孕6-9周胎儿分数扩增的无创DNA筛查可行性

原文

OBJECTIVE: To evaluate the feasibility of prenatal cell-free DNA (cfDNA) screening with fetal fraction amplification between 6 and 9 weeks of gestation. METHODS: Pregnant individuals underwent two blood draws: the first between 6 0/7 and 9 6/7 weeks of gestation and the second at 10 0/7 weeks or later. Samples were processed using a cfDNA screen with fetal fraction amplification. Before the implementation of fetal fraction amplification, 4.8% of samples drawn at 10 0/7 weeks of gestation had low fetal fraction , defined as less than 4%. Logistic regression was used to determine the earliest gestational age after the implementation of fetal fraction amplification at which the proportion of samples with low fetal fraction was 4.8% or less. Positive and negative percent agreements were calculated for samples collected before and after 10 0/7 weeks of gestation. RESULTS: Among 562 patients enrolled, 470 completed two blood draws and were included in the analysis. Median maternal age was 32 years (IQR 29-34 years), and median body mass index (BMI) was 25.7 (IQR 22.7-30.9). Median fetal fraction was 9.0% (IQR 6.5-13.6) for samples drawn at 6 0/7-9 6/7 weeks of gestation and 18.5% (IQR 14.4-23.9%) for those drawn at 10 0/7 weeks or later. Among patients with BMI 30 or higher (n=125), the median fetal fraction was 7.2% (IQR 5.5-10.7%) for samples drawn at 6 0/7-9 6/7 weeks of gestation and 14.7% (IQR 11.3-18.5) for those drawn at 10 0/7 weeks or later. The gestational age at which 4.8% of samples had low fetal fraction was 7 3/7 weeks. The screen failure rate was 1.5% (7/470) for samples drawn at 6 0/7-9 6/7 weeks of gestation and 0.3% (1/291) for samples drawn at 7 3/7-9 6/7 weeks. Because patients often present for routine prenatal care beginning in the 8th week of gestation, we also calculated performance at 8 0/7-9 6/7 weeks. During this period, the screen failure rate was 0.4% (1/241), and both positive and negative percent agreements were 100% for all screened aneuploidies. At 10 0/7 weeks of gestation or later, two samples were called positive for trisomy 21 and one for trisomy 7; their corresponding samples at 8 0/7-9 6/7 weeks were also called positive. Fetal sex call concordance was 100% for both XX (110/110) and XY (130/130). CONCLUSION: Fetal fraction amplification enables cfDNA screening beginning at 7 3/7 weeks of gestation. Performance and concordance data are limited but suggest the clinical feasibility of offering cfDNA screening with fetal fraction amplification beginning at 8 weeks of gestation.