| Summary: | Background and aims: Current clinical risk stratification of gestational diabetes mellitus (GDM) is imprecise and definitive diagnosis requires administration of an oral glucose tolerance test (OGTT). A systematic review and meta-analysis study was conducted to determine the association between maternal serum YKL-40 and GDM, and its potential role in risk stratification and diagnosis. Methods and results: A literature search in Pubmed, Embase and Web of Science was conducted to identify studies examining the association between maternal serum YKL-40 in the context of GDM. We included studies reporting serum YKL-40 levels in GDM participants compared to a referent healthy control group. Studies not reporting serum YKL-40 levels in both cases and controls, or which failed to report mean or median levels with a measure of variability were excluded. Weighted mean differences in serum YKL-40 levels comparing GDM cases to healthy controls were pooled using a random effects model.Four observational studies met the inclusion criteria. Pooled analysis showed an association between serum YKL-40 levels at gestational age >12 weeks among GDM cases compared to controls (WMD=17.58 ng/mL, 95% CI: 3.63-31.53, p=0.014). This finding persisted across several sensitivity analyses. Only a single study investigated serum YKL-40 levels at gestational age <12 weeks and post-partum respectively, reporting null association. Conclusions: Maternal serum YKL-40 levels measured after the first trimester (>12 weeks gestational age) may have a potential role in future risk stratification and diagnosis of GDM. Our findings are presented with an overall moderate confidence level, driven primarily by risk of bias in the body of evidence. Given the small number of studies, we did not formally assess for publication bias and cannot exclude this risk impacting our reported findings.
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