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contemprary strategy for prenatal diagnosis
Citation preview
Contemporary Strategy for
Prenatal Diagnosis
Professor Hassan Nasrat FRCS, FRCOG
The Fetal Medicine Clinic The First Clinic
JUCOG 2013
Sunday, July 28, 13
Maternal characteristics
History
Biophysical finding from US
Findings from biochemical tests
Current Objective Of Prenatal Care Is To Define Patient Specific Risk For Pregnancy Complications At Early Stage.
Through Combining Data Data From:
Sunday, July 28, 13
Diagnosis of aneuploidy
Sunday, July 28, 13
“ Maternal Age Of 35 Should No Longer Be Used By Itself As A Cut-off To Determine Who Is Offered Screening Versus Who Is Offered Invasive Diagnostic Testing,"
“All Pregnant Women, Regardless Of Their Age, Should Have The Option Of Diagnostic Testing”
2007Sunday, July 28, 13
Diagnosis of aneuploidy
Screening For aneuploidy
Sunday, July 28, 13
Diagnosis of aneuploidy
Assessment of patient specific risk for aneuploidy
Screening For aneuploidy
Sunday, July 28, 13
Diagnosis of aneuploidy
Non-‐invasive Methods
Assessment of patient specific risk for aneuploidy
Screening For aneuploidy
Sunday, July 28, 13
Diagnosis of aneuploidy
Non-‐invasive Methods
Invasive Methods
Assessment of patient specific risk for aneuploidy
Screening For aneuploidy
Sunday, July 28, 13
Strategies of Screening For aneuploidy
Sunday, July 28, 13
0 25 50 75 100
95.0090.00
87.0082.00
91.0081.00
75.0087.00
69.00
75.0021.001985-
1990
1991-1995
1996-2010
Maternal Serum AFP
Genetic Ultrasound
Maternal Serum Triple Marker
Genetic UltrasoundFirst Trimester NT
Maternal Serum QUAD markerGenetic Ultrasound
First Trimester NT
First Trimester NT and Serum Plus Selective NT, TR, and DV
First Trimester NT and Serum
First Trimester NT and Serum +Second-trimester QUAD
History of Detection of Fetal Trisomy
Sunday, July 28, 13
PRINCIPLES OF SCREENING
Important proper+es of a screening test are its sensi+vity, specificity, and predic+ve values nega+ve and posi+ve.
Sunday, July 28, 13
PRINCIPLES OF SCREENING
Important proper+es of a screening test are its sensi+vity, specificity, and predic+ve values nega+ve and posi+ve.
The sensi(vity and specificity cannot be used to es+mate the probability of the disease in an individual.
Sunday, July 28, 13
PRINCIPLES OF SCREENING
Important proper+es of a screening test are its sensi+vity, specificity, and predic+ve values nega+ve and posi+ve.
The sensi(vity and specificity cannot be used to es+mate the probability of the disease in an individual.
Posi(ve and nega(ve predic(ve are dependent on the prevalence of the disease
Sunday, July 28, 13
PRINCIPLES OF SCREENING
Important proper+es of a screening test are its sensi+vity, specificity, and predic+ve values nega+ve and posi+ve.
The sensi(vity and specificity cannot be used to es+mate the probability of the disease in an individual.
Posi(ve and nega(ve predic(ve are dependent on the prevalence of the disease
The likelihood ra(o are independent of disease prevalence and integrate the sensi+vity and specificity of screening tests
Sunday, July 28, 13
The likelihood ra(o
Indicate by how much a given test result increases or decreases the probability of developing a condition.
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
The risk may increase or decrease based on the presence (or absence) of certain marker (s)
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
×
The risk may increase or decrease based on the presence (or absence) of certain marker (s)
The Background“Priori Risk”
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
×The Likelihood ratio as Calculated from a
given marker
The risk may increase or decrease based on the presence (or absence) of certain marker (s)
The Background“Priori Risk”
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
×The Likelihood ratio as Calculated from a
given marker
a new priori Posterior Risk For
the next test
The risk may increase or decrease based on the presence (or absence) of certain marker (s)
The Background“Priori Risk”
Sunday, July 28, 13
Every woman has a background (priori) risk of having a chromosomal defective baby.
