VOL. 126, NO. 3, SEPTEMBER 2015 Committee Opinion Cell-free DNA Screening for Fetal Aneuploidy e33
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。
General Obstetric Population1/1,000 Prevalence of Trisomy 21
High-Risk Population1/100 Prevalence of Trisomy 21
Fig.1. The importance of population prevalence on the predictive value for a screening test: an illustration with cell-free DNA. ^
Abbreviations: NPV, negative predictive value; PPV, positive predictive value
mechanisms (24, 25). Screening for these microdeletions has not been validated in clinical studies, and the true sensitivity and specificity of this screening test is uncer-tain. Routine cell-free DNA screening for microdeletion syndromes should not be performed.
Multiple Gestations
Regardless of the method, the accuracy of screening for aneuploidy is limited in multiple gestations. With any method based on maternal blood (serum analytes or DNA), only a single composite result for the entire gestation is provided, with no ability to distinguish a differential risk between fetuses. The data regarding the performance of cell-free DNA screening in twin gesta-tions are limited (26, 27). Although preliminary findings suggest that this screening is accurate, larger prospec-tive studies and published data are needed before this method can be recommended for multiple gestations. Cell-free DNA screening is not recommended for women with multiple gestations. There are no available data on higher-order multiples.
Counseling Patients About Their Options
Counseling regarding the limitations of cell-free DNA screening should include a discussion about how the screening method provides information regarding only
trisomies 13, 18, and 21. If a sex chromosome analysis has been requested or is part of the standard panel, then this information should be conveyed as well. Some patients may request cell-free DNA screening to enable earlier sex identification. Patients should be counseled that cell-free DNA screening also assesses the risk of the aforemen-tioned trisomies; if that information is not desired, the screening should not be performed.
Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Not only can there be false-positive test results, but a positive cell-free DNA test result for aneuploidy does not determine if the trisomy is due to a translocation, which affects the risk of recurrence. If a fetal structural anomaly is identified on ultrasound examination, diagnostic testing should be offered rather than cell-free DNA screening.
The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Given the potential for inaccurate results and to understand the type of trisomy for recurrence-risk counseling, a diagnostic test should be recommended for a patient who has a positive cell-free DNA test result. Management decisions, including termination of the pregnancy, should not be based on the results of the
e34 Committee Opinion Cell-free DNA Screening for Fetal Aneuploidy OBSTETRICS & GYNECOLOGY
CopyrightªbyTheAmericanCollegeofObstetricians
andGynecologists.PublishedbyWoltersKluwerHealth,Inc.
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。
cell-free DNA screening alone. False-positive test results do occur and diagnostic testing with amniocentesis or chorionic villus sampling should be recommended before any pregnancy termination decision. Causes of false-positive test results have been reported, which include but are not limited to placental mosaicism, vanishing twins, and maternal malignancies (28–31).
Before offering cell-free DNA screening, counseling is recommended. The family history should be reviewed to determine if the patient should be offered other forms of screening or prenatal diagnosis for a particular dis-order. In order to ensure accuracy and testing of the appropriate patient population, a baseline ultrasound examination also should be considered to confirm viabil-ity, the number of fetuses, and gestational dating, if not performed previously. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. A negative test result still carries a residual risk of one of the common trisomies and does not ensure that the fetus does not have another chromo-some abnormality or genetic diagnosis. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. Parallel or simultaneous testing with multiple screening methodolo-gies for aneuploidy is not cost-effective and should not be performed. However, use of cell-free DNA screening as a follow-up test for patients with a positive traditional screening test result is reasonable for patients who want to avoid a diagnostic test. Given that the residual risk of a chromosomal abnormality with a normal cell-free DNA screening test result after an abnormal traditional screen-ing test has been reported to be 2%, patients should be informed of this potential limitation (23).