{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:03:55Z","timestamp":1790766235618,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,27]]},"group-title":"Pediatrics","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01HD072267"],"award-info":[{"award-number":["R01HD072267"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HD084515"],"award-info":[{"award-number":["R01HD084515"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Infants &lt;30 weeks gestational age (very preterm (VPT)), are at risk of experiencing multiple serious neonatal morbidities. These morbidities impart serious biological stress, which may be reflected in dysregulated protein expression even after the morbidities have resolved. Recent studies suggest that DNA methylation-based predictors of circulating proteins may reflect the molecular effects of neonatal adversity. The objective of this study is to examine associations between DNA methylation-derived EpiScores, which are externally trained methylation signatures that proxy circulating protein levels, and neonatal morbidity burden in children born VPT. Buccal DNA methylation was obtained at NICU discharge in 537 infants from the NOVI cohort. A total of 111 EpiScores were calculated and tested for association with multimorbidity (0-1 vs. \u22652 morbidities) using adjusted linear regression models. Cross-tissue analyses in an external paired blood-buccal dataset (n=21) were used to identify EpiScores with moderate-to-strong correlations across tissues.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eighteen EpiScores were nominally associated with multimorbidity (p &lt; 0.05), with Melanoma-derived growth regulatory protein (MIA) with FDR &lt; 0.05 (\u03b2 = 0.0023, p = 4.4 \u00d7 10\u25a1\u25a1). In cross-tissue analyses, 35 EpiScores yielded r &gt; 0.50 (p&lt;0.05), 11 of which showed nominal associations with multimorbidity, including MIA. Overall, the morbidity-associated EpiScores reflected immune, inflammatory, metabolic, and growth-related pathways.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Buccal DNA methylation-derived EpiScores capture biological signatures associated with neonatal morbidity burden in very preterm infants.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.25.26363955","type":"posted-content","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:15:10Z","timestamp":1790550910000},"source":"Crossref","is-referenced-by-count":0,"title":["Buccal DNA Methylation-Derived EpiScores are Associated with Neonatal Morbidity Burden in Infants born Very Preterm"],"prefix":"10.64898","author":[{"given":"Priyadarshni","family":"Patel","sequence":"first","affiliation":[{"name":"Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Camerota","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA"},{"name":"Brown Center for the Study of Children at Risk, Alpert Medical School of Brown University and Women and Infants Hospital, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Neonatology, Children\u2019s Mercy Hospital, Kansas City, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Check","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer B.","family":"Helderman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-1480","authenticated-orcid":false,"given":"Julie A.","family":"Hofheimer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Litt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth C.","family":"McGowan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA"},{"name":"Brown Center for the Study of Children at Risk, Alpert Medical School of Brown University and Women and Infants Hospital, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Neal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Pastyrnak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Spectrum Health-Helen DeVos Hospital, Grand Rapids, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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