{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:29:15Z","timestamp":1792592955245,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) is being implemented in many high-income countries due to the association of excisional treatment with preterm birth. However, it is unknown whether active surveillance results in lower risk of preterm birth given that cervical dysplasia itself is associated with higher risk of preterm birth.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the preterm birth risk between women with CIN2 undergoing active surveillance or immediate loop electrosurgical excision procedure (LEEP).<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This historical population-based cohort study included women with a first-time diagnosis of CIN2 and a subsequent singleton birth from 1998 to 2018 in Denmark. Women with prior CIN grade 3 or greater or LEEP were excluded. Data were collected from 4 Danish health care registries. Analyses were conducted from October 2022 to June 2023.<\/jats:p><\/jats:sec>Exposure<\/jats:title>Women were categorized into active surveillance (cervical biopsy and\/or cytology) or immediate LEEP based on their first cervical sample after CIN2 diagnosis. The active surveillance group was further subdivided based on whether a delayed LEEP was performed within 28 months from CIN2 diagnosis.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Risk of preterm birth (&amp;lt;37\u2009+\u20090 weeks) was assessed and relative risks (RRs) were calculated using modified Poisson regression. Analyses used inverse probability treatment weighting of the propensity scores to adjust for age, parity, calendar year, index cytology, and smoking.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 10\u202f537 women with CIN2 and a singleton birth were identified; 4430 (42%) underwent active surveillance and 6107 (58%) were treated with immediate LEEP. For both groups, most were aged 23 to 29 years at CIN2 diagnosis (3125 [70%] and 3907 [64%], respectively). Overall, 869 births (8.2%) were preterm. The risk of preterm birth was comparable between active surveillance and immediate LEEP (RR, 1.03; 95% CI, 0.90-1.18). However, for women undergoing delayed LEEP after active surveillance (1539 of the active surveillance group [35%]), the risk of preterm birth was higher than for women treated with immediate LEEP (RR, 1.29; 95% CI, 1.08-1.55).<\/jats:p><\/jats:sec>Conclusions and relevance<\/jats:title>In this cohort study of women with CIN2, the risk of preterm birth was comparable between active surveillance and immediate LEEP. However, delayed LEEP was associated with 30% higher risk of preterm birth than immediate LEEP. Thus, risk stratification at CIN2 diagnosis is important to identify women with increased risk of delayed LEEP.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.2309","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T15:01:29Z","timestamp":1710428489000},"page":"e242309","source":"Crossref","is-referenced-by-count":19,"title":["Preterm Birth Following Active Surveillance vs Loop Excision for Cervical Intraepithelial Neoplasia Grade 2"],"prefix":"10.1001","volume":"7","author":[{"given":"Kathrine Dyhr","family":"Lycke","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"NIDO, Centre for Research and Education, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina Overgaard","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"NIDO, Centre for Research and Education, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Omann","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"NIDO, Centre for Research and Education, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Henning","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iben","family":"Sundtoft","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Landy","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lone Kjeld","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"NIDO, Centre for Research and Education, G\u00f8dstrup Hospital, Herning, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"zoi240109r1","doi-asserted-by":"publisher","first-page":"k499","DOI":"10.1136\/bmj.k499","article-title":"Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis.","volume":"360","author":"Tainio","year":"2018","journal-title":"BMJ"},{"issue":"5","key":"zoi240109r2","doi-asserted-by":"publisher","first-page":"742.e1","DOI":"10.1016\/j.ajog.2022.06.051","article-title":"Active expectancy as alternative to treatment for cervical intraepithelial neoplasia grade 2 in women aged 25 to 30 years: ExCIN2\u2014a prospective clinical multicenter cohort study.","volume":"227","author":"Kyleb\u00e4ck","year":"2022","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"zoi240109r3","doi-asserted-by":"publisher","first-page":"656.e1","DOI":"10.1016\/j.ajog.2023.08.008","article-title":"Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study.","volume":"229","author":"Lycke","year":"2023","journal-title":"Am J Obstet