1. Objectives Goals of the 11-14 week scanGoals of the 11-14 week scan Fetal nuchal translucency in the detection of aneuploidyFetal nuchal translucency in the detection of aneuploidy The value of first trimester maternal serum markers in the detection of aneuploidyThe value of first trimester maternal serum markers in the detection of aneuploidy Criteria for measurement of fetal nuchal translucencyCriteria for measurement of fetal nuchal translucency Pitfalls in the measurement of fetal nuchal translucencyPitfalls in the measurement of fetal nuchal translucency The significance of an increased nuchal translucency with a normal karyotypeThe significance of an increased nuchal translucency with a normal karyotype Management of an increased nuchal translucencyManagement of an increased nuchal translucency Quality control of a nuchal translucency screening programQuality control of a nuchal translucency screening program Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004 Edchen99 提供 www.myfetus.net

2. The goals of the 11-14 weeks scan Screening for trisomy 21 and other major chromosomal defectsScreening for trisomy 21 and other major chromosomal defects Early diagnosis of major abnormalities, e.g. anencephaly, exomphalosEarly diagnosis of major abnormalities, e.g. anencephaly, exomphalos Diagnosis of twins in about 2% of pregnancies & determination of chorionicityDiagnosis of twins in about 2% of pregnancies & determination of chorionicity Diagnosis of missed miscarriage in about 3% of pregnanciesDiagnosis of missed miscarriage in about 3% of pregnancies Early and accurate dating of pregnancyEarly and accurate dating of pregnancy Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

3. In normal pregnancies, fetal NT thickness increases with gestation In normal pregnancies, fetal NT thickness increases with gestation In trisomy 21 pregnancies fetal NT is increased (above the 95 th centile in about 75% of cases) In trisomy 21 pregnancies fetal NT is increased (above the 95 th centile in about 75% of cases) Nuchal translucency as a function of crown-rump length (gestational age) Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004 Trisomy 21

4. The risk for trisomy 21 is derived by multiplying the a priori maternal age and gestation-related risk by a likelihood ratio (LR)The risk for trisomy 21 is derived by multiplying the a priori maternal age and gestation-related risk by a likelihood ratio (LR) The LR depends on the degree of deviation in fetal NT from the expected normal median for that crown–rump length. The LR depends on the degree of deviation in fetal NT from the expected normal median for that crown–rump length. Screening for trisomy 21 Assessment of risk by maternal age and fetal nuchal translucency Risk (%) Maternal age 30354045 100 10 1 0.1 2025 0.01 A priori risk NT NT Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

5. 20 0 2 4 6 8 10 12 14 16 18 -3.5-2.5-1.5-0.50.51.52.5 PAPP-A (SD) % Normal PAPP-A 0 2 4 6 8 10 12 14 16 18 20 -3.5-2.5-1.5-0.50.51.52.53.5 Free ßhCG (SD) % Normal Free  hCG Trisomy 21 Risk assessment with maternal serum free ß-hCG & PAPP-A Trisomy 21 Alterations in maternal serum biochemistry are independent of fetal NT thicknessAlterations in maternal serum biochemistry are independent of fetal NT thickness Screening for trisomy 21 by a combination of fetal NT and maternal serum free ß-hCG and PAPP-A can identify about 90% of affected fetuses for a false positive rate of 5%.Screening for trisomy 21 by a combination of fetal NT and maternal serum free ß-hCG and PAPP-A can identify about 90% of affected fetuses for a false positive rate of 5%. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

6. 100,000 pregnancies Maternal age 60 30% Serum biochemistry at 16 wks 130 65% Nuchal translucency (NT) at 12 wks 75% 150 Fetal NT & ß-hCG & PAPP- A at 12 wks 180 90% Screening for trisomy 21 Effectiveness of different methods of screening Method of screening Number detected Detection rate Screen positive 5% N=5,000 Trisomy 21 N=200 Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

7. Maternal serum biochemistry and ultrasound parameters in the detection of chromosomal abnormalities other than trisomy 21 Fetal heart rate Crown-rump length Increased NT Ultrasound markers Free ß-hCG PAPP-A Trisomy 18 75% Exomphalos Single umbilical artery  X0 (Turner) 87% Trisomy 13 72% MegacystisHoloprosencephaly  Triploidy59% Small / molar placenta  / / / /  / / / / Screening for trisomy 21 by a combination of fetal nuchal translucency and maternal serum free ß-hCG and PAPP-A can also identify about 90% of fetuses with other major chromosomal defectsScreening for trisomy 21 by a combination of fetal nuchal translucency and maternal serum free ß-hCG and PAPP-A can also identify about 90% of fetuses with other major chromosomal defects Each of these chromosomal defects is associated with its own syndromal pattern of sonographic and biochemical markersEach of these chromosomal defects is associated with its own syndromal pattern of sonographic and biochemical markers Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

