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Maternal serum screening is used to assist in the prenatal detection of congenital anomalies. Its use is controversial, and one concern that has been expressed is its psychological effects on women. The authors examined whether this test leads to an increase in anxiety and depression among women who have a false-positive result as compared with those who have a true-negative result or do not undergo testing.A prospective cohort study with baseline assessment at 15 to 18 weeks' gestation and follow-up at 24 weeks' gestation was conducted. Pregnant women at 8 geographically diverse sites across Ontario were recruited. The main outcome measures were the state portion of the State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale.Of the 2418 potential subjects 2020 (83.5%) were enrolled and eligible; 1741 (86.2%) completed the follow-up. A total of 1177 women (67.6%) underwent maternal serum screening. No overall, adverse psychological effects as a result of testing were found at 24 weeks' gestation. Women with a false-positive result had a mean increase in anxiety score of 1.6 (95% confidence interval [CI] -1.7 to 4.9), whereas women with a true-negative result had a mean decrease of 1.1 (95% CI -1.8 to -0.3) and those not tested had a mean decrease of 0.4 (95% CI -1.3 to 0.5). The mean depression score increased by 0.5 (95% CI -0.9 to 2.0) in the false-positive group, was unchanged (95% CI -0.3 to 0.4) in the true-negative group and increased by 0.2 (95% CI -1.7 to 1.2) in the not tested group. Of the women who underwent testing, 87 (7.6%) were unsure of their result at the time of follow-up.The results suggest that maternal serum screening in Ontario is not causing serious psychological harm to women. Communication regarding test results could be improved, since a substantial proportion of women were unsure of their test result.