{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:37:57Z","timestamp":1776681477835,"version":"3.51.2"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional de Perinatologia in Mexico City","award":["2016-1-568"],"award-info":[{"award-number":["2016-1-568"]}]},{"name":"Instituto Nacional de Perinatologia in Mexico City","award":["2017-2-79"],"award-info":[{"award-number":["2017-2-79"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Pregnant women with diabetes often present impaired fetal growth, which is less common if maternal diabetes is well-controlled. However, developing strategies to estimate fetal body composition beyond fetal growth that could better predict metabolic complications later in life is essential. This study aimed to evaluate subcutaneous fat tissue (femur and humerus) in fetuses with normal growth among pregnant women with well-controlled diabetes using a reproducible 3D-ultrasound tool and offline TUI (Tomographic Ultrasound Imaging) analysis. Additionally, three artificial intelligence classifier models were trained and validated to assess the clinical utility of the fetal subcutaneous fat measurement. A significantly larger subcutaneous fat area was found in three-femur and two-humerus selected segments of fetuses from women with diabetes compared to the healthy pregnant control group. The full classifier model that includes subcutaneous fat measure, gestational age, fetal weight, fetal abdominal circumference, maternal body mass index, and fetal weight percentile as variables, showed the best performance, with a detection rate of 70%, considering a false positive rate of 10%, and a positive predictive value of 82%. These findings provide valuable insights into the impact of maternal diabetes on fetal subcutaneous fat tissue as a variable independent of fetal growth.<\/jats:p>","DOI":"10.3390\/jcm12206485","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T12:46:13Z","timestamp":1697114773000},"page":"6485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["AI-Enhanced Analysis Reveals Impact of Maternal Diabetes on Subcutaneous Fat Mass in Fetuses without Growth Alterations"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7701-9621","authenticated-orcid":false,"given":"Hector","family":"Borboa-Olivares","sequence":"first","affiliation":[{"name":"Community Interventions Research Branch, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-4133","authenticated-orcid":false,"given":"Johnatan","family":"Torres-Torres","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Flores-Pliego","sequence":"additional","affiliation":[{"name":"Department of Immunobiochemistry, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-8017","authenticated-orcid":false,"given":"Aurora","family":"Espejel-Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Immunobiochemistry, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Camacho-Arroyo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Reproducci\u00f3n Humana, Instituto Nacional de Perinatologia-Facultad de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Guzman-Huerta","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otilia","family":"Perichart-Perera","sequence":"additional","affiliation":[{"name":"Nutrition and Bioprogramming Department, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Pi\u00f1a-Ramirez","sequence":"additional","affiliation":[{"name":"Bioinformatics and Statistical Analysis Department, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Estrada-Gutierrez","sequence":"additional","affiliation":[{"name":"Research Division, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1210\/en.2016-1003","article-title":"Developmental Programming, a Pathway to Disease","volume":"157","author":"Padmanabhan","year":"2016","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/nutrit\/nuaa082","article-title":"Intervention during the first 1000 days in Mexico","volume":"78","author":"Zambrano","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/bdrc.21090","article-title":"Effect of maternal diabetes on the embryo, fetus, and children: Congenital anomalies, genetic and epigenetic changes and developmental outcomes","volume":"105","author":"Ornoy","year":"2015","journal-title":"Birth Defects Res. Part C Embryo Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000371628","article-title":"Gestational diabetes mellitus and macrosomia: A literature review","volume":"66","author":"Kc","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1177\/1479164115624681","article-title":"Review of gestational diabetes mellitus effects on vascular structure and function","volume":"13","author":"Jensen","year":"2016","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1056\/NEJMe2100902","article-title":"Gestational Diabetes\u2014On Broadening the Diagnosis","volume":"384","author":"Casey","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"HAPO Study Cooperative Research Group (2009). Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Associations with neonatal anthropometrics. Diabetes, 58, 453\u2013459.","DOI":"10.2337\/db08-1112"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ecl.2019.05.001","article-title":"Gestational Diabetes Mellitus","volume":"48","author":"Szmuilowicz","year":"2019","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1001\/jama.2019.4981","article-title":"Management of Preexisting Diabetes in Pregnancy: A Review","volume":"321","author":"Alexopoulos","year":"2019","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/aogs.12291","article-title":"Ultrasound-guided compared to conventional treatment in gestational diabetes leads to improved birthweight but more insulin treatment: Systematic review and meta-analysis","volume":"93","author":"Balsells","year":"2014","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biocel.2018.09.016","article-title":"Trophoblast: The central unit of fetal growth, protection and programming","volume":"105","author":"Staud","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1159\/000439488","article-title":"Development, Epigenetics and Metabolic Programming","volume":"85","author":"Godfrey","year":"2016","journal-title":"Nestle Nutr. Inst. Workshop Ser."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101082","DOI":"10.1016\/j.plipres.2020.101082","article-title":"Adipose tissue development and lipid metabolism in the human fetus: The 2020 perspective focusing on maternal diabetes and obesity","volume":"81","author":"Desoye","year":"2021","journal-title":"Prog. