Objective To explore the practical value of Down’s syndrome (DS) screening in detecting congenital birth defects and predicting adverse pregnancy outcomes among pregnant women at middle gestation. Methods The serum levels of F-βHCG and AFP in 7076 pregnant women at mid-term gestation of 15-20 weeks were detected by time resolved fluoroisnmunoassay. The corresponding simulation software was utilized considering the factors of gestational weeks, avoirdupois age and weight of pregnant women and etc to calculate the risk rates of fetuses with DS, Neural tube defects (NTD) and Trisomy 18. Karyotype analysis of amniotic fluid cells or B ultrasound examination for follow-up investigations was used for the high risk pregnant women. Results The positive cases among 7076 pregnant women screened were 396 and the positive rate was 5.6%. Among 56 cases of DS pregnant women with voluntary acceptance of amniotic fluid examination, 3 cases of DS and 3 cases of fetal deaths and 3 cases of other congenital anomalies were found. Among the 57 pregnant women with NTD 1 cases no brains was detected by B ultrasound examination. Among 43 case of pregnant women at high risk for trisomy 18, 6 cases accepted karyotype analysis of amniotic fluid cells examination and all results were normal. Conclusion Prenatal screening of detecting serum levels of F-βHCG and AFP at mid-gestation is a beneficial, effective and convenient method for screening the congenital defects, especially the fetal chromosomal abnormalities. The high risk pregnant women should carry out the karyotype analysis of amniotic fluid cells or B ultrasound examination further in order to reduce birth defects of fetus.