Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study

Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study Satoshi Kusuda, Mihoko Bennett, Jeffrey Gould This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4464593/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives : There is a variation in the incidence of necrotizing enterocolitis (NEC) among countries. To investigate the influence of ethnicity, NEC incidents were compared between Japan and California. Study Design : A retrospective cohort study was conducted using neonatal databases in Japan and California, including infants between 2008 and 2019 at 22-29 gestational weeks. Infants born in Japan (JP) were compared to infants born in California to mothers born in Japan (JP-J), to mothers with Japanese ethnicity born outside Japan (JP-CA), and to non-Hispanic White mothers (NHW-CA). Results : Each cohort consisted of 52,049, 115, 226, and 12,275 infants, respectively. Unadjusted NEC incidences were significantly lower in JP (1.7% vs. 4.4% JP-J+JP-C, and 3.3% NHW-CA, respectively; p<0.01). After background adjustment, odds ratios in JP-J, JP-CA, and NHW-CA vs. JP were 3.0 (1.2-7.8), 2.9 (1.5-5.8), and 2.0 (1.6-2.5), respectively. Conclusions : The NEC incidence variation could not be explained solely based on ethnic background. Health sciences/Diseases/Gastrointestinal diseases/Intestinal diseases Health sciences/Medical research/Epidemiology Health sciences/Diseases/Nutrition disorders necrotizing enterocolitis epidemiology ethnicity genetic background extremely preterm infants mortality incidence practices Figures Figure 1 Figure 2 Figure 3 Full Text Additional Declarations There is NO conflict of interest to disclose. Supplementary Files Appendix1.pdf Table1.pdf Table2.pdf Table3.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4464593","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":305867887,"identity":"05f82603-baa5-4442-b116-cefa9cfdb256","order_by":0,"name":"Satoshi Kusuda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBACCRDBA+UwMxjYgOgEIrWwgbWkkayF4TBhh0nOSH8m8aaGwZ5/fvPhzwUF5/PMZzc8YPi4pxanFmmJHDPJOccYEmccY0uTnmFwu1jmzoEExhnPjuPUIieRwybNw/Y/geEYjxkzj8HtxBkSCQnMPAeO4dGS/kya5x+DvfwxHuPPPAbnCGuRlkgwk+ZtY2DccIzHQJrH4ABMSw1u7/e8Mbac28eQuPFYWhpQSzJYy8EZBw7g1CJxPP3hjTffGOzlDh8+/Jnnjx1QS07igw8H6nBqwQZ4Eg4QFUFIgB3kKNJsGQWjYBSMgmENAC/aUMWy0JBIAAAAAElFTkSuQmCC","orcid":"","institution":"Kyorin University","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Kusuda","suffix":""},{"id":305867888,"identity":"faf8c87b-b55a-4079-9ad5-95abb6a9928e","order_by":1,"name":"Mihoko Bennett","email":"","orcid":"https://orcid.org/0000-0002-3449-9538","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Mihoko","middleName":"","lastName":"Bennett","suffix":""},{"id":305867889,"identity":"f22bab72-556d-4f27-afef-07b54fa50424","order_by":2,"name":"Jeffrey Gould","email":"","orcid":"https://orcid.org/0000-0002-8495-077X","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jeffrey","middleName":"","lastName":"Gould","suffix":""}],"badges":[],"createdAt":"2024-05-23 06:20:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4464593/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4464593/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58753522,"identity":"dd36a349-8f15-4255-823d-395dd4ba9f38","added_by":"auto","created_at":"2024-06-20 16:19:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43811,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flow\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNRNJ: the Neonatal Research Network of Japan\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCPQCC: the California Perinatal Quality Care Collaborative\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGA: gestational age\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/e957b1e96c618d5252d30d13.png"},{"id":58754299,"identity":"969fa908-2b9f-478d-9194-2280f9f04a11","added_by":"auto","created_at":"2024-06-20 16:27:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34249,"visible":true,"origin":"","legend":"\u003cp\u003eNecrotising enterocolitis, spontaneous gastro-intestinal perforation, and \u0026nbsp;death/necrotizing enterocolitis rates among different cohorts\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNEC and its composite outcome in infants born in Japan were significantly lower than all other \u0026nbsp;cohorts in California (unadjusted logistic regression, p\u0026lt;0.01). Although spontaneous GI perforation was lowest in non-Hispanic White infants, there was no significant difference \u0026nbsp;among cohorts. (Refer to Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVertical bars show 95% confidential limits.