Pregabalin Abuse During Pregnancy and Global Developmental Delay in Infants

Pregabalin Abuse During Pregnancy and Global Developmental Delay in Infants | 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 Pregabalin Abuse During Pregnancy and Global Developmental Delay in Infants Jahan Zeb Khan, Emma Fletcher, Aishling Collins, Fiona Fenton This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-947031/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Pregabalin is a medication licensed for the treatment of epilepsy and anxiety disorders. In addition, Pregabalin is increasingly recognised as a drug of abuse. Teratogenic effects have been demonstrated in animal models, however, there is a dearth of research relating to potential teratogenic effects in humans. This case highlights the potential role of intrauterine exposure to Pregabalin in contributing to Global Developmental Delay in two children. Internal Medicine pregabalin birth defects developmental delay disorder drug dependence Introduction: Pregabalin is a medication which is classified as a gamma-aminobutyric acid, GABA analogue. In animal models, it has been demonstrated that in the central nervous system it reduces the release of excitatory neurotransmitters, which are probably associated with analgesic and anticonvulsant effects [1]. The United States Food and Drug Administration (FDA) approved Pregabalin for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, spinal cord injury, postherpetic neuralgia and fibromyalgia, and as an adjunctive therapy for partial onset seizures [2]. However, over the last few years there has been increased abuse[3]. The frequent desirable effects reported by people who misuse Pregabalin include euphoria, relaxation, and sleep aid [4].We are presenting an interesting case of Pregabalin abuse in pregnancy and its likely impact on the child’s development. Case Presentation Our case is a 29-year female referred by the general practitioner (GP) for inpatient Pregabalin detoxification. She was 16 weeks pregnant at the time of her admission. She reported that her GP initially prescribed her Pregabalin for anxiety in her early twenties and she could not discontinue due to withdrawal symptoms, she was taking 1400 mg of it daily. She reported using Pregabalin in her last two pregnancies and developmental delay was diagnosed in both children. Child A, who is two and a half years old now, was born at full-term by normal vaginal delivery following an uncomplicated pregnancy. He was late to achieve his developmental milestones. He was diagnosed with global developmental delay by a multidisciplinary team and referred to the Early Intervention Team (EIT) at the age of 18 months. Child B is 15 months old at the time of writing; she was also born at full-term via normal vaginal delivery following an uncomplicated pregnancy. All of child B’s milestones were delayed and she was small for her age. She was diagnosed with Global Developmental Delay at one year of age. Child A made significant improvements with intervention from the EIT and eventually reached his developmental milestones. Child B has not made much progress. There was no significant history of congenital abnormalities, learning disability or developmental delay in the parents or family of either child. The mother was concerned about the impact of Pregabalin on the current pregnancy as she had been using higher dose of Pregabalin (1400mg) than in the previous pregnancies. She completed a four-week detoxification program and was referred to primary care. Discussion Global developmental delay can be defined as significant delay in two or more developmental domains: gross and fine motor; speech and language; cognition; personal and social development; or activities of daily living. “Significant” may be defined as performance at two or more standard deviations below the mean on developmental screening or assessment tests [ 5 ]. The diagnosis requires full clinical history, physical examination, routine baseline blood tests and specific blood tests e.g. creatinine kinase test, calcium assay, DNA studies and imaging CT, MRI and EEG [ 5 ]. We understand that currently there are few studies which examine the effects of pregabalin on pregnancy outcomes. Furthermore, there are even fewer studies which examine the immediate- and medium-term effects of pregabalin on the developmental milestones of children with a history of intrauterine exposure to high-dose pregabalin. One study which looked at the effect on pregnancy outcomes compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs) [ 6 ]. A significantly higher rate of major birth defect and lower number of live births was observed in the pregabalin group, after exclusion of chromosomal aberration syndromes. An Italian study identified 30 pregnancies that had been exposed to pregabalin and relative to unexposed pregnancies, exposure to pregabalin was associated with increased odds of many adverse outcomes; however, none of these were statistically significant [ 7 ]. According to our knowledge this is the first case report of the effect of pregabalin on developmental delay and there is little knowledge about the impact