1. Objectives Goals of the 11-14 week scan
Fetal nuchal translucency in the detection of aneuploidy
The value of first trimester maternal serum markers in the detection of aneuploidy
Criteria for measurement of fetal nuchal translucency
Pitfalls in the measurement of fetal nuchal translucency
The significance of an increased nuchal translucency with a normal karyotype
Management of an increased nuchal translucency
Quality control of a nuchal translucency screening program
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

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

3. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004
Nuchal translucency as a function of crown-rump length (gestational age) 35 45 55 65 75 85
Crown-rump length (mm)
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
Nuchal translucency (mm)
Trisomy 21
In normal pregnancies, fetal NT thickness increases with gestation
In trisomy 21 pregnancies fetal NT is increased (above the 95th centile in about 75% of cases)
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

4. Assessment of risk by maternal age and fetal nuchal translucency
Screening for trisomy 21
Assessment of risk by maternal age and fetal nuchal translucency
Risk (%)
100 NT
A priori risk 10 NT 1
0.1
0.01 20 25 30 35 40 45
Maternal age
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.
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

5. Risk assessment with maternal serum free ß-hCG & PAPP-A
Alterations 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%. 2 4 6 8 10 12 14 16 18 20
-3.5
-2.5
-1.5
-0.5
0.5
1.5
2.5
3.5
Free ßhCG (SD) %
Normal
Free bhCG 20 2 4 6 8 10 12 14 16 18
-3.5
-2.5
-1.5
-0.5
0.5
1.5
2.5
PAPP-A (SD) %
Normal
PAPP-A
Trisomy 21
Trisomy 21
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

6. Effectiveness of different methods of screening
Screening for trisomy 21
Effectiveness of different methods of screening
100,000 pregnancies
Method of screening
Number detected
Detection rate
Screen positive 5%
N=5,000
Trisomy 21
N=200
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%
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

7. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004
Maternal serum biochemistry and ultrasound parameters in the detection of chromosomal abnormalities other than trisomy 21
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 defects
Each of these chromosomal defects is associated with its own syndromal pattern of sonographic and biochemical markers
Fetal heart rate
Crown-rump length
Increased NT
Ultrasound markers
Free ß-hCG
PAPP-A
75% 
Exomphalos
Single umbilical artery
Trisomy 18
72%  
Megacystis
Holoprosencephaly 
Trisomy 13
X0 (Turner)
87%  
Triploidy
59% 
Small / molar placenta
 /  
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

8. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004
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% NT 3%
33%
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. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004
Conditions associated with increased nuchal translucency and normal karyotype
Craniosynostosis
Iniencephaly
Agnathia/micrognathia
Cardiac defects
Diaphragmatic hernia
Exomphalos
Megacystis
Renal agenesis
Polycystic kidneys
Multicystic kidneys
Nephrotic syndrome
Body stalk anomaly
Congenital lymphedema
Beckwith-Wiedemman syndrome GM1-gangliosidosis
Mucopolysaccharidosis type VII
Smith-Lemli-Opitz syndrome
Vitamin D resistant rickets
Zellweger syndrome
Achondrogenesis
Achondroplasia
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
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
Blackfan Diamond anaemia
Dyserythropoietic anaemia
Thalassaemia-a
Parvovirus B19 infection
Akinesia deformation sequence
Myotonic dystrophy
Spinal muscular atrophy
Souka et al. Ultrasound Obstet Gynecol 2001;18:9-17
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

10. Proposed management of increased nuchal translucency
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
Persistent nuchal
TORCH & Parvovirus screen
Genetic testing
20 weeks
Anomaly scan
Echocardiography
No abnormalities
Major abnormalities
Persistent nuchal
TORCH & Parvovirus screen
Genetic testing
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

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

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

13. Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004
Twins gestation
Determine chorionicity
Measure nuchal translucency (NT) in each fetus
Calculate 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-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
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
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
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

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

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

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

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

19. Measurement of nuchal translucency Head position
Hyperextended
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
How to obtain a MIDLINE sagittal plane
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. Measurement of nuchal translucency Use the longest measurement
Risk (%)
Age (years) 30 35 40 45
100 10 1
0.1 20 25
0.01
CRL: 54 mm
1: 100
2.9
1: 3,700
1.5
1: 600
The correct measurement is 2.9
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

23. Measurement of nuchal translucency in the presence of a nuchal cord
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
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
Image size: head & thorax
Neutral position
Callipers on-to-on
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. Evaluation of the images and action
1. PASS: All 5 criteria fulfilled in at least 8 of the 10 images
unsatisfactory images: Submit another 5 images
unsatisfactory images: Submit another 10 images
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

26. 40-60% of measurements above the median
Audit of distribution of nuchal translucency measurements for renewal of certification
40-60% of measurements above the median
0.0
1.0
2.0
3.0
4.0
5.0
6.0 45 50 55 60 65 70 75 80 85
Crown- rump length (mm)
Nuchal translucency (mm)
ACTION: Renew license of the software for 1 year
Nicolaides KH. Fetal nuchal translucency. Am J Obstet Gynecol 2004

27. Audit of distribution of nuchal translucency measurements for renewal of certification
Under-estimating
0.0
1.0 2.
3.0
4.0 45 50 55 60 65 70 75 80 85
Crown- rump length (mm)
Nuchal translucency (mm)
>60% of measurements below the median
0.0
1.0
2.0
3.0
4.0 45 50 55 60 65 70 75 80 85
Crown- rump length (mm)
Nuchal translucency (mm)
Over-estimating
>60% of measurements above the median
ACTION: Renew license of the software for 3 months only and reassess
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 Week Scan The Diagnosis of Fetal Abnormalities
at the following website:
The material is freely available for review