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNEC: necrotizong enterocolitis, GI: gastro-intestinal\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJP: Japan, CA: California, NHW: non-Hispanic White\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/c65db4e16bdafc542b4147e8.png"},{"id":58754298,"identity":"27ddf51d-2dcd-42ba-863b-976e956310ea","added_by":"auto","created_at":"2024-06-20 16:27:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33961,"visible":true,"origin":"","legend":"\u003cp\u003eTrends in necrotizing enterocolitis in Japan and California\u003c/p\u003e\n\u003cp\u003eComparison of annual trends in incidences in three groups revealed no significant differences 4 for Japan (Cochran-Armitage trend test), while significant decreases for the CPQCC (p\u0026lt;0.01) \u0026nbsp;and non-Hispanic White infants born in California (p\u0026lt;0.01).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe NEC incidences in each year group are described at the bottom of the figure. CPQCC: California Perinatal Quality Care Collaborative, NHW-CA: non-Hispanic White \u0026nbsp;infants in Calfornia, JP: infants born in Japan.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/546dce7a04a71aa133696d8f.png"},{"id":58808878,"identity":"4564c8a8-0f16-4a06-be92-cfa41cd95d1f","added_by":"auto","created_at":"2024-06-21 11:29:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":445246,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1_covered_a8708a7d-cb1f-4359-a3ba-86138eb670fa.pdf"},{"id":58753517,"identity":"b8a8a84e-4378-4cfe-af3e-e27eff85b098","added_by":"auto","created_at":"2024-06-20 16:19:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":97142,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Appendix1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/ef146ad78d86f6f02a9533bd.pdf"},{"id":58754300,"identity":"293c131f-bc5d-4dc3-b800-9727e131ab39","added_by":"auto","created_at":"2024-06-20 16:27:04","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":119741,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/816eda16a48174b2017bfd12.pdf"},{"id":58753523,"identity":"85bb1f51-0fe1-4074-9925-277aa3bd716d","added_by":"auto","created_at":"2024-06-20 16:19:04","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":93567,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/2ee1c27794c8bed94dc27318.pdf"},{"id":58753520,"identity":"fe915914-faf7-46c6-b539-e099fe1de8a6","added_by":"auto","created_at":"2024-06-20 16:19:04","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":34232,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4464593/v1/dd64ed226bdb6d73ca0a0487.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"necrotizing enterocolitis, epidemiology, ethnicity, genetic background, extremely preterm infants, mortality, incidence, practices","lastPublishedDoi":"10.21203/rs.3.rs-4464593/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4464593/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: There is a variation in the incidence of necrotizing enterocolitis (NEC) among countries. To investigate the influence of ethnicity, NEC incidents were compared between Japan and California.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e: A retrospective cohort study was conducted using neonatal databases in Japan and California, including infants between 2008 and 2019 at 22-29 gestational weeks. Infants born in Japan (JP) were compared to infants born in California to mothers born in Japan (JP-J), to mothers with Japanese ethnicity born outside Japan (JP-CA), and to non-Hispanic White mothers (NHW-CA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Each cohort consisted of 52,049, 115, 226, and 12,275 infants, respectively. Unadjusted NEC incidences were significantly lower in JP (1.7% vs. 4.4% JP-J+JP-C, and 3.3% NHW-CA, respectively; p\u0026lt;0.01). After background adjustment, odds ratios in JP-J, JP-CA, and NHW-CA vs. JP were 3.0 (1.2-7.8), 2.9 (1.5-5.8), and 2.0 (1.6-2.5), respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: The NEC incidence variation could not be explained solely based on ethnic background.\u003c/p\u003e","manuscriptTitle":"Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 16:18:59","doi":"10.21203/rs.3.rs-4464593/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"00799520-72a3-4c0e-ae6d-5739008870e5","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32301830,"name":"Health sciences/Diseases/Gastrointestinal diseases/Intestinal diseases"},{"id":32301831,"name":"Health sciences/Medical research/Epidemiology"},{"id":32301832,"name":"Health sciences/Diseases/Nutrition disorders"}],"tags":[],"updatedAt":"2024-06-21T11:21:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-20 16:18:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4464593","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4464593","identity":"rs-4464593","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}