Calculation of Patient Specific RISK “Using Positive & Negative Likelihood Ratio”
×The Likelihood ratio as Calculated from a
given marker
a new priori Posterior Risk For
the next test
The different tests are
independent
The risk may increase or decrease based on the presence (or absence) of certain marker (s)
The Background“Priori Risk”
Sunday, July 28, 13
0.6 0.4 2.0
LR=1.7 LR=10.6 LR=2.0
AFP(MOM) UE3(MOM) hCG(MOM)
Age Risk 30 years
1:900
Likelihood RatioAFP UE3 hCG
1.7 × 10.4 × 2.0 × =
Adjusted Risk
1:25
Normal
DS
Calculations of LRs for three analytes. At a MSAFP level of 0.6 MoM, approximately twice as many fetuses with Down syndrome are at this level than chromosomally normal fetuses.
Therefore, the LR for Down syndrome at a MSAFP level of 0.6 MoM is 1.7.Sunday, July 28, 13
Every woman has a background or a priori risk that her fetus/baby has a chromosomal defect.
A new individual “patient-specific” risk is calculated by multiplying the priori risk with a series of likelihood ratios obtained from screening tests.
Summary
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Biochemical Tests
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Biochemical Tests
Sonography Findings
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Sonography Findings
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Sunday, July 28, 13
Risk of Aneuploidy based on Maternal Age and Gestational
Week
Sunday, July 28, 13
Sunday, July 28, 13
The Risk Is Almost Constant At Ages 15 To 25
Rises Slowly Between 25 To 35
Increases Approximately 4-‐fold From Ages 35 To 40 And
10-‐fold From Ages 40 To 45;
Aneuploidy andMaternal Age
Sunday, July 28, 13
The Risk Is Almost Constant At Ages 15 To 25
Rises Slowly Between 25 To 35
Increases Approximately 4-‐fold From Ages 35 To 40 And
10-‐fold From Ages 40 To 45;
Aneuploidy andMaternal Age
Sunday, July 28, 13
The Risk Is Almost Constant At Ages 15 To 25
Rises Slowly Between 25 To 35
Increases Approximately 4-‐fold From Ages 35 To 40 And
10-‐fold From Ages 40 To 45;
Aneuploidy andMaternal Age
Sunday, July 28, 13
Risk of Aneuploidy based on Previous Trisomy
Sunday, July 28, 13
Previous Trisomy 21 increases the risk of recurrence by a factor of 0.75% above the maternal and gestational age-related risk for trisomy 21 at the time of testing.
A previous trisomy 21:
✦For 35 years old woman the risk at 12 weeks of gestation increases from 1 in 249 (0.40%) to 1 in 87 (1.15%).
✦For 25 years old woman the risk increases from 1 in 946 (0.106%) to 1 in 117 (0.856%).
Sunday, July 28, 13
The risk for trisomies increases with maternal age.
The risk of Turner syndrome and triploidy does not change with maternal age.
The earlier the gestation, the higher the risk for chromosomal defects.
A previous fetus or baby with a trisomy increases the risk in a current pregnancy by 0.75% over a priori risk.
Summary
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Biochemical Tests
Sunday, July 28, 13
In order to take account of sources of variation, the concentration of each marker is expressed as a multiple of the median for pregnancies of the same gestational age (MoM).