Gynecol"},{"key":"zoi240109r4","doi-asserted-by":"publisher","first-page":"a1284","DOI":"10.1136\/bmj.a1284","article-title":"Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis.","volume":"337","author":"Arbyn","year":"2008","journal-title":"BMJ"},{"issue":"9","key":"zoi240109r5","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1111\/bjo.2011.118.issue-9","article-title":"The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis.","volume":"118","author":"Bruinsma","year":"2011","journal-title":"BJOG"},{"key":"zoi240109r6","doi-asserted-by":"publisher","first-page":"i3633","DOI":"10.1136\/bmj.i3633","article-title":"Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis.","volume":"354","author":"Kyrgiou","year":"2016","journal-title":"BMJ"},{"issue":"8","key":"zoi240109r7","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/S1470-2045(22)00334-5","article-title":"Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.","volume":"23","author":"Athanasiou","year":"2022","journal-title":"Lancet Oncol"},{"issue":"4","key":"zoi240109r8","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1097\/AOG.0000000000004705","article-title":"Known benefits and unknown risks of active surveillance of cervical intraepithelial neoplasia grade 2.","volume":"139","author":"Lycke","year":"2022","journal-title":"Obstet Gynecol"},{"issue":"4","key":"zoi240109r9","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1097\/AOG.0000000000000174","article-title":"Loop electrosurgical excision procedure and risk of preterm birth: a systematic review and meta-analysis.","volume":"123","author":"Conner","year":"2014","journal-title":"Obstet Gynecol"},{"issue":"3","key":"zoi240109r10","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/bjo.2009.117.issue-3","article-title":"After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy.","volume":"117","author":"\u00d8rtoft","year":"2010","journal-title":"BJOG"},{"issue":"7874","key":"zoi240109r11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e5174","article-title":"Risk of preterm birth after treatment for cervical intraepithelial neoplasia among women attending colposcopy in England: retrospective-prospective cohort study.","volume":"345","author":"Castanon","year":"2012","journal-title":"BMJ"},{"issue":"2","key":"zoi240109r12","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/bjo.2011.119.issue-2","article-title":"Birth outcomes following treatment for precancerous changes to the cervix: a population-based record linkage study.","volume":"119","author":"Reilly","year":"2012","journal-title":"BJOG"},{"issue":"2","key":"zoi240109r13","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0029-7844(98)00386-X","article-title":"Effect of cervical carcinoma in situ and its management on pregnancy outcome.","volume":"93","author":"El-Bastawissi","year":"1999","journal-title":"Obstet Gynecol"},{"issue":"6","key":"zoi240109r14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003665","article-title":"Cervical intraepithelial neoplasia and the risk of spontaneous preterm birth: a Dutch population-based cohort study with 45,259 pregnancy outcomes.","volume":"18","author":"Loopik","year":"2021","journal-title":"PLoS Med"},{"issue":"8","key":"zoi240109r15","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology.","volume":"29","author":"Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"issue":"7","key":"zoi240109r16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1177\/1403494810393563","article-title":"The Danish Pathology Register.","volume":"39","author":"Bjerregaard","year":"2011","journal-title":"Scand J Public Health"},{"issue":"1","key":"zoi240109r17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10654-018-0356-1","article-title":"The Danish Medical Birth Register.","volume":"33","author":"Bliddal","year":"2018","journal-title":"Eur J Epidemiol"},{"key":"zoi240109r18","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2147\/CLEP","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential.","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"issue":"6","key":"zoi240109r19","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1111\/bjo.v127.6","article-title":"Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study.","volume":"127","author":"Skorstengaard","year":"2020","journal-title":"BJOG"},{"issue":"7","key":"zoi240109r20","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1093\/aje\/kwh090","article-title":"A modified Poisson regression approach to prospective studies with binary data.","volume":"159","author":"Zou","year":"2004","journal-title":"Am J Epidemiol"},{"issue":"1","key":"zoi240109r21","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12874-018-0519-5","article-title":"Comparing performance between log-binomial and robust Poisson regression models for estimating risk ratios under model misspecification.","volume":"18","author":"Chen","year":"2018","journal-title":"BMC Med Res Methodol"},{"issue":"4","key":"zoi240109r22","doi-asserted-by":"publisher","first-page":"222","DOI":"10.4103\/2229-3485.167092","article-title":"Common pitfalls in statistical analysis: odds versus risk.","volume":"6","author":"Ranganathan","year":"2015","journal-title":"Perspect Clin Res"},{"key":"zoi240109r23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.2147\/CLEP","article-title":"Control of confounding in the analysis phase\u2014an overview for clinicians.","volume":"9","author":"Kahlert","year":"2017","journal-title":"Clin Epidemiol"},{"issue":"1","key":"zoi240109r24","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/bjo.2007.114.issue-1","article-title":"Precancerous changes in the cervix and risk of subsequent preterm birth.","volume":"114","author":"Bruinsma","year":"2007","journal-title":"BJOG"},{"issue":"17","key":"zoi240109r25","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1001\/jama.291.17.2100","article-title":"Treatment