{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T03:17:35Z","timestamp":1785035855275,"version":"3.55.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HD088393"],"award-info":[{"award-number":["R01HD088393"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The association between assisted reproductive technologies (ARTs) and the body mass index (BMI) of children remains controversial. Confounding by morbidity and other factors associated with parental infertility may have biased studies comparing children born after ART with children born after no treatment. We investigated the associations between different fertility treatments and BMI in children at age 5 to 8 years, adjusting for and stratifying by causes of parental infertility.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>This Danish cohort study included 327,301 children born between 2007 and 2012 (51% males, median age at follow-up 7 years). Of these, 13,675 were born after ART, 7,728 were born after ovulation induction with or without intrauterine insemination [OI\/IUI], and 305,898 were born after no fertility treatments. Using the International Obesity Task Force (IOTF) standards, we defined overweight (BMI \u2265 IOTF-25) and obesity (BMI \u2265 IOTF-30). We compared children born after ART versus OI\/IUI; intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF); and frozen-thawed versus fresh embryo transfer and estimated crude and adjusted prevalences of children with overweight or obesity at age 5 to 8 years, prevalence odds ratios (PORs), and differences in mean BMI z-scores. Adjustment was performed using stabilized inverse probability of treatment weights, including parity, year of conception, parental causes of infertility, age, educational level, comorbidities, maternal country of origin, BMI, and smoking as covariates. The crude prevalence of obesity was 1.9% in children born after ART, 2.0% in those born after OI\/IUI, and 2.7% in those born after no fertility treatment. After adjustment, children born after ART and OI\/IUI had the same prevalence of being overweight (11%; POR 1.00, 95% confidence interval [CI] 0.91 to 1.11; <jats:italic>p<\/jats:italic> = 0.95) or obese (1.9%; POR 1.01, 95% CI 0.79 to 1.29; <jats:italic>p<\/jats:italic> = 0.94). Comparison of ICSI with conventional IVF yielded similar pattern (POR 0.95, 95% CI 0.83 to 1.07; <jats:italic>p<\/jats:italic> = 0.39 for overweight and POR 1.16, 95% CI 0.84 to 1.61; <jats:italic>p<\/jats:italic> = 0.36 for obesity). Obesity was more prevalent after frozen-thawed (2.7%) than fresh embryo transfer (1.8%) (POR 1.54, 95% CI 1.09 to 2.17; <jats:italic>p<\/jats:italic> = 0.01). The associations between fertility treatments and BMI were only modestly different in subgroups defined by the cause of infertility. Study limitations include potential residual confounding, restriction to live births, and lack of detailed technical information about the IVF procedures.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We found no association with BMI at age 5 to 8 years when comparing ART versus OI\/IUI or when comparing ICSI versus conventional IVF. However, use of frozen-thawed embryo transfer was associated with a 1.5-fold increased risk of obesity compared to fresh embryo transfer. Despite an elevated relative risk, the absolute risk difference was low.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004324","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T18:22:50Z","timestamp":1703010170000},"page":"e1004324","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-8223","authenticated-orcid":true,"given":"Kristina","family":"Laugesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-8781","authenticated-orcid":true,"given":"Katalin","family":"Veres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Hernandez-Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-7855","authenticated-orcid":true,"given":"Yu-Han","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sara","family":"Oberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6528-6009","authenticated-orcid":true,"given":"Paolo","family":"Rinaudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3872-005X","authenticated-orcid":true,"given":"Mandy","family":"Spaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"van Leeuwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-7040","authenticated-orcid":true,"given":"Henrik Toft","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"issue":"3","key":"pmed.1004324.ref001","article-title":"ART in Europe, 2017: results generated from European registries by ESHRE\u2020.","volume":"2021","author":"European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE),","year":"2021","journal-title":"Hum Reprod Open."