New Strategies for Genetic Screening in Pregnancy Rita W. Driggers CDR MC USN 1 June 2009
Maternal Serum Screening <ul><li>Goal </li></ul><ul><ul><li>Identify as many abnormal fetuses possible (high detection rat...
Maternal Serum Screening <ul><li>Maternal age </li></ul><ul><ul><li>First recognized screening test </li></ul></ul><ul><ul...
Maternal Serum Screening <ul><li>HCG </li></ul><ul><ul><li>Late 1980’s - high HCG associated with trisomy 21 </li></ul></u...
Maternal Serum Screening <ul><li>Inhibin A </li></ul><ul><ul><li>1990’s – recognized to be elevated with trisomy 21 </li><...
Maternal Serum Screening <ul><li>Quad screen profile in Trisomy 21 </li></ul><ul><ul><li>MSAFP = 0.74 MoM </li></ul></ul><...
Maternal Age Counseling <ul><li>Increasing age associated with increased risk of the baby having abnormalities in number o...
What are chromosomes? <ul><li>Packaging for genetic (inherited) information in a cell </li></ul><ul><ul><li>Chromosomes ar...
 
 
Chromosome abnormalities <ul><li>Having an extra chromosome or a missing chromosome means the body has too much or too lit...
Extra chromosome 21--Down syndrome
Extra chromosome 18—Trisomy 18
What can be done to test for chromosome abnormalities? <ul><li>Screening tests </li></ul><ul><ul><li>1 st  trimester </li>...
What is quad screen testing? <ul><li>A blood test done between 14-20 weeks gestation </li></ul><ul><li>It measures four pr...
What do the results mean? <ul><li>Quad screen gives three pieces of information </li></ul><ul><ul><li>Risk for baby to hav...
Can the test say exactly what my baby has? <ul><li>No!  </li></ul><ul><li>It can only say whether you have a higher or low...
Does the quad screen test find all babies with the problems? <ul><li>The quad screen will identify  </li></ul><ul><ul><li>...
Does the quad screen test look for all types of abnormalities? <ul><li>No </li></ul><ul><li>Only identifies babies with op...
Do I have to have a quad screen? <ul><li>No, it is your choice </li></ul><ul><li>95% of mothers will have a normal test an...
You receive the following quad screen results for a 41 yo G2P1 <ul><li>Screen POSITIVE for Down Syndrome </li></ul><ul><li...
What happens if my test is positive? <ul><li>Test may be positive because dates are wrong </li></ul><ul><ul><li>Test done ...
What if my test is positive and my dates are correct? <ul><li>The next step is to do a detailed ultrasound (called a targe...
What are ultrasound markers? <ul><li>Early 1990’s - “genetic ultrasound” </li></ul><ul><li>Sonographic markers for aneuplo...
Does the ultrasound give 100% answers? <ul><li>No </li></ul><ul><li>The ultrasound needs to be done by an experienced pers...
Who needs a 100% answer? <ul><li>Some people need to have as much information as possible about their babies because that ...
How to get a 100% answer <ul><li>A test called an amniocentesis can be offered  </li></ul><ul><ul><li>Takes small sample o...
Is that a risky test? <ul><li>Amniocentesis is a very safe test and has been done for over 50 years </li></ul><ul><li>15-2...
Prenatal Diagnosis of Aneuploidy
Prenatal Diagnosis of Aneuploidy
Is the amniocentesis reliable? <ul><li>Yes </li></ul><ul><li>If it says there is no problem, there is no problem </li></ul...
Do I have to have an amniocentesis? <ul><li>No </li></ul><ul><li>It is only offered as a way to get the most possible info...
Nuchal translucency <ul><li>Mid-1990’s - strong association between size fluid collection at back fetal neck in 1 st  trim...
Nuchal Translucency www.mums.me.uk/nuchal.htm Dr Eva Pajkrt, University of Amsterdam
Normal Nuchal Translucency Measurement
Increased Nuchal Translucency Measurement
1 st  Trimester Aneuploidy Screening <ul><li>Around this same time period 1 st  trimester analytes recognized </li></ul><u...
Should I get the first trimester test or the quad screen? <ul><li>Advantage of 1st trimester screening </li></ul><ul><ul><...
What is CVS? <ul><li>CVS </li></ul><ul><ul><li>Placental villi obtained through a transcervical or transabdominal approach...
