{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:55:21Z","timestamp":1792173321602,"version":"4.4.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000165","name":"Sick Kids Foundation","doi-asserted-by":"publisher","award":["NI18-1272"],"award-info":[{"award-number":["NI18-1272"]}],"id":[{"id":"10.13039\/501100000165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>The pathophysiology behind the association between obesity and perinatal death is not fully understood but may be in part due to higher rates of pregnancy complications at earlier gestation amongst obese women. We aimed to quantify the proportion of perinatal deaths amongst obese and overweight women mediated by gestational age at stillbirth or live birth.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The study included all singleton births at \u226520 weeks\u2019 gestation in British Columbia, 2004\u20132017, and excluded pregnancy terminations. The proportion of the association between BMI and perinatal death mediated by gestational age at delivery (in weeks) was estimated using natural effect models, with adjustment for potential confounders. Sensitivity analyses for unmeasured confounding and women missing BMI were conducted.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of 392,820 included women, 20.6% were overweight and 12.8% obese. Women with higher BMI had a lower gestational age at delivery. Perinatal mortality was 0.5% (1834 pregnancies); and was elevated in overweight (adjusted odds ratio [AOR] = 1.22, 95% confidence interval [CI] 1.08\u20131.37) and obese women (AOR = 1.55, 95% CI 1.36\u20131.77). Mediation analysis showed that 63.1% of the association between obesity and perinatal death was mediated by gestational age at delivery (natural indirect effect AOR = 1.32, 95% CI 1.23\u20131.42, natural direct effect AOR = 1.18, 95% CI 1.05\u20131.32). Similar, but smaller effects were seen when comparing overweight women vs. women with a normal BMI. Estimated effects were not affected by adjustment for additional risk factors for perinatal death or sensitivity analyses for missing data.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Obese pregnancies have a higher risk of perinatal death in part mediated by a lower gestational age at delivery.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0264565","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T17:24:09Z","timestamp":1648056249000},"page":"e0264565","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["The association between pre-pregnancy body mass index and perinatal death and the role of gestational age at delivery"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7704-1677","authenticated-orcid":true,"given":"Jeffrey N.","family":"Bone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. S.","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Platt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarka","family":"Lisonkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"pone.0264565.ref001","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/S0140-6736(17)32129-3","article-title":"Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults","volume":"390","author":"J Bentham","year":"2017","journal-title":"The Lancet"},{"key":"pone.0264565.ref002","doi-asserted-by":"crossref","first-page":"e0202183","DOI":"10.1371\/journal.pone.0202183","article-title":"Estimated global overweight and obesity burden in pregnant women based on panel data model","volume":"13","author":"C Chen","year":"2018","journal-title":"PLOS ONE"},{"key":"pone.0264565.ref003","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ijgo.2010.03.008","article-title":"SOGC Clinical Practice Guidelines: Obesity in pregnancy. No. 239, February 2010.","volume":"110","author":"GAL Davies","year":"2010","journal-title":"Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet"},{"key":"pone.0264565.ref004","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/j.1471-0528.2005.00437.x","article-title":"Pre-pregnancy weight and the risk of stillbirth and neonatal death","volume":"112","author":"J Kristensen","year":"2005","journal-title":"BJOG Int J Obstet Gynaecol"},{"key":"pone.0264565.ref005","doi-asserted-by":"crossref","first-page":"E1202","DOI":"10.1503\/cmaj.109-5472","article-title":"Overweight or overfat? Many Canadians are both.","author":"L. Vogel","year":"2017","journal-title":"CMAJ: Canadian Medical Association journal = journal de l\u2019Association medicale canadienne"},{"key":"pone.0264565.ref006","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/01.AOG.0000107291.46159.00","article-title":"Maternal Morbid Obesity and the Risk of Adverse Pregnancy Outcome.","volume":"103","author":"MI Cedergren","year":"2004","journal-title":"Obstet Gynecol"},{"key":"pone.0264565.ref007","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1001\/jama.2017.16191","article-title":"Association between prepregnancy body mass index and severe maternal morbidity","volume":"318","author":"S Lisonkova","year":"2017","journal-title":"JAMA\u2014J Am Med Assoc"},{"key":"pone.0264565.ref008","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/AOG.0b013e3182245d49","article-title":"Effect of prepregnancy maternal overweight and obesity on pregnancy outcome.","volume":"118","author":"P Ovesen","year":"2011","journal-title":"Obstet Gynecol"},{"key":"pone.0264565.ref009","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1001\/jama.2014.2269","article-title":"Maternal