To discuss clinical value of prenatal screening and diagnosis for fetal Down syndrome (DS) of pregnant women in Beijing, which combined second trimester serum screening (STSS) and non-invasive prenatal testing (NIPT) used fetal free DNA in maternal peripheral blood (hereinafter referred to as combined screening).

From January 2017 to December 2018, a total of 331 684 singleton pregnancy women of appropriate age maternal age at expected date of childbirth <35 years who took prenatal screening for fetal DS at various prenatal screening or diagnosis institutions (Beijing Obstetrics and Gynecology Hospital, etc.) in Beijing were selected as research subjects. A total of 302 065 pregnant women who took prenatal screening for DS by STSS, including 20 534 cases took combined screening; 29 619 cases who took prenatal screening for DS voluntarily by direct NIPT. Retrospectively analyzed clinical data of pregnant women. Fetal DS false positive rate, detection rate, positive predictive value and specificity of the three methods were compared overall and pairwise using chi-square test and Mann-Whitney U test. The procedure of this study was in line with World Medical Association Declaration of Helsinki revised in 2013. The pregnant women have informed consent to the inspection items accepted and signed the informed consent form.

① Fetal DS false positive rates by STSS, combined screening and direct NIPT were 5.12%, 0.07% and 0.07%, respectively, the detection rates were 76.1%, 100.0% and 93.3%, respectively, positive predictive values were 0.76%, 68.75% and 56.00%, respectively, specificity were 94.9%, 99.9% and 99.9%, respectively. ②Fetal DS detection rate, positive predictive value and specificity of combined screening were significantly higher than those of STSS, while false positive rate was significantly lower than that of STSS, and the above differences were statistically significant (Z=-13.229, P<0.001; Z=-8.307, P=0.029; Z=-13.928, P<0.001; Z=-7.141, P=0.038). Fetal DS detection rate and positive predictive value of combined screening were significantly higher than those of direct NIPT, and the differences were statistically significant (Z=-13.856, -11.136, both P<0.001). There were no significant differences between combined screening and direct NIPT in fetal DS false positive rate and specificity (both P>0.05).

The efficiencies of prenatal screening for fetal DS by combined screening is better than that of STSS and direct NIPT, which can reduce proportion of pregnant women undergoing interventional prenatal diagnosis.