Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments
Aims The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspr...
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| Veröffentlicht in: | Diabetic medicine 2024-02, Vol.41 (2), p.e15243-n/a |
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| creator | Hoorn, E. G. M. Rademaker, D. Wel, A. W. T. DeVries, J. H. Franx, A. Rijn, B. B. Kooy, A. Siegelaar, S. E. Roseboom, T. J. Ozanne, S. E. Hooijmans, C. R. Painter, R. C. |
| description | Aims
The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.
Methods
A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta‐analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup.
Results
We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow‐up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta‐analysis. No significant effects in the overall meta‐analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between‐studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.
Conclusion
This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non‐human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high‐quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date. |
| doi_str_mv | 10.1111/dme.15243 |
| format | Article |
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The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.
Methods
A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta‐analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup.
Results
We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow‐up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta‐analysis. No significant effects in the overall meta‐analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between‐studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.
Conclusion
This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non‐human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high‐quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.</description><identifier>ISSN: 0742-3071</identifier><identifier>EISSN: 1464-5491</identifier><identifier>DOI: 10.1111/dme.15243</identifier><identifier>PMID: 37845186</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>animal ; Animal Experimentation ; Animal models ; Animal research ; Animals ; Anthropometry ; Antidiabetics ; Children ; Diabetes Mellitus - drug therapy ; Female ; Fetuses ; Humans ; Hypoglycemic Agents - adverse effects ; Meta-analysis ; Metabolism ; Metformin ; Metformin - adverse effects ; Mice ; Models, Animal ; Offspring ; Pregnancy ; Pregnancy - drug effects ; Prenatal Care ; Rats ; Reviews ; rodents ; Swine ; Systematic review</subject><ispartof>Diabetic medicine, 2024-02, Vol.41 (2), p.e15243-n/a</ispartof><rights>2023 The Authors. published by John Wiley & Sons Ltd on behalf of Diabetes UK.</rights><rights>2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-6a9f6bf1bc4616189109f55fd69c7052deb05f3966de36f7997a12376740bdf93</citedby><cites>FETCH-LOGICAL-c3883-6a9f6bf1bc4616189109f55fd69c7052deb05f3966de36f7997a12376740bdf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdme.15243$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdme.15243$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37845186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoorn, E. G. M.</creatorcontrib><creatorcontrib>Rademaker, D.</creatorcontrib><creatorcontrib>Wel, A. W. T.</creatorcontrib><creatorcontrib>DeVries, J. H.</creatorcontrib><creatorcontrib>Franx, A.</creatorcontrib><creatorcontrib>Rijn, B. B.</creatorcontrib><creatorcontrib>Kooy, A.</creatorcontrib><creatorcontrib>Siegelaar, S. E.</creatorcontrib><creatorcontrib>Roseboom, T. J.</creatorcontrib><creatorcontrib>Ozanne, S. E.</creatorcontrib><creatorcontrib>Hooijmans, C. R.</creatorcontrib><creatorcontrib>Painter, R. C.</creatorcontrib><title>Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments</title><title>Diabetic medicine</title><addtitle>Diabet Med</addtitle><description>Aims
The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.
Methods
A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta‐analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup.
Results
We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow‐up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta‐analysis. No significant effects in the overall meta‐analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between‐studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.
Conclusion
