California Prenatal Screening California Prenatal Screening ProgramProgram

CPSPCPSPFIRST TRIMESTER COMBINED = FIRST TRIMESTER COMBINED = NTNT Plus 1 Plus 1stst Trimester AnalytesTrimester Analytes

FULL INTEGRATED = FULL INTEGRATED = NTNT Plus 1st & 2 Plus 1st & 2ndnd Trimester Trimester AnalytesAnalytes

SERUM INTERGRATED = 1st & 2SERUM INTERGRATED = 1st & 2ndnd Trimester Analytes Trimester Analytes OnlyOnly

QUAD SCREEN ONLY = 2QUAD SCREEN ONLY = 2ndnd Trimester Analytes Only Trimester Analytes Only

NUCHAL TRANSLUCENCY NUCHAL TRANSLUCENCY (NT) What Is It?(NT) What Is It?

NT is the sonolucent zone at the posterior NT is the sonolucent zone at the posterior aspect of the fetal neck. This space aspect of the fetal neck. This space represents the sonographic appearance of represents the sonographic appearance of subcutaneous fluid behind the fetal neck.subcutaneous fluid behind the fetal neck.

Sonographic Appearance Sonographic Appearance of NTof NT

NUCHAL NUCHAL TRANSLUCENCYTRANSLUCENCY

“Normal” Size Changes “Normal” Size Changes with Gestational Agewith Gestational Age

The “normal” nuchal translucency The “normal” nuchal translucency increases with gestational ageincreases with gestational age

The NT measurement can only be The NT measurement can only be performed with a CRL of 45 mm to performed with a CRL of 45 mm to 84 mm. 84 mm.

~11 ½ weeks to ~14 weeks EGA~11 ½ weeks to ~14 weeks EGA

NUCHAL NUCHAL TRANSLUCENCYTRANSLUCENCYIncreases with Increases with

Gestational AgeGestational AgeMedianMedian

(mm)(mm)95 percentile95 percentile

(mm)(mm)

11 11 22//7 7 weeksweeks

45mm45mm 1.21.2 2.12.1CRLCRL

14 14 22//7 7 weeksweeks

84mm84mm 1.91.9 2.72.7CRLCRL• 3.4 mm is the 99 percentile for all gestational ages up to 14 weeks

NUCHAL TRANSLUCENCY NUCHAL TRANSLUCENCY (NT)(NT)

Why Measure It?Why Measure It? The risk of fetal The risk of fetal GENETICGENETIC AND AND ANATOMICANATOMIC

birth defectsbirth defects increases increases as the as the nuchal nuchal translucencytranslucency increases.increases.

More sensitiveMore sensitive & & comprehensivecomprehensive than than maternal serum analytes alone because an maternal serum analytes alone because an Abnormal NT will detectAbnormal NT will detect chromosomal chromosomal abnormalitiesabnormalities not detected by not detected by analytesanalytes

T13T13Turners SyndromeTurners SyndromeTriploidyTriploidySex Chromosome Sex Chromosome abnormalitiesabnormalities

NUCHAL TRANSLUCENCYNUCHAL TRANSLUCENCYIncrease Size of NTIncrease Size of NT

Increase Risk of Genetic Birth Increase Risk of Genetic Birth DefectDefect

NT size mmNT size mm ½ are T21½ are T2199 percentile = 3.4 mm99 percentile = 3.4 mm

(mm)(mm)½ are T 13, 18, 45x, ½ are T 13, 18, 45x,

TriploidyTriploidy (%)(%)

2.5 – 3.42.5 – 3.4 77

3.5 – 4.43.5 – 4.4 2020

4.5 – 5.44.5 – 5.4 3030

5.5 – 6.45.5 – 6.4 5050

≥ ≥ 6.56.5 6565

> 8.5> 8.5 7575

Obstet Gynecol:2006;107:6Obstet Gynecol:2006;107:6

NUCHAL TRANSLUCENCY NUCHAL TRANSLUCENCY (NT)(NT)

Why Measure It?Why Measure It?

