{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:30:39Z","timestamp":1777451439220,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research (C)","award":["21K11582"],"award-info":[{"award-number":["21K11582"]}]},{"name":"The Nihon University School of Medicine Alumni Association\u2019s 60th anniversary fund research grant","award":["20N601"],"award-info":[{"award-number":["20N601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>We aimed to create percentile-based reference values of the umbilical cord blood insulin-like growth factor-1 (IGF-1) levels in Japanese newborns, as these values have not yet been established. A total of 259 newborns were classified into four gestational-age-at-birth (GA) groups: extremely preterm (&lt;28 weeks); early preterm (28\u201333 weeks); late preterm (34\u201336 weeks); and term (\u226537 weeks). They were further subclassified as small-for-gestational-age (SGA) or non-SGA. The 10th, 25th, 50th, 75th, and 90th percentiles of the umbilical cord blood IGF-1 levels were calculated and compared between the groups by using reference values of 9, 18, 33, 52, and 71 ng\/mL, respectively. In the extremely preterm group, the IGF-1 levels were significantly lower than those in the early preterm, late preterm, and term groups (13.5, 24.0, 44.5, and 47.5 ng\/mL, respectively; p &lt; 0.001). The umbilical cord blood IGF-1 levels in the SGA newborns were significantly lower than those in the non-SGA newborns in all subgroups. In multivariate analyses, the GA and birth weight standard deviation scores were independent determinant factors for the umbilical cord blood IGF-1 levels. Thus, we established percentile-based reference values of umbilical cord blood IGF-1 in Japanese newborns; these reference values can be applied on the basis of the extent of prematurity and the SGA status.<\/jats:p>","DOI":"10.3390\/jcm11071889","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:44:52Z","timestamp":1648590292000},"page":"1889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Percentile-Based Reference Values of Umbilical Cord Blood Insulin-like Growth Factor 1 in Japanese Newborns"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-1626","authenticated-orcid":false,"given":"Nobuhiko","family":"Nagano","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daichi","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoji","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5685-2670","authenticated-orcid":false,"given":"Ichiro","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 1738610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF00293288","article-title":"The Human Gene Encoding Insulin-Like Growth Factor I Is Located on Chromosome 12","volume":"69","author":"Jansen","year":"1985","journal-title":"Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/306609a0","article-title":"Sequence of cDNA Encoding Human Insulin-Like Growth Factor I Precursor","volume":"306","author":"Jansen","year":"1983","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0021-9258(17)40889-1","article-title":"The Amino Acid Sequence of Human Insulin-Like Growth Factor I and Its Structural Homology with Proinsulin","volume":"253","author":"Rinderknecht","year":"1978","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/ajmg.c.31357","article-title":"Endocrine Control of Growth","volume":"163C","author":"Murray","year":"2013","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F198","DOI":"10.1136\/fn.83.3.F198","article-title":"Leptin and Metabolic Hormones in Preterm Newborns","volume":"83","author":"Ng","year":"2000","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/apa.13350","article-title":"Insulin-Like Growth Factor 1 Has Multisystem Effects on Foetal and Preterm Infant Development","volume":"105","author":"Ley","year":"2016","journal-title":"Acta Paediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1210\/jcem.87.5.8457","article-title":"IGF-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1, and Postnatal Growth in Very Low Birth Weight Infants","volume":"87","author":"Kajantie","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1542\/peds.2005-1926","article-title":"Postnatal Head Growth Deficit Among Premature Infants Parallels Retinopathy of Prematurity and Insulin-Like Growth Factor-1 Deficit","volume":"117","author":"Sigurdsson","year":"2006","journal-title":"Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1210\/jc.2010-2440","article-title":"Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants","volume":"96","author":"Larsson","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1651-2227.2009.01677.x","article-title":"Serum Levels of IGFl Are a Useful Predictor of Retinopathy of Prematurity","volume":"99","year":"2010","journal-title":"Acta Paediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/j.1651-2227.2012.02826.x","article-title":"WINROP Consortium Low Postnatal Serum IGF-I Levels Are Associated with Bronchopulmonary Dysplasia (BPD)","volume":"101","author":"Hellgren","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1067\/mob.2003.26","article-title":"Regulation of Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-1 Concentrations in Preterm Fetuses","volume":"188","author":"Verhaeghe","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1046\/j.1442-200x.2000.01167.x","article-title":"Relationship of Insulin-Like Growth Factor-\u2160, Insulin-Like Growth Factor Binding protein-3, Insulin, Growth Hormone in Cord Blood and Maternal Factors with Birth Height and Birthweight","volume":"42","author":"Yang","year":"2000","journal-title":"Pediatr. Int."