body mass index and the risk of fetal death, stillbirth, and infant death: A systematic review and meta-analysis","volume":"311","author":"D Aune","year":"2014","journal-title":"JAMA\u2014J Am Med Assoc"},{"key":"pone.0264565.ref010","doi-asserted-by":"crossref","first-page":"858","DOI":"10.3945\/ajcn.115.112250","article-title":"Maternal prepregnancy obesity and cause-specific stillbirth","volume":"102","author":"LM Bodnar","year":"2015","journal-title":"Am J Clin Nutr"},{"key":"pone.0264565.ref011","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1067\/mob.2001.109591","article-title":"Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth","volume":"184","author":"O Stephansson","year":"2001","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0264565.ref012","doi-asserted-by":"crossref","first-page":"212.e1","DOI":"10.1016\/j.ajog.2012.06.002","article-title":"Prepregnancy maternal body mass index and preterm delivery.","volume":"207","author":"A Khatibi","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0264565.ref013","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1001\/jama.2013.6295","article-title":"Maternal obesity and risk of preterm delivery","volume":"309","author":"S Cnattingius","year":"2013","journal-title":"JAMA\u2014J Am Med Assoc"},{"key":"pone.0264565.ref014","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/ije\/31.1.163","article-title":"Fallibility in estimating direct effects","volume":"31","author":"SR Cole","year":"2002","journal-title":"Int J Epidemiol"},{"key":"pone.0264565.ref015","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4310\/SII.2009.v2.n4.a7","article-title":"Conceptual issues concerning mediation, interventions and composition.","volume":"2","author":"TJ Vanderweele","year":"2009","journal-title":"Stat Interface"},{"key":"pone.0264565.ref016","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/EDE.0000000000000034","article-title":"Effect decomposition in the presence of an exposure-induced mediator-outcome confounder","volume":"25","author":"TJ Vanderweele","year":"2014","journal-title":"Epidemiology"},{"key":"pone.0264565.ref017","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/aje\/kwr525","article-title":"A simple unified approach for estimating natural direct and indirect effects","volume":"176","author":"T Lange","year":"2012","journal-title":"Am J Epidemiol"},{"key":"pone.0264565.ref018","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1214\/10-STS321","article-title":"Identification, Inference and Sensitivity Analysis for Causal Mediation Effects.","volume":"25","author":"K Imai","year":"2010","journal-title":"Stat Sci"},{"key":"pone.0264565.ref019","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1136\/jech.2002.006361","article-title":"A definition of causal effect for epidemiological research","author":"MA Hern\u00e1n","year":"2004","journal-title":"Journal of Epidemiology and Community Health"},{"key":"pone.0264565.ref020","author":"PB Services","journal-title":"British Columbia Perinatal Data Registry Reference Manual"},{"key":"pone.0264565.ref021","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s12884-015-0563-7","article-title":"Validating the British Columbia Perinatal Data Registry: a chart re-abstraction study","volume":"15","author":"G Frosst","year":"2015","journal-title":"BMC Pregnancy Childbirth"},{"key":"pone.0264565.ref022","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S1701-2163(16)30414-5","article-title":"Theory of Obstetrics: \u201cThe Fetuses-At-Risk Approach\u201d as a Causal Paradigm.","author":"KS Joseph","year":"2004","journal-title":"Journal of Obstetrics and Gynaecology Canada."},{"key":"pone.0264565.ref023","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","article-title":"Mediation Analysis: A Practitioner\u2019s Guide.","volume":"37","author":"TJ VanderWeele","year":"2016","journal-title":"Annu Rev Public Health"},{"key":"pone.0264565.ref024","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/biomet\/73.1.13","article-title":"Longitudinal Data Analysis Using Generalized Linear Models","volume":"73","author":"K-Y Liang","year":"1986","journal-title":"Biometrika"},{"key":"pone.0264565.ref025","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10654-019-00494-6","article-title":"Principles of confounder selection","volume":"34","author":"TJ VanderWeele","year":"2019","journal-title":"Eur J Epidemiol"},{"key":"pone.0264565.ref026","author":"T. VanderWeele","year":"2015","journal-title":"Explanation in causal inference: methods for mediation and interaction"},{"key":"pone.0264565.ref027","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1515\/2161-962X.1014","article-title":"Imputation Strategies for the Estimation of Natural Direct and Indirect Effects","volume":"1","author":"S Vansteelandt","year":"2012","journal-title":"Epidemiol Methods"},{"key":"pone.0264565.ref028","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/biomet\/asw012","article-title":"Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding","volume":"103","author":"P Ding","year":"2016","journal-title":"Biometrika"},{"key":"pone.0264565.ref029","first-page":"300","article-title":"Quantifying Biases in Causal Models: Classical Confounding vs Collider-Stratification Bias.","author":"S. Greenland","year":"2003","journal-title":"Epidemiology Lippincott Williams & Wilkins"},{"key":"pone.0264565.ref030","volume-title":"Multiple imputation for nonresponse in surveys","author":"DB