Ultrasound markers of chromosomal abnormalities
Prof. Z. Babay
General Facts:
The general incidence of Down is 1:1000 The risk by maternal age:
at the age of 35 -----------1:365
at the age of 40-----------1:109
at the age of 45-----------1:32 Risk of recurrence is 1% ( 0.75% higher than maternal age
related risk ** In case of parental aneuploidy---- 30% risk of Trisomy in
offspring
Methods available for screening
Maternal age Biochemical---1st trimester---PAPPA&β HCG, Adam12
2nd trimester---Triple & quadriple Test
Ultrasound NT + Other markers
Fetal DNA
Sensitivity of screening
1st trimester (Biochemical)
Detection rate
61% for Down
63% for Trisomy 18
False Positive Rate
5%
2nd trimester (Biochemical)70% for Down
80% for Trisomy 18
<5% for Down
<1% for Trisomy 18
Age alone33%10%
Ultrasound NT82% for Down
78% for Trisomies
8%
First trimester markers:
Fetal growth: CRL< 7mm indicate 3 times higher risk of Chromosomal abnormality
Fetal heart rate: Normal is 100 beats/min at 6 weeks
160-170 beats /min at 9 weeks
A significant increase in heart rate is seen in trisomies
Fetal structural malformations:11-14 weeks
Holoprosencephaly: 3% of trisomy 18
39% of trisomy 13
Facial clefts: 1% of trisomy 21
10% of trisomy 18
39% of trisomy 13
2% of triploidy
Central cleft palate & lip
Fetal Structural malformations:
Micrognathia: 1% of trisomy 21
53% of trisomy 18
9% of trisomy 13
44% of triploidy
Cystic Hygroma: 88% of Turners
Fetal Structural malformations:
Chest & cardiac malformations:
26% of trisomy 21
52% of trisomy 18
43% of trisomy 13
48% of turners
16% of triploidy
Fetal structural malformations:
Malformations of the abdomen:Exomphalos 31% of trisomy 1817% of trisomy 13
Nasal bone hypoplasia at 15-24 weeks (<2.5 mm): 2/3 of trisomy 21
If combined with N.T. –90% sensitivity 3% false positive
Fetal Structural abnormality:
Megacystis: Normally the bladder is seen at 10-14 weeks Megacystis if longitudinal diameter is 6-8mm
or bladder / CRL ratio is 13% or more It resolve in 60% of cases 20% risk of chromosomal abnormality
Megacystis
N.T .
Skin fold thickness behind the fetal cervical spine Due to Venous or lymphatic engorgement Landmarks: Cavum septum pellucidum, Cerebral
peduncles, Cerebellar hemispheres Timing: 11-13 +6days weeks of pregnancy
N.T. Continuation
Risk estimate:
3 mm----3 times the incidence by maternal age 4mm----18 times
5mm----28times
6mm----36times
Measurement of N.T.
CRL between 45-84mm Good sagital section Fetal head lines with the spine Enlarge the view Measure the widest part of the thickness
Measurement of N.T. (cont.)
Measure from the inner border of the horizontal line of the calliper placed on the line that defines the N.T. thickness
Cont.
The gain should be low in the magnified image
Distinguish between fetal skin & amnion Take more than one measurement
N.T.
N.T.
N.T.
N.T.
75-80% of trisomy 21
5-10% normal karyotype ( but could be associated with cardiac defects, diaphragmatic hernia, Exomphalos)
If NT is abnormal ---indicate fetal ecchocardiogram
Fetal Structural malformation:
Umbilical cord diameter:
At 10-14 weeks
Increase in diameter above the 95th centile is associated with abnormal karyotype
Umbilical cord pulsatility index:
Trisomy fetus show small muscular artery/villi ratio
UAPI increase in trisomy (controversial)
Ductus venosus velocimetry:
Absence of or inversion of ductus venosus atrial (ACV)---- 70-90% of abnormal karyotype
Second trimester markers:
Nuchal fold: Cut off 5mm---at 14- 18 weeks
6 mm--- at 18-20 weeks
The most sensitive and specific marker in the second trimester
Sensitivity 77.8%
False positive rate 2%
Nuchal fold
BPD/FL
BPD/FL ratio Its value varies with gestational age PPV= 1/294 for general population PPV= 1/112 for maternal age >35
1.5 S.D. above the mean of BPD/FL
Sensitivity 50%
False positive 7%
Humerus length:
Measured to expected length <0.9 50% sensitivity 6.2% false positive
Pyelectasis:
Found in 1% of fetuses
Mild--A-P diameter of renal pelvis >4mm at 15-19 weeks
A-P diameter of renal pelvis >5mm at 20-29 weeks
A-P diameter of renal pelvis > 7mm at 30-40 weeks
Moderate-- > A-P diameter of renal pelvis >10 mm + pelvi-calyceal dilatation
Pyelectasis:
17% incidence of Down 2% false positive rate
In severe hydronephrosis, multicystic kidneys, renal agenesis---risk of trisomy 18 &13
Echogenic intra-cardiac focus:
18% incidence of Down
2 fold increase over the age based risk
More significant if Right ventricle is involved
Choroid Plexus cyst:
Present in 1/3 of trisomy 18 present in 1-2% of normal fetuses If isolated the risk is 1/374 If an additional abnormality is found the risk
increase 20 folds
Choroid plexus cyst
Echogenic bowel(compared to surrounding bone)
Risk of abnormality is 0.5-1%
Also seen in meconium ileus, congenital infection, severe IUGR, intra-amniotic bleeding, cystic fibrosis
Increase the risk by 3-5 times the maternal age risk
Short proximal bones
Syndactaly is associated with Triploidy
Sandal gap with Trisomy 21
Polydactaly with Trisomy 13
Overlapping fingers, Rocker bottom feet and talipes with trisomy 18
Simian crease
Trisomy 18
Double pubble
30-40% risk of aneuploidy ( trisomy 13& 18)
Minor markers:
Wide iliac crest angle >90 degree Brachycephaly Frontal lobe shortening Abnormal short ear length Flat face Clinodactaly Hypo-plasia of middle phalanx of the 5th digit Sandal gap of great toe Simian crease Small cerebellar diameter
Wide iliac crest
Mild Ventricolomegaly (10-12 mm)
5% risk of later severe brain abnormality
15% risk of mild problems later
The commonest abnormality is trisomy 21, 18, 13 & Triploidy
Combination of markers: Score of > 2 ----–81% detection rate & 4.4% false +veScore of 0----- risk is 1.5/1000
FindingsScore
Major anomaly2
Nuchal fold> 6 mm2
Short femur1
Short humerus1
Pylectasis > 4mm1
Hyper-Echoic bowel1
Echogenic intra-cardiac focus
1
Absence of any markers conveys 70% reduction in Down Syndrome
Final remarks:
Detection by ultrasound depend on personal experience
Proper timing of scan
Good Day