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BackgroundDepression is a prevalent psychological challenge during pregnancy, with established links to adverse outcomes like preterm birth (PTB) globally. However, epidemiological data from China’s multiethnic regions are scarce, and experimental evidence supporting a causal relationship remains limited. This study aimed to investigate the association between prenatal depressive symptoms and the risk of PTB in a cohort from Yunnan, China, and to provide supportive evidence using a mouse model of depression.MethodsWe recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), a screening tool, with a score ≥12 indicating elevated symptoms suggestive of depression. PTB was defined as delivery before 37 gestational weeks, confirmed by ultrasound. In parallel, a mouse model of depression was established using Chronic Unpredictable Mild Stress (CUMS) for 6 weeks prior to mating. PTB in mice was defined as delivery before 19 days of gestation.ResultsIn the cohort study, the incidence of PTB was significantly higher in women with prenatal depressive symptoms compared to those without (8.43% vs. 3.83%, P ConclusionThis study demonstrates a significant association between prenatal depressive symptoms and an increased risk of preterm birth in a Chinese multiethnic cohort. Experimental findings from a mouse model further suggest a potential contributory role of depression to PTB. These results underscore the importance of screening for and addressing maternal mental health during pregnancy. Future research should focus on underlying mechanisms and intervention strategies to mitigate this risk.