Is CVS riskier than amniocentesis? <ul><li>Overall pregnancy loss rate after CVS is greater than after amniocentesis </li>...
What are the complications from CVS? <ul><li>Other CVS complications   </li></ul><ul><ul><li>Vaginal spotting or bleeding ...
Prenatal Diagnosis of Aneuploidy
What tests should be done after 1 st  trimester screening or CVS? <ul><li>1 st  trimester screening does not include MSAFP...
Can other information be gained from 1 st  trimester screening? <ul><li>Abnormal 1st-trimester serum markers or increased ...
Aneuploidy Screening *87% at 11 wks, 85% at 12 wks, 82% at 13 wks Test Trisomy 21 Detection Rate FPR Triple screen 70% 5% ...
Aneuploidy Screening <ul><li>ACOG recommendations (Jan 2007) </li></ul><ul><ul><li>All women be offered aneuploidy screeni...
Prenatal Diagnosis of Aneuploidy <ul><li>Criteria for invasive testing traditionally maternal age  </li></ul><ul><li>ACOG ...
Aneuploidy Screening *Best when 1st trimester screen at 11 wks Screening method Trisomy 21 detection   FPR   Comments   Se...
Aneuploidy Screening <ul><li>So which screening test(s) should be offered?!! </li></ul>
Aneuploidy Screening <ul><li>Before deciding which strategy or strategies to offer your patients </li></ul><ul><ul><li>Ide...
Aneuploidy Screening <ul><li>Women who present in the 1st trimester </li></ul><ul><ul><li>Strategy incorporating both 1st ...
Aneuploidy Screening <ul><li>If NT measurement is not available or cannot be obtained in an individual </li></ul><ul><ul><...
Aneuploidy Screening <ul><li>Reporting results to patients </li></ul><ul><ul><li>Provide numerical risk (rather than posit...
Summary <ul><ul><li>1st and 2 nd  trimester screening tests for fetal chromosomal abnormalities, correct timing for, and a...
<ul><li>Questions??? </li></ul>
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  • however, using a maternal age of 35 detects only approximately 20% of pregnancies complicated by fetal trisomy 21
  • however, using a maternal age of 35 detects only approximately 20% of pregnancies complicated by fetal trisomy 21
  • The average MSAFP level in pregnancies complicated by trisomy 21 is reduced to 0.74 multiples of the median (MoM) observed in euploid pregnancies, intact hCG is increased to an average level of 2.06 MoM, uE3 is reduced to an average level of 0.75 MoM, and maternal inhibin A level is increased to 1.77 MoM. Typically, AFP, HCG, and uE3 levels are all reduced when the fetus has trisomy 18. Inhibin A is not used in the calculation of risk for trisomy 18.
  • Small head with flattened occiput Flat nasal bridge and wide-spaced eyes with epicanthal folds and upslanting palpebral fissures Large tongue (often protruding) Loose skin in nape of neck Short stubby fingers, simean crease, 5 th finger clinodactyly due to absence of hypoplasia of middle phalanx. GI atresias and endocardial cushion defects
  • Overlapping digits/clenched fist; hypertonicity; short sternum (arrow); narrow pelvis Clubbed feet Skull abnormalities – prominent occiput Micrognathia, posterior rotated/low set ears Hypoplasia of 5 th fingernail; low arch dermal ridge configuration on fingertip Dorsiflexed short hallux
  • In several studies, it has been confirmed that the incidence of pregnancy loss, blood-contaminated specimens, leaking of amniotic fluid, and the need for more than one needle puncture are related to the experience of the operator, the use of small-gauge needles, and ultrasound guidance.
  • In several studies, it has been confirmed that the incidence of pregnancy loss, blood-contaminated specimens, leaking of amniotic fluid, and the need for more than one needle puncture are related to the experience of the operator, the use of small-gauge needles, and ultrasound guidance.
  • If mosaicism is found by CVS, amniocentesis typically is performed at 15-20 weeks to assess whether mosaicism is present in amniocytes. In most cases, the amniocentesis result is normal, and the mosaicism is assumed to be confined to the trophoblast (confined placental mosaicism). Although this is unlikely to cause defects in the fetus, it may result in third-trimester growth restriction.
