{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:47:44Z","timestamp":1792691264941,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.<\/jats:p>","DOI":"10.3390\/ijms21249688","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-8591","authenticated-orcid":false,"given":"Toshiko","family":"Minamoto","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoka","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamrunnahar","family":"Shanta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossain Mohammad","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultana","family":"Razia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyosuke","family":"Sakashita","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Shimane Prefectural Central Hospital, Izumo 693-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kyo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajhb.20590","article-title":"Early life events and their consequences for later disease: A life history and evolutionary perspective","volume":"19","author":"Gluckman","year":"2007","journal-title":"Am. J. Hum. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","article-title":"The fetal and infant origins of adult disease","volume":"301","author":"Barker","year":"1990","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1126\/science.1095292","article-title":"Living with the past: Evolution, development, and patterns of disease","volume":"305","author":"Gluckman","year":"2004","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/aje\/kwj346","article-title":"Leukocyte telomere length and cardiovascular disease in the cardiovascular health study","volume":"165","author":"Fitzpatrick","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2337\/diacare.29.02.06.dc05-1715","article-title":"Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes","volume":"29","author":"Sampson","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K.A., Dunning, A.M., Svenson, U., Roos, G., Hosgood, H.D., and Shen, M. (2011). Shortened telomere length is associated with increased risk of cancer: A meta-analysis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020466"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1083\/jcb.90.2.515","article-title":"Tandemly repeated C-C-C-C-A-A hexanucleotide of Tetrahymena rDNA is present elsewhere in the genome and may be related to the alteration of the somatic genome","volume":"90","author":"Yao","year":"1981","journal-title":"J. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"g4227","DOI":"10.1136\/bmj.g4227","article-title":"Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta-analysis","volume":"349","author":"Haycock","year":"2014","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0140-6736(07)60071-3","article-title":"Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: A nested case-control study","volume":"369","author":"Brouilette","year":"2007","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1203\/00006450-200209000-00012","article-title":"Telomere length in the newborn","volume":"52","author":"Okuda","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12661","DOI":"10.1111\/aji.12661","article-title":"Telomere length and fetal programming: A review of recent scientific advances","volume":"77","author":"Whiteman","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s004390050755","article-title":"Synchrony in telomere length of the human fetus","volume":"102","author":"Youngren","year":"1998","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.arr.2015.12.006","article-title":"Systematic review of the association between chronic social stress and telomere length: A life course perspective","volume":"26","author":"Oliveira","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.placenta.2014.11.011","article-title":"Telomeres are shorter in placentas from pregnancies with uncontrolled diabetes","volume":"36","author":"Naboani","year":"2015","journal-title":"Placenta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Martens, D.S., Plusquin, M., Gyselaers, W., De Vivo, I., and Nawrot, T.S. (2016). Maternal pre-pregnancy body mass index and newborn telomere length. BMC Med., 14.","DOI":"10.1186\/s12916-016-0689-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2014.08.026","article-title":"Impact of intrauterine tobacco exposure on fetal telomere length","volume":"212","author":"Salihu","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/j.1471-0528.2005.00839.x","article-title":"Telomere length in small-for-gestational-age babies","volume":"113","author":"Akkad","year":"2006","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/ng.2528","article-title":"Identification of seven loci affecting mean telomere length and their association with disease","volume":"45","author":"Codd","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E2358","DOI":"10.1073\/pnas.1720427115","article-title":"Diagnostic utility of telomere length testing in a hospital-based setting","volume":"115","author":"Alder","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/j.neurobiolaging.2009.12.006","article-title":"Telomere length and cognitive function in community-dwelling elders: Findings from the Health ABC Study","volume":"32","author":"Yaffe","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_21","first-page":"169","article-title":"Telomere shortening and ageing of the immune system","volume":"59","author":"Kaszubowska","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Willeit, P., Raschenberger, J., Heydon, E.E., Tsimikas, S., Haun, M., Mayr, A., Weger, S., Witztum, J.L., Butterworth, A.S., and Willeit, J. (2014). Leucocyte telomere length and risk of type 2 diabetes mellitus: New prospective cohort study and literature-based meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112483"},{"key":"ref_23","first-page":"637","article-title":"Vascular aging: Insights from studies on cellular senescence, stem cell aging, and progeroid syndromes","volume":"5","author":"Minamino","year":"2008","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1001\/jama.2010.897","article-title":"Telomere