},{"key":"pmed.1004324.ref002","author":"The World Health Organization","journal-title":"Infertility is a global public health issue"},{"key":"pmed.1004324.ref003","article-title":"Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology","author":"L Cui","year":"2020","journal-title":"Diabetologia"},{"issue":"9","key":"pmed.1004324.ref004","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1210\/jc.2006-2896","article-title":"Body composition in children and adolescents born after in vitro fertilization or spontaneous conception","volume":"92","author":"M Ceelen","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"pmed.1004324.ref005","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1210\/jc.2007-2432","article-title":"Cardiometabolic differences in children born after in vitro fertilization: follow-up study","volume":"93","author":"M Ceelen","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"pmed.1004324.ref006","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12916-018-1203-7","article-title":"The growth of assisted reproductive treatment-conceived children from birth to 5 years: a national cohort study.","volume":"16","author":"M Hann","year":"2018","journal-title":"BMC Med."},{"issue":"3","key":"pmed.1004324.ref007","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/humupd\/dms062","article-title":"The longer-term health outcomes for children born as a result of IVF treatment: Part I\u2014General health outcomes.","volume":"19","author":"R Hart","year":"2013","journal-title":"Hum Reprod Update"},{"issue":"4","key":"pmed.1004324.ref008","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1017\/S2040174417000228","article-title":"The health outcomes of human offspring conceived by assisted reproductive technologies (ART).","volume":"8","author":"M Chen","year":"2017","journal-title":"J Dev Orig Health Dis"},{"issue":"9","key":"pmed.1004324.ref009","doi-asserted-by":"crossref","first-page":"e1003723","DOI":"10.1371\/journal.pmed.1003723","article-title":"Cardiovascular disease, obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort 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children conceived from fresh and thawed embryos in in vitro fertilization compared with naturally conceived children","volume":"99","author":"MP Green","year":"2013","journal-title":"Fertil Steril"},{"issue":"4","key":"pmed.1004324.ref016","doi-asserted-by":"crossref","first-page":"e94001","DOI":"10.1371\/journal.pone.0094001","article-title":"Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI.","volume":"9","author":"A Gkourogianni","year":"2014","journal-title":"PLoS ONE."},{"issue":"3","key":"pmed.1004324.ref017","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.rbmo.2014.11.006","article-title":"Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood","volume":"30","author":"M Pontesilli","year":"2015","journal-title":"Reprod Biomed 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Pelkonen","year":"2010","journal-title":"Hum Reprod"},{"key":"pmed.1004324.ref024","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":"K Laugesen","year":"2021","journal-title":"Clin Epidemiol."},{"issue":"7 Suppl","key":"pmed.1004324.ref025","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1177\/1403494811399957","article-title":"Danish registers on aspects of reproduction","volume":"39","author":"LT Blenstrup","year":"2011","journal-title":"Scand J Public Health"},{"key":"pmed.1004324.ref026","author":"Ramb\u00f8ll Management Consulting","year":"2018","journal-title":"Unders\u00f8gelse af hjemmeundervisning, frav\u00e6r, og b\u00f8rn uden for undervisningstilbud."},{"key":"pmed.1004324.ref027","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential.","volume":"7","author":"M Schmidt","year":"2015","journal-title":"Clin Epidemiol."},{"issue":"3","key":"pmed.1004324.ref028","first-page":"798","article-title":"Data Resource Profile: The Danish National Prescription Registry.","volume":"46","author":"A Pottegard","year":"2017","journal-title":"Int J Epidemiol."},{"issue":"8","key":"pmed.1004324.ref029","doi-asserted-by":"crossref","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":"M Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"pmed.1004324.ref030","first-page":"320","article-title":"The Danish Medical Birth Registry.","volume":"45","author":"LB Knudsen","year":"1998","journal-title":"Dan Med Bull."