Sunday, July 28, 13
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
9
Down’s syndrome Unaffected
AFP (MoM) uE3 (MoM)
UnaffectedDown’s syndrome
Nuchal translucency (MoM)
Down’s syndromeUnaffected
Down'ssyndrome
Unaffected
Inhibin-A (MoM)
Down’s syndrome
PAPP-A (MoM)
Unaffected
Unaffected Down’s syndrome
free ß-hCG (MoM)
Unaffected D Syndrome
Unaffected D Syndrome
D SyndromeUnaffected
Unaffected Unaffected
Unaffected D Syndrome
D Syndrome D Syndrome
Sunday, July 28, 13
✦Maternal Weight: ✦Ethnic Group: ✦In Vitro Fertilization (IVF): ✦Insulin Dependent Diabetes Mellitus (IDDM): ✦Smoking: ✦Previous affected pregnancies✦Vaginal bleeding
✦Results of screening in a previous pregnancy
FACTORS AFFECTING THE TEST
Sunday, July 28, 13
THREE SCREENING OPTIONS
2nd TrimesterQuad
1st TrimesterCombined Test
1st and 2nd TrimesterFully Integrated Test
Serum IntegratedStepwise Sequential Contingent
Sequential Screen
Sunday, July 28, 13
THREE SCREENING OPTIONS
1st TrimesterCombined Test
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
10 to 14 wks
Blood Draw
COMBINED INTEGRATED
11 to 14 wks Nuchal
Translucency
PAPPA-A hCG
+Measurement of CRL
Sunday, July 28, 13
COMBINED TEST
1Blood Drawn: 10 Weeks 0 days to 13 weeks 6 days Test: PAPPA-A and hCG
2 ULTRASOUND: 11 Weeks 2 days to 14 weeks 2 days Test: Measure Nuchal Translucency
First Trimester Cut off (mid-
trimester risk)
False Positive
Rate
Detection Rate
1:80 2.02% 72.57%
1:100 2.54% 74..99%
1:120 3.03% 76.89%
Risk Assessment
•Trisomy 21•Trisomy 18
Sunday, July 28, 13
0
10.00
20.00
30.00
40.00
50.00
60.00
70.00
80.00
90.00
100.00
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Combined TestOverall Detection Rate 85%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
85%
50%
Sunday, July 28, 13
THREE SCREENING OPTIONS
2nd TrimesterQuad
1st TrimesterCombined Test
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
15 to 20wks
Blood Draw
Quad TestQuad
AFPhCGUe3Inhibin
Sunday, July 28, 13
QUAD TEST
0
25
50
75
100
80.00
67.00
97.00
80.0085.00
60.00
Tri 21 Tri 18 Anecephaly Spina Bifida Abd W D SLOS
Detection Rate
Sunday, July 28, 13
What Does A Negative Test Miss?
0
10
20
30
40
20
33
3
2015
40
Tri 21 Tri 18 Anecephaly Spina Bifida Abd W D SLOS
Percent of Birth Defects Not Detected
Sunday, July 28, 13
THREE SCREENING OPTIONS
2nd TrimesterQuad
1st TrimesterCombined Test
1st and 2nd TrimesterFully Integrated Test
Serum Integrated Sequential Screen Contingent Screen
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
10 to 14 wks
Fully Integrated
Measurement of CRL+
PAPPA-A hCG
11 to 14 wks Nuchal
Translucency
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
10 to 14 wks
Results are Reported after The Second Blood Test
15 to 20 wks
Fully Integrated
AFPhCGUe3InhibinMeasurement of CRL
+
PAPPA-A hCG
11 to 14 wks Nuchal
Translucency
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
10 to 14 wks
Serum Integrated
Measurement of CRL+
PAPPA-A hCG
Sunday, July 28, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......40
10 to 14 wks
Results are Reported after The Second Blood Test
15 to 20 wks
Serum Integrated
AFPhCGUe3InhibinMeasurement of CRL
+
PAPPA-A hCG
Sunday, July 28, 13
First-trimester Screening
Screen Positive
CVS
Final Result incorporate 1st and 2nd
results
Screen Negative
CVS
QUAD
Sequential Screen
Sunday, July 28, 13
First-trimester Screening
Very High Risk >1 in 50
CVS
Contingent Screen
Intemediate Risk
(1in 50 to 1 in 1000
QUAD
Low Risk <1 in 2000
No Additional Test
CVSSunday, July 28, 13
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
100
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
85
NT NT+
PAPP-A &
β-hCG
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
8575
NTAFP+
Ue3 &
β-hCG
NT+
PAPP-A &
β-hCG
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
8575
NTAFP+
Ue3 &
β-hCG
NT+
PAPP-A &
β-hCG
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
8575
NTAFP+
Ue3 &
β-hCG
NT+
PAPP-A &
β-hCG
85
AFP+
Ue3 &
β-hCG&
Inhibin
“QUAD “
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
85
NT NT+
PAPP-A &
β-hCG
85
AFP+
Ue3 &
β-hCG&
Inhibin
“QUAD “
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
85
NT NT+
PAPP-A &
β-hCG
85
AFP+
Ue3 &
β-hCG&
Inhibin
“QUAD “
95
NT+
PAPP-A &
β-hCG
“QUAD”
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
85
NT NT+
PAPP-A &
β-hCG
85
AFP+
Ue3 &
β-hCG&
Inhibin
“QUAD “
95
NT+
PAPP-A &
β-hCG
“QUAD”
What if NT is Not Available?
