Noninvasive prenatal genetic testing in 6804 pregnant women aged less than 35 years with positive results in serum screening

OBJECTIVE: To investigate the feasibility of noninvasive prenatal genetic testing for detecting chromosome aneuploid in pregnant women aged less than 35 years with positive results in serum screening. METHODS: We analyzed the plasma cellfree fetal DNA in a total of 6804 pregnant women aged less than 35 years with singleton pregnancy from Foshan maternal and child health care hospital, whose weeks of gestation ranged from 12 to 24 weeks with ages on the expected date of confinement of 21-34 years. According to the results of serum screening, the women were divided to high-risk group and critical-risk group. Amniocentesis or cordocentesis was carried out if the results of noninvasive prenatal genetic testing were positive, and karyotyping or/and high-throughput sequencing was performed as the golden standard. All the women were followed up by telephone calls to assess the accuracy of the prenatal testing. RESULTS: Noninvasive prenatal testing was successfully completed in all the 6081 cases. In the high-risk group, 70 women with positive results were tested by noninvasive prenatal testing, among whom 53 were confirmed by karyotyping or high-throughput sequencing. In this group, the sensitivity, specificity and positive predictive value of trisomy 21 syndrome detection was 95.65%, 99.91% and 88.0%, respectively, with a false positive rate of 0.09% and a false negative rate of 4.35%; the sensitivity, specificity and positive predictive value for trisomy 18 syndrome was 100%, 100% and 100%, respectively, with false positive and false negative rates of 0; the false positive rate and false negative rate for trisomy 13 syndrome was 0.09% and 0, respectively; the sensitivity, specificity and positive predictive value for sex chromosome aneuploid as 100%, 99.80% and 30.0%, respectively, with a false positive rate of 0.2% and a false negative rate of 0; the sensitivity, specificity and positive predictive value for other chromosome aneuploid was 100%, 99.88% and 16.60%, respectively, with a false positive rate of 0.18% and a false negative rate of 0. In the critical risk group, 54 women with positive results received noninvasive prenatal genetic testing, among whom 36 were confirmed by karyotyping or high-throughput sequencing. The sensitivity, specificity and positive predictive value for trisomy 21 syndrome were all 100% and the false positive rate and false negative rate were both 0; the false positive rate was 0.11% and the false negative rate was 0 for trisomy 18 syndrome; the false positive rate and false negative rate for trisomy 13 syndrome was 0.04% and 0, respectively; the sensitivity, specificity and positive predictive value for sex chromosome aneuploid was 100%, 99.79% and 50.0%, respectively, with a false positive rate of 0.21% and a false negative rate of 0; the false positive rate for other chromosome aneuploid was 0.18% and the false negative rate was 0. No significant differences were found between the two groups in the sensitivity, specificity, positive predictive value and false positive rate for detection of trisomy 21 syndrome and sex chromosome aneuploid (P>0.05). CONCLUSIONS: Noninvasive prenatal genetic testing is necessary for high-risk pregnant women with critical-risk in serum screening who refuse invasive prenatal diagnosis, and it is highly sensitive and specific fir detecting chromosome aneuploid with low false positive and false negative rates.