1. 3/9/2008
1
ULTRASOUND SCREENING
ULTRASOUND SCREENING
IN THE FIRST TRIMESTER
IN THE FIRST TRIMESTER
A Salim, G H Wiknjosastro, B Karsono, S Pudiyastuti, A Wibawa, N Wibowo,
W Andonotopo
I trimester
I trimester II trimester
SCREENING OF FETAL CHROMOSOMAL
SCREENING OF FETAL CHROMOSOMAL
ABNORMALITIES
ABNORMALITIES
I trimester
I trimester
„
„ Maternal age
Maternal age
II trimester
„ Maternal age
„
„ Serum markers
Serum markers
„
„ Genetic sonogram
Genetic sonogram
„ Serum markers
„ Genetic sonogram
2. 3/9/2008
2
107
107 c
centres with
entres with
40
40
COUNTRIES
COUNTRIES
FMF
FMF
operators qualified
operators qualified
by the
by the f
fetal
etal m
medicine
edicine
f
foundation
oundation
WORLDWIDE
WORLDWIDE
•
• T
TAS, TVS
AS, TVS scan
scan
i i
i i 5 MH b
5 MH b
NUCHAL TRANSLUCENCY
NUCHAL TRANSLUCENCY
(10
(10th
th-
- 14
14th
th week)
week)
FMF criteria:
FMF criteria:
•
• minimum
minimum 5 MHz probe
5 MHz probe
•
• caliper setting
caliper setting at least 0.1 mm
at least 0.1 mm
•
• 45
45 <
< CRL
CRL <
< 8
85mm
5mm
•
• f
fetal sagittal view
etal sagittal view, head and thorax
, head and thorax
•
• magnification maximal
magnification maximal
•
• c
clear separation between
lear separation between
f t l ki d i
f t l ki d i
fetal skin and amnion
fetal skin and amnion
•
• largest
largest thickness
thickness
•
• n
neutral position
eutral position
•
• a
avoid the
void the amnion and
amnion and nuchal cord
nuchal cord
•
• c
calipers
alipers “
“ in
inner
ner-
- t
to
o-
- in
inner “
ner “
4. 3/9/2008
4
SCREENING STUDIES FOR TRISOMY 21 BY
SCREENING STUDIES FOR TRISOMY 21 BY
NUCHAL TRANSLUCENCY
NUCHAL TRANSLUCENCY MEASUREMENT
MEASUREMENT
(10th
(10th-
- 14th week)
14th week) COMBINED WITH
COMBINED WITH
2nd TRIMESTER BIOCHEMISTRY
2nd TRIMESTER BIOCHEMISTRY
Increased NT
Increased NT Combined test
Combined test
Study
Study N screen detection screen detection
N screen detection screen detection
positive(%) rate (%) positive(%)
positive(%) rate (%) positive(%) rate(%)
Schuchter 2001.
Schuchter 2001. 9342
9342 2,4
2,4 11 / 19 ( 57,9% ) 7,2 18 / 19 ( 94,7% )
11 / 19 ( 57,9% ) 7,2 18 / 19 ( 94,7% )
Audibert 2001. 4130
Audibert 2001. 4130 2,0
2,0 7 / 12 ( 58,3% ) 5,0 11 / 12 ( 91,7% )
7 / 12 ( 58,3% ) 5,0 11 / 12 ( 91,7% )
Total
Total 13472
13472 2 3 18 / 31
2 3 18 / 31 ( 58 1%)
( 58 1%) 6 5 29 / 31
6 5 29 / 31 (93 5%)
(93 5%)
Nicolaides
Nicolaides,
, AJOG,
AJOG, 2004,191:45
2004,191:45-
-67
67
Total
Total 13472
13472 2,3 18 / 31
2,3 18 / 31 ( 58,1%)
( 58,1%) 6,5 29 / 31
6,5 29 / 31 (93,5%)
(93,5%)
NASAL BONE
NASAL BONE
•
• Nasal
Nasal b
bones are formed by intramembranous
ones are formed by intramembranous
Sandikciouglu, J Craniofac Genet Dev Biol 1993
Sandikciouglu, J Craniofac Genet Dev Biol 1993
Nasal
Nasal b
bones are formed by intramembranous
ones are formed by intramembranous
ossification of connective tissue of the nasal capsule
ossification of connective tissue of the nasal capsule
•
• Ossification
Ossification of
of n
nasal
asal b
bones first appears at a
ones first appears at a
CRL of
CRL of 42 mm
42 mm and increases linearly with gestation.
and increases linearly with gestation.