of pregabalin on the developmental milestones of children who were exposed to pregabalin during pregnancy. We hypothesize there may be different factors at play e.g., limited clinical trials studying the effect, more focus on other causes of developmental delay, reporting issues and pregabalin being a relatively newer drug. Conclusions This case explores the possible aetiological role of pregabalin in developmental delay in children exposed to it during intrauterine life but more research in this field is required to conclude this. Declarations i. Funding. The authors declared that this research received no specific grant from any funding agency, commercial or not-for-profit sectors. ii. Conflicts of interest/Competing interests. The authors declared there is no conflict of interest with this research article. iii. Ethics approval. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation with the Helsinki Declaration of 1975, as revised in 2008. The authors assert that ethical approval for publication of this case report was not required by their local Ethics Committee. A written informed consent was obtained from the patient for preparation, publication, and presentation of this case report. iv. Authors' contribution. All authors contributed to the case report. Initial case was identified by JK, initial template was also made by JK, formatting and final submission was done by JK. AC wrote abstract and proofread the completed manuscript. EF completed case report and a full proofread of manuscript. FF proofread the manuscript and provided advice about formatting. References Bian, F., Li, Z., Offord, J., Davis, M. D., McCormick, J., Taylor, C. P., & Walker, L. C. (2006). Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain research , 1075 (1), 68-80. Tassone, D. M., Boyce, E., Guyer, J., & Nuzum, D. (2007). Pregabalin: a novel γ-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clinical therapeutics , 29 (1), 26-48. Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European neuropsychopharmacology , 27 (12), 1185-1215. Schifano, F., Chiappini, S., Corkery, J. M., & Guirguis, A. (2018). Abuse of prescription drugs in the context of novel psychoactive substances (NPS): a systematic review. Brain sciences , 8 (4), 73. McDonald L, Rennie A, Tolmie J, Galloway P, McWilliam R. Investigation of global developmental delay. Arch Dis Child . 2006;91(8):701-705. doi:10.1136/adc.2005.078147. Winterfeld, U., Merlob, P., Baud, D., Rousson, V., Panchaud, A., Rothuizen, L. E., ... & Buclin, T. (2016). Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology , 86 (24), 2251-2257. Mostacci, B., Poluzzi, E., D’Alessandro, R., Cocchi, G., & Tinuper, P. (2018). Adverse pregnancy outcomes in women exposed to gabapentin and pregabalin: data from a population-based study. Journal of Neurology, Neurosurgery & Psychiatry , 89 (2), 223-224. Supplementary Files CARE.jpg Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Minor revisions 11 Jan, 2022 Reviews received at journal 01 Jan, 2022 Reviewers invited by journal 31 Dec, 2021 First submitted to journal 28 Sep, 2021 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-947031","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":73517855,"identity":"c91a5efd-2ced-43cc-b1e1-6b84dd0c6d8c","order_by":0,"name":"Jahan Zeb Khan","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-1664-8210","institution":"St Vincent's University Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jahan","middleName":"Zeb","lastName":"Khan","suffix":""},{"id":73517856,"identity":"32081957-326e-4cd0-9851-06918afd750e","order_by":1,"name":"Emma Fletcher","email":"","orcid":"","institution":"Saint John Of God Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Emma","middleName":"","lastName":"Fletcher","suffix":""},{"id":73517857,"identity":"a325f4b5-15db-464a-baf3-33a968fc68b1","order_by":2,"name":"Aishling Collins","email":"","orcid":"","institution":"St Patrick's University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aishling","middleName":"","lastName":"Collins","suffix":""},{"id":73517858,"identity":"375a5ce7-e812-4dd4-825c-d80f408cf63a","order_by":3,"name":"Fiona Fenton","email":"","orcid":"","institution":"National Drug Dependence Treatment Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fiona","middleName":"","lastName":"Fenton","suffix":""}],"badges":[],"createdAt":"2021-09-28 21:10:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-947031/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-947031/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":16952095,"identity":"c188639d-7500-4f0f-a775-4b1af5edf78c","added_by":"auto","created_at":"2022-01-03 21:36:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":147165,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-947031/v1/0af0191f-e443-40db-9ea0-d4522b27ee0d.pdf"},{"id":16952094,"identity":"f5f92efd-1f34-4def-a7b1-bbee4525c8f6","added_by":"auto","created_at":"2022-01-03 21:36:56","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2125387,"visible":true,"origin":"","legend":"","description":"","filename":"CARE.jpg","url":"https://assets-eu.researchsquare.com/files/rs-947031/v1/41f3eb03b4a259845ec7ea8a.jpg"}],"financialInterests":"","formattedTitle":"\u003cp\u003ePregabalin Abuse During Pregnancy and Global Developmental Delay in Infants\u003c/p\u003e","fulltext":[{"header":"Introduction:","content":"\u003cp\u003ePregabalin is a medication which is classified as a gamma-aminobutyric acid, GABA analogue. In animal models, it has been demonstrated that in the central nervous system it reduces the release of excitatory neurotransmitters, which are probably associated with analgesic and anticonvulsant effects [1].