The authors evaluated the efficiency of prenatal screening in 40,796 pregnant women of the Smolensk Region and estimated the importance of different isolated and combined biochemical and echographic markers in the detection of fetal chromosomal abnormalities (CA). Second-trimester biochemical screening revealed the markers of CA in 1512 pregnant women; ultrasound screening showed them in 313; 115 of the latter had them in combination with biochemical markers and 198 had isolated echographic markers of CA. Prenatal fetal karyotyping established 34 cases of CA with a poor outcome; 47 cases of CA were diagnosed in newborn infants. Fetal and neonatal cytogenetic studies ascertained chromosomal syndromes, such as Down syndrome (n = 62), Edwards syndrome (n=9), Patau's syndrome (n = 5), other chromosomal abnormalities (n=4), and triploidy (n=1). The role of biochemical and echographic markers of fetal CA in the second trimester of pregnancy was defined in forming indications for its invasive diagnosis and in achieving the efficiency of prenatal karyotyping. The sensitivity of combined second-trimester prenatal screening in the Smolensk Region was found to be 75%, which was below the international value of as high as 95% in the first trimester of pregnancy. It has been shown that it is necessary to change organizational and methodological approaches to prenatal diagnosis in order to early detect chromosomal abnormalities in a future baby.