5. 3/9/2008
5
PATTERN OF MALFORMATIONS IN THE AXIAL
PATTERN OF MALFORMATIONS IN THE AXIAL
SKELETON IN
SKELETON IN TRISOMY 21
TRISOMY 21 FETUSES
FETUSES
1. Malformation or agenesis of the nasal bone in
g
19/31 (61%) of trisomy 21 fetuses
2.
2. 19/ 31 fetuses had vertebral malformations (14
19/ 31 fetuses had vertebral malformations (14
in the cervical, 4 in the thoracic and 8 in the
in the cervical, 4 in the thoracic and 8 in the
lumbosacral region)
lumbosacral region)
3
3 In 1/31 malformation in the basilar part of the
In 1/31 malformation in the basilar part of the
Keeling, 1997
3.
3. In 1/31 malformation in the basilar part of the
In 1/31 malformation in the basilar part of the
occipital bone
occipital bone
Post- mortem radiographic study of the axial skeleton,
comprising the cranial base and the spine, in 31 fetuses with
Trisomy 21 at 12 – 24 weeks
PATTERN OF MALFORMATIONS IN THE AXIAL
SKELETON IN HUMAN TRISOMY 18
TRISOMY 18 FETUSES
1 In 10/10 fetuses malformation in the basilar
1. In 10/10 fetuses malformation in the basilar
part of the occipital bone
2.
2. Absent or hypoplastic the
Absent or hypoplastic the n
nasal
asal b
bone in 8/10
one in 8/10
(80%) of trisomy 18 fetuses
(80%) of trisomy 18 fetuses
3. 7/ 10 fetuses had vertebral malformations
Keeling, 1996
(in the thoracic and in the lumbosacral region)
Post- mortem radiographic study of the axial
skeleton, comprising the cranial base and the spine, in 10
fetuses with Trisomy 18
6. 3/9/2008
6
ABSENCE OF NASAL BONE
AND FRAGILE X
FRAGILE X SYNDROME
In 5/6 (83%)
(83%) fetuses with Fragile X
nasal bone was absent at X-ray
Keeling, 2002
•
• Gestation 11
Gestation 11-
-14 wks
14 wks
•
• CRL 45
CRL 45-
-8
85
5 mm
mm
•
• S
Size: caliper movement 0.1 mm
ize: caliper movement 0.1 mm
•
• Mid
Mid-
-sagital view
sagital view
Fi t li l ki
Fi t li l ki
ULTRASO
ULTRASONOGRAPHY OF
NOGRAPHY OF NASAL BONE
NASAL BONE
•
• First line: nasal skin
First line: nasal skin
•
• Second line:
Second line: hyperechoic
hyperechoic bone
bone
•
• Third line: cartilaginous tip
Third line: cartilaginous tip
9. 3/9/2008
9
Lancet. 2001
Nov 17;358(9294):1665-7.
Related Articles, Links
Absence
Absence of nasal bone in fetuses with trisomy 21 at 11
11-
-14
14
y
weeks of gestation: an observational study.
Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K.
• nasal bone absent in 43/59 (73%) trisomy 21fetuses
(73%) trisomy 21fetuses
l b b t i 3/603 (0 5%) l f t
• nasal bone absent in 3/603 (0,5%) normal fetuses
Prenat Diagn. 2003
Apr;23(4):306-10.
Related Articles, Links
Integrated ultrasound and biochemical screening for
g g
trisomy 21 using fetal nuchal translucency, absent
absent fetal
nasal bone, free beta-hCG and PAPP-A at 11
11-
-14
14 weeks.
Cicero S, Bindra R, Rembouskos G, Spencer K, Nicolaides KH.
• nasal bone absent in 69/100 trisomy 21 fetuses
69/100 trisomy 21 fetuses
• nasal bone present in 31/100 trisomy 21 fetuses
• integrated sonographic and biochemical
screening identifies 90% of trisomy 21 fetuses
• false positive rate 0,5%
10. 3/9/2008
10
Ultrasound Obstet Gynecol.
2003 Jan;21(1):15-8.
Related Articles, Links
N l b h l i
h l i i t i 21 t 15
15 22
22
Nasal bone hypoplasia
hypoplasia in trisomy 21 at 15
15-
-22
22
weeks' gestation.
Cicero S, Sonek JD, McKenna DS, Croom CS, Johnson L,
Nicolaides KH.
