Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

Autor: van Hoorn EGM; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Rademaker D; Amsterdam Reproduction and Development, Amsterdam, The Netherlands.; Department of Obstetrics and Gynecology, Amsterdam University Medical Center location AMC, Amsterdam, The Netherlands., van der Wel AWT; Department of Obstetrics and Gynecology, Amsterdam University Medical Center location AMC, Amsterdam, The Netherlands., DeVries JH; Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Franx A; Department of Obstetrics and Gynecology Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands., van Rijn BB; Department of Obstetrics and Gynecology Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands., Kooy A; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Bethesda Diabetes Research Center, Hoogeveen, The Netherlands.; Department of Internal Medicine, Care Group Treant, Location Bethesda Hoogeveen, Hoogeveen, The Netherlands., Siegelaar SE; Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, The Netherlands., Roseboom TJ; Amsterdam Reproduction and Development, Amsterdam, The Netherlands.; Department of Obstetrics and Gynecology, Amsterdam University Medical Center location AMC, Amsterdam, The Netherlands.; Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Ozanne SE; Welcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Hooijmans CR; Department of Anesthesiology, Pain and Palliative Care (Meta Research Team), Radboud University Medical Center, Nijmegen, The Netherlands., Painter RC; Amsterdam Reproduction and Development, Amsterdam, The Netherlands.; Department of Obstetrics and Gynecology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Diabetic medicine : a journal of the British Diabetic Association [Diabet Med] 2024 Feb; Vol. 41 (2), pp. e15243. Date of Electronic Publication: 2023 Oct 26.
DOI: 10.1111/dme.15243
Abstrakt: 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.
(© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)
Databáze: MEDLINE
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