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Background: Antenatal depression (AD) is considered as one of the major health burdens and has adverse effects on the outcome of expectant mothers and newborns. The present study aims to investigate the prevalence of antenatal depression (AD), and to explore the potential risk factors of AD among pregnant women in Chengdu, including personal background, related social factors, family factors and cognitive factors.Methods: The prospective nested case-control study included pregnant women who were in their second pregnancy and attended prenatal care at three tertiary hospitals and one regional hospital in Chengdu, China, between March 2015 and May 2016. Self-designed questionnaires were given to participants in their second and third trimesters to collect information on clinical and demographic characteristics, and a modified edition of Edinburgh Postnatal Depression Scale (EPDS) were used to measure AD. The logistic regression was applicated in analyses.Results: A total of 996 pregnant women were included in analysis. Ninety-three women suffered from AD symptoms only in their second trimester, 96 only in their third trimester, and 107 displayed persistent depression in both trimesters. In the univariate analyses, age and marital relationships were linked with AD occurrence in both second and third trimester. In addition, increasing age, full-time job, higher education level, and no gender preference of spouse were associated with reduced persistent depression. Multivariate analysis showed that gender preference and marital relationship were the potential risk factors of persistent depression.Conclusions: Age, marital relationship relationships, with parents-in-law, the negative recognition of this pregnancy and husband's gender preference were found as risk factors of AD occurrence in some specific trimester. Gender preference of husbands and marital relationships were independently associated with persistent depression. These findings suggest that stronger family support can help improve mental health of pregnant women. [ABSTRACT FROM AUTHOR]