• Hypoplastic = nonvisible or shorter than 2,5mm
Hypoplastic = nonvisible or shorter than 2,5mm
• Hypoplastic nasal bone in 21/34 (61,8%) trisomy 21 fetuses
21/34 (61,8%) trisomy 21 fetuses
yp p ( , ) y
( , ) y
• Hypoplastic nasal bone in 12/982 (1,2%) normal fetuses
• Hypoplastic nasal bone in 1/30 ( 3,3%) fetuses with other
chromosomal defects
Interpretation:
ULTRASO
ULTRASONOGRAPHY OF
NOGRAPHY OF NASAL BONE
NASAL BONE
NORMAL
NORMAL versus
versus ABNORMAL
ABNORMAL
HYPOPLASTIC
HYPOPLASTIC
ABSENT
ABSENT
11. 3/9/2008
11
DUCTUS VENOSUS SCREENING
DUCTUS VENOSUS SCREENING
“intimal - pillow” theory:
Ductus
Ductus
venosus
venosus
12 w
12 w
intimal - pillow theory:
the intimal hyperplasia
is a soft pillow for very
l h di i
early haemodinamic
adaptation
DUCTUS VENOSUS SCREENING
DUCTUS VENOSUS SCREENING
UMBILICAL VEIN
UMBILICAL VEIN
DUCTUS VENOSUS
DUCTUS VENOSUS
VENA CAVA INFERIOR
VENA CAVA INFERIOR
13. 3/9/2008
13
DUCTUS VENOSUS SCREENING:
DUCTUS VENOSUS SCREENING:
ACV
ACV = ATRIAL CONTRACTION VELOCITY
= ATRIAL CONTRACTION VELOCITY
NORMAL
NORMAL ABNORMAL
ABNORMAL
ACV ACV
+
+
FETAL DUCTUS VENOSUS ANALYSIS:
FETAL DUCTUS VENOSUS ANALYSIS:
CLINICAL INDICATIONS
CLINICAL INDICATIONS
„
„ Analysis of venous return and myocardial decompensation
Analysis of venous return and myocardial decompensation
in severe fetal hypoxia
in severe fetal hypoxia
„
„ Abnormal venous return in
Abnormal venous return in congenital heart defects
congenital heart defects
„
„ Early detection of circulatory changes associated with
Early detection of circulatory changes associated with
increased nuchal translucency
increased nuchal translucency
„
„ “Second
“Second-
-level” screening test for fetal
level” screening test for fetal
chromosomal
chromosomal abnormalities and heart defects
abnormalities and heart defects
„
„ TTTS
TTTS –
– vital prognosis of anemic
vital prognosis of anemic-
-twin ( + MCA velocities )
twin ( + MCA velocities )
14. 3/9/2008
14
THE
THE FIRST TRIMESTER DUCTUS VENOSUS VELOCIMETRY
FIRST TRIMESTER DUCTUS VENOSUS VELOCIMETRY
IN RELATION TO
IN RELATION TO NUCHAL
NUCHAL TRANSLUCENCY
TRANSLUCENCY THICKNESS
THICKNESS:
:
NT
NT Fetuses
Fetuses DV
DV ACV
ACV +
+ ACV
ACV
NT
NT Fetuses
Fetuses DV
DV ACV
ACV ACV
ACV
Thickness
Thickness measured
measured
>
>95
95th
th centile
centile 156
156 152
152 93 (61%)
93 (61%) 59 (39%)
59 (39%)
<95
<95th
th centile
centile 174
174 173
173 171 (98%)
171 (98%) 2 (1%)
2 (1%)
Total
Total 330
330 325
325 264 (81%)
264 (81%) 61 (19%)
61 (19%)
DV = Ductus venosus
ACV+ = Presence of forward velocity during atrial contraction
ACV - = Absence or inverted forward velocity during atrial contraction
Zoppi, Fetal Diagn Ther 2002
BJOG. 2002 Sep;109(9):1015-9. Related Articles, Links
Screening for aneuploidy in the first trimester by
g p y y
assessment of blood flow in the ductus venosus.
Mavrides E, Sairam S, Hollis B, Thilaganathan B.
