prenatal genetic testing in obstetrics · 01-12-2017 · acog now recommends offering pan-ethnic...
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Prenatal Genetic Testing in Obstetrics
What's available, what's recommended, and what do patients pay?
DOUGLAS S. RICHARDS, M.D. DIVISION OF MATERNAL FETAL MEDICINE
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Who can have which genetic diagnostic or
screening tests?
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Anyone can have any test, regardless
of risk status!
ACOG Practice bulletin 162, 2016
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Outline Aneuploidy screening
Traditional CFDNA
Carrier screeningTraditionalExpanded panels
Diagnostic testing How cells obtained (procedures) Standard karyotype FISHMicroarrayWhole exome sequencing
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Disclaimer-All costs are approximate 2014 numbers May vary widely by labs and
insurance contracts
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“Traditional” aneuploidy screening
Test What WhenQuad Four analytes 14-24 wksIntegrated/sequential Analytes + NT, then
analytes11-13, 15-24 wks
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“Traditional” aneuploidy screening
Test Geneticcounseling
Ultrasound Lab Total
Quad $200 $200
Integrated $125 $325+ $325 $150 + $300 $1225
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Cell-free DNA testing- widely available since 2011
Fetal DNA comprises 3–13% of the total cell-free DNA in maternal blood
TS 21, TS 18, TS 13 and sex chromosome composition
Can be performed at 10 weeks until delivery
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Cost of cell-free DNA aneuploidy screening
• Insurance only covers for high risk- may require preauthorization
• Labs bill insurance $600-$750 if contracted, sometimes > $1000
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Cost of cell-free DNA aneuploidy screening (continued)
• Self- pay, insurance denial, out of network, or deductible not met- $100-$350
• Patient assistance program often available
• Medicaid doesn’t cover
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Accuracy vs cost of screeningTest Sensitivity
TS 21Specificity False
positivePositive predictive value?
Cost
Quad 85% 94% 6% Pt specificrisk-usually <1%
$200
Integrated 85% 99.1% 0.9% Low $1275
CFDNA 99.3% 99.8% 0.2% $100-$1000+
CF DNA Sensitivity for T18- 95% T13- 91%
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Maternal Carrier Screening for Genetic Conditions
Historically- based on family history
Since about 2000 Offer all cystic fibrosis screening ($325)“Jewish panel” ($1625)
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Carrier Screening
ACOG now recommends offering pan-ethnic screening for 4 conditions CF ($325) SMA ($575) Fragile X ($325) Hemoglobinopathies ($75)
2017 ACOG Committee Opinion 691 “Carrier screening for genetic conditions”
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Expanded carrier screening- ECS Screens for many genes simultaneously (200+ conditions
in some panels) 25-50% of population screens positive for one or more
conditions!
Similar or lower cost than “a la carte” screening
Commercial labs developed and offered ECS without guidance by professional organizations
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Application of Society CriteriaOnly 20% of conditions on commercial panels
meet criteria for inclusion
Low carrier prevalence (less than 1/100) Detection rate of less than 70%Uncertain significance / residual riskMany labs don’t meet QA guidelines
Parental anxiety a big consideration
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Cost of expanded carrier screening
Bill to insurance company $500-1500
Many carriers cover, Select Health does not
Some labs guarantee max out of pocket of $200
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Diagnostic Testing-Procedures for procuring tissue
Procedure When GC Ultrasound Procedure TotalCVS 10-13
wks$125 $325 $375 $825
Amnio 15-20 wks
$125 $450 $150 $725
Stillbirth/neonate $0POC’s $0IVF PGS Pre-
implant$1500 $1500
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Standard karyotype
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FISH
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Microarray
Measures gains and losses of DNA Identifies chromosomal
aneuploidy Submicroscopic abnormalities
not seen with karyotype
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MicroarrayCNV= “Copy number variants”Duplicated or deleted sections of DNA
VUS= “Variants of uncertain significance”Potential for significant patient anxiety!
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Microarray vs. Standard karyotype
Major structural abnormalities Fetal death or products of conception
Microarray recommendedStructurally normal fetus
Either test
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Cost of diagnostic testsTest CostKaryotype $1,200-$1,500
FISH + $1,500
Microarray $4,800
Microarray- POC’s $3,100
• Insurance will pay for most “indicated” tests with prior auth• Because microarray is new, insurance may not pay
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Whole-Exome Sequencing
Looks at all coding genes in human genome
Commonly used in Pediatric genetic evaluation
Not yet used for prenatal testing
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Bottom line: Many more choices
Much better information available
Complex counseling
Not for everyone- I start the discussion with “is it important for you to know…”