CC Jan 2016 Cell-Free Fetal DNA

echoecho's version from 2016-03-23 06:43


Question Answer
Over the last 2 decades, what techniques have yielded a great deal more information about the origin of cell-free fetal DNA and its variable presence in maternal circulation?1) refinement in detection 2) refinement in isolation 3) refinement in sequencing techniques
Where does fetal DNA come from?from the apoptosis of a fetal-derived syncytiotrophoblastic layer of cells that covers the placental villous tree and then is released into maternal circulation
Much research into the origin of fetal DNA does not revolve around aneuploidy detection, but rather what?the pro-inflammatory role played by syncytiotrophoblastic particles, including fetal DNA in preeclampsia
An increased overall percentage of cell-free fetal DNA has been seen in pregnancies affected by what? Considerable attention is being made to creating a variant of fetal DNA testing to be used for what screening?1) preeclampsia 2) early preeclampsia screening
Fetal DNA is detectable as early as _____ days postimplantation?18
Fetal DNA represents between 3-13% of all cell-free DNA in maternal ______, though the percentage can be highly variable?plasma
Fetal DNA percentages increase slowly before ____ weeks (about 0.1%/week), rise sharply after _____ weeks (around 1% per week), but rapidly disappear from maternal circulation post-delivery?21; 21
The clinical implications for cell-free fetal DNA testing have improved the accuracy of what testing?NIPT (non-invasive prenatal testing
In August 2011, the Sequenom Center for Molecular Medicine launched "MaterniT21", the first noninvasive test using fetal DNA for the detection of what?trisomy 21
The test was quickly followed by the "MaterniT21 PLUS" test in October 2011 that added what?1) trisomy 18 2) trisomy 13 3) fetal gender 4) fetal sex aneuploides 5) lesser common aneuploidies 6) select microdeletions
Since that time, multiple other commercial tests have come on the market with expanded applicability to include screening for what additional testing?1) high-risk genetic disorders 2) Rhesus testing 3) prenatal paternity testing
The newer Digital Analysis of Selected Regions (DANSR) combined with a statistical analysis algorithm and Fetal-fraction optimized Risk of Trisomy Evaluation (FORTE), which considers age-related risk factors and the percentage of fetal DNA, have improved testing while reducing fetal DNA amounts required to accurately diagnose what two things?trisomy and fetal gender
According to an ACOG 2015 summary of pooled test performance, the sensitivity and specificity for trisomy 21, 18, 13 and gender detection?99.3/99.8; 97.4/99.8; 91.6/99.9; and 91.0/99.6 respectively
Positive predictive values for the 3 aneuploides in pregnant women age > 40 years were what respectively?87, 68, 57%
The sensitivites for trisomies 21, 18 and 13 are what?99.3%, 97.4% and 91.6% respectively, with a specificity exceeding 99% for all three
ACOG and the Society for Maternal-Fetal Medicine have issued multiple committee opinions and recommendations on the use of cell-free fetal DNA testing in clinical practice. The Dec 2012 Committee Opinion listed 5 indications for testing, list these?1) maternal age > 35 years age at delivery 2) fetal US findings indicating an increased aneuploidy risk 3) hx of a prior pregnancy with a trisomy 4) positive test results for aneuploidy, including first trimester, sequential or integrated screening or quadruple screen 5) parental balanced Robertsonian translocation with increased risk of trisomy 21
An updated 2015 committee opinion removed the language of specific indications but reiterated recommendations to avoid fetal DNA testing for screening ___ risk pregnancies?low
Due to what in this younger group, ACOG recommends use of traditional serum analyte screening methods?performance degradation of fetal DNA
The committee opinion reported positive predictive values for 25 year old pregnant mothers as what %?33; 13; 9
Regarding other specific committee recommendations, risks, benefits and alternatives of various methods of prenatal screening and diagnostic testing, including an option of what, should be discussed with all patients?option of no testing
*** Regarding other specific committee recommendations, given the possibility of an inaccurate result and to understand the type of trisomy for recurrence-risk counseling, what should be recommended for patients who have a positive cell-free fetal DNA test result?1) diagnostic test like chorionic villus sampling OR 2) amniocentesis
Regarding other specific committee recommendations, parallel or simultaneous testing with multiple screening methodologies ______(is or is not effective and should or should be done)?is not; should not
Regarding other specific committee recommendations, cell free fetal DNA screening is not recommended for what type of pregnancies?multiple gestation pregnancies
Regarding other specific committee recommendations, cell free fetal DNA screening does NOT assess for what defects? Patients should be offered what instead?1) neural tube defects or ventral wall defects 2) maternal serum alpha-fetoprotein screening OR ultrasound for risk assessment in addition to cell free fetal DNA testing
Regarding other specific committee recommendations, if a fetal structural anomaly is identified on US exam, what diagnostic testing should be offered rather than cell-free fetal DNA screening?CVS or amniocentesis
*** Regarding other specific committee recommendations, cell-free fetal DNA screening does NOT replace the precision obtained with diagnostic tests, such as what?chorionic villus sampling or amniocentesis
For most commercially-available tests, including Ariosa's Harmony Prenatal Test, a minimum ratio of ___% fetal/maternal cell-free DNA is needed for reliable results?4
Fetal DNA in the maternal circular appears to rise modestly (about 0.1%/week) before week ____ (specifically ___ to ___ weeks), but statistically, no significant difference in test outcomes exists between ___ to ___ weeks?21; 10-21; 10-21
This finding supports the ACOG recomemndation of offering fetal DNA testing beginning at ____ weeks of gestation?9
Maternal weight also influences the percentage of patients with serum fetal DNA < ____%?4
For patients between 50-90kg, what % of pregnancies had >4% fetal DNA?98-99%
Above a maternal weight of 90 kg, that percentage drops, decreasing to ____% in women weighing > 140 kg?71.2%
A second blood draw done an average of _____ weeks later from the same patients demonstrated an equally poor inverse relationship between weight and fetal DNA percentage?3.6
While the authors of the study acknowledged that weight only (not BMI, height and/or body type) was studied, counseling should be done regarding?the limitations of cell-free fetal DNA testing in patients with high body weight may be appropriate and other tests may be more appropriate
What is the gold standard testing currently?CVS (chorionic villus sampling) or amniocentesis
*** SUMMARY = Cell-free fetal DNA testing for aneuploidy is recommended for what type of pregnant women?specific subgroups of pregnant women
*** SUMMARY = Cell-free fetal DNA testing for aneuploidy is not recommended for what type of pregnant women?low-risk women
*** SUMMARY = Cell-free fetal DNA screening is not recommended for multiple gestation pregnancies, true or false?true
*** SUMMARY = Cell-free fetal DNA screening does not assess for what 2 defects?neural tube defects OR ventral wall defects