length and risk of incident cancer and cancer mortality","volume":"304","author":"Willeit","year":"2010","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"80175","DOI":"10.18632\/oncotarget.20706","article-title":"Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States","volume":"8","author":"Mazidi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2012.11.033","article-title":"Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length","volume":"208","author":"Entringer","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2016.01.177","article-title":"Prenatal stress and newborn telomere length","volume":"215","author":"Marchetto","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"559","DOI":"10.5665\/sleep.4570","article-title":"Association between maternal symptoms of sleep disordered breathing and fetal telomere length","volume":"38","author":"Salihu","year":"2015","journal-title":"Sleep"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.nutres.2016.01.009","article-title":"A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming","volume":"36","author":"Salihu","year":"2016","journal-title":"Nutr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/jp.2015.178","article-title":"Cord blood telomere length in Latino infants: Relation with maternal education and infant sex","volume":"36","author":"Wojcicki","year":"2016","journal-title":"J. Perinatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.jacc.2018.06.060","article-title":"Association of assisted reproductive technologies with arterial hypertension during adolescence","volume":"72","author":"Meister","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1161\/CIRCULATIONAHA.111.071183","article-title":"Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies","volume":"125","author":"Scherrer","year":"2012","journal-title":"Circulation"},{"key":"ref_33","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":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1477-7827-10-49","article-title":"The effects of oxidative stress on female reproduction: A review","volume":"10","author":"Agarwal","year":"2012","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0968-0004(02)02110-2","article-title":"Oxidative stress shortens telomeres","volume":"27","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.fertnstert.2004.02.121","article-title":"Differential growth of human embryos in vitro: Role of reactive oxygen species","volume":"82","author":"Bedaiwy","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0015-0282(02)04948-8","article-title":"Role of reactive oxygen species in the pathophysiology of human reproduction","volume":"79","author":"Agarwal","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e204057","DOI":"10.1001\/jamanetworkopen.2020.4057","article-title":"Association of Parental Socioeconomic Status and Newborn Telomere Length","volume":"3","author":"Martens","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1900227","DOI":"10.1002\/bies.201900227","article-title":"Cross-Generational effects of parental age on offspring longevity: Are telomeres an important underlying mechanism?","volume":"42","author":"Heidinger","year":"2020","journal-title":"BioEssays"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2217\/bmm.14.13","article-title":"Telomere length analysis and preterm infant health: The importance of assay design in the search for novel biomarkers","volume":"8","author":"Turner","year":"2014","journal-title":"Biomark. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Menon, R., Yu, J., Basanta-Henry, P., Brou, L., Berga, S.L., Fortunato, S.J., and Taylor, R.N. (2012). Short Fetal Leukocyte Telomere Length and Preterm Prelabor Rupture of the Membranes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031136"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.placenta.2009.03.005","article-title":"Fetal Growth Restriction is Associated with Accelerated Telomere Shortening and Increased Expression of Cell Senescence Markers in the Placenta","volume":"30","author":"Davy","year":"2009","journal-title":"Placenta"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"World Health Organization, and WHO Expert Consultation (2004). Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet, 363, 157\u2013163.","DOI":"10.1016\/S0140-6736(03)15268-3"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0022-3999(67)90012-8","article-title":"The social readjustment rating scale","volume":"11","author":"Homas","year":"1967","journal-title":"J. Psychosom. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1126\/science.790570","article-title":"Life Events, Stress, and Illness Their nature and effects","volume":"194","author":"Judith","year":"1976","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1203\/00006450-200102000-00020","article-title":"Telomeres in Neonates: New Insights in Fetal Hematopoiesis","volume":"49","author":"Friedrich","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_47","unstructured":"(2020, November 12). Introduction of new gestational age standard values at birth. Available online: https:\/\/www.jpeds.or.jp\/uploads\/files\/saisin_100826.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1177\/0898264316661390","article-title":"Telomere Length Among Older U.S. Adults: Differences by Race\/Ethnicity, Gender, and Age","volume":"29","author":"Brown","year":"2017","journal-title":"J. Aging Health"},{"key":"ref_49","first-page":"876","article-title":"Genetic determination of telomere size in humans: A twin study of three age groups","volume":"55","author":"Slagboom","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/30.10.e47","article-title":"Telomere measurement by quantitative PCR","volume":"30","author":"Cawthon","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9688\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:06Z","timestamp":1760179626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":50,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249688"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249688","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}