},{"key":"pmed.1004324.ref031","author":"WorldObesity","journal-title":"Obesity 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adolescence in Sweden.","volume":"2","author":"K Barclay","year":"2016","journal-title":"SSM Popul Health"},{"key":"pmed.1004324.ref036","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12887-015-0443-3","article-title":"Socioeconomic position and childhood-adolescent weight status in rich countries: a systematic review, 1990\u20132013","volume":"15","author":"L Barriuso","year":"2015","journal-title":"BMC Pediatr"},{"issue":"4","key":"pmed.1004324.ref037","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1159\/000446482","article-title":"Ethnic Inequalities in Overweight and Obesity Prevalence among Copenhagen Schoolchildren from 2002 to 2007.","volume":"9","author":"DC Pedersen","year":"2016","journal-title":"Obes Facts."},{"issue":"2","key":"pmed.1004324.ref038","doi-asserted-by":"crossref","first-page":"e1002744","DOI":"10.1371\/journal.pmed.1002744","article-title":"Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.","volume":"16","author":"E Voerman","year":"2019","journal-title":"PLoS Med."},{"issue":"1","key":"pmed.1004324.ref039","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1038\/s41598-022-07122-6","article-title":"Smoking during pregnancy is associated with child overweight independent of maternal pre-pregnancy BMI and genetic predisposition to adiposity.","volume":"12","author":"TM Schnurr","year":"2022","journal-title":"Sci Rep."},{"issue":"1","key":"pmed.1004324.ref040","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12916-023-02742-9","article-title":"Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study.","volume":"21","author":"LKL \u00d8yri","year":"2023","journal-title":"BMC Med."},{"issue":"5","key":"pmed.1004324.ref041","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.jpeds.2007.01.034","article-title":"Longitudinal Relationship of Parental Hypertension with Body Mass Index, Blood Pressure, and Cardiovascular Reactivity in Children","volume":"150","author":"R Li","year":"2007","journal-title":"J Pediatr"},{"issue":"11","key":"pmed.1004324.ref042","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1007\/s00125-018-4688-x","article-title":"Associations of maternal type 1 diabetes with childhood adiposity and metabolic health in the offspring: a prospective cohort study","volume":"61","author":"A Pitchika","year":"2018","journal-title":"Diabetologia"},{"issue":"2","key":"pmed.1004324.ref043","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1161\/HYPERTENSIONAHA.114.03492","article-title":"Maternal parity, fetal and childhood growth, and cardiometabolic risk factors","volume":"64","author":"R Gaillard","year":"2014","journal-title":"Hypertension"},{"issue":"3","key":"pmed.1004324.ref044","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/eurpub\/ckad024","article-title":"Changes in adult obesity prevalence in Denmark, 1987\u20132021: age\u2013period\u2013cohort analysis of nationally representative data.","volume":"33","author":"S Schramm","year":"2023","journal-title":"Eur J Public Health."},{"key":"pmed.1004324.ref045","doi-asserted-by":"crossref","first-page":"l5657","DOI":"10.1136\/bmj.l5657","article-title":"Alternative approaches for confounding adjustment in observational studies using weighting based on the propensity score: a primer for practitioners","volume":"367","author":"RJ Desai","year":"2019","journal-title":"BMJ"},{"key":"pmed.1004324.ref046","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molmet.2018.04.007","article-title":"Sex and gender differences in developmental programming of metabolism","volume":"15","author":"L Dearden","year":"2018","journal-title":"Mol Metab"},{"issue":"7","key":"pmed.1004324.ref047","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/humrep\/deac073","article-title":"Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis","volume":"37","author":"A Busnelli","year":"2022","journal-title":"Hum Reprod"},{"issue":"3","key":"pmed.1004324.ref048","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1161\/HYPERTENSIONAHA.118.12043","article-title":"Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum","volume":"73","author":"F von Versen-H\u00f6ynck","year":"2019","journal-title":"Hypertension"},{"issue":"4","key":"pmed.1004324.ref049","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1530\/EJE-21-0846","article-title":"Prenatal exposure to glucocorticoids and the prevalence of overweight 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birthweight differences induced by assisted reproductive technologies","volume":"14","author":"E Carlsen","year":"2022","journal-title":"Clin Epigenetics"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T18:23:24Z","timestamp":1703010204000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004324"}},"subtitle":[],"editor":[{"given":"Sarah 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