{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:35:55Z","timestamp":1790825755846,"version":"4.1.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016055","name":"Mercy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004914","name":"Ferring Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004914","id-type":"DOI","asserted-by":"publisher"}]}],"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>In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (\n                      <jats:italic>n<\/jats:italic>\n                      = 173,200) and defined as scoring &lt;10th percentile in \u22652\/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program\u2013Literacy and Numeracy (NAPLAN) data (\n                      <jats:italic>n<\/jats:italic>\n                      = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects.\n                    <\/jats:p>\n                    <jats:p>The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of \u22120.3% (95% CI \u22123.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI \u22120.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004148","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:22:06Z","timestamp":1674566526000},"page":"e1004148","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["School-age outcomes among IVF-conceived children: A population-wide cohort study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-8102","authenticated-orcid":true,"given":"Amber L.","family":"Kennedy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-3994","authenticated-orcid":true,"given":"Beverley J.","family":"Vollenhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5375-041X","authenticated-orcid":true,"given":"Richard J.","family":"Hiscock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharyn J.","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-0455","authenticated-orcid":true,"given":"Jeanie L. Y.","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon L.","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-1943","authenticated-orcid":true,"given":"Roxanne","family":"Hastie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McBain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle C.","family":"Gurrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"MacLachlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Agresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P.","family":"Baohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2319-0586","authenticated-orcid":true,"given":"Stephen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-5188","authenticated-orcid":true,"given":"Anthea C.","family":"Lindquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"pmed.1004148.ref001","article-title":"International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology","author":"GD Adamson","year":"2017"},{"key":"pmed.1004148.ref002","article-title":"More than 8 million babies born from IVF since the world\u2019s first in 1978: European IVF pregnancy rates now steady at around 36 percent, according to ESHRE monitoring.","author":"European Society of Human Reproduction and Embryology","year":"2018","journal-title":"ScienceDaily."},{"key":"pmed.1004148.ref003","article-title":"World\u2019s number of IVF and ICSI babies has now reached a calculated total of 5 million.","author":"European Society of Human Reproduction and Embryology","year":"2012","journal-title":"ScienceDaily."},{"key":"pmed.1004148.ref004","article-title":"Assisted reproductive technology in Australia and New Zealand 2018.","author":"JE Newman","year":"2020","journal-title":"National Perinatal Epidemiology and Statistics Unit, the University of New South Wales, Sydney"},{"key":"pmed.1004148.ref005","volume-title":"Births, Australia","author":"Australian Bureau of Statistics","year":"2018"},{"issue":"5","key":"pmed.1004148.ref006","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/humupd\/dms018","article-title":"Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF\/ICSI: a systematic review and meta-analysis","volume":"18","author":"S Pandey","year":"2012","journal-title":"Hum Reprod Update"},{"issue":"1","key":"pmed.1004148.ref007","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":"J Qin","year":"2016","journal-title":"Fertil Steril"},{"issue":"1","key":"pmed.1004148.ref008","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":"JL Marino","year":"2014","journal-title":"PLoS ONE."