  • Currently, there are no data indicating whether or not fetal surveillance in the third trimester will be helpful in the care of these patients
  • Traditionally, maternal age of &gt; 35 was the criteria used to determine who would be offered invasive prenatal diagnosis for fetal aneuploidy because this was the age at which the risk approached the risk of invasive testing This change in recommendation evolved because studies have shown that many factors - in addition to the risk that the fetus will have a chromosomal abnormality - influence a woman’s decision to undergo an invasive procedure to include the risk of pregnancy loss from an invasive procedure and the consequences of having an affected child if diagnostic testing is not done. Furthermore, recent studies have suggested lower loss rates from these invasive procedures than previously accepted when studies were performed prior to the use of high-resolution concurrent ultrasonography.
  • Several approaches to trisomy 21 screening in the 1st and 2nd trimester Integrated approach Patient has 1st trimester screening (serum only or serum and NT) and 2 nd trimester quad screen No results are given until following the second trimester quad screen Integrated result is given Amniocentesis is offered for those at high risk (usually &gt;1:270) Sequential test 1st trimester results reported Those at high risk (usually &gt;1:60 to 1:100) undergo CVS Remaining get quad screen in the 2nd trimester and combined result reported Amniocentesis is offered for those with high risk (usually &gt;1:270) Contingency approach CVS is offered to those at high risk (usually &gt;1:60 to 1:100) following 1st trimester screening No further testing offered if 1st trimester results are very low (usually &lt;1:1500) Only those with intermediate results get 2nd trimester quad screen
  • Counseling should be provided regarding the specific detection rates and false-positive rates of the screening strategy or strategies used
  • New Strategies in Genetic Screening for Pregnancy

    1. 1. New Strategies for Genetic Screening in Pregnancy Rita W. Driggers CDR MC USN 1 June 2009
    2. 2. Maternal Serum Screening <ul><li>Goal </li></ul><ul><ul><li>Identify as many abnormal fetuses possible (high detection rate) </li></ul></ul><ul><ul><li>Minimize number of normal pregnancies with abnormal test result (false positives) </li></ul></ul><ul><li>Abnormalities identified </li></ul><ul><ul><li>Number of chromosomes (aneuploidy) </li></ul></ul><ul><ul><li>Structural birth defects </li></ul></ul>
    3. 3. Maternal Serum Screening <ul><li>Maternal age </li></ul><ul><ul><li>First recognized screening test </li></ul></ul><ul><ul><li>Detects only 20% of trisomy 21 cases </li></ul></ul><ul><li>Maternal serum alpha-fetoprotein (MSAFP) </li></ul><ul><ul><li>Late 1970’s - association between high MSAFP and open neural tube defects </li></ul></ul><ul><ul><li>1980’s - association between low MSAFP and trisomy 21 </li></ul></ul><ul><ul><li>Increased sensitivity of trisomy 21 detection to 42% </li></ul></ul>
    4. 4. Maternal Serum Screening <ul><li>HCG </li></ul><ul><ul><li>Late 1980’s - high HCG associated with trisomy 21 </li></ul></ul><ul><ul><li>Combined with maternal age and MSAFP, increased trisomy 21 detection rate to 67% </li></ul></ul><ul><li>Unconjugated estriol (uE3) </li></ul><ul><ul><li>1988 - data published on low uE3 </li></ul></ul><ul><ul><li>Triple screen (MSAFP, HCG, and uE3) increased trisomy 21 detection rate to 70% </li></ul></ul>
    5. 5. Maternal Serum Screening <ul><li>Inhibin A </li></ul><ul><ul><li>1990’s – recognized to be elevated with trisomy 21 </li></ul></ul><ul><ul><li>Addition of inhibin A to triple screen (the quad screen) improved trisomy 21 detection rate to 80% </li></ul></ul>
    6. 6. Maternal Serum Screening <ul><li>Quad screen profile in Trisomy 21 </li></ul><ul><ul><li>MSAFP = 0.74 MoM </li></ul></ul><ul><ul><li>hCG = 2.06 MoM </li></ul></ul><ul><ul><li>uE3 = 0.75 MoM </li></ul></ul><ul><ul><li>Inhibin A = 1.77 MoM </li></ul></ul><ul><li>Quad screen profile in Trisomy 18 </li></ul><ul><ul><li>AFP, HCG, and uE3 levels all reduced </li></ul></ul><ul><ul><li>Inhibin A not used </li></ul></ul>