First Trimester
Second Trimester
1st & 2nd Trimester
Sunday, July 28, 13
0
25
50
75
10075
85
NT NT+
PAPP-A &
β-hCG
85
AFP+
Ue3 &
β-hCG&
Inhibin
“QUAD “
9585
NT+
PAPP-A &
β-hCG
“QUAD”
PAPP-A &
β-hCG What if NT is Not Available?
First Trimester
Second Trimester
1st & 2nd Trimester
“QUAD”
Sunday, July 28, 13
0
10
20
30
40
50
60
70
80
90
100
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Fully Integrated Overall Detection Rate 95%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
90%
50%
Sunday, July 28, 13
0
25
50
75
100
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Serum Integrated Overall Detection Rate 85%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
80%72%
Sunday, July 28, 13
0
10
20
30
40
50
60
70
80
90
100
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Fully Integrated Overall Detection Rate 95%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
90%
50%
Sunday, July 28, 13
0
10
20
30
40
50
60
70
80
90
100
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Fully Integrated Overall Detection Rate 95%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
90%
50%
Sunday, July 28, 13
0
10
20
30
40
50
60
70
80
90
100
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 45
Fully Integrated Overall Detection Rate 95%
MATERNAL AGE
DETECTION RATE OF TRISOMY 21 BASED ON MATERNAL AGE
90%
50%
HOW?90+%
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Biochemical Tests
Sunday, July 28, 13
Screening for Fetal Aneuploidy
Maternal AgePrevious History Tests
Biochemical Tests
Sonography Findings
Sunday, July 28, 13
FIRST TRIMESTER
SECOND TRIMESTER
Sunday, July 28, 13
1ST TRIMESTER SCREENING
Sunday, July 28, 13
Nasal Bone
Tricuspid Regurgitation
Ductus Venousus
Editorial 515
Figure 3 Four-chamber view illustrating an endocardial cushiondefect in which a ventricular (VSD) and atrial (ASD) septal defectare present. LA, left atrium; LV, left ventricle; RA, right atrium;RV, right ventricle.
SUGGESTED USE OF FETALECHOCARDIOGRAPHY AS PART OF THEGENETIC SONOGRAM GIVEN CURRENTSCREENING TECHNOLOGIES
At present, common screening tests for trisomy 21 mayinclude any of the following: (1) first-trimester combinedNT and serum screening, (2) first-trimester combinedNT and serum screening plus second-trimester QUADscreening, (3) first-trimester serum and second-trimester
serum screening, or (4) second-trimester QUAD screen-ing. Because of the technical skills of the sonogra-pher/sonologist required to detect over 90% of trisomy 21fetuses using non-cardiac and cardiac markers (Table 8),genetic sonography should only be used as an adjunctto the above screening protocols or in women who reg-ister for prenatal care after 20 weeks of gestation. Thefollowing two scenarios illustrate when genetic sono-graphy, coupled with fetal echocardiography, should beconsidered.
Genetic sonography as an adjunct to first-trimester NTand serum and/or second-trimester serum screening
When genetic sonography was first introduced in theearly 1990s it was an option for screening for trisomy21 in women less than 35 years of age for two reasons:(1) the detection rate was similar to or higher than thatusing MSAFP screening, and (2) the ultrasound exam onlyrequired measurements of the biparietal diameter, femurlength and nuchal skin fold (Table 1). However, as moreanalytes were added, second-trimester maternal serum(triple and QUAD) screening increased the detectionrate for trisomy 21, was easier to use, and did notrequire the specialized ultrasound skills needed to keepthe genetic sonogram comparable in terms of detectionrates (Table 2).
Investigators have reported the use of genetic sono-graphy as an adjunct to other screening protocols.In 2001, Roberto Romero and I11 reported offer-ing genetic sonography to women considered to beat moderate risk (1 : 190–1 : 1000) for trisomy 21
Figure 4 Four-chamber view illustrating a ventricular septal defect (VSD) at the level of the inflow tracts. (a) B-mode image; (b) powerDoppler image confirming flow at the level of the VSD. LV, left ventricle; RV, right ventricle.
Copyright ! 2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 35: 509–521.
