000_sextrans-2025-056761v1.21","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftv107","article-title":"TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women","volume":"74","author":"Verweij","year":"2016","journal-title":"Pathog Dis"},{"key":"2026090810201599000_sextrans-2025-056761v1.22","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-017-2376-y","article-title":"The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women","volume":"17","author":"Hoenderboom","year":"2017","journal-title":"BMC Infect Dis"},{"key":"2026090810201599000_sextrans-2025-056761v1.23","doi-asserted-by":"crossref","DOI":"10.1071\/SH24101","article-title":"Comparison of IgG serum antibodies, electronic health records and self-report in estimating past infection with Chlamydia trachomatis in a cohort of men who have sex with men","volume":"21","author":"Waters","year":"2024","journal-title":"Sex Health"},{"key":"2026090810201599000_sextrans-2025-056761v1.24","doi-asserted-by":"publisher","DOI":"10.3310\/hta20220"},{"key":"2026090810201599000_sextrans-2025-056761v1.25","doi-asserted-by":"publisher","DOI":"10.1097\/OLQ.0b013e3182383097"},{"key":"2026090810201599000_sextrans-2025-056761v1.26","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftw010","article-title":"Specific polymorphisms in the vitamin D metabolism pathway are not associated with susceptibility to Chlamydia trachomatis infection in humans","volume":"74","author":"Lanjouw","year":"2016","journal-title":"Pathog Dis"},{"key":"2026090810201599000_sextrans-2025-056761v1.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6187"},{"key":"2026090810201599000_sextrans-2025-056761v1.28","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/ijgo.15965","article-title":"Risk factors for ectopic pregnancy occurrence: Systematic review and meta-analysis","volume":"168","author":"Brim","year":"2025","journal-title":"Int J Gynaecol Obstet"},{"key":"2026090810201599000_sextrans-2025-056761v1.29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00439-016-1636-z","article-title":"Improved prediction of complex diseases by common genetic markers: state of the art and further perspectives","volume":"135","author":"M\u00fcller","year":"2016","journal-title":"Hum Genet"},{"key":"2026090810201599000_sextrans-2025-056761v1.30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/14787210.2025.2526846","article-title":"The evolving debate around screening for","volume":"23","author":"Van Der Pol","year":"2025","journal-title":"Expert Rev Anti-Infe"}],"container-title":["Sexually Transmitted Infections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/sextrans-2025-056761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:20:28Z","timestamp":1788888028000},"score":1,"resource":{"primary":{"URL":"https:\/\/sti.bmj.com\/lookup\/doi\/10.1136\/sextrans-2025-056761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":30,"alternative-id":["10.1136\/sextrans-2025-056761"],"URL":"https:\/\/doi.org\/10.1136\/sextrans-2025-056761","relation":{},"ISSN":["1368-4973","1472-3263"],"issn-type":[{"value":"1368-4973","type":"print"},{"value":"1472-3263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}