ABNORMAL NT IS ASSOCIATED ABNORMAL NT IS ASSOCIATED

WITH WITH ANATOMICAL ANATOMICAL DEFECTSDEFECTS NOT DETECTED BY NOT DETECTED BY SERUM SCREENINGSERUM SCREENING

NUCHAL TRANSLUCENCYNUCHAL TRANSLUCENCYIncreased NT with Normal Increased NT with Normal

Chromosomes Chromosomes Increased Risk of Cardiac or Increased Risk of Cardiac or

Other Major ANATOMIC Other Major ANATOMIC ANOMALIESANOMALIES

NT size mmNT size mm CardiacCardiac//Other Other MajorMajor

% % // % %

2.5 – 3.42.5 – 3.4 1 1 // 1 1

3.5 – 4.43.5 – 4.4 3 3 // 10 10

4.5 – 5.44.5 – 5.4 7 7 // 20 20

5.5 – 6.45.5 – 6.4 20 20 / / 25 25

> 6.5> 6.5 30 30 // 45 45Souka AJOG 2005 ; 192: 1005Souka AJOG 2005 ; 192: 1005

NUCHAL NUCHAL TRANSLUCENCY TRANSLUCENCY Why Measure It? Why Measure It? Increases Sensitivity vs Increases Sensitivity vs Maternal AnalytesMaternal Analytes QUAD screenQUAD screen < 35yo will < 35yo will

detectdetect 68%68% of T21 at 16 weeks. of T21 at 16 weeks.

SERUM INTEGRATEDSERUM INTEGRATED < 35yo will < 35yo will

detectdetect 77 %77 % of T21 at 16 weeks. of T21 at 16 weeks.

FULL INTEGRATEDFULL INTEGRATED < 35yo will < 35yo will

detect detect 85%85% of T21 at 16 weeks. of T21 at 16 weeks.

NUCHAL TRANSLUCENCY NUCHAL TRANSLUCENCY Why Measure It?Why Measure It?

Earlier results with analytes drawn as early as Earlier results with analytes drawn as early as 10 weeks 0 days & NT performed @ 11 1/2 10 weeks 0 days & NT performed @ 11 1/2 weeks. The CPSP allows an weeks. The CPSP allows an Instant Risk Instant Risk CalculationCalculation with the addition of the NT with the addition of the NT measurement when analytes are available.measurement when analytes are available.

If a woman is found to be at an increased risk for fetal aneuploidy, she can be offered genetic counseling and choose to proceed with CVS as early as 11 ½ weeks providing chromosome results @ 12 ½ weeks EGA

COMPLETE THE COMPLETE THE SCREENINGSCREENING

For women < 35 yo tFor women < 35 yo the first trimester combined result is PRELIMINARY and will detect ~ 62% of babies affected with a Down syndrome utilizing the CPSP screen positive cut off of 1 %.

To complete the full integrated CPSP program a second blood test ( Quad Screen) is required between 15 and 20 weeks which allows the test to detect an additional 20 % or more of Down syndrome babies for a final detection rate of ~ 85 %.

Overall < 5 % of patients may have a positive test in the second trimester indicating an increased risk for a genetic birth defect.

NT MORE THAN 99 PERCENTILE NT MORE THAN 99 PERCENTILE 3.5 OR MORE FROM 45-84 MM3.5 OR MORE FROM 45-84 MM

NT > 99 % tile @ 3.5 mm NT > 99 % tile @ 3.5 mm or moreor more

By Early spring 2011 an By Early spring 2011 an NT of 3.5 NT of 3.5 alonealone will be considered screen positive will be considered screen positive by the CPSP with no maternal analyte by the CPSP with no maternal analyte testing recommended for aneuploidy.testing recommended for aneuploidy.

The result will be The result will be screen positive @ screen positive @ 1/51/5 and remain screen positive @ 1/5 and remain screen positive @ 1/5 regardless of additional maternal regardless of additional maternal analyte results.analyte results.

AFP and SLOS testing is still AFP and SLOS testing is still recommended between 15-20 weeks.recommended between 15-20 weeks.

