{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T21:19:42Z","timestamp":1781990382238,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nordic Trial Alliance"},{"name":"Nordic Council of Ministers and NordForsk","award":["71450"],"award-info":[{"award-number":["71450"]}]},{"name":"Central Norway Regional Health Authorities","award":["46045000"],"award-info":[{"award-number":["46045000"]}]},{"name":"Nordic Federation of Obstetrics and Gynaecology","award":["NF13041, NF15058"],"award-info":[{"award-number":["NF13041, NF15058"]}]},{"name":"Nordic Federation of Obstetrics and Gynaecology","award":["NF16026"],"award-info":[{"award-number":["NF16026"]}]},{"name":"Nordic Federation of Obstetrics and Gynaecology","award":["NF17043"],"award-info":[{"award-number":["NF17043"]}]},{"name":"Interreg \u00d6resund-Kattegat-Skagerrak European Regional Development Fund"},{"name":"Research Council of Norway\u2019s Centre of Excellence","award":["262700"],"award-info":[{"award-number":["262700"]}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["101021566"],"award-info":[{"award-number":["101021566"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/6"],"award-info":[{"award-number":["MC_UU_00011\/6"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bristol National Institute of Health"},{"name":"Research Biomedical Research Centre","award":["NF-0616\u201310102"],"award-info":[{"award-number":["NF-0616\u201310102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Within-sibship analyses show lower perinatal mortality after assisted reproductive technology (ART) compared with natural conception (NC), a finding that appears biologically unlikely. We investigated whether this may be attributed to bias from selective fertility and carryover effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using data from national registries in Denmark (1994\u20132014), Finland (1990\u20132014) and Norway and Sweden (1988\u20132015), we studied 5\u200a722\u200a826 singleton pregnancies, including 119\u200a900 ART-conceived and 37\u200a590 exposure-discordant sibships. Perinatal mortality at the population level and within sibships was compared using multilevel logistic regression with random and fixed intercepts, respectively. We estimated selective fertility as the proportion of primiparous women with and without perinatal loss who had a second delivery, and carryover effects through bidirectional and crosswise associations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Population analysis showed higher perinatal mortality among ART conception compared with NC (odds ratio 1.21, 95% CI 1.13 to 1.30), whereas within-sibship analysis showed the opposite (OR 0.36, 95% CI 0.31 to 0.43). Primiparous women with perinatal loss were more likely to give birth again (selective fertility) and to use ART in this subsequent pregnancy (carryover effects), resulting in strong selection of double-discordant sibships with death of the naturally conceived and survival of the ART-conceived sibling. After controlling for conception method and outcome in the first pregnancy, ART was not consistently associated with perinatal mortality in the second pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Whereas population estimates may be biased by residual confounding, within-sibship estimates were biased by selective fertility and carryover effects. It remains unclear whether ART conception contributes to perinatal mortality.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ije\/dyad003","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T10:23:42Z","timestamp":1675074222000},"page":"403-413","source":"Crossref","is-referenced-by-count":6,"title":["The challenges of selective fertility and carryover effects in within-sibship analyses: the effect of assisted reproductive technology on perinatal mortality as an example"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-5559","authenticated-orcid":false,"given":"Kjersti","family":"Westvik-Johari","sequence":"first","affiliation":[{"name":"Department of Fertility, Women and Children\u2019s Centre, St Olavs Hospital , Trondheim, Norway"},{"name":"Department of Public Health and Nursing, Norwegian University of Science and Technology , Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2199-5225","authenticated-orcid":false,"given":"Siri E","family":"H\u00e5berg","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo, Norway"},{"name":"MRC Integrative Epidemiology Unit at the University of Bristol , Bristol, UK"},{"name":"Population Health Science, Bristol Medical School , Bristol, UK"},{"name":"NIHR Bristol Biomedical Research Centre , Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liv Bente","family":"Romundstad","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo, Norway"},{"name":"Spiren Fertility Clinic , Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bergh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital , Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla-Britt","family":"Wennerholm","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital , Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-7525","authenticated-orcid":false,"given":"Mika","family":"Gissler","sequence":"additional","affiliation":[{"name":"Department of Knowledge Brokers, THL Finnish Institute for Health and Welfare , Helsinki, Finland"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm, Sweden"},{"name":"Academic Primary Health Care Centre, Region Stockholm , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Karina