Risk Factors for Gestational Diabetes: An Umbrella Review of Meta-analyses of Observational Studies

Background/objective: Gestational diabetes mellitus (GDM) is a common pregnancy complication, with complex disease mechanisms, and several risk factors may contribute to its onset. We performed an umbrella review to summarize the evidence from meta-analyses of observational studies on risk factors associated with GDM, evaluate whether there are indications of biases in this literature and identify which of the previously reported associations are supported by convincing evidence.

Methods: We searched PubMed and ISI Web of Science from inception to December 2018 to identify meta-analyses examining associations between putative risk factors for GDM. For each meta-analysis we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias.

Results: Thirty eligible meta-analyses were identified, providing data on 61 associations. Fifty (82%) associations had nominally statistically significant findings (P<0.05), while only 15 (25%) were significant at P<10-6 under the random-effects model. Only four risk factors presented convincing evidence:, low vs. normal BMI (cohort studies), BMI ~30-35 kg/m2 vs. normal BMI, BMI >35 kg/m2 vs. normal BMI, and hypothyroidism.

Conclusions: The compilation of results from synthesis of observational studies suggests that increased BMI and hypothyroidism show the strongest consistent evidence for an association with GDM. Diet and lifestyle modifications in pregnancy should be tested in large randomized trials. Our findings suggest that women with known thyroid disease may be offered screening for GDM earlier in pregnancy.