Presentatie mw. prof. dr. C.M. Bilardo - UMC Utrecht

12-13 weken echo,
meer dan screening voor
trisomieen of eerste trimester
echoscopie:
een nieuwe dimensie
Lustrum SPSRU
Katia Bilardo
UMCG, Groningen

First trimester US Screening:
1. Screening for Aneuploidies
2. Screening for Structural anomalies
3. Screening for Pre-eclampsia
4. and a lot more…….(premature labour, macrosomia
etc.)
= Early pregnancy global risk assessment

In NL
1) Eerste trimester echoscopie is onderdeel
van verloskundige zorg
2) Voornamelijk reden (en) om een eerste
trimester echo te laten doen:
1) Vitaliteit, Termijnbepaling, aantal
foetussen (meestal < 11 weken)
2) Combinatie Test = screening voor
trisomieen
(counseling is ook puur daarop gericht)

Early screening
for aneuploidies

Median MoM
The Fetal Medicine
Foundation
Early screening
for aneuploidies
Maternal age, fetal NT and serum free ß-hCG &PAPP-A
Maternal blood
5.0
ß-hCG
Trisomy 21
Detection rate for FPR 5%
100
90
80
1.0
0.5
0.1
Euploid
PAPP-A
Trisomy 21
75 80 85 90 95 100
Gestation (days)
70
60
50
40
30
20
10
0

The Fetal Medicine
Foundation
Nuchal translucency
- correct measurement -

Nuchal translucency (mm)
The Fetal Medicine
Foundation
Effect of deviation in the
measurement of fetal NT
0 – 25°
4.0
3.5
Median NT
-0.4mm
Median NT
-0.6mm
3.0
Deviation of 15°
2.5
2.0
1.5
1.0
0.5
Deviation of 25° 0
45 55 65 75
85
45 55 65 75
85 45 55 65 75
85
CRL (mm)
CRL (mm)
CRL (mm)
Operator I
Operator II

Maternal serum (MoM)
The Fetal Medicine
Foundation
Early screening
for aneuploidies
Maternal serum free ß-hCG & PAPP-A
2.5
2.0
PAPP-A
2.0
1.5
ß-hCG
Free ß-hCG
Black
PAPP-A
1.5
1.0
ß-hCG
1.0
Smoker
0.5
0.5
PAPP-A
0.0
0.0
IVF
45 65 85 105 125
Maternal weight (kg)
45 55 65 75 85
Crown rump length (mm)
0.8 1 1.4
0.8 1 1.6
Kagan et al 2008

The Fetal Medicine
Foundation
Early screening
for aneuploidies
Age, ultrasound and serum ß-hCG & PAPP-A
Detection rate for FPR 2.5%
100
90
80
70
60
50
40
30
20
10
0

Deelname combinatietest
34%
66%
Ja
Nee
56%
44%
82%
18%
82% van de vrouwen in het noorden willen GEEN CT

KEUZE CT
NOORDWEST

REDENEN OM VAN DE COMBINATIETEST AF TE ZIEN
50%
45%
40%
35%
30%
25%
20%
15%
10%

Enlarged NT and Normal Karyotype
Increased nuchal translucency thickness and normal karyotype: time for
parental reassurance C. M. BILARDO*, et al. UOG 2007
78
60
% 40
20
9
16
29
44
1 op 5
Foetussen
Slechte
uitkomst
0
NT (mm)

Normal karyotype
451
+ Outcome
81%
Spont.abortion
IUD 4%
- Outcome
19%
TOP 3%
Struct. anomalies
7%
Genetic
syndromes 5%

Craniosynostosis
Iniencephaly
Agnathia/micrognathia
Cardiac defects
Diaphragmatic hernia
Exomphalos
Megacystis
Renal agenesis
Polycystic kidneys
Multicystic kidneys
Nephrotic syndrome
Body stalk anomaly
Congenital lymphedema
................
Akinesia deformation sequence
Myotonic dystrophy
Spinal muscular atrophy
..............
Bijvangst bij Verdikte NT en
Normale Karyotype
Beckwith-Wiedemman syndrome
GM1-gangliosidosis
Mucopolysaccharidosis type VII
Smith-Lemli-Opitz syndrome
Vitamin D resistant rickets
Zellweger syndrome
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
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
Apert syndrome
.................
Blackfan Diamond anaemia
Dyserythropoietic anaemia
Thalassaemia-a
Parvovirus B19 infection
Noonan syndrome is the most common disorder encountered in 6%
Souka et al 2001,2004, Bilardo 1998
of the chrom. normal fetuses with enlarged NT (Pergament 2011)

