Progestogens for the prevention of preterm birth and risk of developing gestational diabetes mellitus: a meta-analysis

Abstract Background Several articles have implied that progestogen supplementation during pregnancy to reduce the risk of preterm birth (PTB) may increase the risk for developing GDM. Objective The purpose of the present meta-analysis is to accumulate existing evidence concerning this correlation. Data sources We searched Medline (1966–2019), Scopus (2004–2019), Clinicaltrials.gov (2008–2019), EMBASE (1980-2019), Cochrane Central Register of Controlled Trials CENTRAL (1999-2019) and Google Scholar (2004-2019) databases. Study eligibility criteria Randomized trials and observational studies were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses we avoided language, country and date restrictions. Study appraisal and synthesis methods The methodological quality of included studies was evaluated with the Cochrane risk of bias and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with the Open Meta-Analyst software. Trial sequential analysis was conducted with the TSA program. Results Overall, 11 studies were included in the present meta-analysis that recruited 8,085 women. The meta-analysis revealed that women that received 17-OH progesterone caproate (17OHPC) had increased risk of developing gestational diabetes mellitus (RR 1.73, 95% CI 1.32 – 2.28), whereas women that received vaginal progesterone had a decreased risk, although the effect did not reach statistical significance due to the unstable estimate of CI`s (RR 0.82, 95% CI 0.50, 1.12). Meta-regression analysis indicated that neither the methodological rationale for investigating the prevalence of GDM (incidence investigated as primary or secondary outcome) (Coefficient of covariance -0.36, 95% CI -0.85, 0.13 , p=.154 ) nor the type of investigated study (RCT/observational) (Coefficient of covariance -0.361, 95% CI -1.049, 0.327, p=.304 ) significantly altered the results of the primary analysis. Trial sequential analysis suggested that the meta-analysis concerning the correlation of 17OHPC was of adequate power to reach firm conclusions; whereas, this was not confirmed in the case of vaginal progesterone. Conclusion The results of the present meta-analysis clearly indicate that women which receive supplemental 17OHPC for the prevention of PTB have increased risk of developing GDM. On the other hand, evidence concerning women treated with vaginal progesterone remains inconclusive.