},{"issue":"9305","key":"pmed.1004148.ref009","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(02)07674-2","article-title":"Neurological sequelae in children born after in-vitro fertilisation: a population-based study","volume":"359","author":"B Stromberg","year":"2002","journal-title":"Lancet"},{"key":"pmed.1004148.ref010","doi-asserted-by":"crossref","first-page":"f3978","DOI":"10.1136\/bmj.f3978","article-title":"Fertility treatment 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Knoester","year":"2008","journal-title":"Fertil Steril"},{"issue":"10","key":"pmed.1004148.ref016","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1093\/humrep\/deq218","article-title":"Achievement test performance in children conceived by IVF","volume":"25","author":"L Mains","year":"2010","journal-title":"Hum Reprod"},{"issue":"7","key":"pmed.1004148.ref017","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/humrep\/dex102","article-title":"Cognitive development in children up to age 11 years born after ART-a longitudinal cohort study","volume":"32","author":"A Barbuscia","year":"2017","journal-title":"Hum Reprod"},{"issue":"10","key":"pmed.1004148.ref018","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1093\/humrep\/dey273","article-title":"School performance in singletons born after assisted reproductive technology","volume":"33","author":"E Norrman","year":"2018","journal-title":"Hum 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Health"},{"issue":"5","key":"pmed.1004148.ref024","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1136\/jech-2017-210102","article-title":"How consistent are associations between maternal and paternal education and child growth and development outcomes across 39 low-income and middle-income countries?","volume":"72","author":"J Jeong","year":"2018","journal-title":"J Epidemiol Community Health."},{"issue":"15","key":"pmed.1004148.ref025","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMp2113319","article-title":"Methods of Public Health Research\u2014Strengthening Causal Inference from Observational Data","volume":"385","author":"MA Hernan","year":"2021","journal-title":"N Engl J Med"},{"issue":"8","key":"pmed.1004148.ref026","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/aje\/kwv254","article-title":"Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available","volume":"183","author":"MA Hern\u00e1n","year":"2016","journal-title":"Am J Epidemiol"},{"issue":"15","key":"pmed.1004148.ref027","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMp2113319","article-title":"Methods of Public Health Research\u2014Strengthening Causal Inference from Observational Data","volume":"385","author":"MA Hern\u00e1n","year":"2021","journal-title":"N Engl J Med"},{"issue":"3","key":"pmed.1004148.ref028","first-page":"113","article-title":"Data accuracy in the Victorian Perinatal Data Collection: Results of a validation study of 2011 data.","volume":"46","author":"MM Flood","year":"2017","journal-title":"Health Inf Manag."},{"issue":"3","key":"pmed.1004148.ref029","first-page":"12","article-title":"Methodological processes in validating and analysing the quality of population-based data: a case study using the Victorian Perinatal Data Collection.","volume":"42","author":"MA Davey","year":"2013","journal-title":"Health Inf Manag"},{"key":"pmed.1004148.ref030","author":"The Australian Early Development Census","year":"2020","journal-title":"ABOUT THE AEDC 2022"},{"key":"pmed.1004148.ref031","unstructured":"The Australian Curriculum Assessment and Reporting Aurthority (ACARA). The National Assessment Program for Literacy and Numeracy. 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Findings from a South Australian data linkage study","volume":"35","author":"A Pearce","year":"2016","journal-title":"Early Child Res Q."},{"key":"pmed.1004148.ref045","doi-asserted-by":"crossref","first-page":"112476","DOI":"10.1016\/j.socscimed.2019.112476","article-title":"How do grandparents influence child health and development? A systematic review.","volume":"239","author":"AFA Sadruddin","year":"2019","journal-title":"Soc Sci Med."},{"issue":"8","key":"pmed.1004148.ref046","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2019-002181","article-title":"The contribution of grandmother involvement to child growth and development: an observational study in rural Pakistan.","volume":"5","author":"EO Chung","year":"2020","journal-title":"BMJ Global Health"},{"key":"pmed.1004148.ref047","article-title":"Committee on the Science of Children Birth to Age 8: Deepening and Broadening the Foundation for Success.","author":"L Allen","year":"2015","journal-title":"Transforming the Workforce for Children Birth Through Age 8: A Unifying Foundation. editors. Washington (DC"},{"issue":"4","key":"pmed.1004148.ref048","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in Observational Research: Introducing the E-Value","volume":"167","author":"TJ VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"issue":"2","key":"pmed.1004148.ref049","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1097\/EE9.0000000000000131","article-title":"Environmental hazards, social inequality, and fetal loss: Implications of live-birth bias for estimation of disparities in birth outcomes.","volume":"5","author":"DE Goin","year":"2021","journal-title":"Environ Epidemiol."}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:22:44Z","timestamp":1674566564000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,24]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004148","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,24]]}}}