A","family":"Henningsen","sequence":"additional","affiliation":[{"name":"Fertility Clinic, Copenhagen University Hospital , Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3088-5594","authenticated-orcid":false,"given":"Aila","family":"Tiitinen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki , Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-104X","authenticated-orcid":false,"given":"Anja","family":"Pinborg","sequence":"additional","affiliation":[{"name":"Fertility Clinic, Copenhagen University Hospital , Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-8433","authenticated-orcid":false,"given":"Signe","family":"Opdahl","sequence":"additional","affiliation":[{"name":"Department of Public Health and Nursing, Norwegian University of Science and Technology , Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"2023061420112682800_dyad003-B1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-43742-2_8","volume-title":"Secondary Analysis of Electronic Health Records","author":"Danziger","year":"2016"},{"key":"2023061420112682800_dyad003-B2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/aje\/kwq196","article-title":"Invited commentary: the use of sibship studies to detect familial confounding","volume":"172","author":"Susser","year":"2010","journal-title":"Am J Epidemiol"},{"key":"2023061420112682800_dyad003-B3","first-page":"1866","article-title":"Triangulation in aetiological epidemiology","volume":"45","author":"Lawlor","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2023061420112682800_dyad003-B4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-statistics-040120-024521","article-title":"Sibling comparison studies","volume":"9","author":"Sj\u00f6lander","year":"2022","journal-title":"Annu Rev Stat Appl"},{"key":"2023061420112682800_dyad003-B5","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1097\/EDE.0b013e31825fa230","article-title":"Sibling comparison designs: bias from non-shared confounders and measurement error","volume":"23","author":"Frisell","year":"2012","journal-title":"Epidemiology"},{"key":"2023061420112682800_dyad003-B6","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1097\/EDE.0000000000000541","article-title":"Carryover effects in sibling comparison designs","volume":"27","author":"Sj\u00f6lander","year":"2016","journal-title":"Epidemiology"},{"key":"2023061420112682800_dyad003-B7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/EDE.0b013e31828c7381","article-title":"On sibling designs","volume":"24","author":"Keyes","year":"2013","journal-title":"Epidemiology"},{"key":"2023061420112682800_dyad003-B8","doi-asserted-by":"crossref","first-page":"e1003683","DOI":"10.1371\/journal.pmed.1003683","article-title":"Separating parental and treatment contributions to perinatal health after fresh and frozen embryo transfer in assisted reproduction: a cohort study with within-sibship analysis","volume":"18","author":"Westvik-Johari","year":"2021","journal-title":"PLoS Med"},{"key":"2023061420112682800_dyad003-B9","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0140-6736(08)61041-7","article-title":"Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study","volume":"372","author":"Romundstad","year":"2008","journal-title":"Lancet"},{"key":"2023061420112682800_dyad003-B10","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.fertnstert.2010.07.1075","article-title":"Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study","volume":"95","author":"Henningsen","year":"2011","journal-title":"Fertil Steril"},{"key":"2023061420112682800_dyad003-B11","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.fertnstert.2015.11.015","article-title":"Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: a population-based study using siblings","volume":"105","author":"Seggers","year":"2016","journal-title":"Fertil Steril"},{"key":"2023061420112682800_dyad003-B12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/humupd\/dms044","article-title":"Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis","volume":"19","author":"Pinborg","year":"2013","journal-title":"Hum Reprod Update"},{"key":"2023061420112682800_dyad003-B13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.fertnstert.2015.09.007","article-title":"Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies","volume":"105","author":"Qin","year":"2016","journal-title":"Fertil Steril"},{"key":"2023061420112682800_dyad003-B14","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1093\/oxfordjournals.aje.a115088","article-title":"Selective fertility and the distortion of perinatal mortality","volume":"128","author":"Skjaerven","year":"1988","journal-title":"Am J Epidemiol"},{"key":"2023061420112682800_dyad003-B15","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1097\/01.ede.0000142148.51230.60","article-title":"Smoking and the risk of oral clefts: exploring the impact of study designs","volume":"15","author":"Meyer","year":"2004","journal-title":"Epidemiology"},{"key":"2023061420112682800_dyad003-B16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/ije\/dyz228","article-title":"Data resource profile: Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) cohort","volume":"49","author":"Opdahl","year":"2020","journal-title":"Int J Epidemiol"},{"key":"2023061420112682800_dyad003-B17","first-page":"357","article-title":"The Danish in vitro fertilisation (IVF) register","volume":"46","author":"Andersen","year":"1999","journal-title":"Dan Med