Transcript First Trimester Sonography

Sonographic Detection
of Aneuploidy
Eric H. Dellinger, MD
Director, Division of Maternal-Fetal Medicine
Greenville Hospital System
Greenville, South Carolina
Introduction
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The Future of Science and Medicine:
Exploring the extremes
Evolution of Ultrasound
Aneuploidy
Benefits of Early Detection
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Privacy issues
Decreased maternal bonding
Safer pregnancy termination
Higher detection rate
Nuchal Translucency
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Clear space in posterior neck
Imaged between 11 and 14 weeks or when
CRL is 36 to 84 mm
Nuchal thickening is associated with:
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Aneuploidy
Anomalies
Infections
Metabolic and hematologic disorders
Incidence of chromosomal defects
Nuchal
translucency (mm)
Total n
< 3.4
3.5 - 4.4
4.5 - 5.4
5.5 - 6.4
> 6.5
95,086
568
207
97
166
Chromosomal defects (%)
0.33
21.12
33.33
50.51
64.45
Snijders et al. 1998
Trisomy 21 Detection Rate
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96,127 patients studied
NT and age
Median age 31 years
5% screen positive rate
77% of affected fetuses detected
Snijders et al, Lancet 1998; 352: 343.
Other Associations
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Genetic syndromes:
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Anomalies:
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Cardiac, diaphragmatic hernia
Adverse outcome:
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Cornelia de Lange, Noonan, Smith-Lemli-Opitz,
Apert
Early demise
Targeted scan indicated if euploid
Anomalies with Increased NT
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Cardiac defects
Diaphragmatic hernia
Omphalocele
Duodenal atresia
Esophageal atresia
Skeletal dysplasias
Lethal congenital
arthryogryposis
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Smith-Lemli-Optiz
syndrome
Megacystis
Fryn syndrome
Joubert syndrome
Meckel-Gruber
syndrome
VATER association
NT and CHD
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In 29,154 chromosomally normal fetuses, 56%
of major abnormalities of the heart and great
arteries were found in the subgroup with nuchal
translucency above the 95th centile.
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Nuchal translucency thickness at 11–14 weeks
may constitute the most effective method of
screening for cardiac defects.
Hyett JA, et al, Br Med J 1999:318:81–5
NT and Cardiac Defects
NT
CHD per 1000
< 2.0 mm
2.0 to 2.4 mm
2.5 to 3.4 mm
> 3.4 mm
1.9
4.8
6.0
23
Bahado-Singh et al, Am J Obstet Gynecol. 2005 May;192(5):1357-61
NT Technique
Proper CRL is a MSLL
MSLL = maximum straight line length
Enlarge
Caliper Placement
NT Increase at 11 – 14 weeks
NT Interpretation
From 10 - 14 weeks, the 99th percentile remains constant
at 3.5 millimeters, independent of gestational age or
crown-rump length.
Nicolaides , Semin Perinatol. 2005;29(4):190.
NT measurement in 326 trisomy 21 fetuses
NT thickness and chromosomal abnormalities other
than trisomy 21
Adverse Outcome with Increased NT
NT
3.5 - 4.4 mm
4.5 - 5.4 mm
5.5 - 6.4 mm
> 6.5 mm
Poor Outcome
32%
49%
67%
89%
Ultrasound Obstet Gynecol 2001;18:9-17
Cutoff
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3 mm threshold identifies 80% of Downs
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5% SPR
High risk population
Br J ObGyn 1994; 101:782
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95th percentile is a better threshold
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NT between 95th and 99th percentile carries 3.7%
risk of aneuploidy
Lancet 1998; 352: 343
Pitfalls
Beware
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NT cannot be obtained in all patients (~6%)
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Fetal position
Maternal body habitus
Time constraints (allot 20 min)
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Identify the amnion
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Nuchal thickening may decrease over time
Essential for proper NT
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Magnify the image until the fetal head and
thorax occupy the whole screen.
Obtain a mid-sagittal view of the face.
Minor deviations: non-visualization of the
tip of the nose and visibility of the
zygomatic process of the maxilla.
The fetus should be in a neutral position.
Essential for proper NT
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Widest part of NT must be measured.
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The crossbar of the calliper should be such that
it is hardly visible as it merges with the white
line of the border, not in the nuchal fluid.
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Turn the gain down. This helps avoid placing
the calliper on the fuzzy edge of the line which
can underestimate the nuchal measurement.
Amnion vs. NT
Nasal Bone
Nasal Bone
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Conflicting results in European vs. US
studies
May reflect the technical difficulty of
imaging
Review of over 35,000 nasal bone exams
from 9 studies:
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Successful study in 94.3%
Absent in 65% of Downs (0.8% of normals)
Obstet Gynecol 2007; 110:300
Nasal Bone
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The optimum time for nasal bone
assessment is at crown rump length of 65
to 74 mm (13 to 13.5 weeks of gestation).
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Absent nasal bone earlier in gestation
could reflect delayed maturation, rather
than actual absence of the structure.
Ville, Am J Obstet Gynecol. 2006;195(1):1.
