{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:58:43Z","timestamp":1790308723029,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU H2020 Marie Sklodowska-Curie Innovative Training Networks","award":["H2020-MSCAITN-2018-812660"],"award-info":[{"award-number":["H2020-MSCAITN-2018-812660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Has the average birthweight (BW) for singletons born in the UK through ART changed between 1991 and 2018 relative to the general population?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>The average gestation-adjusted BW for ART singletons increased steadily between 1991 and 2012 before becoming almost static until 2018; these changes were not observed in the general UK population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Many older studies have shown that ART babies are low BW (LBW) compared to naturally conceived babies. Some subsequent evidence suggests that the average BW for fresh and frozen transfer ART babies has increased over recent years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This cohort study utilized the UK Human Fertilisation and Embryology Authority (HFEA) dataset of 140\u00a0859 singleton ART babies born between 1991 and 2018 in the UK following both fresh and frozen embryo transfer (FET). Comparative aggregated data of 11\u00a0790\u00a0372 singleton babies born in the UK general population during the same period were obtained from NHS Digital.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>The HFEA dataset was used to explore ART BW (raw or gestation-adjusted) and gestational age trends between 1991 and 2018. Appropriate regression models assessed the outcomes and adjusted for child sex, available treatment factors (fresh\/frozen ET, embryo transfer stage (cleavage or blastocyst transfer), number of embryos transferred, ovarian stimulation, ICSI, treatment centre\/clinic, and pre-implantation genetic screening of embryos) and patient factors (maternal age, previous IVF attempts, previous live births, previous pregnancies, ethnicity, country of treatment within the UK (England, Northern Ireland, Scotland, and Wales), funding source, total number of oocytes retrieved, and infertility causes (endometriosis, idiopathic, ovulatory, tubal diagnosis, and male factor)). BW, LBW, and macrosomia models were additionally adjusted for gestational age. Segmented trend analysis using linear splines was used to capture non-linear time effects for BW and gestation outcomes. For the general population data, mean BW and gestation outcomes were assessed as raw, unadjusted yearly averages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Unadjusted raw BW trends show that ART babies were initially smaller than the general population, but over time, are becoming closer to it. Fully adjusted mean ART BW increased by \u223c75\u2009g between 1991 and 2012, and after that, it was almost static. A drop in ART raw BW starting in 2013 was concurrent with a drop in average gestation by an overall average of 2.5\u2009days between 2012 and 2018. The mean raw BW in the general population remained almost static over the study period and consistently higher than the ART BW average, with a notable drop beginning in 2013, concurrent with a decline in average gestation. Between 1991 and 2000, and 2012 and 2018, average gestation trends were comparable in the ART and general population, with varying patterns between 2001 and 2012.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>We could only explore factors available in the dataset, possibly missing some unobserved\/unrecorded covariates such as socio-economic and lifestyle factors. The ART dataset used required patient consent, leading to the exclusion of \u223c40% of all cycles conducted during the study period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>ART singletons getting bigger over time is reassuring, as fewer ART babies now have adverse birth outcomes such as LBW. This is desirable within the developmental origins of health and disease (DOHaD) framework, which links adverse child outcomes to later-life disease predisposition. These changes in ART singletons (not observed in the general population) might be the result of changes or improvements in ART technologies, clinic practices, and ART patient population characteristics. Therefore, there is a need to continue monitoring BW-related outcomes such as large for gestational age and macrosomia, which are more prevalent in frozen ET ART babies and, though directly associated with the observed increase in average ART BW, can be detrimental to child health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This study was funded by the EU H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN) grant Dohartnet (H2020-MSCA-ITN-2018-812660).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>The authors have no competing interests to declare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>n\/a.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag140","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:23:46Z","timestamp":1788521026000},"source":"Crossref","is-referenced-by-count":0,"title":["Birthweight trends for babies born using Assisted Reproductive Treatments between 1991 and 2018: a national cohort study"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2433-5994","authenticated-orcid":false,"given":"Fiskani J M","family":"Kondowe","sequence":"first","affiliation":[{"name":"Division of Population Health, Health Services Research & Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, Centre for Biostatistics, The University of Manchester, Manchester Academic Health Science Centre , Manchester,","place":["UK"]},{"name":"Mathematical Sciences Department, University of Malawi , Zomba,","place":["Malawi"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gittins","sequence":"additional","affiliation":[{"name":"Division of Population Health, Health Services Research & Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, Centre for Biostatistics, The University of Manchester, Manchester Academic Health Science Centre , Manchester,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-4537","authenticated-orcid":false,"given":"Peter","family":"Clayton","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology and Medicine, Child Health & Paediatric Endocrinology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Sciences Centre , Manchester,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-1293","authenticated-orcid":false,"given":"Daniel R","family":"Brison","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology and Medicine, Maternal & Fetal Health Research Centre, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Sciences Centre , Manchester,","place":["UK"]},{"name":"Maternal and Fetal Health, St Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre , Manchester,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7477-7731","authenticated-orcid":false,"given":"Stephen A","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Population Health, Health Services Research & Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, Centre for Biostatistics, The University of Manchester, Manchester Academic Health Science Centre , Manchester,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"2026092423090687000_deag140-B1","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1136\/adc.66.11.1304","article-title":"Trends in prevalence and survival of very low birthweight infants, England and Wales: 1983-7","volume":"66","author":"Alberman","year":"1991","journal-title":"Arch Dis Child"},{"key":"2026092423090687000_deag140-B2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/humupd\/dmad001","article-title":"Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing","volume":"29","author":"Alteri","year":"2023","journal-title":"Hum Reprod Update"},{"key":"2026092423090687000_deag140-B3","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1365-2796.2007.01809.x","article-title":"The origins of the developmental origins theory","volume":"261","author":"Barker","year":"2007","journal-title":"J Intern Med"},{"key":"2026092423090687000_deag140-B4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0140-6736(89)90710-1","article-title":"Weight in infancy and death from ischaemic heart disease","volume":"2","author":"Barker","year":"1989","journal-title":"Lancet"},{"key":"2026092423090687000_deag140-B5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12958-023-01140-3","article-title":"Cleavage-stage or blastocyst-stage embryo biopsy has no impact on growth and health in children up to 2 years of age","volume":"21","author":"Belva","year":"2023","journal-title":"Reprod Biol Endocrinol"},{"key":"2026092423090687000_deag140-B6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1471-2393-8-5","article-title":"Centile charts for birthweight for gestational age for Scottish singleton births","volume":"8","author":"Bonellie","year":"2008","journal-title":"BMC Pregnancy Childbirth"},{"key":"2026092423090687000_deag140-B7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s13669-012-0019-2","article-title":"Recent advances in assisted reproductive technology","volume":"1","author":"Brezina","year":"2012","journal-title":"Curr Obstet Gynecol Rep"},{"key":"2026092423090687000_deag140-B8","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.rbmo.2013.09.006","article-title":"How should we assess the safety of IVF technologies?","volume":"27","author":"Brison","year":"2013","journal-title":"Reprod Biomed Online"},{"key":"2026092423090687000_deag140-B9","doi-asserted-by":"crossref","first-page":"hoz031","DOI":"10.1093\/hropen\/hoz031","article-title":"The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study","volume":"2020","author":"Castillo","year":"2020","journal-title":"Hum Reprod Open"},{"key":"2026092423090687000_deag140-B10","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/humrep\/dez025","article-title":"The impact of IVF on birthweight from 1991 to 2015: a cross-sectional study","volume":"34","author":"Castillo","year":"2019","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B11","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1093\/humrep\/deaa244","article-title":"Associations of IVF singleton birthweight and gestation with clinical treatment and laboratory factors: a multicentre cohort study","volume":"35","author":"Castillo","year":"2020","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/uog.18930","article-title":"Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF\/ICSI treatment: meta-analysis of cohort studies","volume":"51","author":"Cavoretto","year":"2018","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2026092423090687000_deag140-B13","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":"Chen","year":"2017","journal-title":"J Dev Orig Health Dis"},{"key":"2026092423090687000_deag140-B14","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1365-3016.2010.01188.x","article-title":"Discordant time trends in maternal body size and offspring birthweight of term deliveries in France between 1972 and 2003: data from the French National Perinatal Surveys","volume":"25","author":"Diouf","year":"2011","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2026092423090687000_deag140-B15","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: causes and consequences","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"2026092423090687000_deag140-B16","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12884-015-0777-8","article-title":"A retrospective cohort study of factors relating to the longitudinal change in birth weight","volume":"15","author":"Gibson","year":"2015","journal-title":"BMC Pregnancy Childbirth"},{"key":"2026092423090687000_deag140-B17","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/humrep\/dead021","article-title":"Preimplantation genetic testing and child health: a national register-based study","volume":"38","author":"Ginstr\u00f6m Ernstad","year":"2023","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B18","first-page":"CD002118","article-title":"Blastocyst-stage versus cleavage-stage embryo transfer in assisted reproductive technology","volume":"1","author":"Glujovsky","year":"2026","journal-title":"Cochrane Database Syst Rev"},{"key":"2026092423090687000_deag140-B19","doi-asserted-by":"crossref","first-page":"e115703","DOI":"10.1371\/journal.pone.0115703","article-title":"Changes in birth weight between 2002 and 2012 in Guangzhou, China","volume":"9","author":"Guo","year":"2014","journal-title":"PLoS One"},{"key":"2026092423090687000_deag140-B20","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/humrep\/deu345","article-title":"Trends in perinatal health after assisted reproduction: a Nordic study from the CoNARTaS group","volume":"30","author":"Henningsen","year":"2015","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B21","author":"HFEA","year":"2023"},{"key":"2026092423090687000_deag140-B22","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.fertnstert.2021.06.040","article-title":"Impact of preimplantation genetic testing on obstetric and neonatal outcomes: a