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To investigate the relationship between pregnancy-associated plasma protein A (PAPP-A) and gestational diabetes mellitus (GDM), and to determine whether PAPP-A has improved value for predicting GDM in a Chinese population.Clinical data for 599 GDM patients and 986 unaffected pregnant women undergoing both antenatal examinations and delivery were retrospectively analyzed. First-trimester serum PAPP-A levels were compared between the groups. Binary logistic regression analysis was used to explore the risk factors for GDM, and the area under the receiver operating characteristic curve was used to determine the value of PAPP-A for predicting GDM.GDM-affected and unaffected pregnant women were significantly different in terms of age (P < 0.001), BMI (P < 0.001), family history of diabetes (P = 0.002), α-thalassemia trait (P < 0.01), parity (P < 0.001), conception methods (P < 0.001), gestational weeks at the time of labor (P < 0.001) and corrected PAPP-A multiples of the median values (P < 0.001). Binary logistic regression analysis showed that PAPP-A levels were negatively related to the subsequent development of GDM (odds ratio 0.798, 95% confidence interval 0.647–0.984). The area under the receiver operating characteristic curve for maternal factors was 0.684 (95% CI: 0.657–0.711), and did not significantly differ from that for the combination of maternal factors and serum PAPP-A levels, which was 0.686 (95% CI: 0.660–0.713; χ2 = 0.625, P = 0.429).Serum PAPP-A was an independent factor for the development of GDM in pregnant Chinese women. Serum-PAPP-A does not have improved value with respect to predicting GDM when combined with other maternal factors.As China is a developing country where in some districts remain low-resource settings, a biomarker that is not only effective in screening for GDM but is also economical would be optimal. Therefore, we focused on serum pregnancy-associated plasma protein A (PAPP-A), which is a routine indicator used for Down syndrome screening. The added utility of this biomarker with respect to predicting GDM came at no extra cost. The aim of this study was to assess whether serum PAPP-A levels were altered at 11–13+6 weeks gestation in Chinese women who eventually developed GDM and to determine whether this biomarker can predict GDM or demonstrate improved value for predicting GDM when combined with maternal factors.