{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:05:36Z","timestamp":1779725136983,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,22]]},"group-title":"Developmental Biology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HD-100593"],"award-info":[{"award-number":["HD-100593"]}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["MH-138481"],"award-info":[{"award-number":["MH-138481"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["OD023349"],"award-info":[{"award-number":["OD023349"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Primary tooth development is shaped by prenatal experience and has consequences for childhood caries and lifelong oral health. However, evidence linking prenatal conditions to dental development has relied largely on postnatal proxies, such as parent-recalled eruption timing, that conflate prenatal programming with postnatal exposures. Here, we directly phenotype developing dentition in vivo using routinely acquired neonatal brain MRI. Using T2-weighted imaging from the HEALthy Brain and Child Development Study, we trained a 3D U-Net on 100 semi-automatic labels and applied the model to 1,433 quality-controlled neonatal scans. Automated post-processing extracted quantitative features of tooth volume, mineralization, and arch geometry. These features were used to predict postmenstrual age at MRI and to derive a bias-corrected tooth age gap (TAG), indexing relative dental maturity at birth. The segmentation model achieved mean cross-validated Dice = 0.94. Dental features predicted postmenstrual age with R\n                  <jats:sup>2<\/jats:sup>\n                  = 0.30 and mean absolute error = 6.7 days, outperforming standard anthropometric measures (R\n                  <jats:sup>2<\/jats:sup>\n                  = 0.22). In adjusted models, TAG varied by infant sex and was associated with gestational age at delivery, maternal pre-pregnancy BMI, and prenatal tobacco use. In infants with longitudinal dental follow-up, greater dental maturity at birth predicted earlier first tooth emergence and more teeth at one year. Automated segmentation and age prediction generalized to an independent cohort. These findings establish neonatal dental MRI phenotyping as an objective, scalable index of dental maturation and a potential readout of prenatal influences on a developmental system relevant to lifelong oral health.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Primary tooth development begins before birth and is shaped by intrauterine experience, with consequences for eruption timing, enamel quality, childhood caries, and lifelong oral health. Yet newborn dentition has been difficult to study because unerupted primary teeth are not routinely measurable at birth, forcing reliance on postnatal proxies that mix prenatal influences with later exposures. We show that standard newborn brain MRI can be repurposed to quantify dental maturity before postnatal exposures accumulate. Applied to 1,433 newborns, this open-source pipeline provides spatially localized measures of unerupted tooth development and links neonatal dental maturity to clinical, environmental, and eruption outcomes. These findings establish neonatal dental MRI as a scalable tool for studying how intrauterine experience becomes biologically embedded in dental development.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.21.726980","type":"posted-content","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T08:50:14Z","timestamp":1779439814000},"source":"Crossref","is-referenced-by-count":0,"title":["MRI-based dental maturity in newborns reflects prenatal exposures and predicts timing of primary tooth eruption"],"prefix":"10.64898","author":[{"given":"Ying","family":"Meng","sequence":"first","affiliation":[{"name":"School of Nursing, University of Rochester, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Neuroscience, Obstetrics and Gynecology, University of Rochester, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas B.","family":"Bidlack","sequence":"additional","affiliation":[{"name":"Craniofacial Biology and Bioengineering, ADA Forsyth Institute, Inc., Somerville, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scotty A.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-7750","authenticated-orcid":false,"given":"Jerod M.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Biomedical Engineering, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052508400488000_2026.05.21.726980v1.1","unstructured":"C. Centers for Disease, Prevention (2024) Oral Health Surveillance Report: Dental Caries, Tooth Retention, and Edentulism, United States, 2017\u2013March 2020. (U.S. Department of Health and Human Services, Atlanta, GA)."},{"key":"2026052508400488000_2026.05.21.726980v1.2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jdent.2017.03.006","article-title":"Developmental defects of enamel and dental caries in the primary dentition: A systematic review and meta-analysis","volume":"60","year":"2017","journal-title":"Journal of Dentistry"},{"key":"2026052508400488000_2026.05.21.726980v1.3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1017\/S2040174415001130","article-title":"Maternal and early life factors of tooth emergence patterns and number of teeth at 1 and 2 years of age","volume":"6","year":"2015","journal-title":"Journal of Developmental Origins of Health and Disease"},{"key":"2026052508400488000_2026.05.21.726980v1.4","first-page":"287","article-title":"Tooth Eruption and Early Childhood Caries: A Multisite Longitudinal Study","volume":"43","year":"2021","journal-title":"Pediatric