Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis.

OBJECTIVE: To analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. MATERIALS AND METHODS: Traditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. RESULTS: In this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. CONCLUSIONS: Our results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.

The ratio of cavum septi pellucidi width to anteroposterior cerebellar diameter: A novel index as a diagnostic adjunct for prenatal diagnosis of trisomy 18.

AIM: To explore the effectiveness of cavum septi pellucidi (CSP) width to anteroposterior cerebellar diameter (APCD) ratio as a diagnostic adjunct for prenatal diagnosis of trisomy 18. METHODS: Images of normal fetal brain within 15 and 35 weeks were stored in our center from 2016 to 2017. Images of aneuploid fetuses were retrospectively collected from 2004 to 2017. The transverse cerebellar diameter, APCD and CSP width were measured. CSP/APCD and APCD/transverse cerebellar diameter ratios were calculated and compared between euploid and aneuploid fetuses. RESULTS: One thousand and forty one fetuses were analyzed, including 817 euploid fetuses and 224 aneuploid fetuses (trisomy 21 117 cases, trisomy 18 82 cases, trisomy 13 9 cases, sex-linked 16 cases). No correlation had been found between both ratios and gestational weeks (P > 0.05). In aneuploid groups, means of ratios were both significantly different just between trisomy 18 group and euploid group (P < 0.05). The best area under the curve was shown by the CSP/APCD ratio. The cutoff value of CSP/APCD was 0.46 (sensitivity 87.0%, specificity 85.0%). CONCLUSION: A wide CSP or cerebellar hypoplasia warrants a more detailed ultrasound screening and genetic counseling. A larger CSP/APCD ratio alerts us to trisomy 18 syndrome, especially in cases with subtle anomalies.