Prepregnancy fasting insulin as an early indicator of the risk of spontaneous preterm birth: A retrospective cohort study

Prepregnancy fasting insulin as an early indicator of the risk of spontaneous preterm birth: 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 Research Article Prepregnancy fasting insulin as an early indicator of the risk of spontaneous preterm birth: A retrospective cohort study Xiang Jiang, Xiaoyuan Mao, Xiang Li, Yuping Tang, Xiaoxian Qu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6372507/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 Background: Identifying modifiable risk factors for spontaneous preterm birth (sPTB) is crucial for developing effective interventions. While maternal overt diabetes is known to increase the risk of sPTB, the impact of impaired insulin sensitivity and insulin response\textemdash early stages of glucose dysmetabolism affecting a larger proportion of reproductive-age individuals\textemdash remains underexplored. This study aimed to identify maternal prepregnancy insulin sensitivity and response indices with prognostic value for the risk of dysmetabolic-associated sPTB. Methods: This retrospective study included 1,898 non-diabetic individuals who underwent an oral glucose tolerance test (OGTT) before pregnancy and had recorded delivery outcomes. Adjusted odds ratios (aORs) for quintiles of prepregnancy OGTT-derived insulin sensitivity and response indices in relation to sPTB before 37 weeks were estimated using multivariable logistic regression models, with the middle quintile as the reference group. The index of interest was selected based on its accessibility and prognostic significance. Models incorporating restricted cubic splines, a statistical method for modeling nonlinear associations, were developed to assess the relationship between the index of interest as a continuous variable and sPTB risk. The relationships between the identified index and individual characteristics were analyzed to explore possible mechanisms. Results: Most participants (85.2%) exhibited normal prepregnancy glucose tolerance. Prepregnancy fasting insulin was selected as the index of interest due to its accessibility and comparable aORs for sPTB risk relative to other OGTT-derived insulin sensitivity and response indices. The highest and lowest quintiles of prepregnancy fasting insulin had sPTB rates of 11.8% and 7.9%, respectively, approximately twice the rate observed in the middle quintile (4.2%). The aORs were 2.81 [95% confidence interval (CI): 1.47\textendash5.65] and 2.36 (95% CI: 1.21\textendash4.78). A significant nonlinear relationship was identified between prepregnancy fasting insulin as a continuous variable and sPTB risk ($P$ for nonlinearity = 0.018). Additionally, prepregnancy fasting insulin correlated significantly with prepregnancy body mass index (BMI) and glucose levels. Conclusions: Prepregnancy fasting insulin is associated with an increased risk of sPTB at both high and low levels in individuals predominantly exhibiting normal glucose tolerance. Spontaneous preterm birth Fasting insulin Oral glucose tolerance test Insulin response Insulin resistance Prepregnancy Full Text Additional Declarations No competing interests reported. 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. 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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-6372507","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":457151906,"identity":"f43c416a-6357-417e-ae61-6b5d6878d38c","order_by":0,"name":"Xiang Jiang","email":"","orcid":"","institution":"Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Jiang","suffix":""},{"id":457151907,"identity":"2e5641bb-e0f4-40bc-880d-12d933953666","order_by":1,"name":"Xiaoyuan Mao","email":"","orcid":"","institution":"Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyuan","middleName":"","lastName":"Mao","suffix":""},{"id":457151908,"identity":"6192d36d-86fe-4643-b0f3-d081849b6a35","order_by":2,"name":"Xiang Li","email":"","orcid":"","institution":"Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Li","suffix":""},{"id":457151909,"identity":"a5b5996c-fc6c-4917-b37b-c4960ba9db30","order_by":3,"name":"Yuping Tang","email":"","orcid":"","institution":"Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Yuping","middleName":"","lastName":"Tang","suffix":""},{"id":457151910,"identity":"b9c96ec8-57d3-40d1-b980-b20b69c0191a","order_by":4,"name":"Xiaoxian Qu","email":"","orcid":"","institution":"Shanghai First Maternity 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resistance, Prepregnancy","lastPublishedDoi":"10.21203/rs.3.rs-6372507/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6372507/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Identifying modifiable risk factors for spontaneous preterm birth (sPTB) is crucial for developing effective interventions. While maternal overt diabetes is known to increase the risk of sPTB, the impact of impaired insulin sensitivity and insulin response\\textemdash early stages of glucose dysmetabolism affecting a larger proportion of reproductive-age individuals\\textemdash remains underexplored. This study aimed to identify maternal prepregnancy insulin sensitivity and response indices with prognostic value for the risk of dysmetabolic-associated sPTB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective study included 1,898 non-diabetic individuals who underwent an oral glucose tolerance test (OGTT) before pregnancy and had recorded delivery outcomes. Adjusted odds ratios (aORs) for quintiles of prepregnancy OGTT-derived insulin sensitivity and response indices in relation to sPTB before 37 weeks were estimated using multivariable logistic regression models, with the middle quintile as the reference group. The index of interest was selected based on its accessibility and prognostic significance. Models incorporating restricted cubic splines, a statistical method for modeling nonlinear associations, were developed to assess the relationship between the index of interest as a continuous variable and sPTB risk. The relationships between the identified index and individual characteristics were analyzed to explore possible mechanisms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Most participants (85.2%) exhibited normal prepregnancy glucose tolerance. Prepregnancy fasting insulin was selected as the index of interest due to its accessibility and comparable aORs for sPTB risk relative to other OGTT-derived insulin sensitivity and response indices. The highest and lowest quintiles of prepregnancy fasting insulin had sPTB rates of 11.8% and 7.9%, respectively, approximately twice the rate observed in the middle quintile (4.2%). The aORs were 2.81 [95% confidence interval (CI): 1.47\\textendash5.65] and 2.36 (95% CI: 1.21\\textendash4.78). A significant nonlinear relationship was identified between prepregnancy fasting insulin as a continuous variable and sPTB risk ($P$ for nonlinearity = 0.018). Additionally, prepregnancy fasting insulin correlated significantly with prepregnancy body mass index (BMI) and glucose levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Prepregnancy fasting insulin is associated with an increased risk of sPTB at both high and low levels in individuals predominantly exhibiting normal glucose tolerance.\u003c/p\u003e","manuscriptTitle":"Prepregnancy fasting insulin as an early indicator of the risk of spontaneous preterm birth: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 04:47:12","doi":"10.21203/rs.3.rs-6372507/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":"dcef7a2c-a96c-488a-8822-6e307f875c82","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-27T01:53:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-16 04:47:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6372507","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6372507","identity":"rs-6372507","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}