NT 3.5 mm or GreaterNT 3.5 mm or GreaterLevel 2 Sono and Fetal Echo Level 2 Sono and Fetal Echo

Recommended by ACOG & CPSPRecommended by ACOG & CPSP Chromosomal abnormalitiesChromosomal abnormalities Genetic syndromesGenetic syndromes Cardiac AnomaliesCardiac Anomalies Other structural anomaliesOther structural anomalies Fetal InfectionFetal Infection Fetal AnemiaFetal Anemia Fetal Hypoproteinemia Fetal Hypoproteinemia Souka AJOG 2005;192:1005-21 Kagan Obstet Gynecol 2006;107:6Souka AJOG 2005;192:1005-21 Kagan Obstet Gynecol 2006;107:6

CYSTIC HYGROMACYSTIC HYGROMA50% RISK OF 50% RISK OF ANEUPLOIDYANEUPLOIDY

Other Sono Markers to Other Sono Markers to evaluate evaluate

T13 T 18T13 T 18

MEGACYSTIS

20% ANEUPLOIDY

OMPHALOCELE

60% ANEUPLOIDY

First TrimesterFirst TrimesterSerum AnalytesSerum Analytes

PAPP -A PAPP -A Low levels in the first trimester have been Low levels in the first trimester have been associated with preeclampsia, fetal growth restriction, associated with preeclampsia, fetal growth restriction, preterm birth, and fetal demise. PAPP-A levels less than preterm birth, and fetal demise. PAPP-A levels less than the 5%tile are associated with a 1 to 4 %risk of pregnancy the 5%tile are associated with a 1 to 4 %risk of pregnancy loss before 20 weeks, and increased risk of IUGR wit a PPV loss before 20 weeks, and increased risk of IUGR wit a PPV

of up to 24%.of up to 24%.

hHCGhHCG Low levels (below the 5%tile) in the first Low levels (below the 5%tile) in the first trimester have been associated with a 1-4% risk of trimester have been associated with a 1-4% risk of pregnancy loss before 20 weeks. hHcg levels below the pregnancy loss before 20 weeks. hHcg levels below the 1%tile have been associated with significantly increase 1%tile have been associated with significantly increase drisk of IUGR with a PPV of 14%.drisk of IUGR with a PPV of 14%.

First Trimester First Trimester Serum AnalytesSerum Analytes

PAPP-A levels <5%tile (<0.38 MOM) PAPP-A levels <5%tile (<0.38 MOM) Serial ultrasounds at 26 and 32 weeksSerial ultrasounds at 26 and 32 weeks Maternal education regarding s/s of PTLMaternal education regarding s/s of PTL Heightened clinical awareness of Heightened clinical awareness of

development of PIH and IUGRdevelopment of PIH and IUGR Consider follow up appointments every 2 Consider follow up appointments every 2

weeks after 20 weeks due to prematurityweeks after 20 weeks due to prematurity Consider referral to perinatologist if Consider referral to perinatologist if

concerns developconcerns develop

First TrimesterFirst TrimesterSerum analytesSerum analytes

PAPP-A <1PAPP-A <1stst %tile (<0.23 MOM) %tile (<0.23 MOM) Serial ultrasound examinations monthly Serial ultrasound examinations monthly

starting at 24 weeksstarting at 24 weeks Maternal education regarding s/s of PTLMaternal education regarding s/s of PTL Heightened clinical awareness of Heightened clinical awareness of

development of PIH and IUGRdevelopment of PIH and IUGR Serial antenatal testing beginning at 32-34 Serial antenatal testing beginning at 32-34

weeksweeks Consider follow up appointments every 2 Consider follow up appointments every 2

weeks after 20 weeks due to prematurity. weeks after 20 weeks due to prematurity. Refer to perinatology if concerns developRefer to perinatology if concerns develop

First Trimester First Trimester Serum AnalytesSerum Analytes

hHcg <1hHcg <1stst%tile (0.38 MOM)%tile (0.38 MOM) Serial ultrasound examinations at 26 Serial ultrasound examinations at 26

and 32 weeksand 32 weeks Maternal education regarding s/s PTLMaternal education regarding s/s PTL Consider appointments every 2 weeks Consider appointments every 2 weeks

after 20 weeksafter 20 weeks Refer to perinatology if concerns Refer to perinatology if concerns

developdevelop