Sunday, July 28, 13
Nasal Bone
Sunday, July 28, 13
note THREE distinct lines:Sunday, July 28, 13
note THREE distinct lines:Sunday, July 28, 13
The Nasal Bone Is Absent In:
0
18
35
53
70 65.00
50.00
30.00
2.00
Tri 21 Tri 18 Tri 13 Normal
Sunday, July 28, 13
0
15.00
30.00
45.00
60.00
18.00 19.00
52.00 52.00
45-54 55-64 65-74 75-84
Absent Nasal Bone and CRL Likelihood Ratio for DS
Cicero S et al US Ob&Gyn, 2004, 23
Sunday, July 28, 13
In chromosomal normal fetuses the incidence of absent nasal bone is less than 1% in Caucasian populations and about 10% in Afro-‐Caribbean.
31.00
9.0014.00 15.00
Caucasian Asian
Ethnicity of Mother Cicero et al US OB and Gyn 2004
Liklihood Ratios For Down Syndrome -Absent Nasal Bone
Sunday, July 28, 13
For a false positive rate of 5%, screening by a combination of sonography for fetal NT and nasal bone and maternal serum free b-‐hCG and PAPP-‐A can potentially identify more than 95% of trisomy 21 pregnancies.
The Nasal Bone
Sunday, July 28, 13
DV Blood
FlowSunday, July 28, 13
In more than 5,000 pregnancies, including 280 fetuses with trisomy 21:
0
20
40
60
80
DV Nomral
5
80
Abnormal DV flow in about 80% of trisomy 21 fetuses and in about 5% of chromosomally normal fetuses
(Nicolaides 2004) Sunday, July 28, 13
Sunday, July 28, 13
Tricuspid Rugurge
Sunday, July 28, 13
Tricuspid regurgitation in screening for trisomies
Tricuspid regurgitation in screening for trisomies 21, 18 and 13 and Turner syndrome at 11 + 0 to 13 + 6 weeks of gestationK. O. KAGAN*†, C. VALENCIA*, P. LIVANOS*, D. WRIGHT‡ and K. H. NICOLAIDESUltrasound Obstet Gynecol 2009; 33: 18–22, 2008
Sunday, July 28, 13
0
15
30
45
60
0.9
55.7
33.3 3037
Normal Tr1 21 Tri 18 Tri 13 Turner
Percentage of Tricuspid regurgitation among normal and abnormal
Sunday, July 28, 13
0102030405060
7080
90100
91100 100 100
T21 T18 Tris 13 Turner S
Detection rates at 3% FPR using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow
Total 96%+ 6%
Sunday, July 28, 13
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
0102030405060
70
80
90
100
80.0086.00 91.00 93.00 94.00
FPR 1.0 FPR 2.0 FPR 3.0 FPR 4.0 FPR 5.0
Detection rates at given FPR levels using screening by maternal age, fetal NT, FHR, free β-hCG and PAPP-A with and without assessment of tricuspid blood flow.
Total 92%
+ 12%
Total 95%
Total 96%
Total 96%
Total 96%
+ 11% + 5% + 3% + 2%
Sunday, July 28, 13
Nasal BoneTricuspid Regurgitation
Ductus Venousus
Editorial 515
Figure 3 Four-chamber view illustrating an endocardial cushiondefect in which a ventricular (VSD) and atrial (ASD) septal defectare present. LA, left atrium; LV, left ventricle; RA, right atrium;RV, right ventricle.
SUGGESTED USE OF FETALECHOCARDIOGRAPHY AS PART OF THEGENETIC SONOGRAM GIVEN CURRENTSCREENING TECHNOLOGIES
At present, common screening tests for trisomy 21 mayinclude any of the following: (1) first-trimester combinedNT and serum screening, (2) first-trimester combinedNT and serum screening plus second-trimester QUADscreening, (3) first-trimester serum and second-trimester
serum screening, or (4) second-trimester QUAD screen-ing. Because of the technical skills of the sonogra-pher/sonologist required to detect over 90% of trisomy 21fetuses using non-cardiac and cardiac markers (Table 8),genetic sonography should only be used as an adjunctto the above screening protocols or in women who reg-ister for prenatal care after 20 weeks of gestation. Thefollowing two scenarios illustrate when genetic sono-graphy, coupled with fetal echocardiography, should beconsidered.