for cervical intraepithelial neoplasia and risk of preterm delivery.","volume":"291","author":"Sadler","year":"2004","journal-title":"JAMA"},{"issue":"3","key":"zoi240109r26","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1097\/LGT.0000000000000604","article-title":"The natural history of cervical intraepithelial neoplasia grades 1, 2, and 3: a systematic review and meta-analysis.","volume":"25","author":"Loopik","year":"2021","journal-title":"J Low Genit Tract Dis"},{"issue":"1","key":"zoi240109r27","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1006\/gyno.1995.1100","article-title":"Association between colposcopic findings and histology in cervical lesions: the significance of the size of the lesion.","volume":"57","author":"Kierkegaard","year":"1995","journal-title":"Gynecol Oncol"},{"issue":"6","key":"zoi240109r28","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1097\/AOG.0b013e3181bf1ef2","article-title":"Depth of cervical cone removed by loop electrosurgical excision procedure and subsequent risk of spontaneous preterm delivery.","volume":"114","author":"Noehr","year":"2009","journal-title":"Obstet Gynecol"},{"issue":"9","key":"zoi240109r29","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1111\/bjo.2015.122.issue-9","article-title":"Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?","volume":"122","author":"Casta\u00f1on","year":"2015","journal-title":"BJOG"},{"issue":"7","key":"zoi240109r30","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1111\/aogs.2013.92.issue-7","article-title":"Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia: nationwide population-based study.","volume":"92","author":"Barken","year":"2013","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"1","key":"zoi240109r31","doi-asserted-by":"publisher","first-page":"33.e1","DOI":"10.1016\/j.ajog.2009.02.004","article-title":"Loop electrosurgical excision of the cervix and subsequent risk for spontaneous preterm delivery: a population-based study of singleton deliveries during a 9-year period.","volume":"201","author":"Noehr","year":"2009","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"zoi240109r32","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.ygyno.2021.06.019","article-title":"Predictor factors for conservative management of cervical intraepithelial neoplasia grade 2: cytology and HPV genotyping.","volume":"162","author":"Salvad\u00f3","year":"2021","journal-title":"Gynecol Oncol"},{"issue":"9","key":"zoi240109r33","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.25308","article-title":"Association between human papillomavirus infection among pregnant women and preterm birth.","volume":"4","author":"Niyibizi","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"4","key":"zoi240109r34","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1097\/pgp.0b013e31805152ab","article-title":"CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of population-based cervical samples.","volume":"26","author":"Carreon","year":"2007","journal-title":"Int J Gynecol Pathol"},{"issue":"9","key":"zoi240109r35","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1111\/aogs.v102.9","article-title":"High prevalence of HPV16 and high-grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.","volume":"102","author":"Damgaard","year":"2023","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"5","key":"zoi240109r36","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1093\/ije\/dyn112","article-title":"Socioeconomic position and the risk of preterm birth\u2014a study within the Danish National Birth Cohort.","volume":"37","author":"Morgen","year":"2008","journal-title":"Int J Epidemiol"},{"key":"zoi240109r37","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2021.100205","article-title":"Association of neighbourhood socioeconomic trajectories with preterm birth and small-for-gestational-age in the Netherlands: a nationwide population-based study.","volume":"10","author":"Burgos Ochoa","year":"2021","journal-title":"Lancet Reg Health Eur"},{"issue":"2","key":"zoi240109r38","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1136\/tobaccocontrol-2014-051630","article-title":"Socioeconomic position and early adolescent smoking development: evidence from the British Youth Panel Survey (1994-2008).","volume":"25","author":"Green","year":"2016","journal-title":"Tob Control"},{"issue":"3","key":"zoi240109r39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/uog.v22:3","article-title":"Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review.","volume":"22","author":"Honest","year":"2003","journal-title":"Ultrasound Obstet Gynecol"},{"key":"zoi240109r40","unstructured":"Danish Society of Obstetrics & Gynecology. Cervix-scanning i singleton graviditeter. Accessed May 10, 2023. http:\/\/static.squarespace.com\/static\/5467abcce4b056d72594db79\/546e7748e4b0d969a4f6cf10\/546e7745e4b0d969a4f6cae7\/1389626681000\/Cervix-guideline_2013_final.pdf?format=original"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2816196\/lycke_2024_oi_240109_1709918736.33549.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T15:01:32Z","timestamp":1710428492000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2816196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,14]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,4]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.2309","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,14]]}}}