Prevalence major CHD (per 1000)
CHD in fetuses with N karyotype according to NT
enlargement (N.37/640= 5,8%)
Prevalence of major CHD (per 1000) against
NT measurement (mm)
100
90
94,1
80
70
60
50
51,7
40
30
20
10
20
33,6
0
>/=95th centile-
3,4mm
3,5-4,4mm 4,5-5,4mm >5,5mm
Nuchal translucency measurement (mm)
Clur et al. Pren. Diagn. 2008

Chance of N outcome after ˝normal˝ scan
100
80
%
60
40
20
0
204 120 33 12 7
95th 3.5 3.6-4.5 4.6-5.5 5.6-6.5 >6.5
Nuchal Translucency (mm)
High chance of favorable outcome after normal US,
regardless of initial NT enlargement

Early detection
of fetal defects

1 st trimester screening for fetal anomalies
(Syngelaki et al. 2011)
Author Total Scan
route
GA
(weeks)
Fetal anomalies
Total CyHy Aneuploidy Detected
Hernadi and Torocsic, 1997 3991 TA, TV 11–14 49 (1.2%) 7 (14.3%) 4 (8.2%) 20 (40.8%)
D’Ottavio et al., 1998 4078 TV 13–15 88 (2.2%) 30 (34.1%) 19 (21.6%) 54 (61.4%)
Bilardo et al., 1998 1690 TA, TV 10–14 23 (1.4%) 3 (13.0%) — 10 (43.5%)
Hafner et al., 1998 4233 TA 10–13 56 (1.3%) — — 7 (12.5%)
Whitlow et al., 1999a 6443 TA, TV 11–14 63 (1.0%) 14 (22.2%) 14 (22.2%) 37 (58.7%)
Guariglia and Rosati, 2000 3478 TV 10–16b 57 (1.6%) 15 (26.3%) 8 (14.0%) 33 (57.9%)
Taipale et al., 2004 4789 TV 10–16c 33 (0.7%) — 4 (12.1%) 6 (18.2%)
Chen et al., 2004 1609 TA, TV 12–14 26 (1.6%) 1 (3.8%) 11 (42.3%) 14 (53.8%)
Becker and Wegner, 2006 3094 TA, TV 11–13 86 (2.8%) — 56 (65.1%) 72 (83.7%)
Cedergren and Selbing, 2006 2708 TA 11–14d 32 (1.2%) 3 (9.4%) 1 (3.1%) 13 (40.6%)
Saltvedt et al., 2006 18053 TA 11–14 371 (2.1%) Not stated — 74 (19.9%)
Dane et al., 2007 1290 TA 11–14 24 (1.9%) 3 (12.5%) 5 (20.8%) 17 (70.8%)
Chen et al., 2008 7642 TA 10–14 127 (1.7%) 30 (23.6%) 32 (25.2%) 51 (40.2%)
Oztekin et al., 2009 1805 TA 11–14 21 (1.2%) 3 (14.3%) — 14 (66.7%)
Ebrashy et al., 2010 2876 TA, TV 13–14 31 (1.1%) 7 (22.6%) — 21 (67.7%)
Total 67779 — 10–16 1087 (1.6%) 116 (10.7%) 154 (14.2%) 443 (40.8%)

The Fetal Medicine
Foundation
Early detection of
fetal defects
Total 3,094
pregnancies
Major defects 2.8%
Prenatal
diagnosis 94%
11-13 +6 w
89%
NT >2.5 mm
67%
Becker & Wegner 2006

1st Trimester :
Detection rate of Structural Defects
Always detected
31%
Major defects
in euploid fetuses
488/44859 (1,09%)
Sometimes detected
43%
Undetectable
26%
Syngelaki et al. 2011

1st Trimester :
Detection rate of Structural Defects
50%
100%
60%
100%

Mid-sagittal section
Diaphragm

Bladder:
10 wks visible in 50%
11 wks visible in 80%
12 wks visible in 90%
13 wks visible in all
Rosati et al 1996
Gender:
is the angle that
counts!
Midline sagittal plane
Tubercle/spine angle
From 13th week
(32mm DBP, 100% accuracy )
(Effrat, Mazza)
Angle > 27° = XY
(Youssef et al. 2011)