    7. 7. Maternal Age Counseling <ul><li>Increasing age associated with increased risk of the baby having abnormalities in number of chromosomes </li></ul>
    8. 8. What are chromosomes? <ul><li>Packaging for genetic (inherited) information in a cell </li></ul><ul><ul><li>Chromosomes are like filing cabinet drawers packed with pieces of paper, where each piece of paper is a gene </li></ul></ul><ul><ul><ul><li>Each chromosome is in a pair, one of which comes from mother and the other from father </li></ul></ul></ul><ul><ul><li>The number and shape of the chromosomes are critically important </li></ul></ul>
    9. 11. Chromosome abnormalities <ul><li>Having an extra chromosome or a missing chromosome means the body has too much or too little genetic information </li></ul><ul><li>If the baby has an extra one of the very big or gene rich chromosomes, there is usually a very early miscarriage </li></ul><ul><li>Pregnancies which have extra chromosomes 21, 13, or 18 may have live born babies who have serious problems </li></ul>
    10. 12. Extra chromosome 21--Down syndrome
    11. 13. Extra chromosome 18—Trisomy 18
    12. 14. What can be done to test for chromosome abnormalities? <ul><li>Screening tests </li></ul><ul><ul><li>1 st trimester </li></ul></ul><ul><ul><li>2 nd trimester </li></ul></ul><ul><li>Diagnostic tests </li></ul><ul><ul><li>1 st trimester </li></ul></ul><ul><ul><li>2 nd trimester </li></ul></ul>
    13. 15. What is quad screen testing? <ul><li>A blood test done between 14-20 weeks gestation </li></ul><ul><li>It measures four proteins found in your blood which actually are passed from the baby or the placenta into your blood stream </li></ul><ul><ul><li>Alpha fetoprotein (AFP) </li></ul></ul><ul><ul><li>Human chorionic gonadotropin (HCG) </li></ul></ul><ul><ul><li>Unconjugated estriol (uE3) </li></ul></ul><ul><ul><li>Inhibin A </li></ul></ul>
    14. 16. What do the results mean? <ul><li>Quad screen gives three pieces of information </li></ul><ul><ul><li>Risk for baby to have an open spine </li></ul></ul><ul><ul><li>Risk for baby to have an extra chromosome 18 </li></ul></ul><ul><ul><li>Risk for baby to have an extra chromosome 21 </li></ul></ul><ul><ul><ul><li>Given in a number: Ex: 1/400, 1/1000 </li></ul></ul></ul><ul><ul><ul><li>If greater than risk for a woman age 35 to have a baby with Down syndrome or Trisomy 21 (1/270), the test is called positive </li></ul></ul></ul>
    15. 17. Can the test say exactly what my baby has? <ul><li>No! </li></ul><ul><li>It can only say whether you have a higher or lower risk of the problem than was originally thought </li></ul><ul><li>IT IS NOT AN EXACT TEST! </li></ul>
    16. 18. Does the quad screen test find all babies with the problems? <ul><li>The quad screen will identify </li></ul><ul><ul><li>90-100% of babies with open spines or brains </li></ul></ul><ul><ul><li>75% of babies with openings in the abdomen </li></ul></ul><ul><ul><li>81% of babies with Down syndrome </li></ul></ul><ul><li>It can miss some babies with Down syndrome </li></ul>
    17. 19. Does the quad screen test look for all types of abnormalities? <ul><li>No </li></ul><ul><li>Only identifies babies with open spines or abdomens, trisomy 18, or trisomy 21 </li></ul><ul><li>It is not designed to identify babies with heart, kidney, or arm or leg problems </li></ul><ul><li>It cannot identify all kinds of mental retardation </li></ul>
    18. 20. Do I have to have a quad screen? <ul><li>No, it is your choice </li></ul><ul><li>95% of mothers will have a normal test and may feel reassured about their pregnancy </li></ul><ul><li>5% will have a positive test and will need some additional evaluation </li></ul><ul><ul><li>Of those who are positive, only 1 in 20 will in fact have a baby with Down syndrome </li></ul></ul>
