Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA)

Abstract

Objective Evaluate patient choices and outcomes following positive cfDNA.Method Retrospective cohort study of women with positive cfDNA through two academic centers between March 2012 and December 2014. Patients were screened based on ACOG indications. Medical records reviewed for counseling, ultrasound findings, diagnostic testing, karyotype and outcome.Results CfDNA was positive in 114 women; 105 singletons and 9 twin pairs. CfDNA was positive for autosomal trisomy (21, 18, 13) in 96 (84.2%) and sex chromosome aneuploidy in 18 (15.8%). Certified genetic counselors performed 95% of post-cfDNA counseling. Prenatal diagnostic testing was pursued by 71/114 (62%). Karyotype was available in 91/105 (86.7%) singletons and confirmed aneuploidy in 75/91 (82.4%); the PPV of cfDNA with any ultrasound finding was 93.6% versus 58.6% without a finding. An abnormal sonographic finding was seen in 4/16 (25%) singletons with false positive cfDNA. Fetal termination occurred in 53/79 (67%) singletons and 3/5 (60%) twins with prenatal abnormal or unknown karyotype for autosomal trisomy. Eleven fetuses (11/56, 19.6%) were terminated for suspected autosomal trisomy without karyotype confirmation.Conclusion Patient choices following positive cfDNA are varied. Ultrasound modifies the PPV of cfDNA. Termination rates for aneuploidy are not higher than historical controls. Recommendation for karyotype confirmation prior to termination is not universally followed.

Sex chromosome aneuploidy detection by noninvasive prenatal testing: helpful or hazardous?

“…No patients with ongoing pregnancies suspected ( n = 6) or prenatally confirmed ( n = 4) to have SCA elected pregnancy termination. For comparison, in our center over the same time period, 28% of patients with trisomy 21 suspected by NIPT declined diagnostic testing, while 80% of patients with NIPT showing fetal trisomy 21 chose pregnancy termination when diagnostic testing confirmed NIPT results . Our high rate of continuation of pregnancies with SCA contrasts with other studies, although the small number of truly affected pregnancies limits our ability to make strong conclusions.…”

Cell-free DNA screening in clinical practice: abnormal autosomal aneuploidy and microdeletion results

“…CfDNA has become widely adopted into routine prenatal care [10], and studies have reviewed its impact on patient decision-making [11]. However, most studies have focused on large, laboratory-funded validation trials.…”

When ultrasound anomalies are present: An estimation of the frequency of chromosome abnormalities not detected by cell‐free DNA aneuploidy screens

“…Study samples were retained for initial statistical analysis if they met the following criteria: a prenatal sample such as amniotic fluid or chorionic villi and an abnormal cytogenetic or array finding and a fetal ultrasound finding. The experience of cfDNA in this population and our aneuploidy screening protocol has previously been described by Dobson et al, and in the time frame there were 114 women with positive cfDNA of whom 71 (62%) underwent diagnostic testing …”