Abstract: Objective To compare depression among high and low risk pregnant women undergoing prenatal screening, and explore factors associated with depression at different pregnant periods.Methods A total of 924 pregnant women undergoing prenatal screening were recruited, and they were divided into high-risk group(231 cases) and low-risk group(693 cases). Self-rating Depression Scale was used to assess the level of depression before prenatal screening, after prenatal screening, late pregnancy(≥ 28 weeks) and 6 weeks postpartum. The pregnancy outcomes of the two groups were investigated at 6 weeks postpartum.Results The overall detection rate of depression among pregnant women undergoing prenatal screening was 18.3%, of which 30.5% in high-risk group and 9.2 in low-risk group. Depression detection rates were higher in the high-risk group than those in the low-risk group both after prenatal screening and 6 weeks postpartum(χ²=62.556, P<0.001; χ²=27.389,P<0.001). Before prenatal screening, physical labor was a protective factor for maternal depression(OR=0.380, 95%CI:0.170-0.850); After prenatal screening, high risk of prenatal screening was a risk factor for depression(OR=7.302, 95%CI:4.019-13.267); At late pregnancy, depression pre-and post-prenatal screening was a risk factor for depression(OR=12.911,95%CI:4.316-38.622; OR=10.601,95%CI:4.854-23.195). At 6 weeks postpartum, high risk of prenatal screening, depression after prenatal screening and depression at late pregnancy were risk factors for depression(OR=3.117, 95%CI:1.618-6.003; OR=4.510, 95%CI:2.126-9.566; OR=7.999,95%CI:3.306-19.353).Conclusion High risk pregnant women diagnosed by prenatal screening have a high incidence of adverse mood and pregnancy outcomes, and close attention should be paid to their mental health after the results of prenatal screening and at 6 weeks postpartum, and targeted psychological intervention should be given to them.