    19. 21. You receive the following quad screen results for a 41 yo G2P1 <ul><li>Screen POSITIVE for Down Syndrome </li></ul><ul><li>Quad screen ONTD Risk <1:5000 </li></ul><ul><li>Age Risk Down Syndrome 1:76 </li></ul><ul><li>Quad screen Down Risk 1:265 </li></ul><ul><li>Quad screen Trisomy 18 Risk 1:1663 </li></ul>
    20. 22. What happens if my test is positive? <ul><li>Test may be positive because dates are wrong </li></ul><ul><ul><li>Test done between 14-20 weeks </li></ul></ul><ul><ul><li>Usually first ultrasound is used to date your pregnancy </li></ul></ul><ul><ul><li>If you haven’t had an ultrasound, your test may be corrected just by doing an ultrasound and correcting your dates </li></ul></ul>
    21. 23. What if my test is positive and my dates are correct? <ul><li>The next step is to do a detailed ultrasound (called a targeted or level II) to look at the baby </li></ul><ul><ul><li>The ultrasound can pick up over 95% of all problems with the baby’s spine or abdomen </li></ul></ul><ul><ul><li>It can also look for other abnormalities or changes in the baby which might suggest a greater chance of Down syndrome or Trisomy 18 </li></ul></ul>
    22. 24. What are ultrasound markers? <ul><li>Early 1990’s - “genetic ultrasound” </li></ul><ul><li>Sonographic markers for aneuploidy </li></ul><ul><ul><li>Short humerus </li></ul></ul><ul><ul><li>Short femur </li></ul></ul><ul><ul><li>Pyelectasis </li></ul></ul><ul><ul><li>Echogenic bowel </li></ul></ul><ul><ul><li>Echogenic intracardiac focus </li></ul></ul><ul><ul><li>Nuchal thickening </li></ul></ul><ul><li>Addition genetic US quad screen increases trisomy 21 detection rate to 90% </li></ul>
    23. 25. Does the ultrasound give 100% answers? <ul><li>No </li></ul><ul><li>The ultrasound needs to be done by an experienced person who has a good ultrasound machine </li></ul><ul><ul><li>If no problems are seen in the detailed ultrasound the chance for the baby to have a birth defect is reduced, but not zero </li></ul></ul>
    24. 26. Who needs a 100% answer? <ul><li>Some people need to have as much information as possible about their babies because that information may influence what they would do in their pregnancy </li></ul><ul><li>Some people need to know for planning purposes </li></ul>
    25. 27. How to get a 100% answer <ul><li>A test called an amniocentesis can be offered </li></ul><ul><ul><li>Takes small sample of fluid from around the baby by passing a thin needle through the mother’s abdomen into the sac around the baby </li></ul></ul><ul><ul><ul><li>The fluid has some of baby’s cells in it, so the baby’s chromosomes can be counted </li></ul></ul></ul><ul><ul><ul><li>Proteins in the fluid which suggest an open spine can also be measured </li></ul></ul></ul>
    26. 28. Is that a risky test? <ul><li>Amniocentesis is a very safe test and has been done for over 50 years </li></ul><ul><li>15-20 weeks </li></ul><ul><li>Earlier amniocentesis results in significantly higher rates of pregnancy loss and complications </li></ul><ul><li>Procedure-related loss rate at 15-20 weeks as low as 1 in 300–500 </li></ul><ul><ul><li>May be even lower with experienced individuals or centers </li></ul></ul>
    27. 29. Prenatal Diagnosis of Aneuploidy
    28. 30. Prenatal Diagnosis of Aneuploidy
    29. 31. Is the amniocentesis reliable? <ul><li>Yes </li></ul><ul><li>If it says there is no problem, there is no problem </li></ul><ul><li>If it says the baby has a chromosome problem, then there is truly a problem </li></ul>
    30. 32. Do I have to have an amniocentesis? <ul><li>No </li></ul><ul><li>It is only offered as a way to get the most possible information about the baby </li></ul><ul><li>Not everyone wants or needs that information </li></ul><ul><li>If you didn’t want an amniocentesis, you would still get the same careful prenatal care </li></ul>
    31. 33. Nuchal translucency <ul><li>Mid-1990’s - strong association between size fluid collection at back fetal neck in 1 st trimester, “nuchal translucency,” and risk of trisomy 21 </li></ul><ul><li>Increased NT now recognized as early presenting feature of broad range of fetal chromosomal, genetic, and structural abnormalities </li></ul>