\u003c/p\u003e\n\u003cp\u003eThe United States Food and Drug Administration (FDA) approved Pregabalin for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, spinal cord injury, postherpetic neuralgia and fibromyalgia, and as an adjunctive therapy for partial onset seizures [2]. However, over the last few years there has been increased abuse[3]. The frequent desirable effects reported by people who misuse Pregabalin include euphoria, relaxation, and sleep aid [4].We are presenting an interesting case of Pregabalin abuse in pregnancy and its likely impact on the child\u0026rsquo;s development.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eOur case is a 29-year female referred by the general practitioner (GP) for inpatient Pregabalin detoxification. She was 16 weeks pregnant at the time of her admission. She reported that her GP initially prescribed her Pregabalin for anxiety in her early twenties and she could not discontinue due to withdrawal symptoms, she was taking 1400 mg of it daily.\u003c/p\u003e \u003cp\u003eShe reported using Pregabalin in her last two pregnancies and developmental delay was diagnosed in both children. Child A, who is two and a half years old now, was born at full-term by normal vaginal delivery following an uncomplicated pregnancy. He was late to achieve his developmental milestones. He was diagnosed with global developmental delay by a multidisciplinary team and referred to the Early Intervention Team (EIT) at the age of 18 months.\u003c/p\u003e \u003cp\u003eChild B is 15 months old at the time of writing; she was also born at full-term via normal vaginal delivery following an uncomplicated pregnancy. All of child B\u0026rsquo;s milestones were delayed and she was small for her age. She was diagnosed with Global Developmental Delay at one year of age.\u003c/p\u003e \u003cp\u003eChild A made significant improvements with intervention from the EIT and eventually reached his developmental milestones. Child B has not made much progress. There was no significant history of congenital abnormalities, learning disability or developmental delay in the parents or family of either child.\u003c/p\u003e \u003cp\u003eThe mother was concerned about the impact of Pregabalin on the current pregnancy as she had been using higher dose of Pregabalin (1400mg) than in the previous pregnancies. She completed a four-week detoxification program and was referred to primary care.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eGlobal developmental delay can be defined as significant delay in two or more developmental domains: gross and fine motor; speech and language; cognition; personal and social development; or activities of daily living. \u0026ldquo;Significant\u0026rdquo; may be defined as performance at two or more standard deviations below the mean on developmental screening or assessment tests [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The diagnosis requires full clinical history, physical examination, routine baseline blood tests and specific blood tests e.g. creatinine kinase test, calcium assay, DNA studies and imaging CT, MRI and EEG [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe understand that currently there are few studies which examine the effects of pregabalin on pregnancy outcomes. Furthermore, there are even fewer studies which examine the immediate- and medium-term effects of pregabalin on the developmental milestones of children with a history of intrauterine exposure to high-dose pregabalin. One study which looked at the effect on pregnancy outcomes compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A significantly higher rate of major birth defect and lower number of live births was observed in the pregabalin group, after exclusion of chromosomal aberration syndromes.\u003c/p\u003e \u003cp\u003eAn Italian study identified 30 pregnancies that had been exposed to pregabalin and relative to unexposed pregnancies, exposure to pregabalin was associated with increased odds of many adverse outcomes; however, none of these were statistically significant [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to our knowledge this is the first case report of the effect of pregabalin on developmental delay and there is little knowledge about the impact of pregabalin on the developmental milestones of children who were exposed to pregabalin during pregnancy. We hypothesize there may be different factors at play e.g., limited clinical trials studying the effect, more focus on other causes of developmental delay, reporting issues and pregabalin being a relatively newer drug.