Dentistry"},{"key":"2026052508400488000_2026.05.21.726980v1.5","first-page":"226","article-title":"A curriculum vitae of teeth: evolution, generation, regeneration","volume":"5","year":"2009","journal-title":"International Journal of Biological Sciences"},{"key":"2026052508400488000_2026.05.21.726980v1.6","doi-asserted-by":"crossref","first-page":"106335","DOI":"10.1016\/j.archoralbio.2025.106335","article-title":"Insight into perinatal health by investigating the neonatal line: A systematic review","volume":"177","year":"2025","journal-title":"Archives of Oral Biology"},{"key":"2026052508400488000_2026.05.21.726980v1.7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.24018\/ejdent.2021.2.3.63","article-title":"The Impact of Maternal, Perinatal, and Early Infancy Period on the Eruption Timing of the First Primary Tooth","volume":"2","year":"2021","journal-title":"European Journal of Dental and Oral Health"},{"key":"2026052508400488000_2026.05.21.726980v1.8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000534793","article-title":"Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors Using Bayesian Model Selection","volume":"58","year":"2024","journal-title":"Caries Research"},{"key":"2026052508400488000_2026.05.21.726980v1.9","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.3390\/nu15183863","article-title":"The Impact of Prenatal Vitamin D on Enamel Defects and Tooth Erosion: A Systematic Review","volume":"15","year":"2023","journal-title":"Nutrients"},{"key":"2026052508400488000_2026.05.21.726980v1.10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1159\/000513257","article-title":"Does the Trimester of Smoking Matter in the Association between Prenatal Smoking and the Risk of Early Childhood Caries?","volume":"55","year":"2021","journal-title":"Caries Research"},{"key":"2026052508400488000_2026.05.21.726980v1.11","doi-asserted-by":"crossref","unstructured":"C. L. McDermott et al., Early life stress is associated with earlier emergence of permanent molars. Proceedings of the National Academy of Sciences of the United States of America 118 (2021).","DOI":"10.1073\/pnas.2105304118"},{"key":"2026052508400488000_2026.05.21.726980v1.12","doi-asserted-by":"crossref","first-page":"101441","DOI":"10.1016\/j.dcn.2024.101441","article-title":"An introduction to the HEALthy Brain and Child Development Study (HBCD) study","volume":"69","year":"2024","journal-title":"Developmental Cognitive Neuroscience"},{"key":"2026052508400488000_2026.05.21.726980v1.13","doi-asserted-by":"crossref","first-page":"15607","DOI":"10.1038\/s41598-022-19944-5","article-title":"Validity of age estimation methods and reproducibility of bone\/dental maturity indices for chronological age estimation: a systematic review and meta-analysis of validation studies","volume":"12","year":"2022","journal-title":"Scientific Reports"},{"key":"2026052508400488000_2026.05.21.726980v1.14","first-page":"1","article-title":"Estimation of age in forensic anthropology: historical perspective and recent methodological advances","volume":"4","year":"2019","journal-title":"Forensic Sciences Research"},{"key":"2026052508400488000_2026.05.21.726980v1.15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/jphd.12154","article-title":"Timing of primary tooth emergence among U.S. racial and ethnic groups","volume":"76","year":"2016","journal-title":"Journal of Public Health Dentistry"},{"key":"2026052508400488000_2026.05.21.726980v1.16","first-page":"1","article-title":"American black-white differences in primary tooth crown dimensions","volume":"15","year":"2001","journal-title":"Dental Anthropology"},{"key":"2026052508400488000_2026.05.21.726980v1.17","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1017\/S2040174415001130","article-title":"Maternal and early life factors of tooth emergence patterns and number of teeth at 1 and 2 years of age","volume":"6","year":"2015","journal-title":"Journal of Developmental Origins of Health and Disease"},{"key":"2026052508400488000_2026.05.21.726980v1.18","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26582"},{"key":"2026052508400488000_2026.05.21.726980v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.03.049"},{"key":"2026052508400488000_2026.05.21.726980v1.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2105304118"},{"key":"2026052508400488000_2026.05.21.726980v1.21","article-title":"nnInteractive: Redefining 3D Promptable Segmentation","year":"2025","journal-title":"arXiv"},{"key":"2026052508400488000_2026.05.21.726980v1.22","doi-asserted-by":"crossref","unstructured":"\u00d6. \u00c7i\u00e7ek , A. Abdulkadir , S. S. Lienkamp , T. Brox , O. Ronneberger (2016) 3D U-Net: Learning Dense Volumetric Segmentation from Sparse Annotation. in Medical Image Computing and Computer-Assisted Intervention \u2013 MICCAI 2016, pp 424\u2013432.","DOI":"10.1007\/978-3-319-46723-8_49"},{"key":"2026052508400488000_2026.05.21.726980v1.23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184661."},{"key":"2026052508400488000_2026.05.21.726980v1.24","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"2026052508400488000_2026.05.21.726980v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.06.017"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.21.726980","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T15:40:17Z","timestamp":1779723617000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.21.726980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":25,"URL":"https:\/\/doi.org\/10.64898\/2026.05.21.726980","relation":{},"subject":[],"published":{"date-parts":[[2026,5,22]]},"subtype":"preprint"}}