    32. 34. Nuchal Translucency www.mums.me.uk/nuchal.htm Dr Eva Pajkrt, University of Amsterdam
    33. 35. Normal Nuchal Translucency Measurement
    34. 36. Increased Nuchal Translucency Measurement
    35. 37. 1 st Trimester Aneuploidy Screening <ul><li>Around this same time period 1 st trimester analytes recognized </li></ul><ul><ul><li>Free  -HCG elevated to 1.98MoM </li></ul></ul><ul><ul><li>Pregnancy-associated plasma protein A (PAPP-A) reduced to 0.43MoM </li></ul></ul><ul><li>Used alone, 1st trimester serum analytes detect 65% of trisomy 21 </li></ul><ul><li>Combined with NT, 82-87% of trisomy 21 fetuses detected </li></ul>
    36. 38. Should I get the first trimester test or the quad screen? <ul><li>Advantage of 1st trimester screening </li></ul><ul><ul><li>Women who present before 14 wks have information sooner </li></ul></ul><ul><ul><li>Can be offered genetic counseling and chorionic villus sampling (CVS) </li></ul></ul>
    37. 39. What is CVS? <ul><li>CVS </li></ul><ul><ul><li>Placental villi obtained through a transcervical or transabdominal approach </li></ul></ul><ul><ul><li>Performed after 9 completed weeks - 13th weeks </li></ul></ul><ul><ul><li>Primary advantage over amniocentesis is earlier results </li></ul></ul><ul><ul><ul><li>Earlier reassurance for when results normal </li></ul></ul></ul><ul><ul><ul><li>Allow for earlier and safer methods of pregnancy termination when results are abnormal </li></ul></ul></ul>
    38. 40. Is CVS riskier than amniocentesis? <ul><li>Overall pregnancy loss rate after CVS is greater than after amniocentesis </li></ul><ul><ul><li>increased background rate of spontaneous pregnancy loss 9-16 weeks </li></ul></ul><ul><li>In experienced hands, the CVS loss rate appears to approach rate for midtrimester amniocentesis </li></ul><ul><li>No difference in loss rates after transcervical or transabdominal CVS </li></ul><ul><li>Transverse limb deficiencies more common performed before 9 weeks </li></ul>
    39. 41. What are the complications from CVS? <ul><li>Other CVS complications </li></ul><ul><ul><li>Vaginal spotting or bleeding </li></ul></ul><ul><ul><ul><li>in up to 32.2% of transcervical CVS patients </li></ul></ul></ul><ul><ul><li>Culture failure, amniotic fluid leakage, and infection (< 0.5%) </li></ul></ul><ul><ul><li>Chromosomal mosaicism (1%) </li></ul></ul><ul><ul><ul><li>amniocentesis performed at 15-20 weeks to assess whether mosaicism is present in amniocytes </li></ul></ul></ul><ul><ul><ul><li>amniocentesis result usually normal, and the mosaicism is assumed to be confined to the trophoblast </li></ul></ul></ul><ul><ul><ul><li>unlikely to cause defects but may result in 3 rd trimester growth restriction </li></ul></ul></ul>
    40. 42. Prenatal Diagnosis of Aneuploidy
    41. 43. What tests should be done after 1 st trimester screening or CVS? <ul><li>1 st trimester screening does not include MSAFP </li></ul><ul><ul><li>Neural tube defect screening by 2nd-tri MSAFP screening or US </li></ul></ul><ul><li>NT > 3.5 mm with negative result on aneuploidy screen, normal fetal chromosomes, or both, at risk for </li></ul><ul><ul><li>Nonchromosomal anomalies </li></ul></ul><ul><ul><li>Congenital heart defects </li></ul></ul><ul><ul><li>Abdominal wall defects </li></ul></ul><ul><ul><li>Diaphragmatic hernias </li></ul></ul><ul><ul><li>Genetic syndromes </li></ul></ul>
    42. 44. Can other information be gained from 1 st trimester screening? <ul><li>Abnormal 1st-trimester serum markers or increased NT may also increased risk for adverse pregnancy outcome </li></ul><ul><ul><li>Fetal loss before 24 weeks </li></ul></ul><ul><ul><li>IUFD </li></ul></ul><ul><ul><li>IUGR </li></ul></ul><ul><ul><li>Preterm birth </li></ul></ul><ul><li>NT > 3.5 mm should be offered: </li></ul><ul><ul><li>Targeted ultrasound examination </li></ul></ul><ul><ul><li>Fetal echocardiogram </li></ul></ul><ul><ul><li>Genetic counseling </li></ul></ul>
