2. سونوگرافی سه ماهه دوم و Soft Markers
Dr. F Rahimi
Tehran University of Medical Scienc
Yas Hospital

3. سونوگرافی سه ماهه دوم و Soft Markers
As part of standard prenatal care recommends ultrasound examination for all pregnant patients on mid-trimester usually done at 16 to 22 weeks. 6

4. Components of second ultrasound examinations
Components of second and third trimester ultrasound examinations
Components of second ultrasound examinations
Presence or absence of fetal cardiac activity, fetal heart rate and rhythm
Fetal number
Fetal presentation
Assessment of amniotic fluid volume
Placental appearance and location
Umbilical cord vessel number and placental insertion site, if technically possible
Fetal biometry (biparietal diameter, head circumference, femoral length, abdominal circumference)
Evaluation of the uterus, cervix, and adnexa when clinically appropriate
Fetal anatomic survey*
Presence or absence of fetal movement
Evaluation of each fetus of a multiple gestation

6. سونوگرافی سه ماهه دوم و Soft Markers
Sonographic examination is useful:
1- structural anomaly abnormal karyotypes often have anatomic changes or anomalies
Geneti sonogram 
Two types of sonographic markers suggestive of aneuploidy
Major fetal structural abnormalities
less significance as "possible markers" of aneuploidy, and these are collectively called "soft markers" of aneuploidy

7. سونوگرافی سه ماهه دوم و Soft Markers
These markers are nonspecific, often transient, and can be readily detected during the second-trimester ultrasound.
Prenatal ultrasonography during the second trimester provides a "genetic sonogram" that is used to identify morphologic features of fetal Down syndrome
ultrasound in the second trimester currently diagnoses 50% to 70% of cases of Down syndrome, 70% to 100% trisomy 18, and 90% to100% trisomy 13.

8. Ultrasound Soft markers
Several markers identified on 2nd trimester ultrasound are associated with increased risk of Down syndrome
Soft markers are ultrasound findings of uncertain significance
Associated with normal fetuses (normal variants)
Have no clinical sequelae, and are transient, resolving with advancing gestation or after birth
Carry an increased risk for fetal aneuploidy

9. Ultrasound Soft markers
Screening for soft markers is not a component of a basic obstetrical ultrasound examination.
Detection and reporting of soft markers (ie, echogenic intracardiac focus and choroid plexus cysts) is controversial

10. Recommended minimum requirements for basic mid-trimester fetal anatomical survey
Head: Intact cranium
No evidence of diaphragmatic hernia
Cavum septi pellucidi
Abdomen Stomach in normal position
Midline falx
Bowel not dilated
Thalami
Both kidneys present
Cerebral ventricles
Skeletal Cord insertion site
Cerebellum
No spinal defects or masses (transverse and
Cisterna magna
sagittal views)
Face : Both orbits present
Arms and hands present, normal relationships
Median facial profile*
Mouth present
Legs and feet present, normal relationships
Upper lip intact
Neck: Absence of masses (e.g. cystic hygroma)
Placenta Position
No masses present
Chest/Heart Normal appearing shape/size of chest and lungs
Accessory lobe
Umbilical cord Three-vessel cord*
Heart activity present
Genitalia Male or female*
Four-chamber view of heart in normal position
Aortic and pulmonary outflow tracts*

11. Ultrasound Soft markers
Use of soft markers for screening for, or excluding, fetal aneuploidy is inefficient
Isolated soft markers are identified in 11 to 17 percent of normal fetuses
More than one marker =>likelihood of aneuploidy is significantly increased
A detailed evaluation of fetal anatomy should be performed whenever one or more soft markers has been identified.

12. Which soft markers impact Down Syndrome risk?
Significantly increased risk:
Nuchal thickness ≥ 6mm
Echogenic bowel (equal or greater than bone)
Absent nasal bone (2nd T)
Ventriculomegaly
Small impact on Down Syndrome risk:
Echogenic intracardiac focus (EICF)
Choroid plexus cysts
Pyelectasis 4mm-10mm
Shortened long bones 

13. Increased Nuchal fold 
The most sensitive (40 to 50 percent) and specific (99 percent) single ultrasound marker for Down syndrome in the second trimester (15 to 20 weeks but not later)
An increased nuchal fold is detected in 20 to 33 percent of fetuses with Down syndrome and 0.5 to 2 percent of euploid fetuses
Measurement between the outer edge of the occipital bone to the outer margin of the skin and is taken in the axial plane

