• Anita Semertzidou, Harriet Grout-Smith, Ilkka Kalliala, Akanksha Garg, Vasso Terzidou, Julian Marchesi, David MacIntyre, Phillip Bennett, Konstantinos Tsilidis, and Maria Kyrgiou.
• Department of Metabolism, Digestion and Reproduction - Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
• Bmc Med. 2023 Apr 18; 21 (1): 152152.

BackgroundDiabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions.MethodsDesign: Umbrella review of systematic reviews and meta-analyses.Data SourcesPubMed, Medline, Embase, Cochrane Database of Systematic Reviews, manual screening of references.Eligibility CriteriaSystematic reviews and meta-analyses of observational and interventional studies investigating the relationship between diabetes and anti-diabetic interventions with gynaecological or obstetric outcomes. Meta-analyses that did not include complete data from individual studies, such as relative risk, 95% confidence intervals, number of cases/controls, or total population were excluded.Data AnalysisThe evidence from meta-analyses of observational studies was graded as strong, highly suggestive, suggestive or weak according to criteria comprising the random effects estimate of meta-analyses and their largest study, the number of cases, 95% prediction intervals, I2 heterogeneity index between studies, excess significance bias, small study effect and sensitivity analysis using credibility ceilings. Interventional meta-analyses of randomised controlled trials were assessed separately based on the statistical significance of reported associations, the risk of bias and quality of evidence (GRADE) of included meta-analyses.ResultsA total of 117 meta-analyses of observational cohort studies and 200 meta-analyses of randomised clinical trials that evaluated 317 outcomes were included. Strong or highly suggestive evidence only supported a positive association between gestational diabetes and caesarean section, large for gestational age babies, major congenital malformations and heart defects and an inverse relationship between metformin use and ovarian cancer incidence. Only a fifth of the randomised controlled trials investigating the effect of anti-diabetic interventions on women's health reached statistical significance and highlighted metformin as a more effective agent than insulin on risk reduction of adverse obstetric outcomes in both gestational and pre-gestational diabetes.ConclusionsGestational diabetes appears to be strongly associated with a high risk of caesarean section and large for gestational age babies. Weaker associations were demonstrated between diabetes and anti-diabetic interventions with other obstetric and gynaecological outcomes.Trial RegistrationOpen Science Framework (OSF) (Registration https://doi.org/10.17605/OSF.IO/9G6AB ).© 2023. The Author(s).

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