    43. 45. Aneuploidy Screening *87% at 11 wks, 85% at 12 wks, 82% at 13 wks Test Trisomy 21 Detection Rate FPR Triple screen 70% 5% Quad screen 81% 5% Quad + genetic US 90% 3.1% NT alone 64-70% 5% PAPP-A + free  -HCG 65% 5% NT + PAPP-A + HCG 82-87%* 5%
    44. 46. Aneuploidy Screening <ul><li>ACOG recommendations (Jan 2007) </li></ul><ul><ul><li>All women be offered aneuploidy screening, regardless of age </li></ul></ul><ul><ul><li>A strategy which incorporates both 1st and 2nd trimester screening be offered to women who present in the 1 st trimester </li></ul></ul>
    45. 47. Prenatal Diagnosis of Aneuploidy <ul><li>Criteria for invasive testing traditionally maternal age </li></ul><ul><li>ACOG Practice Bulletin (December 2007) </li></ul><ul><ul><li>“ Invasive diagnostic testing for aneuploidy should be available to all women, regardless of maternal age.” </li></ul></ul><ul><ul><li>Many factors influence a woman’s decision </li></ul></ul><ul><ul><ul><li>Risk fetus will have a chromosomal abnormality </li></ul></ul></ul><ul><ul><ul><li>Risk of pregnancy loss from procedure </li></ul></ul></ul><ul><ul><ul><li>Consequences of having an affected child </li></ul></ul></ul><ul><ul><li>Recent studies suggest lower loss rates </li></ul></ul><ul><ul><ul><li>Older studies performed prior to concurrent use of high-resolution US </li></ul></ul></ul>
    46. 48. Aneuploidy Screening *Best when 1st trimester screen at 11 wks Screening method Trisomy 21 detection FPR Comments Serum Integrated 85-88%* 5% No 1st tri detection, no NT 100% get 2nd tri screen Integrated 94-96%* 5% No 1st tri detection, with NT 100% get 2nd tri screen Sequential 95%* 5% 2% require CVS 98% get 2nd tri screen Contingent 88-94%* 4% 2% require CVS Only 22% get 2nd tri screen 3% require amnio
    47. 49. Aneuploidy Screening <ul><li>So which screening test(s) should be offered?!! </li></ul>
    48. 50. Aneuploidy Screening <ul><li>Before deciding which strategy or strategies to offer your patients </li></ul><ul><ul><li>Identify tests available in your area </li></ul></ul><ul><ul><li>Determine which strategy or strategies will best meet your needs and the needs of your patients </li></ul></ul><ul><li>Women first seen during 2nd trimester </li></ul><ul><ul><li>Options limited to quad screen and genetic ultrasound </li></ul></ul>
    49. 51. Aneuploidy Screening <ul><li>Women who present in the 1st trimester </li></ul><ul><ul><li>Strategy incorporating both 1st and 2 nd trimester screening should be offered </li></ul></ul><ul><li>If CVS is not available </li></ul><ul><ul><li>Offer integrated screening to patients who present in 1st trimester in order to take advantage of improved detection rate and low false-positive rate </li></ul></ul><ul><ul><li>Offer 2 nd trimester screening to patients who present after 13-6/7 weeks </li></ul></ul>
    50. 52. Aneuploidy Screening <ul><li>If NT measurement is not available or cannot be obtained in an individual </li></ul><ul><ul><li>Offer serum integrated screening to patients who present early and 2 nd trimester screening to those who present later </li></ul></ul><ul><li>Counsel about screening strategy or strategies used </li></ul><ul><ul><li>Detection rates </li></ul></ul><ul><ul><li>False-positive rates </li></ul></ul>
    51. 53. Aneuploidy Screening <ul><li>Reporting results to patients </li></ul><ul><ul><li>Provide numerical risk (rather than positive versus negative) </li></ul></ul><ul><ul><li>Contrast this risk with general population risk and age-related risk </li></ul></ul>
    52. 54. Summary <ul><ul><li>1st and 2 nd trimester screening tests for fetal chromosomal abnormalities, correct timing for, and associated sensitivities of these tests </li></ul></ul><ul><ul><li>Options for screening tests that combine 1st and 2nd trimester results </li></ul></ul><ul><ul><li>Options for 1st and 2nd trimester prenatal diagnosis of aneuploidy, correct timing and associated loss rates </li></ul></ul>
    53. 55. <ul><li>Questions??? </li></ul>
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