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case explores the possible aetiological role of pregabalin in developmental delay in children exposed to it during intrauterine life but more research in this field is required to conclude this.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003ei. Funding. The authors declared that this research received no specific grant from any funding agency, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eii. Conflicts of interest/Competing interests. The authors declared there is no conflict of interest with this research article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eiii. Ethics approval. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation with the Helsinki Declaration of 1975, as revised in 2008. The authors assert that ethical approval for publication of this case report was not required by their local Ethics Committee. A written informed consent was obtained from the patient for preparation, publication, and presentation of this case report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eiv. Authors\u0026apos; contribution. All authors contributed to the case report. Initial case was identified by JK, initial template was also made by JK, formatting and final submission was done by JK. AC wrote abstract and proofread the completed manuscript. EF completed case report and a full proofread of manuscript. FF proofread the manuscript and provided advice about formatting.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBian, F., Li, Z., Offord, J., Davis, M. D., McCormick, J., Taylor, C. P., \u0026amp; Walker, L. C. (2006). Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. \u003cem\u003eBrain research\u003c/em\u003e, \u003cem\u003e1075\u003c/em\u003e(1), 68-80.\u003c/li\u003e\n\u003cli\u003eTassone, D. M., Boyce, E., Guyer, J., \u0026amp; Nuzum, D. (2007). Pregabalin: a novel \u0026gamma;-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. \u003cem\u003eClinical therapeutics\u003c/em\u003e, \u003cem\u003e29\u003c/em\u003e(1), 26-48.\u003c/li\u003e\n\u003cli\u003eBonnet, U., \u0026amp; Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. \u003cem\u003eEuropean neuropsychopharmacology\u003c/em\u003e, \u003cem\u003e27\u003c/em\u003e(12), 1185-1215.\u003c/li\u003e\n\u003cli\u003eSchifano, F., Chiappini, S., Corkery, J. M., \u0026amp; Guirguis, A. (2018). Abuse of prescription drugs in the context of novel psychoactive substances (NPS): a systematic review. \u003cem\u003eBrain sciences\u003c/em\u003e, \u003cem\u003e8\u003c/em\u003e(4), 73.\u003c/li\u003e\n\u003cli\u003eMcDonald L, Rennie A, Tolmie J, Galloway P, McWilliam R. Investigation of global developmental delay. \u003cem\u003eArch Dis Child\u003c/em\u003e. 2006;91(8):701-705. doi:10.1136/adc.2005.078147.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eWinterfeld, U., Merlob, P., Baud, D., Rousson, V., Panchaud, A., Rothuizen, L. E., ... \u0026amp; Buclin, T. (2016). Pregnancy outcome following maternal exposure to pregabalin may call for concern. \u003cem\u003eNeurology\u003c/em\u003e, \u003cem\u003e86\u003c/em\u003e(24), 2251-2257.\u003c/li\u003e\n\u003cli\u003eMostacci, B., Poluzzi, E., D\u0026rsquo;Alessandro, R., Cocchi, G., \u0026amp; Tinuper, P. (2018). Adverse pregnancy outcomes in women exposed to gabapentin and pregabalin: data from a population-based study. \u003cem\u003eJournal of Neurology, Neurosurgery \u0026amp; Psychiatry\u003c/em\u003e, \u003cem\u003e89\u003c/em\u003e(2), 223-224.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pregabalin, birth defects, developmental delay disorder, drug dependence","lastPublishedDoi":"10.21203/rs.3.rs-947031/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-947031/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePregabalin is a medication licensed for the treatment of epilepsy and anxiety disorders. In addition, Pregabalin is increasingly recognised as a drug of abuse. Teratogenic effects have been demonstrated in animal models, however, there is a dearth of research relating to potential teratogenic effects in humans. This case highlights the potential role of intrauterine exposure to Pregabalin in contributing to Global Developmental Delay in two children.\u003c/p\u003e","manuscriptTitle":"Pregabalin Abuse During Pregnancy and Global Developmental Delay in Infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-01-03 21:36:54","doi":"10.21203/rs.3.rs-947031/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revisions","date":"2022-01-12T03:48:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-01-01T08:22:35+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-12-31T12:59:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2021-09-28T04:17:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7e4683ce-82dd-4a64-bc5f-3a3abe8e7d2f","owner":[],"postedDate":"January 3rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":9492405,"name":"Internal Medicine"}],"tags":[],"updatedAt":"2022-01-17T08:01:56+00:00","versionOfRecord":[],"versionCreatedAt":"2022-01-03 21:36:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-947031","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-947031","identity":"rs-947031","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}