1. Ultrasound markers of chromosomal abnormalities
Prof. Z. Babay

2. General Facts: The general incidence of Down is 1:1000
The risk by maternal age:
at the age of :365
at the age of :109
at the age of :32
Risk of recurrence is 1% ( 0.75% higher than maternal age related risk
** In case of parental aneuploidy % risk of Trisomy in offspring

3. Methods available for screening
Maternal age
Biochemical---1st trimester---PAPPA&β HCG, Adam12
2nd trimester---Triple & quadriple Test
Ultrasound NT + Other markers
Fetal DNA

4. Sensitivity of screening
False Positive Rate 5%
Detection rate
61% for Down
63% for Trisomy 18
1st trimester (Biochemical)
<5% for Down
<1% for Trisomy 18
70% for Down
80% for Trisomy 18
2nd trimester (Biochemical)
10%
33%
Age alone 8%
82% for Down
78% for Trisomies
Ultrasound NT

5. 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
beats /min at 9 weeks
A significant increase in heart rate is seen in trisomies

6. 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
2% of triploidy

7. Central cleft palate & lip

8. Fetal Structural malformations:
Micrognathia: 1% of trisomy 21
53% of trisomy 18
9% of trisomy 13
44% of triploidy
Cystic Hygroma: 88% of Turners

9. Fetal Structural malformations:
Chest & cardiac malformations:
26% of trisomy 21
52% of trisomy 18
43% of trisomy 13
48% of turners
16% of triploidy

10. Fetal structural malformations:
Malformations of the abdomen:
Exomphalos 31% of trisomy 18
17% of trisomy 13
Nasal bone hypoplasia at weeks (<2.5 mm): /3 of trisomy 21
If combined with N.T. –90% sensitivity
3% false positive

11. Fetal Structural abnormality:
Megacystis:
Normally the bladder is seen at 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

12. Megacystis

13. 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: days weeks of pregnancy

14. N.T. Continuation Risk estimate:
3 mm----3 times the incidence by maternal age
4mm times
5mm----28times
6mm----36times

15. 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

16. 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

17. Cont. The gain should be low in the magnified image
Distinguish between fetal skin & amnion
Take more than one measurement

18. N.T.

19. N.T.

20. N.T.

21. 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

22. Fetal Structural malformation:
Umbilical cord diameter:
At weeks
Increase in diameter above the 95th centile is associated with abnormal karyotype

23. Umbilical cord pulsatility index:
Trisomy fetus show small muscular artery/villi ratio
UAPI increase in trisomy (controversial)

24. Ductus venosus velocimetry:
Absence of or inversion of ductus venosus atrial (ACV) % of abnormal karyotype

25. Second trimester markers:
Nuchal fold:
Cut off 5mm---at weeks
6 mm--- at weeks
The most sensitive and specific marker in the second trimester
Sensitivity 77.8%
False positive rate 2%

26. Nuchal fold

27. 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%

28. Humerus length: Measured to expected length <0.9 50% sensitivity
6.2% false positive

29. Pyelectasis: Found in 1% of fetuses
Mild--A-P diameter of renal pelvis >4mm at weeks
A-P diameter of renal pelvis >5mm at weeks
A-P diameter of renal pelvis > 7mm at weeks
Moderate-- > A-P diameter of renal pelvis >10 mm + pelvi-calyceal dilatation

30. Pyelectasis: 17% incidence of Down 2% false positive rate
In severe hydronephrosis, multicystic kidneys, renal agenesis---risk of trisomy 18 &13

32. Echogenic intra-cardiac focus:
18% incidence of Down
2 fold increase over the age based risk
More significant if Right ventricle is involved

33. 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

34. Choroid plexus cyst

35. 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

36. 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

37. Simian crease

38. Trisomy 18

39. Double pubble
30-40% risk of aneuploidy ( trisomy 13& 18)

40. 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

41. Wide iliac crest

42. 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

43. Echogenic intra-cardiac focus
Combination of markers: Score of > –81% detection rate & 4.4% false +ve Score of risk is 1.5/1000
Score
Findings 2
Major anomaly
Nuchal fold> 6 mm 1
Short femur
Short humerus
Pylectasis > 4mm
Hyper-Echoic bowel
Echogenic intra-cardiac focus

44. Absence of any markers conveys 70% reduction in Down Syndrome

45. Final remarks: Detection by ultrasound depend on personal experience
Proper timing of scan

46. Good Day