e32 Committee Opinion Cell-free DNA Screening for Fetal Aneuploidy OBSTETRICS & GYNECOLOGY
国际母胎医学会遗传学专业委员会(Committee on Genetics, Society for Maternal–Fetal Medicine)针对利用游离胎儿DNA筛查非整倍体(cell-free DNA screening for fetal aneuploidy)的建议。
Table 1. Cell-free DNA Test Performance Characteristics in Patients Who Receive an Interpretable Result* ^ Trisomy 21 Trisomy 18 Trisomy 13
Sex chromosome aneuploidy 99.3 97.4 91.6 91.0
99.8 99.8 99.9 99.6
33 13 9
876857
-- --
Abbreviation: PPV, positive predictive value.
*This table is modeled on 25- and 40-year-old patients based on aneuploidy prevalence at 16 weeks of gestation. Negative predictive values are not included in the table but are greater than 99% for all patient populations who receive a test result. Negative predictive values decrease when patients who do not receive a result are included. Test performance characteristics are derived from a summary of published reports and as assessed and compiled in published reviews.
The positive and negative predictive values for the sex chromosome aneuploidies depend on the particular condition identified. In gen-eral, however, the PPV ranges from 20% to 40% for most of these conditions.
Applicability to clinical practice:
Positive predictive value (defined as true positives divided by true positives plus false positives) is directly related to the prevalence of the condition in the population screened. Based on the sensitivity and specificity of the test, when a population with an overall preva-lence of 1/1,000 for trisomy 21 is screened, the positive predictive value of an abnormal result is 33%—only one in three women who get an abnormal result will have an affected fetus. If the prevalence is 1/75, the positive predictive value is 87%.
Data from Gil MM, Quezada MS, Revello R, Akolekar R, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 2015;45:249–66; Porreco RP, Garite TJ, Maurel K, Marusiak B, Ehrich M, van den Boom D, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Obstetrix Collaborative Research Network. Am J Obstet Gynecol 2014;211:365.e1–365.12; Snijders RJ, Sebire NJ, Nicolaides KH. Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 1995;10:356–67; Benn P, Cuckle H, Pergament E. Non-invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound Obstet Gynecol 2013;42:15–33; and Verweij EJ, de Boer MA, Oepkes D. Non-invasive prenatal testing for trisomy 13: more harm than good? Ultrasound Obstet Gynecol 2014;44:112–4.
Use in the General Obstetric Population
Data on the performance of cell-free DNA testing in the general obstetric population have become available (1, 8, 11, 16, 17). The sensitivity and specificity in the general obstetric population are similar to the levels previously published for the aforementioned high-risk population. The positive predictive value, however, is lower in this population, given the lower prevalence of aneuploidy in the general obstetric population. That is, fewer women with a positive test result will actually have an affected fetus, and there will be more false-positive test results (Fig. 1).
Another limitation of cell-free DNA screening in the general obstetric population is that trisomies 13, 18, and 21 comprise a smaller proportion of the chromosome abnormalities found in the general obstetric population (21–23). Traditional serum analyte screening methods allow for higher detection rates of these other chromo-some abnormalities as well as the risk of other adverse pregnancy outcomes. For example, a positive integrated screening test result may indirectly identify a fetus with
an unbalanced rearrangement of a chromosome other
than trisomies 13, 18, or 21. One study of women with abnormal traditional screening test results who had diagnostic testing estimated that up to 17% of clini-cally significant chromosomal abnormalities would not be detectable with most of the current cell-free DNA techniques (23). Given the performance of conventional screening methods and the limitations of cell-free DNA, conventional screening methods remain the most appro-priate choice for first-line screening for most women in the general obstetric population.
Testing for Other Genetic Conditions With Cell-free DNA
Although all laboratories that currently offer cell-free DNA screening for aneuploidy include trisomies 13, 18, and 21 as part of their standard panel, the approach to the sex chromosomes and other chromosome abnormali-ties vary. Some laboratories offer routine sex chromo-some, microdeletion, and rare trisomy (eg, trisomy 16 or trisomy 22) assessment, whereas others require that sex chromosome and other assessments be requested in order for those results to be reported. Microdeletion syndromes occur sporadically or are due to other genetic