Cell-free DNA screening performance table
Performance of cell-free DNA screening by condition
|
Sensitivity |
Specificity |
False positive rate |
Positive predictive value1 |
|
|
|
|
|
|
|
High risk2 |
General population |
|
Trisomy 21 |
99% |
>99% |
<1% |
91% |
91.8% |
|
Trisomy 18 |
97% |
>99% |
<1% |
84% |
65.8% |
|
Trisomy 13 |
92% |
>99% |
<1% |
87% |
37.2% |
|
Other sex chromosome conditions3 |
>99% |
>99% |
<1% |
25-52% |
43% (ranges from 30% 45,X to 74% 47,XXY and 47, XYY) |
|
Rare autosomal trisomies |
92.3% |
>99% |
<1% |
n/a |
13.4% |
|
Microdeletion conditions4 |
Unknown |
Unknown |
Unknown |
Unknown |
Unknown |
Note that each laboratory may have different conditions offered for cfDNA screening and their own lab-specific analytic data.
2High risk = advanced maternal age, personal/family history, positive other screening, ultrasound abnormality
3Includes XO (Monosomy X, Turner syndrome), XXY (Klinefelter syndrome), Trisomy X (Triple X syndrome), and XYY (Jacob syndrome). Limited validity data available.
4Includes 22q11.2 deletion syndrome (DiGeorge syndrome), 1p36 deletion syndrome, 15q11.2 deletion (Angelman and Prader-Willi syndromes), 5p deletion (Cri-du-chat syndrome), 4p deletion (Wolf-Hirschhorn syndrome), 8q24 deletion (Langer-Giedion syndrome), and 11q deletion (Jacobsen's syndrome). Limited validity data available. Even with high sensitivity and specificity, the PPV will be low in the absence of other risk factors (family history, ultrasound findings, etc.) because of the rarity of these conditions.
References
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020 Oct;136(4):e48-e69.Bianchi DW et al. Sequencing of Circulating Cell-Free DNA During Pregnancy. N Eng J Med 2018; 379:464-473.
Gil, M.M., et al., Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol, 2017; 50(3):302-314.
Gregg, A.R., et al., Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med, 2016.
Mackie, F.L., et al., The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. BJOG, 2016.
Rose NC, Barrie ES, Malinowski J, Jenkins GP, McClain MR, LaGrave D, Leung ML; ACMG Professional Practice and Guidelines Committee. Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies. Genet Med. 2022 May 10:S1098-3600(22)00714-6.
Stevens B. Impact of Emerging Technologies in Prenatal Genetic Counseling. Cold Spring Harb Perspect Med. 2020 Dec 1;10(12):a036517.
Taylor-Phillips, S., et al., Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open, 2016; 6(1): p. e010002.
Updated June 2022