Genetic sonography as an adjunct to first-trimester NTand serum and/or second-trimester serum screening
When genetic sonography was first introduced in theearly 1990s it was an option for screening for trisomy21 in women less than 35 years of age for two reasons:(1) the detection rate was similar to or higher than thatusing MSAFP screening, and (2) the ultrasound exam onlyrequired measurements of the biparietal diameter, femurlength and nuchal skin fold (Table 1). However, as moreanalytes were added, second-trimester maternal serum(triple and QUAD) screening increased the detectionrate for trisomy 21, was easier to use, and did notrequire the specialized ultrasound skills needed to keepthe genetic sonogram comparable in terms of detectionrates (Table 2).
Investigators have reported the use of genetic sono-graphy as an adjunct to other screening protocols.In 2001, Roberto Romero and I11 reported offer-ing genetic sonography to women considered to beat moderate risk (1 : 190–1 : 1000) for trisomy 21
Figure 4 Four-chamber view illustrating a ventricular septal defect (VSD) at the level of the inflow tracts. (a) B-mode image; (b) powerDoppler image confirming flow at the level of the VSD. LV, left ventricle; RV, right ventricle.
Copyright ! 2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 35: 509–521.
Value of Adding Multiple Markers
Sunday, July 28, 13
Benefit of Multiple Ultrasound Markers
NT+
Serum
NT+Serum +
Nasal Bone +
Heart +
DV
Tri 21 Tri 81
1st Trimester
75%
96%
69%
90%
NT+
Serum
NT+Serum +
Nasal Bone +
Heart +
DV
Sunday, July 28, 13
2ND TRIMESTER SCREENING
“Genetic Sonography”
Sunday, July 28, 13
Is based on the application of the likelihood ratios obtained from multiple independent ultrasound markers markers in adjusting a priori risk to determine a patient’s specific risk of carrying a fetus with DS
Genetic Ultrasound
Sunday, July 28, 13
Likelihood ratios (LR): for each marker are calculated by dividing the sensitivity of a particular marker by its false- positive rate.
LR < 1
LR > 1-5
LR > 5-10
LR > 10
Small increase
Moderate increase
Large Increase
Decrease Probability
Sunday, July 28, 13
The relative risk “RR”: is the probability of a fetus having trisomy 21 when compared with a fetus without this condition.
e.g. The presence of an ultrasound marker with a RR of 4 suggests a four-fold increase from the previous risk.
Sunday, July 28, 13
Example: A pericardial effusion with a relative risk 10.02.
A Patient With Prior Risk For Trisomy 21 Is 1 In 270
Sunday, July 28, 13
Calculation of Risk:1. Divide 1/(270–1) = 0.00372. Multiply the prior risk (0.0037) by (10.02)
Calculation = 0.0037 × 10.02 = 0.0373. Divide 1/0.037 = 28
Example: A pericardial effusion with a relative risk 10.02.
A Patient With Prior Risk For Trisomy 21 Is 1 In 270
The New Risk For Trisomy 21 is 1 in 28Sunday, July 28, 13
Example: Normal ultrasound examination study in which none of the ultrasound markers is present
Patient with Prior risk for trisomy 21 is 1 in 100The RR following a normal study is 0.11
Sunday, July 28, 13
Calculation of Risk:1.Divide 1/(100–1) = 0.012.Multiply the prior risk (0.01) by the RR for
both findings, 0.11 3.Calculation = 0.01 × 0.11 = 0.0011 4.Divide 1/00.11 = 900
Example: Normal ultrasound examination study in which none of the ultrasound markers is present
Patient with Prior risk for trisomy 21 is 1 in 100The RR following a normal study is 0.11
The New Risk For Trisomy 21 is 1 in 900Sunday, July 28, 13
Head
Heart
Abdomen
Sunday, July 28, 13
Head
Heart
Abdomen
➡CP
➡CNS (other than CP)
➡NSF
Sunday, July 28, 13
Head
Heart
Abdomen
➡CP
➡CNS (other than CP)
➡NSF
➡VSD
➡Rt to Lt. Disp
➡Outflow tract abnormalities*
➡Pericardial Effusion
➡Tricuspid or mitral regurgitation
Sunday, July 28, 13
Head
Heart
Abdomen
➡CP
➡CNS (other than CP)
➡NSF
➡VSD
➡Rt to Lt. Disp
➡Outflow tract abnormalities*
➡Pericardial Effusion
➡Tricuspid or mitral regurgitation
➡Hyperechoic Bowel
➡Pyelectasis Sunday, July 28, 13
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
5.89
10.02
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
5.89
10.02
4.57
5.65
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
5.89
10.02
4.57
5.65
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
5.89
10.02
4.57
5.65
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
20.00
40.00
60.00
80.0071.31
24.85
CNS abno
rmalities
Increas
ed NFS VSD
R-L Dispr
oportio
n
Pericar
idal Effu
sion
Tricusp
id Regu
rg
Hyperec
hoic B
owel
Pyelect
asis
88.26
12.54
5.89
10.02
4.57
5.65
Head Structural heart defects
Functional heart defects Abdomen
(RR) for CV and non- CV ultrasound markers in 80 second-trimester fetuses with trisomy 215 (with sensitivity 91% and false-positive rate 14%)
DeVore GR. 2000Sunday, July 28, 13
0
25
50
75
100
60
91
Without Color Doppler
With Color Doppler
The use of fetal echocardiography when performing the genetic sonogram: 98% detection rate for trisomy 21 in high-risk womenDevore, 2006
Sunday, July 28, 13
Meta-analysis of second-trimester markers for trisomy 21Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK (2012)
The aim: to examine the screening p e r f o r m a n c e o f s e c o n d - t r i m e s t e r sonographic markers for the detection of trisomy 21.