CONCLUSION:
CONCLUSION:
There is
There is clear association
clear association between abnormal flow in the ductus
between abnormal flow in the ductus
venosus and fetal aneuploidy. The sensitivities of abnormal nuchal
venosus and fetal aneuploidy. The sensitivities of abnormal nuchal
translucency measurement alone, ductus venosus velocimetry
translucency measurement alone, ductus venosus velocimetry
alone or
alone or nuchal translucency and ductus venosus combined
nuchal translucency and ductus venosus combined
alone or
alone or nuchal translucency and ductus venosus combined
nuchal translucency and ductus venosus combined
for Down's Syndrome were 80.4%, 58.7% and 93.5%,
for Down's Syndrome were 80.4%, 58.7% and 93.5%,
respectively. The use of ductus venosus velocimetry in
respectively. The use of ductus venosus velocimetry in
combination with nuchal translucency is better than either test
combination with nuchal translucency is better than either test
alone, since it increases the
alone, since it increases the sensitivity in the detection of
sensitivity in the detection of
Down's Syndrome to 94%.
Down's Syndrome to 94%.
15. 3/9/2008
15
Ultrasound Obstet Gynecol. 1999
Nov;14(5):307-10.
Related Articles, Links
Cardiac defects in chromosomally normal fetuses with
abnormal ductus venosus blood flow at 10-14 weeks.
Matias A, Huggon I, Areias JC, Montenegro N, Nicolaides KH.
RESULTS:
RESULTS:
Reverse or absent flow during atrial contraction was observed in
Reverse or absent flow during atrial contraction was observed in
11 of the 142 chromosomally normal fetuses with increased nuchal
11 of the 142 chromosomally normal fetuses with increased nuchal
translucency. Major defects of the heart and/or great arteries were
translucency. Major defects of the heart and/or great arteries were
i f h 11 i h b l d l fl d i d h l
i f h 11 i h b l d l fl d i d h l
present in 7 of the 11 with abnormal ductal flow and increased nuchal
present in 7 of the 11 with abnormal ductal flow and increased nuchal
translucency, but in none of the 131 with normal flow.
translucency, but in none of the 131 with normal flow.
CONCLUSION
CONCLUSION:
:
These preliminary results suggest that
These preliminary results suggest that abnormal ductus venosus blood
abnormal ductus venosus blood
flow in chromosomally normal fetuses with increased nuchal
flow in chromosomally normal fetuses with increased nuchal
translucency identifies those with an underlying major cardiac defect.
translucency identifies those with an underlying major cardiac defect.
DUCTUS VENOSUS SCREENING
DUCTUS VENOSUS SCREENING
INCREASED
INCREASED
NUCHAL
NUCHAL
TRANSLUCENCY
TRANSLUCENCY
DUCTUS
DUCTUS
CONGENITAL
CONGENITAL
HEART DEFECT
HEART DEFECT
FETAL
FETAL
ANEUPLOIDY
ANEUPLOIDY
VENOSUS
VENOSUS
ABNORMALITIES
ABNORMALITIES
16. 3/9/2008
16
CURRENTLY
CURRENTLY AVAILABLE
AVAILABLE METHODS
METHODS
FOR
FOR THE
THE FIRST TRIMESTER
FIRST TRIMESTER SCREENING
SCREENING OF
OF
DOWN SYNDROME
DOWN SYNDROME
„
„ Maternal age
Maternal age (MA)
(MA) 33%
33%
„
„ Biochemistry
Biochemistry (PAPP
(PAPP-
-A
A,
,ß
ßhCG)
hCG) 6
60
0-
-65
65%
%
„
„ Nuchal translucency
Nuchal translucency (NT)
(NT) 70
70-
-75
75%
%
„
„ Combined
Combined (MA
(MA,
,biochemistry
biochemistry,
,NT)
NT) 8
80
0-
-85
85%
%
SENSITIVITY
SENSITIVITY
„
„ Combined
Combined (MA
(MA,
,biochemistry
biochemistry,
,NT)
NT) 8
80
0 85
85%
%
„
„ Integrated (biochemistry,NT,MA,
Integrated (biochemistry,NT,MA,NB
NB )
) 93
93-
-94%
94%
false positive 5%
false positive 5%
NB= nasal bone
NB= nasal bone
Nicolaides:
Nicolaides:
Other sonographic markers in the first trimester,
2004, AJOG
„ CROWN-RUMP LENGTH