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yumani, D.F.J., Calor, A.K., and van Weissenbruch, M.M. (2020). The Course of IGF-1 Levels and Nutrient Intake in Extremely and Very Preterm Infants During Hospitalisation. Nutrients, 12.","DOI":"10.3390\/nu12030675"},{"key":"ref_15","first-page":"91","article-title":"Relationship Between Insulin-Like Growth Factor Type 1 and Intrauterine Growth","volume":"59","author":"Banjac","year":"2020","journal-title":"Acta Clin. Croat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s13312-018-1422-1","article-title":"Growth Patterns in Small for Gestational Age Babies and Correlation with Insulin-Like Growth Factor-1 Levels","volume":"55","author":"Rustogi","year":"2018","journal-title":"Indian Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4274\/Jcrpe.867","article-title":"Impact of Insulin Resistance on Insulin-Like Growth Factor-1\/Insulin Like Growth Factor-Binding Protein-3 Axis and on Early Weight Gain in Small for Gestational Age Infants","volume":"5","author":"Dizdarer","year":"2013","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1111\/ped.12331","article-title":"New Japanese Neonatal Anthropometric Charts for Gestational Age at Birth","volume":"56","author":"Itabashi","year":"2014","journal-title":"Pediatr. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1210\/jc.2016-1257","article-title":"VARIETE Investigators Reference Values for IGF-I Serum Concentrations: Comparison of Six Immunoassays","volume":"101","author":"Chanson","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ghir.2009.09.004","article-title":"The Current Status of IGF-I Assays\u2014A 2009 Update","volume":"20","author":"Frystyk","year":"2010","journal-title":"Growth Horm. IGF Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1056\/NEJM196709212771208","article-title":"Radioimmunoassays of Peptide Hormones in Plasma","volume":"20","author":"Berson","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"ref_22","first-page":"2680","article-title":"The Expression of Insulin-Like Growth Factor (IGF) and IGF-Binding Protein (IGFBP) Genes in the Human Placenta and Membranes: Evidence for IGF-IGFBP Interactions at the Feto-Maternal Interface","volume":"81","author":"Han","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13148-018-0489-9","article-title":"Fetal Growth Is Associated with CpG Methylation in the P2 Promoter of the IGF1 Gene","volume":"10","author":"Castell","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1152\/physrev.1978.58.2.499","article-title":"Principal Substrates of Fetal Metabolism","volume":"58","author":"Battaglia","year":"1978","journal-title":"Physiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4103\/2230-8210.107851","article-title":"In Utero Fuel Homeostasis: Lessons for a Clinician","volume":"17","author":"Rao","year":"2013","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/cen.13057","article-title":"Neonatal Adiposity Increases with Rising Cord Blood IGF-1 Levels","volume":"85","author":"Kadakia","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"544","DOI":"10.5603\/GP.2020.0087","article-title":"The Concentration of Insulin-Like Growth Factor-1 in Pregnancies Complicated by Pregnancy-Induced Hypertension and\/or Intrauterine Hypotrophy","volume":"91","author":"Gazy","year":"2020","journal-title":"Ginekol. Pol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12238","DOI":"10.1038\/s41598-019-48785-y","article-title":"Incidence and Neonatal Risk Factors of Short Stature and Growth Hormone Treatment in Japanese Preterm Infants Born Small for Gestational Age","volume":"9","author":"Matsumoto","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/IAE.0000000000001247","article-title":"Postnatal Serum Insulin-Like Growth Factor I and Retinopathy of Prematurity","volume":"37","author":"Jensen","year":"2017","journal-title":"Retina"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.21873\/invivo.12260","article-title":"IGF-1 Protects Neurons in the Cortex and Subventricular Zone in a Periventricular Leucomalacia Model","volume":"35","author":"Kim","year":"2021","journal-title":"In Vivo"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.expneurol.2009.03.021","article-title":"Intranasal Administration of IGF-1 Attenuates Hypoxic-Ischemic Brain Injury in Neonatal Rats","volume":"217","author":"Lin","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/jbmr.20","article-title":"Elevated Serum Levels of IGF-1 Are Sufficient to Establish Normal Body Size and Skeletal Properties Even in the Absence of Tissue IGF-1","volume":"25","author":"Elis","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"602047","DOI":"10.3389\/fped.2020.602047","article-title":"Supplemental Insulin-Like Growth Factor-1 and Necrotizing Enterocolitis in Preterm Pigs","volume":"8","author":"Holgersen","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1055\/s-0036-1586109","article-title":"Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants","volume":"33","author":"Ley","year":"2016","journal-title":"Am. J. Perinatol."},{"key":"ref_36","first-page":"5964","article-title":"IGF-1 as a Drug for Preterm Infants: A Step-Wise Clinical Development","volume":"23","author":"Ley","year":"2017","journal-title":"Curr. Pharm. Des."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/1889\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:47Z","timestamp":1760136347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/1889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["jcm11071889"],"URL":"https:\/\/doi.org\/10.3390\/jcm11071889","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}