Sunday, July 28, 13
0.460.710.740.800.920.900.800.940.80
23.2621.48
4.803.72
7.77
10.82
19.18
25.78
5.80
ICF
Ventriculomegal
y
Increase
d NF
Hyperechogenic B
.
Mild hydronephrosis
Short Femur
Short Humerus
ARSA
Absent Nasa
l Bone
Sunday, July 28, 13
0.460.710.740.800.920.900.800.940.80
23.2621.48
4.803.72
7.77
10.82
19.18
25.78
5.80
ICF
Ventriculomegal
y
Increase
d NF
Hyperechogenic B
.
Mild hydronephrosis
Short Femur
Short Humerus
ARSA
Absent Nasa
l Bone
✤Ventriculomegaly, NF And ARSA Increases The Risk By 3-4 Fold✤Hypoplastic Nasal Bone Increases The Risk By 6-7 Fold
Sunday, July 28, 13
✤In The Absence Of All Major Defects And Markers There Is A 7.7-fold Reduction In Risk For Trisomy 21.
✤The Detection Of Any One Of The Markers Should Stimulate The Sonographer To Look For All Other Markers Or Defects.
✤The Post- Test Odds For Trisomy 21 Is Derived By Multiplying The Pre-test Odds With The Positive LR For Each Detected Marker And The Negative LR For Each Marker Demonstrated To Be Absent.
✤In The Case Of Most Isolated Markers, Including Intracardiac Echogenic Focus, Echogenic Bowel, Mild Hydronephrosis And Short Femur, There Is Only A Small Effect On Modifying The Pre-test Odds.
Sunday, July 28, 13
0
0.25
0.50
0.75
1.00
LR
0.37
LR
0.10
The LR for trisomy 21 in the absence of sonographic markersLR 0.37 RR 0.11
Nicoloides et al DevoreSunday, July 28, 13
Genetic sonography as an adjunct to first-trimester NT and serum and/or second-trimester serum screening
0
25.00
50.00
75.00
100.00
90.0098.00
90.00
81.0093.00
81.00
Combined Test 1st &2nd Trim
IntegratedQUAD
Aagaard-Tillery KM, et al First and Second Trimester Evaluation of Risk Research Consortium. Role of second-trimester genetic sonography after Down syndrome screening. Obstet Gynecol 2009; 114
Sunday, July 28, 13
NT plus Serum NT, Serum, NB, TR, DV, Heart
83% 96%
1st Trimester Options1st Trimester Options
Sunday, July 28, 13
Serum Integrated
Fully Integrated
80% 85%
2nd Trimester Detection Rate
2nd Trimester Options
QUAD
90%
QUAD + Genetic U/S
2nd Trimester Detection Rate
99%
2nd + 1st Trimester Options
Sunday, July 28, 13
Putting It Together
Sunday, July 28, 13
Initial Testing
Maternal Age
Serum Screening
Nuchal Translucency
+
+
Sunday, July 28, 13
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Ultrasound Examination for•Absent Nasal Bone•Abnormal Ductus Venosus Flow•Tricuscupid Rrgurgitation
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Ultrasound Examination for•Absent Nasal Bone•Abnormal Ductus Venosus Flow•Tricuscupid Rrgurgitation
Positive
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Ultrasound Examination for•Absent Nasal Bone•Abnormal Ductus Venosus Flow•Tricuscupid Rrgurgitation
Positive Negative
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Ultrasound Examination for•Absent Nasal Bone•Abnormal Ductus Venosus Flow•Tricuscupid Rrgurgitation
Positive Negative
If This is Not Available
Sunday, July 28, 13
High-Risk(>1 in 100)
(2% of Polulation)
CVS
Low-Risk(>1 in 1001 in 10,100)
(82% of Polulation)
No Further Testing
Intermediate-Risk(1 in 101 to 1 in 1,000)
(16% of Polulation)
> 90% Detection Rate False Positive Rate 2%
Estimated Risk For Trisomy 21
Ultrasound Examination for•Absent Nasal Bone•Abnormal Ductus Venosus Flow•Tricuscupid Rrgurgitation
Positive Negative
If This is Not Available
Genetic SonographySunday, July 28, 13
Examination of fetal cells from maternal peripheral blood:
Cell-free fetal DNA in maternal plasma:
Non-‐invasive diagnosis
Sunday, July 28, 13