Rubin","year":"2004"},{"key":"pone.0264565.ref031","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/j.1541-0420.2012.01777.x","article-title":"Natural Direct and Indirect Effects on the Exposed: Effect Decomposition under Weaker Assumptions","volume":"68","author":"S Vansteelandt","year":"2012","journal-title":"Biometrics"},{"key":"pone.0264565.ref032","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/EDE.0000000000000034","article-title":"Effect decomposition in the presence of an exposure-induced mediator-outcome confounder","volume":"25","author":"TJ Vanderweele","year":"2014","journal-title":"Epidemiology"},{"key":"pone.0264565.ref033","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/EDE.0000000000000596","article-title":"Interventional Effects for Mediation Analysis with Multiple Mediators.","volume":"28","author":"S Vansteelandt","year":"2017","journal-title":"Epidemiology"},{"key":"pone.0264565.ref034","article-title":"R: A language and environment for statistical computing.","author":"R Foundation for Statistical Computing","year":"2014","journal-title":"Internet]"},{"key":"pone.0264565.ref035","author":"J Steen","journal-title":"Medflex: An R Package for Flexible Mediation Analysis using Natural Effect Models"},{"key":"pone.0264565.ref036","doi-asserted-by":"crossref","first-page":"457.e1","DOI":"10.1016\/j.ajog.2014.01.044","article-title":"Obesity and the risk of stillbirth: A population-based cohort study","volume":"210","author":"R Yao","year":"2014","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0264565.ref037","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ajog.2007.03.027","article-title":"Maternal obesity and risk of stillbirth: a metaanalysis.","author":"SY Chu","year":"2007","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"pone.0264565.ref038","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1093\/humrep\/der052","article-title":"Maternal body mass index and the risk of fetal and infant death: a cohort study from the North of England","volume":"26","author":"PWG Tennant","year":"2011","journal-title":"Hum Reprod"},{"key":"pone.0264565.ref039","author":"T Navaneelan","journal-title":"Adjusting the scales: Obesity in the Canadian population after correcting for respondent bias"},{"key":"pone.0264565.ref040","doi-asserted-by":"crossref","first-page":"524.e1","DOI":"10.1016\/j.ajog.2014.04.028","article-title":"The utility of ultrasound surveillance of fluid and growth in obese women","author":"LM Harper","year":"2014","journal-title":"American Journal of Obstetrics and Gynecology. Mosby Inc."},{"key":"pone.0264565.ref041","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1001\/jama.2011.1823","article-title":"Causes of death among stillbirths","volume":"306","author":"R Bukowski","year":"2011","journal-title":"JAMA\u2014J Am Med Assoc"},{"key":"pone.0264565.ref042","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/j.1471-0528.2008.01694.x","article-title":"Maternal obesity, length of gestation, risk of postdates pregnancy and spontaneous onset of labour at term","volume":"115","author":"F Denison","year":"2008","journal-title":"BJOG Int J Obstet Gynaecol"},{"key":"pone.0264565.ref043","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/aogs.13194","article-title":"The fetuses-at-risk approach: survival analysis from a fetal perspective","author":"KS Joseph","year":"2018","journal-title":"Acta Obstetricia et Gynecologica Scandinavica"},{"key":"pone.0264565.ref044","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/aje\/kwi256","article-title":"Respond to \u201cHypothetical Interventions to Define Causal Effects","volume":"162","author":"MJ van der Laan","year":"2005","journal-title":"Am J Epidemiol"},{"key":"pone.0264565.ref045","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1097\/EDE.0b013e3181f5d3fd","article-title":"On the consistency rule in causal inference: Axiom, definition, assumption, or theorem?","volume":"21","author":"J. Pearl","year":"2010","journal-title":"Epidemiology"},{"key":"pone.0264565.ref046","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/jci-2012-0002","article-title":"Causal inference under multiple versions of treatment","volume":"1","author":"TJ VanderWeele","year":"2013","journal-title":"J Causal Inference"},{"key":"pone.0264565.ref047","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/EDE.0b013e3182109296","article-title":"Compound treatments and transportability of causal inference","volume":"22","author":"MA Hern\u00e1n","year":"2011","journal-title":"Epidemiology"},{"key":"pone.0264565.ref048","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1038\/ijo.2008.82","article-title":"Does obesity shorten life? The importance of well-defined interventions to answer causal questions","volume":"32","author":"MA Hern\u00e1n","year":"2008","journal-title":"Int J Obes"},{"key":"pone.0264565.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/biom.12248","article-title":"Causal mediation analysis with multiple mediators","volume":"71","author":"RM Daniel","year":"2015","journal-title":"Biometrics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T17:25:10Z","timestamp":1648056310000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264565"}},"subtitle":[],"editor":[{"given":"Angela","family":"Lupattelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,23]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264565","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,23]]}}}