This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non‐human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high‐quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.</description><subject>animal</subject><subject>Animal Experimentation</subject><subject>Animal models</subject><subject>Animal research</subject><subject>Animals</subject><subject>Anthropometry</subject><subject>Antidiabetics</subject><subject>Children</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Female</subject><subject>Fetuses</subject><subject>Humans</subject><subject>Hypoglycemic Agents - adverse effects</subject><subject>Meta-analysis</subject><subject>Metabolism</subject><subject>Metformin</subject><subject>Metformin - adverse effects</subject><subject>Mice</subject><subject>Models, Animal</subject><subject>Offspring</subject><subject>Pregnancy</subject><subject>Pregnancy - drug effects</subject><subject>Prenatal Care</subject><subject>Rats</subject><subject>Reviews</subject><subject>rodents</subject><subject>Swine</subject><subject>Systematic review</subject><issn>0742-3071</issn><issn>1464-5491</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1uFSEYhkmjaU-rC2-gIXGji2lhYGDorumPmtS40fWEmfkwNMNwCoz17LyEeou9Er_21C5MZAN58_B8gZeQN5wdcVzHY4Aj3tRS7JAVl0pWjTT8BVkxLetKMM33yH7O14zx2gizS_aEbmXDW7Uivy-h2InaeaTrmMv9r7vZPgRxKUMMkKmfaXQur5Ofv1PrCiSMSrILnvwMNEBxMQXE4CcalgQn9JTmTS4QbPEDTfDDw-3jBGQtTrCznTbZZxRj7AOOw7uoCzCX_Iq8dHbK8PppPyDfLi--nn2srr58-HR2elUNom1Fpaxxqne8H6TiireGM-Oaxo3KDJo19Qg9a5wwSo0glNPGaMtroZWWrB-dEQfk3da7TvFmgVy64PMA02RniEvu6la3teFCCkTf_oNexyXhK5AyXBrV1rpB6v2WGlLMOYHr8NOCTZuOs-6hpw576h57Qvbwybj0AcZn8m8xCBxvgVs_web_pu7888VW-QdJgaBv</recordid><startdate>202402</startdate><enddate>202402</enddate><creator>Hoorn, E. G. M.</creator><creator>Rademaker, D.</creator><creator>Wel, A. W. T.</creator><creator>DeVries, J. H.</creator><creator>Franx, A.</creator><creator>Rijn, B. B.</creator><creator>Kooy, A.</creator><creator>Siegelaar, S. E.</creator><creator>Roseboom, T. J.</creator><creator>Ozanne, S. E.</creator><creator>Hooijmans, C. R.</creator><creator>Painter, R. C.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>202402</creationdate><title>Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments</title><author>Hoorn, E. G. M. ; Rademaker, D. ; Wel, A. W. T. ; DeVries, J. H. ; Franx, A. ; Rijn, B. B. ; Kooy, A. ; Siegelaar, S. E. ; Roseboom, T. J. ; Ozanne, S. E. ; Hooijmans, C. R. ; Painter, R. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3883-6a9f6bf1bc4616189109f55fd69c7052deb05f3966de36f7997a12376740bdf93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>animal</topic><topic>Animal Experimentation</topic><topic>Animal models</topic><topic>Animal research</topic><topic>Animals</topic><topic>Anthropometry</topic><topic>Antidiabetics</topic><topic>Children</topic><topic>Diabetes Mellitus - drug therapy</topic><topic>Female</topic><topic>Fetuses</topic><topic>Humans</topic><topic>Hypoglycemic Agents - adverse effects</topic><topic>Meta-analysis</topic><topic>Metabolism</topic><topic>Metformin</topic><topic>Metformin - adverse effects</topic><topic>Mice</topic><topic>Models, Animal</topic><topic>Offspring</topic><topic>Pregnancy</topic><topic>Pregnancy - drug effects</topic><topic>Prenatal Care</topic><topic>Rats</topic><topic>Reviews</topic><topic>rodents</topic><topic>Swine</topic><topic>Systematic review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoorn, E. G. M.</creatorcontrib><creatorcontrib>Rademaker, D.</creatorcontrib><creatorcontrib>Wel, A. W. T.</creatorcontrib><creatorcontrib>DeVries, J. H.</creatorcontrib><creatorcontrib>Franx, A.</creatorcontrib><creatorcontrib>Rijn, B. B.</creatorcontrib><creatorcontrib>Kooy, A.</creatorcontrib><creatorcontrib>Siegelaar, S. E.</creatorcontrib><creatorcontrib>Roseboom, T. J.</creatorcontrib><creatorcontrib>Ozanne, S. E.</creatorcontrib><creatorcontrib>Hooijmans, C. R.</creatorcontrib><creatorcontrib>Painter, R. C.</creatorcontrib><collection>Wiley Online Library</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoorn, E. G. M.</au><au>Rademaker, D.</au><au>Wel, A. W. T.</au><au>DeVries, J. H.</au><au>Franx, A.</au><au>Rijn, B. B.</au><au>Kooy, A.</au><au>Siegelaar, S. E.</au><au>Roseboom, T. J.</au><au>Ozanne, S. E.</au><au>Hooijmans, C. R.</au><au>Painter, R. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments</atitle><jtitle>Diabetic medicine</jtitle><addtitle>Diabet Med</addtitle><date>2024-02</date><risdate>2024</risdate><volume>41</volume><issue>2</issue><spage>e15243</spage><epage>n/a</epage><pages>e15243-n/a</pages><issn>0742-3071</issn><eissn>1464-5491</eissn><abstract>Aims
The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.
Methods
A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta‐analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup.
Results
We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow‐up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta‐analysis. No significant effects in the overall meta‐analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between‐studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.
Conclusion
This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non‐human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high‐quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37845186</pmid><doi>10.1111/dme.15243</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | animal Animal Experimentation Animal models Animal research Animals Anthropometry Antidiabetics Children Diabetes Mellitus - drug therapy Female Fetuses Humans Hypoglycemic Agents - adverse effects Meta-analysis Metabolism Metformin Metformin - adverse effects Mice Models, Animal Offspring Pregnancy Pregnancy - drug effects Prenatal Care Rats Reviews rodents Swine Systematic review |
| title | Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments |
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