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