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/S0002-9378(03)00828-7","article-title":"Increased fetal adiposity: A very sensitive marker of abnormal in utero development","volume":"189","author":"Catalano","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13098-021-00634-7","article-title":"Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: Potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia","volume":"13","author":"Stanirowski","year":"2021","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/uog.7575","article-title":"Growth of fetal lean mass and fetal fat mass in gestational diabetes","volume":"36","author":"Taricco","year":"2010","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.2337\/dc11-0728","article-title":"Determinants of body fat in infants of women with gestational diabetes mellitus differ with fetal sex","volume":"34","author":"Lingwood","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00404-017-4433-6","article-title":"Measurement and evaluation of fetal fat layer in the prediction of fetal macrosomia in pregnancies complicated by gestational diabetes","volume":"296","author":"Elessawy","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13041","DOI":"10.1111\/obr.13041","article-title":"Assessment of body composition in pediatric overweight and obesity: A systematic review of the reliability and validity of common techniques","volume":"21","author":"Orsso","year":"2020","journal-title":"Obes. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100792","DOI":"10.1016\/j.ajogmf.2022.100792","article-title":"Use of artificial intelligence in obstetrics: Not quite ready for prime time","volume":"5","author":"Sarno","year":"2023","journal-title":"Am. J. Obstet Gynecol. MFM"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Borboa-Olivares, H., Rodr\u00edguez-Sibaja, M.J., Espejel-Nu\u00f1ez, A., Flores-Pliego, A., Mendoza-Ortega, J., Camacho-Arroyo, I., Gonz\u00e1lez-Camarena, R., Echeverr\u00eda-Arjonilla, J.C., and Estrada-Gutierrez, G. (2023). A Novel Predictive Machine Learning Model Integrating Cytokines in Cervical-Vaginal Mucus Increases the Prediction Rate for Preterm Birth. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202308.1890.v2"},{"key":"ref_22","first-page":"17455065211046132","article-title":"Perinatal health predictors using artificial intelligence: A review","volume":"17","author":"Ramakrishnan","year":"2021","journal-title":"Womens Health"},{"key":"ref_23","first-page":"9","article-title":"Tomographic ultrasound imaging (TUI)\u2014Technique and methodological study","volume":"47","author":"Markov","year":"2008","journal-title":"Akush. Ginekol."},{"key":"ref_24","unstructured":"Rasmussen, K.M., and Yaktine, A.L. (2009). Weight Gain during Pregnancy: Reexamining the Guidelines, National Academies Press."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2020). 14. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2020. Diabetes Care, 43, S183\u2013S192.","DOI":"10.2337\/dc20-S014"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"442","DOI":"10.23736\/S2724-606X.21.04829-6","article-title":"Soft tissue assessment for fetal growth restriction","volume":"73","author":"Lee","year":"2021","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/uog.926","article-title":"Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies","volume":"22","author":"Larciprete","year":"2003","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ejcn.2015.117","article-title":"Body composition during fetal development and infancy through the age of 5 years","volume":"69","author":"Paley","year":"2015","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00125-016-4166-2","article-title":"Increased fetal adiposity prior to diagnosis of gestational diabetes in South Asians: More evidence for the \u2018thin-fat\u2019 baby","volume":"60","author":"Venkataraman","year":"2017","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Herath, M.P., Beckett, J.M., Hills, A.P., Byrne, N.M., and Ahuja, K.D.K. (2021). Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040835"},{"key":"ref_31","first-page":"775","article-title":"Fetal macrosomia and gestational diabetes: What\u2019s the problem?","volume":"81","author":"Sacks","year":"1993","journal-title":"Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"708767","DOI":"10.3389\/fendo.2021.708767","article-title":"Newer Insights Into Fetal Growth and Body Composition","volume":"12","author":"Ikenoue","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11304","DOI":"10.1038\/s41598-019-47839-5","article-title":"Heterogeneity in fetal growth velocity","volume":"9","author":"Sato","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ikenoue, S., Akiba, Y., Endo, T., Kasuga, Y., Yakubo, K., Ishii, R., Tanaka, M., and Ochiai, D. (2021). Defining the Normal Growth Curve of Fetal Fractional Limb Volume in a Japanese Population. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030485"},{"key":"ref_35","first-page":"143","article-title":"Adipose tissue magnetic resonance imaging in the newborn","volume":"62","author":"Uthaya","year":"2004","journal-title":"Horm. Res."},{"key":"ref_36","first-page":"951954","article-title":"Ultrasound estimates of visceral and subcutaneous-abdominal adipose tissues in infancy","volume":"2013","author":"Modi","year":"2013","journal-title":"J. Obes."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1542\/peds.2005-0832","article-title":"Fetal programming and risk of metabolic syndrome: Prevention efforts for high-risk populations","volume":"116","author":"Lobelo","year":"2005","journal-title":"Pediatrics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/uog.6319","article-title":"Fractional limb volume--a soft tissue parameter of fetal body composition: Validation, technical considerations and normal ranges during pregnancy","volume":"33","author":"Lee","year":"2009","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Garc\u00e9s, M.F., Sanchez, E., Cardona, L.F., Simanca, E.L., Gonz\u00e1lez, I., Leal, L.G., Mora, J.A., Bedoya, A., Alzate, J.P., and S\u00e1nchez, \u00c1.Y. (2015). Maternal Serum Meteorin Levels and the Risk of Preeclampsia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131013"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1016\/j.placenta.2015.11.015","article-title":"Fetal programming and gestational diabetes mellitus","volume":"48","author":"Monteiro","year":"2016","journal-title":"Placenta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-physiol-020911-153245","article-title":"Fetal programming and metabolic syndrome","volume":"74","author":"Rinaudo","year":"2012","journal-title":"Annu. Rev. Physiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6485\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:05:36Z","timestamp":1760130336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":41,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["jcm12206485"],"URL":"https:\/\/doi.org\/10.3390\/jcm12206485","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]}}}