Transverse Section
Skull
Midline
Ventrikels / choroid plexus
Can be visualized from 8-9wks
Always from 12-13 wks

Skull
calcification completed by 11
weeks
Eyes, Lips, palate

The Fetal Medicine
Foundation
Early detection of
fetal defects
Acrania, exencephaly, anencephaly

The Fetal Medicine
Foundation
Early detection of
fetal defects
Megacystis
• Prevalence: 1/1,600
• Trisomy 13 or 18 (31%)
• Bladder length
7-15 mm resolution 90%
>15 mm resolution 0%
35 of 57,119 singleton pregnancies
Kagan et al 2010

Normal fetus
Cleft lip and palate

Extremities
Limb shortening / fractures may be noted in the First Trimester
Stephens et al 1983
Bronshtein et al 1992
Dimaio et al 1993
Macrydimas et al 1996

Assessment of digits
1
2 3 4 5
6
Polydactyly

The Fetal Medicine
Foundation
Early detection of
fetal defects
Skeletal dysplasia

Hart
• Vier-kamerbeeld met symetrische atria en ventrikels
• Kruising grote vaten
• ‘V-sign’

The Fetal Medicine
Foundation
Early detection of
fetal defects
Major cardiac defects
AVSD
Hypoplastic L heart Tetralogy of Fallot

Early detection of fetal defects:
Spina Bifida
Spina bifida
DR
History 5%
MS AFP 75%
Ultrasound 98%

Open SB at 13 weeks
R. Chaoui UOG 2011

The brain @ 11-14 weeks scan
Sphenoid bone
Thalamus
Midbrain
Brain stem
(Pons )
4th ventricle

Normal
IT not visible in Spina bifida
Spina Bifida
Chaoui et al. UOG Sept. 2009

Additional measurements help in
increasing the accuracy of detecting
opened NTD @11-14 w scan
-Brain stem diameter
-Brain Stem-Occipital Bone
dist.
-Ratio of Brain stem/
Posterior Fossa/
R. Lachmann, R. Chaoui, J.Moratalla, G.Picciarelli, K.H. Nicolaides, Prenatal Diagnosis (Jan 2011)

BS / BSOB Ratio
R. Lachmann, R. Chaoui, J.Moratalla, G.Picciarelli, K.H. Nicolaides, Prenatal Diagnosis (Jan 2011)

UOG 2012
In fetuses with
SB the BPD is
already small
from the 1 st
trim, probably
due to loss of
CS fluid.
BPD

Screening op vasa praevia bij 12 weken
Foetale navelstrengvaten over het ostium internum
Velamenteuze insertie

Velamenteuze insertie
44

The Fetal Medicine
Foundation
Early prediction
of preeclampsia

Uterine artery PI MoM
The Fetal Medicine
Foundation
PE: Prediction at 11-13 wks
Uterine artery Doppler at 11-13 wks
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Normal
Early
PE
Middle
PE
Late
PE
• 20,798 pregnancies; Early-PE n= 84 (0.4%), Middle-PE 144 (0.7%), Late-PE 342 (1.6%)
• Mean uterine PI, adjusted for CRL, BMI, age, race

The Fetal Medicine
Foundation
PE: Prediction at 11-13 wks
Combined testing
History
BMI (Kg/m 2 )
Racial origin
White
Black
S Asian
Parous
No previous PE
Previous PE
100
%
90
80
70
60
50
40
30
Detection rate for FPR 10% (5%)
95% (90%)
81% (70%)
63% (50%)
46%
38%
35%
Maternal history of PE
20
History of hypertension
Ovulation drugs
10
0
Early-PE
Middle-PE
Late-PE

Conclusie:
Zelfs wordt de CT door NIPD vervangen blijft er
(m.i.) een rol voor de 12-13 weken echo voor
wat betreft:
– Vroege Diagnose van ernstige structurele
afwijkingen ( met VOOR en na/delen)
– (Screening voor pre-eclampsie)
– En mogelijk veel meer….
Tijd voor een herevaluatie van de rol van
de 12-13 weken echo!

The Fetal Medicine
Foundation
Turning the pyramid
of pregnancy care
12w
20w
12w
16w
24w
28w
Specialist care
12-32w
20w
30w 32w 34w 36w
37w 38w 39w 40w 41w
41w
www.fetalmedicine.com

Dank!