Examination of fetal cells from maternal peripheral blood:
Cell-free fetal DNA in maternal plasma “cffDNA”:
Non-‐invasive diagnosis
Sunday, July 28, 13
NIPTNon Invasive Prenatal Testing
Screening or Diagnosis
Sunday, July 28, 13
It is now established that trisomy 21 can be detected reliably from 10 weeks’ gestation in high-risk singleton pregnancies with superior sensitivity (> 99%) and specificity (false-positive rate < 1%) compared with conventional screening methods.
Trisomy 18 and 13 are also detectable, but test accuracy is less consistent than that for trisomy 21.
Sunday, July 28, 13
Clinical validity:
The clinical utility:
Sunday, July 28, 13
The ability of a test to predict the risk of an outcome and to categorize patients with different outcomes into separate risk classes.
Clinical validity:
The clinical utility:
Sunday, July 28, 13
The ability of a test to predict the risk of an outcome and to categorize patients with different outcomes into separate risk classes.
Clinical validity:
The clinical utility:
The ability of a test to improve health outcomes for patients. Specifically, the test results must change clinical decision- making, and these changes should be beneficial to patients.
Sunday, July 28, 13
The ability of a test to predict the risk of an outcome and to categorize patients with different outcomes into separate risk classes.
Clinical validity:
The clinical utility:
The ability of a test to improve health outcomes for patients. Specifically, the test results must change clinical decision- making, and these changes should be beneficial to patients.
There are currently no studies on the impact of DNA- based NIPT on patient management or outcome.
Sunday, July 28, 13
Current Screening and/or ultrasound
High risk for aneuploidyPretest counseling
Invasive diagnosis
Genetic Counseling
TOP •Continue Pregnancy•Prepare for affected infant•Deliver at hospital with special newborn services
Serum screening and/or ultrasound examination
Invasive cytogenetic diagnosis
Trisomy 21
Genetic counseling
TOP •Continue pregnancy•Prepare for affectedt infavnct
•Deliver at hospital with special newborn servcie
Treat Fetus
Sequencing of Cell Free DNA
Current Future
And /Or
Sunday, July 28, 13
From prenatal genomic diagnosis to fetal personalized medicine: progress and challengesDiana W Bianchi
Nature Medicine 18, 1041–1051 (2012) doi:10.1038/nm.2829Published online 06 July 2012
Thus far, the focus of personalized medicine has been the prevention and treatment of conditions that affect adults. Although advances in genetic technology have been applied more frequently to prenatal diagnosis than to fetal treatment, genetic and genomic information is beginning to influence pregnancy management. Recent developments in sequencing the fetal genome combined with progress in understanding fetal physiology using gene expression arrays indicate that we could have the technical capabilities to apply an individualized medicine approach to the fetus. Here I review recent advances in prenatal genetic diagnostics, the challenges associated with these new technologies and how the information derived from them can be used to advance fetal care. Historically, the goal of prenatal diagnosis has been to provide an informed choice to prospective parents. We are now at a point where that goal can and should be expanded to incorporate genetic, genomic and transcriptomic data to develop new approaches to fetal treatment.
Sunday, July 28, 13
Sunday, July 28, 13
Thanks
Sunday, July 28, 13