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. 2023 Apr 18;21(1):152.
doi: 10.1186/s12916-023-02758-1.

Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature

Anita Semertzidou  1 , Harriet Grout-Smith  1 , Ilkka Kalliala  1   2 , Akanksha Garg  3 , Vasso Terzidou  1   3 , Julian Marchesi  1   4 , David MacIntyre  1 , Phillip Bennett  1   3 , Konstantinos Tsilidis  5   6 , Maria Kyrgiou  7   8
Affiliations

Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature

Anita Semertzidou et al. BMC Med. .

Abstract

Background: Diabetes 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.

Methods: Design: Umbrella review of systematic reviews and meta-analyses.

Data sources: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, manual screening of references.

Eligibility criteria: Systematic 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 analysis: The 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.

Results: A 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.

Conclusions: Gestational 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 registration: Open Science Framework (OSF) (Registration https://doi.org/10.17605/OSF.IO/9G6AB ).

Keywords: Cancer; Congenital malformations; Diabetes; Gynaecology; Large for gestational age; Macrosomia; Obstetrics; Prematurity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Graphical presentation of main and sensitivity analyses of meta-analyses investigating diabetes and anti-diabetic interventions and gynaecological/obstetric conditions
Fig. 2
Fig. 2
Flow diagram of the selection process of meta-analyses included in the review
See this image and copyright information in PMC

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References

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