{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:03:48Z","timestamp":1789542228851,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC08671"],"award-info":[{"award-number":["R01 DC08671"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI168643"],"award-info":[{"award-number":["U19AI168643"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI168487"],"award-info":[{"award-number":["K08AI168487"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1K01HL175261"],"award-info":[{"award-number":["1K01HL175261"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Otitis media is highly prevalent during early life, yet the molecular factors that predispose children to recurrent episodes are poorly defined. Metabolomics captures dynamic biochemical changes and may help identify pathways influencing otitis susceptibility. We examined whether longitudinal infant plasma metabolomic profiles were associated with development of stringently\u2010defined otitis proneness in the Rochester Combined Cohort (RCC; Rochester, NY).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Global plasma metabolomic profiling was performed in RCC samples collected between ~6 and 18\u2009months of age using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS). Children were classified as stringently\u2010defined otitis prone (sOP) if they experienced \u22653 acute otitis media (AOM) episodes within a 6\u2010month period or \u22654 AOM episodes within a 12\u2010month period during the first 3\u2009years of life; all AOM episodes were tympanocentesis\u2010confirmed. Generalized additive mixed models (GAMMs) assessed age\u2010dependent differences in plasma metabolite levels between sOP and non\u2010otitis\u2010prone (nOP) children, adjusting for potential confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Several metabolites demonstrated age\u2010related declines in lipid and amino acid pathways, with consistently lower metabolite trajectories in the sOP group. Compared with nOP children, sOP children exhibited significantly lower levels of 16 metabolites related to inflammatory lipid signaling, redox metabolism, and fatty acid metabolism (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20094.4\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ) and higher levels of glycerophosphoinositol (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092.9\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). These findings were directionally consistent in a sensitivity analysis additionally adjusted for recent antibiotic use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Children who subsequently met sOP criteria by age 3\u2009years exhibited distinct plasma metabolomic signatures during infancy, suggesting altered immune\u2013metabolic programming preceding recurrent otitis media. Longitudinal metabolomics provides a promising framework to identify biochemical mechanisms underlying otitis proneness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70428","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:59:37Z","timestamp":1787032777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma metabolomics in infancy reveals early signatures of a stringently\u2010defined otitis\u2010prone phenotype"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8506-1122","authenticated-orcid":false,"given":"Nicole","family":"Prince","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts 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