8. Frequency of death and/or major anomaly in fetuses with an increased nuchal translucency and a normal karyotype Death or major anomaly 69% > 6.5 mm 14% 3.5-4.42.5-3.4NT 3% 5.5-6.4 33% 4.5-5.4 23% Souka et al. Ultrasound Obstet Gynecol 2001;18:9-17; n=1,320 Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

9. AchondrogenesisAchondroplasia Asphyxiating thoracic dystrophy Blomstrand osteochondrodysplasia Campomelic dysplasia Hypophosphatasia Jarcho-Levin syndrome Nance-Sweeney syndrome Osteogenesis imperfecta Roberts syndrome Short-rib-polydactily syndrome Sirenomelia Thanatophoric dysplasia CraniosynostosisIniencephalyAgnathia/micrognathia Cardiac defects Diaphragmatic hernia ExomphalosMegacystis Renal agenesis Polycystic kidneys Multicystic kidneys Nephrotic syndrome Body stalk anomaly Congenital lymphedema Akinesia deformation sequence Myotonic dystrophy Spinal muscular atrophy Beckwith-Wiedemman syndrome GM1-gangliosidosis Mucopolysaccharidosis type VII Smith-Lemli-Opitz syndrome Vitamin D resistant rickets Zellweger syndrome Blackfan Diamond anaemia Dyserythropoietic anaemia Thalassaemia-  Parvovirus B19 infection Brachmann-de Lange syndrome Charge association di George syndrome EEC syndrome Fryn syndrome Noonan syndrome Perlman syndrome Stickler syndrome Treacher-Collins syndrome Trigonocephaly C syndrome VACTER association Conditions associated with increased nuchal translucency and normal karyotype Souka et al. Ultrasound Obstet Gynecol 2001;18:9-17 Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

10. 11-14 weeks Fetal karyotyping Anomaly scan Chromosomal defects Major abnormalities Normal karyotype No abnormalities 14-16 weeks Anomaly scan Echocardiography No abnormalities Resolving nuchal Major abnormalities No abnormalities Persistent nuchal TORCH & Parvovirus screen Genetic testing 20 weeks Anomaly scan Echocardiography No abnormalities Major abnormalities No abnormalities Persistent nuchal TORCH & Parvovirus screen Genetic testing Proposed management of increased nuchal translucency Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

11.  Dichorionic 80%  Monochorionic 20% Diagnosis of monochorionic or dichorionic twins Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

12. Frequency of complications as a function of chorionicity in twin gestations 2%12% Miscarriage (11-23 weeks) 1.5%3% Perinatal death (>23 weeks) 10%20% Fetal growth restriction 5%10% Preterm delivery (<32 weeks) DichorionicMonochorionic Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

13. Twins gestation Determine chorionicityDetermine chorionicity Measure nuchal translucency (NT) in each fetusMeasure nuchal translucency (NT) in each fetus Calculate the combined maternal age and fetal NT risk for each fetusCalculate the combined maternal age and fetal NT risk for each fetus The risk can be adjusted by multiplying with the likelihood ratio derived from maternal serum free ß-hCG and PAPP-AThe risk can be adjusted by multiplying with the likelihood ratio derived from maternal serum free ß-hCG and PAPP-A Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

14. Twin gestation: counselling Dichorionic twins Counsel the parents on the risks of having one or two affected fetuses Counsel the parents on the risks of having one or two affected fetuses If parents choose invasive testing the preferred option is chorionic villous sampling, because if one fetus is affected and the parents want selective fetocide the risk of miscarriage is considerably lower if fetocide is performed in the first rather than the second trimester If parents choose invasive testing the preferred option is chorionic villous sampling, because if one fetus is affected and the parents want selective fetocide the risk of miscarriage is considerably lower if fetocide is performed in the first rather than the second trimester Monochorionic twins Counsel the parents that the risk of both fetuses being affected is the average one derived from that calculated for each fetus Counsel the parents that the risk of both fetuses being affected is the average one derived from that calculated for each fetus If parents choose invasive testing the preferred option is chorionic villous sampling, because if the fetuses are affected the parents can have early termination If parents choose invasive testing the preferred option is chorionic villous sampling, because if the fetuses are affected the parents can have early termination If there is a large discordancy in NT between the two fetuses consider the diagnosis of twin-to-twin transfusion syndrome If there is a large discordancy in NT between the two fetuses consider the diagnosis of twin-to-twin transfusion syndrome Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