Bull"},{"key":"2023061420112682800_dyad003-B18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research","volume":"24","author":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"key":"2023061420112682800_dyad003-B19","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1093\/humrep\/dex234","article-title":"The International Glossary on Infertility and Fertility Care, 2017","volume":"32","author":"Zegers-Hochschild","year":"2017","journal-title":"Hum Reprod"},{"key":"2023061420112682800_dyad003-B20","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0140-6736(15)00837-5","article-title":"Stillbirths: rates, risk factors, and acceleration towards 2030","volume":"387","author":"Lawn","year":"2016","journal-title":"Lancet"},{"key":"2023061420112682800_dyad003-B21","volume-title":"Multilevel and Longitudinal Modeling Using Stata, Volumes I and II","author":"Rabe-Hesketh","year":"2012","edition":"3rd ed"},{"key":"2023061420112682800_dyad003-B22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/humrep\/dex340","article-title":"Gestational age-specific perinatal mortality rates for assisted reproductive technology (ART) and other births","volume":"33","author":"Chughtai","year":"2018","journal-title":"Hum Reprod"},{"key":"2023061420112682800_dyad003-B23","first-page":"193","article-title":"Pregnant after assisted reproduction: a risk pregnancy is born! 18-years perinatal outcome results from a population-based registry in Flanders, Belgium","volume":"8","author":"Ombelet","year":"2016","journal-title":"Facts Views Vis Obgyn"},{"key":"2023061420112682800_dyad003-B24","doi-asserted-by":"crossref","first-page":"e80398","DOI":"10.1371\/journal.pone.0080398","article-title":"Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort","volume":"9","author":"Marino","year":"2014","journal-title":"PLoS One"},{"key":"2023061420112682800_dyad003-B25","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/S0140-6736(98)08500-6","article-title":"Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis","volume":"353","author":"Draper","year":"1999","journal-title":"Lancet"},{"key":"2023061420112682800_dyad003-B26","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1136\/bmj.38336.616806.8F","article-title":"Subfecundity and neonatal mortality: longitudinal study within the Danish national birth cohort","volume":"330","author":"Basso","year":"2005","journal-title":"BMJ"},{"key":"2023061420112682800_dyad003-B27","doi-asserted-by":"crossref","first-page":"226.e1","DOI":"10.1016\/j.ajog.2020.02.030","article-title":"Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries","volume":"223","author":"Petersen","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"2023061420112682800_dyad003-B28","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2147\/CLEP.S314959","article-title":"Nordic health registry-based research: a review of health care systems and key registries","volume":"13","author":"Laugesen","year":"2021","journal-title":"Clin Epidemiol"},{"key":"2023061420112682800_dyad003-B29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12884-016-0800-8","article-title":"From grief, guilt, pain and stigma to hope and pride: a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth","volume":"16","author":"Burden","year":"2016","journal-title":"BMC Pregn Childbirth"},{"key":"2023061420112682800_dyad003-B30","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1651-2227.1996.tb14164.x","article-title":"Intrauterine growth curves based on ultrasonically estimated foetal weights","volume":"85","author":"Mars\u00e1l","year":"1996","journal-title":"Acta Paediatr"},{"key":"2023061420112682800_dyad003-B31","author":"Royal College of Obstetricians and Gynaecologists","year":"2010"},{"key":"2023061420112682800_dyad003-B32","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1093\/humrep\/dey269","article-title":"Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis","volume":"33","author":"Lalani","year":"2018","journal-title":"Hum Reprod"},{"key":"2023061420112682800_dyad003-B33","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bpobgyn.2015.11.017","article-title":"Pregnancy outcome and uterine fibroids","volume":"34","author":"Parazzini","year":"2016","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2023061420112682800_dyad003-B34","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/humupd\/dmv029","article-title":"Pregnancy complications in women with polycystic ovary syndrome","volume":"21","author":"Palomba","year":"2015","journal-title":"Hum Reprod Update"},{"key":"2023061420112682800_dyad003-B35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.fertnstert.2016.05.014","article-title":"Uterine septum: a guideline","volume":"106","author":"Practice Committee of the American Society of Reproductive Medicine","year":"2016","journal-title":"Fertil Steril"}],"container-title":["International Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/52\/2\/403\/50606527\/dyad003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/52\/2\/403\/50606527\/dyad003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T20:12:23Z","timestamp":1686773543000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ije\/article\/52\/2\/403\/7008683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,28]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1,28]]},"published-print":{"date-parts":[[2023,4,19]]}},"URL":"https:\/\/doi.org\/10.1093\/ije\/dyad003","relation":{},"ISSN":["0300-5771","1464-3685"],"issn-type":[{"value":"0300-5771","type":"print"},{"value":"1464-3685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,1]]},"published":{"date-parts":[[2023,1,28]]}}}