systematic review and meta-analysis","volume":"116","author":"Hou","year":"2021","journal-title":"Fertil Steril"},{"key":"2026092423090687000_deag140-B23","doi-asserted-by":"crossref","first-page":"e1002220","DOI":"10.1371\/journal.pmed.1002220","article-title":"The World Health Organization fetal growth charts: a multinational longitudinal study of ultrasound biometric measurements and estimated fetal weight","volume":"14","author":"Kiserud","year":"2017","journal-title":"PLoS Med"},{"key":"2026092423090687000_deag140-B25","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/humrep\/dead018","article-title":"Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort","volume":"38","author":"Kondowe","year":"2023","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B26","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/deaf045","article-title":"Bias due to non-consent in assisted reproductive treatment cohort studies: consent for disclosure to non-contact research in the Human Fertilisation and Embryology Authority register","volume":"40","author":"Kondowe","year":"2025","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12958-016-0225-2","article-title":"Systematic review of worldwide trends in assisted reproductive technology 2004\u20132013","volume":"15","author":"Kushnir","year":"2017","journal-title":"Reprod Biol Endocrinol"},{"key":"2026092423090687000_deag140-B28","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/humrep\/dew173","article-title":"No change in live birthweight of IVF singleton deliveries over an 18-year period despite significant clinical and laboratory changes","volume":"31","author":"Maas","year":"2016","journal-title":"Hum Reprod"},{"key":"2026092423090687000_deag140-B29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/humupd\/dmx031","article-title":"Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer?","volume":"24","author":"Maheshwari","year":"2018","journal-title":"Hum Reprod Update"},{"key":"2026092423090687000_deag140-B30","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.fertnstert.2012.05.019","article-title":"Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis","volume":"98","author":"Maheshwari","year":"2012","journal-title":"Fertil Steril"},{"key":"2026092423090687000_deag140-B31","doi-asserted-by":"publisher","DOI":"10.1111\/mcn.12297","article-title":"Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis","volume":"13","author":"Martin","year":"2017","journal-title":"Matern Child Nutr"},{"key":"2026092423090687000_deag140-B32","author":"NHS Digital","year":"2021"},{"key":"2026092423090687000_deag140-B33","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.fertnstert.2023.04.022","article-title":"Long-term outcomes for children conceived by assisted reproductive technology","volume":"120","author":"Pinborg","year":"2023","journal-title":"Fertil Steril"},{"key":"2026092423090687000_deag140-B34","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00404-016-4250-3","article-title":"Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization\/intracytoplasmic sperm injection: a systematic review and meta-analysis","volume":"295","author":"Qin","year":"2017","journal-title":"Arch Gynecol Obstet"},{"key":"2026092423090687000_deag140-B35","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1515\/JPM.2009.068","article-title":"Temporal trends in pregnancy weight gain and birth weight in Bavaria 2000\u20132007: slightly decreasing birth weight with increasing weight gain in pregnancy","volume":"37","author":"Schiessl","year":"2009","journal-title":"J Perinat Med"},{"key":"2026092423090687000_deag140-B36","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.18203\/2320-1770.ijrcog20253928","article-title":"Frontiers in fertility: a review of breakthroughs in assisted reproductive technology","volume":"14","author":"Vijay","year":"2025","journal-title":"Int J Reprod Contracept Obstet Gynecol"},{"key":"2026092423090687000_deag140-B37","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1186\/s12916-025-04445-9","article-title":"Assisted reproductive technology and reproductive, perinatal, and maternal outcomes: evidence from an umbrella review of systematic reviews with meta-analyses of randomized controlled trials","volume":"23","author":"Wang","year":"2025","journal-title":"BMC Med"},{"key":"2026092423090687000_deag140-B38","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/03009734.2020.1726534","article-title":"Perinatal outcome in children born after assisted reproductive technologies","volume":"125","author":"Wennerholm","year":"2020","journal-title":"Ups J Med Sci"},{"key":"2026092423090687000_deag140-B39","doi-asserted-by":"crossref","first-page":"e0250150","DOI":"10.1371\/journal.pone.0250150","article-title":"Stillbirth rates, service outcomes and costs of implementing NHS England\u2019s Saving Babies\u2019 Lives care bundle in maternity units in England: a cohort study","volume":"16","author":"Widdows","year":"2021","journal-title":"PLoS One"},{"key":"2026092423090687000_deag140-B40","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1186\/s12967-025-07045-6","article-title":"Predictive models for live birth outcomes following fresh embryo transfer in assisted reproductive technologies using machine learning","volume":"23","author":"Wu","year":"2025","journal-title":"J Transl Med"},{"key":"2026092423090687000_deag140-B41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tjog.2024.10.001","article-title":"Artificial intelligence and assisted reproductive technology: a comprehensive systematic review","volume":"64","author":"Wu","year":"2025","journal-title":"Taiwan J Obstet Gynecol"},{"key":"2026092423090687000_deag140-B42","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/humupd\/dmab027","article-title":"Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis","volume":"27","author":"Zheng","year":"2021","journal-title":"Hum Reprod Update"},{"key":"2026092423090687000_deag140-B43","doi-asserted-by":"crossref","first-page":"35141","DOI":"10.1038\/srep35141","article-title":"Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci Rep"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag140\/71383986\/deag140.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag140\/71383986\/deag140.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:09:21Z","timestamp":1790305761000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article\/doi\/10.1093\/humrep\/deag140\/8834053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag140","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"deag140"}}