15. Theoretical course & examination Theoretical course & examination Practical training Practical training Logbook of 10 images Logbook of 10 images Install software for risk assessment Yearly audit Yearly audit Distribution of NTs Distribution of NTs Quality of 5 images Quality of 5 images Training and quality assurance in the 11-14 weeks scan by the Fetal Medicine Foundation Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

16. Principles of screening, pre-test and post-test counselling. Principles of screening, pre-test and post-test counselling. Amniocentesis and chorionic villus sampling. Fetal cells and free DNA in maternal blood. Amniocentesis and chorionic villus sampling. Fetal cells and free DNA in maternal blood. FMF guidelines on the measurement of NT. FMF guidelines on the measurement of NT. Screening for chromosomal defects by fetal NT and maternal serum biochemistry. Screening for chromosomal defects by fetal NT and maternal serum biochemistry. Management of pregnancies with increased NT after the diagnosis of normal karyotype. Management of pregnancies with increased NT after the diagnosis of normal karyotype. Diagnosis and management of major fetal defects, such as anencephaly & exomphalos Diagnosis and management of major fetal defects, such as anencephaly & exomphalos These are found in about 1% of pregnancies Diagnosis of multiple pregnancies, determination of chorionicity and management. Diagnosis of multiple pregnancies, determination of chorionicity and management. These are found in about 2% of pregnancies. Diagnosis and management of missed miscarriage detected at the 11-14 weeks scan Diagnosis and management of missed miscarriage detected at the 11-14 weeks scan This is found in about 3% of pregnancies. Theoretical course: content Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

17. Gestation 11-14 wks Gestation 11-14 wks Crown-rump length 45-84 mm Crown-rump length 45-84 mm Mid-sagittal view Mid-sagittal view Image size: head and thorax Image size: head and thorax Neutral position Neutral position Away from amnion Away from amnion Maximum lucency Maximum lucency Callipers on-to-on Callipers on-to-on Criteria for proper measurement of nuchal translucency Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

18. The image should have the head and thorax only Each movement of the calliper gives a 0.1 mm change of the measurement Measurement of nuchal translucency The importance of image magnification Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

19. Hyperextended Measurement of nuchal translucency Head position Hyperextended head may falsely increase NT measurement Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

20. Measurement of nuchal translucency Mid-sagittal section Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

21. Measurement of nuchal translucency: calliper placement Underestimate Overestimate Correct(inner-to-inner) Correct placement of the callipers to assess nuchal translucency based upon published nomograms by the Fetal Medicine Foundation Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

22. CRL: 54 mm Risk (%) Age (years) 30354045 100 10 1 0.1 2025 0.01 1: 600 1: 3,700 1.5 1: 100 2.9 The correct measurement is 2.9 Measurement of nuchal translucency Use the longest measurement Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

23. A nuchal cord is found in 5% of cases Measure the NT above and below the umbilical cord and use the average measurement for calculation of risk Measurement of nuchal translucency in the presence of a nuchal cord Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

24. Criteria to obtain and maintain certification Submit 10 images for review by quality control center True sagittal section True sagittal section Image size: head & thorax Image size: head & thorax Neutral position Neutral position Callipers on-to-on Callipers on-to-on Maximum lucency Maximum lucency Criteria for evaluating the images by the quality control center (Fetal Medicine Foundation) Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

25. 1. PASS: All 5 criteria fulfilled in at least 8 of the 10 images 2. 3-5 unsatisfactory images: Submit another 5 images 3. 6-10 unsatisfactory images: Submit another 10 images Evaluation of the images and action Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

26. 0.0 1.0 2.0 3.0 4.0 5.0 6.0 455055606570758085 Crown- rump length (mm) Nuchal translucency (mm) 40-60% of measurements above the median ACTION: Renew license of the software for 1 year Audit of distribution of nuchal translucency measurements for renewal of certification Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

27. Under-estimating 0.0 1.0 2. 3.0 4.0 455055606570758085 Crown- rump length (mm) Nuchal translucency (mm) >60% of measurements below the median ACTION: Renew license of the software for 3 months only and reassess 0.0 1.0 2.0 3.0 4.0 455055606570758085 Crown- rump length (mm) Nuchal translucency (mm) Over-estimating >60% of measurements above the median Audit of distribution of nuchal translucency measurements for renewal of certification Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

28. For more images and information of the 11-14 weeks scan, the reader is referred to The 11-14 Week Scan The Diagnosis of Fetal Abnormalities at the following website: http://www.fetalmedicine.com/f-books11-14.htm The material is freely available for review