„ MAXILLARY LENGTH
„ EAR LENGTH
„ FEMUR AND HUMERUS
LENGTH
„ SINGLE UMBILICAL ARTERY
„ MEGACYSTIS
„ EXOMPHALOS
„ CHOROID PLEXUS CYST
„ PYELECTASIS
„ CARDIAC ECHOGENIC FOCI
20. 3/9/2008
20
Fetal heart rate
Fetal heart rate
„
„ Early increase in heart rate coincides
Early increase in heart rate coincides
„
„ Early increase in heart rate coincides
Early increase in heart rate coincides
with the morphological development
with the morphological development
of the heart
of the heart
–
– 5 weeks
5 weeks -
- 100 beats/min
100 beats/min
–
– 10 weeks
10 weeks -
- 170 beats/min
170 beats/min
–
– 14 weeks
14 weeks -
- 155 beats/min
155 beats/min
Nicolaides:
Nicolaides:
Other sonographic markers in the first trimester,
2004, AJOG
21. 3/9/2008
21
Single umbilical artery
Single umbilical artery
„
„ SUA in one percent of deliveries
SUA in one percent of deliveries
„
„ SUA in one percent of deliveries
SUA in one percent of deliveries
„
„ 717 fetuses
717 fetuses
„
„ 3.3% normal cariotype
3.3% normal cariotype
„
„ 77.8% trisomy 18
77.8% trisomy 18
Megacystis
Megacystis
„
„ Visualization of the fetal bladder
Visualization of the fetal bladder
„
„ Visualization of the fetal bladder
Visualization of the fetal bladder
–
– 10 weeks
10 weeks –
– 50%
50%
–
– 11 weeks
11 weeks –
– 80%
80%
–
– 13 weeks
13 weeks –
– 100%
100%
„
„ Normal diametar is < 6mm
Normal diametar is < 6mm
22. 3/9/2008
22
Megacystis
Megacystis
„
„ 7
7 –
– 15mm
15mm -
-> 23 6% chromosomal
> 23 6% chromosomal
„
„ 7
7 15mm
15mm > 23.6% chromosomal
> 23.6% chromosomal
abnormalities (13, 18)
abnormalities (13, 18)
„
„ ≥ 15mm
≥ 15mm -
->
> 11.4%
11.4% chromosomal
chromosomal
abnormalities
abnormalities
„
„ Spontaneous resolution in normal
Spontaneous resolution in normal
kariotype is 90%
kariotype is 90%
kariotype is 90%
kariotype is 90%
„
„ Megacystis increases the likelihood for
Megacystis increases the likelihood for
trisomy 13 or 18 by a factor of 6.7
trisomy 13 or 18 by a factor of 6.7
Exomphalos
Exomphalos
„
„ Retraction into the abdominal cavity is
Retraction into the abdominal cavity is
„
„ Retraction into the abdominal cavity is
Retraction into the abdominal cavity is
completed by 11 weeks 5 days
completed by 11 weeks 5 days
„
„ Bowel in the sac
Bowel in the sac -
-> abnormal kariotype
> abnormal kariotype
„
„ Liver and bowel
Liver and bowel -
-> normal kariotype
> normal kariotype
„
„ 14 cases with exomphalos
14 cases with exomphalos
p
p
–
– 8 with abnormal NT
8 with abnormal NT
–
– 7 with abnormal kariotype
7 with abnormal kariotype
23. 3/9/2008
23
Exomphalos
Exomphalos
„
„ Decreases with gestational age
Decreases with gestational age
„
„ Decreases with gestational age
Decreases with gestational age
„
„ Increases with maternal age
Increases with maternal age
„
„ First trimester
First trimester –
– 61 % of trisomy
61 % of trisomy
Mid gestation
Mid gestation 30% of trisomy
30% of trisomy
„
„ Mid gestation
Mid gestation –
– 30% of trisomy
30% of trisomy
„
„ Neonates
Neonates –
– 15% of trisomy
15% of trisomy
• Down syndrome
NUCHAL TRANSLUCENCY
NUCHAL TRANSLUCENCY
(10
(10th
th-
- 14
14th
th week)
week)
Down syndrome
• Chromosomopathies
• Congenital heart defects
• Structural defects
• Genetic syndromes
• Intrathoracic compression
• Intrathoracic compression
• Abnormal lymphatic system
• Neuromuscular abnormalities
• Altered composition of dermis
24. 3/9/2008
24
Souka et al:
Souka et al:
Increased nuchal translucency with normal
karyotype, 2005, AJOG
Nicolaides:
Nicolaides:
Nuchal translucency followed by second
Nuchal translucency followed by second-
-trimester
trimester
U
Ultrasonography
ltrasonography, 2004, AJOG
, 2004, AJOG