Cystic Hygroma
Doppler
Umbilical
Ductus
Tricuspid Regurgitation
Normal
Tricuspid Regurgitation
Anomalies and Aneuploidy
Normal newborns
0.5% aneuploid
Structural anomalies
11% aneuploid
Am J Med Genet 1988;29:289
Type of Defect Matters
Omphalocele with liver
3 of 34 aneuploid
Omphalocele without liver
12 of 14 aneuploid
AJR 1992;158:133; J Ultra Med 1989;8:299
Growth Restriction
Finding
Aneuploid
Isolated IUGR
2%
IUGR + anomaly
20 %
Am J Obstet Gynecol 1993;168:547
Detecting Down Syndrome
Major Malformation
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33% of Down fetuses have one or more
major malformations
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Heart
CNS
GI
Face/neck
Hydrops
Ped Clin N Am 1984;31:1331
Cardiovascular
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40-50% manifest heart anomalies
Cardiovascular
AV Canal is the Sine Qua Non
Of Down Syndrome
Cardiovascular
AV Canal defect
Ventricular septal defect
Isolated secundum ASD
Isolated persistent PDA
Isolated tetralogy of Fallot
Other
45 percent
35 percent
8 percent
7 percent
4 percent
1 percent
CNS
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Brachycephaly, frontal hypoplasia,
ventriculomegaly
GI
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Duodenal atresia
40% risk, “late” finding
Face, Nuchal Fold
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In 40-50% nuchal fold > 6 mm at 15-20 wks
Seen in 0.5% of normals
Nuchal Thickening
Cystic Hygroma
Hydrops
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Strong association with non-immune
hydrops
Soft Markers
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Short femur
Short humerus
EIF
Echogenic bowel
Pyelectasis
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Hypoplastic 5th digit
Sandal gap
Wide iliac angle
Short nasal bone
Short Femur and Humerus
Expected FL = -9.3105 + 0.9028 x BPD
Measured/Expected FL ≤ 0.91 is ABNORMAL
53% of Downs
5% of normals
Expected HL = -7.9404 + 0.8492 x BPD
Measured/Expected HL <0.90 is ABNORMAL
48% of Downs
2% of normals
Echogenic Intracardiac Focus
25 - 34% of Downs
4% of Normals
15 - 30% of Asians
Echogenic Bowel
15% of Downs
0.6% of Normals
3.6% aneuploid
2.9% CF
Think intra-amniotic bleeding,
CF, infection, transducer
Pyelectasis
> 4.0 mm
21% of Downs
2% of normals
SOFT MARKERS NOT ESTABLISHED
FOR CLINICAL PRACTICE
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Seen in many normals
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Predictive value unclear
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Good to know
Hypoplastic 5th Digit
Clinodactyly
19% Downs
3.4% normals
5th/4th ratio of 0.70
Sandal Gap
Seen in 45% of newborns with Downs
Subtle finding on scan
Brachycephaly
Shortening of the frontal
occipital brain length
Smaller frontal lobes
Not an effective screen
Wide Iliac Angle
Angle of 90 degrees should
be considered the upper
limit of normal
Nasal Bone
Nasal Bone
Other Findings
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Mild ventriculomegaly (10-14 mm)
Enlarged cisternal magna (> 10 mm)
Small low-set ears
Effusions
Duodenal bulb
Case Study
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31 year old G3 P2
Down Syndrome risk from Quad screen is
1:430
Level II scan reveals:
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EIF
Short humerus
Should she have an amniocentesis?
Are You Confused?
Likelihood Ratio (LR)
LR = sensitivity / false-positive rate
= + test with disease / + test no disease
An LR > 1 suggests a positive association with
a particular finding
An LR of 10 or more suggests a strong
association with a particular finding
Calculated LRs of Sonographic
Findings for Fetal Down Syndrome
J Ultrasound Med 20:1053–1063, 2001
Adjusted Aneuploidy Risk
www.fetalcenter.org
AAURA.xls
www.perinatology.com
Trisomy 18
CPC
Choroid Plexus Cysts
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Seen in 33% of Trisomy 18 fetuses
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Perform a detailed sonogram
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Seen in 2-5% of normals
Face, heart, great vessels, extremities
An open hand is significant
Meta-analysis
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In 748 cases of isolated CPC, risk 1/374
Am J Obstet Gynecol 1995;172:83
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In 1016 cases, no cases seen (age < 35)
Am J Obstet Gynecol 2002;187:1246
Hands, Feet
Trisomy 18
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Nuchal thickening
Choroid plexus cysts
NTDs
Cisterna magna, ACC,
cerebellar hypoplasia
Ventriculomegaly
Clenched hands
Rocker bottom feet
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Strawberry cranium
Facial clefts
Low set ears
Diaphragmatic hernia
Omphalocele
Renal
2 vessel cord
Cord cysts
Trisomy 13
Trisomy 13
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Alobar
holoprosencephaly
Cyclopia, facial clefts
Anopthalmia
Polycystic kidneys
ACC
Ventriculomegaly
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NTDs
Cardiac
Polydactyly
Nuchal thickening
Urogenital
Omphalocele
Turner Syndrome
Turner Syndrome
Turner Syndrome
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Septate cystic
hygroma
Lymphangiectasia
Coarctation
Nuchal thickening
Short femur
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60% of fetuses
become hydropic
Hydrops + hygroma =
near 100% mortality
Triploidy
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69xxx (xxy)
Severe asymmetric IUGR
Small calcified placenta with oligo, vs. …
Hydropic placenta (partial mole)
Facial defects
Holoprosencephaly, Dandy-Walker
Syndactyly of 3rd and 4th digits