15. Echogenic bowel  
The bowel is considered to be echogenic when it is bright compared to the adjacent bone.
A echogenic bowel is reported to be present in 0.2–1.4% of 2nd trimester USs and be diffuse or focal.
When present it can be associated with aneuploidy (trisomy 21), congenital infection (CMV, toxoplasmosis, parvovirus), cystic fibrosis, intra amniotic bleeding, IUGR

19. Absent or Hypoplastic Nasal Bone
Fetal profile is viewed in the midsagittal plane, the nasal bone synostosis appears as a thin echogenic line within the bridge of the nose
Is absent in about 30 to 40 percent of Down syndrome fetuses and 0.3 to 0.7 percent of euploid fetuses
Is hypoplastic in about 50 to 60 percent of Down syndrome fetuses and 6 to 7 percent of euploid fetuses
A single pre-defined threshold for abnormal nasal bone length (≤2.5 mm)
a gestational age-based threshold (<2.5th or 5th centile) based on the di stribution of nasal bone length in normal fetuses

22. Mild ventriculomegaly
Ventriculomegaly is a condition caused when there is dilated atrium beyond 10 mm. The mild ventriculomegaly (MVM), or what is called borderline ventriculomegaly, range between 10–12 mm and 10–15 mm . It can be an isolated finding or be associated with an underlying cranial defect or anomaly such as agenesis of the corpus callosum

24. Ventriculomegaly
Isolated ventriculomegaly is a risk factor for Down syndrome
Mild ventriculomegaly is detected in 4 to 13 percent of fetuses with Down syndrome and 0.1 to 0.4 percent of euploid fetuses
The risk of abnormal outcome, such as Down syndrome, increases with the degree of ventriculomegaly, progression of ventriculomegaly, and presence of other anomalies.

25. Echogenic focus (EF) of the heart
An is definced as an echogenic area located in the region of the papillary muscles but not attached to the ventricular walls. They move with the atrioventricular valve and can occur in either cardiac ventricle, but are mainly seen in the left ventricle
EF are seen in approximately 4% of obstetric sonograms with the lowest prevalence in Black populations and highest rates seen in Asian women

28. Choriod plexus (CP) cysta
Cysts that are seen within the substance of the choroid plexus. They can be single or multiple, unilateral or bilateral, and occur with an incidence of approximately 1%.
They may result from entrapement of cerebral spinal fluid with tangled villi. As the stroma of decreases with increasing gestational age this fluid is relased and the the cyst resolves. For this reason more than 95% of these cysts resolve by the end of the second trimester

30. Renal Pyelectasis
Mild pyelectasis refers to dilatation of the renal pelvis >4–5 mm and <10 mm in the antero-posterior diameter measured in transverse section of the fetal abdomen.
The cut-off value which is most frequently used in this dimesion is >4 mm in the 2nd trimester and >7 mm thereafter

31. Renal Pyelectasis
Dilatation of the renal pelvis is a common finding with an incidence reported to be between 0.3 and 4.5%.
It is more common in male fetuses, and is often bilateral
In unilateral it is more likely to present on the left side. according to one study unilateral pylectasis is associated with a higher rate of urinary tract abnormalities at birth

33. Single umibical artery
Is the most common anomaly of the cord and occurs in approximately 1% of all deliveries. It may result from primary aplasia of one of the two umbilical arteries or as a consequence of atrophy of one artery.
It is more commen in the left artery and occurs more often in twin gestation. It is sometimes accompanied with abnormal cord insertion in the placenta, i.e. marginal and velamentous cord insertions

34. Single umbilical artery
single umbilical artery (SUA) and an increased risk of aneuploidy when additional fetal malformations are detected. The rate of aneuploidy with isolated SUA is not known, but most experts do not recommend routine chromosomal analysis if there are no other malformations or other indications for genetic amniocentesis.

36. Aneuploidy association
Soft marker
Imaging criteria
Aneuploidy association
Management
Second trimester: echogenic intracardiac foci
Echogenic tissue in one or both ventricles of the heart seen on standard four-chamber view
LR 1.4 to 1.8 for Down syndrome
Seen in 15 to 30% of Down syndrome and 4 to 7% euploid fetuses
If isolated finding, aneuploidy screening should be offered if not done previously
If aneuploidy screen result is negative, no further evaluation is required
Second trimester: pyelectasis
Renal pelvis measuring ≥4 mm in anteroposterior diameter up to 20 weeks of gestation
LR 1.5 to 1.6 for Down syndrome
If isolated finding, aneuploidy screening should be offered if not performed previously
Repeat ultrasonography in third trimester for potential urinary tract obstruction
Second trimester: echogenic bowel
Fetal small bowel as echogenic as bone
LR 5.5 to 6.7 for Down syndrome
Associated with aneuploidy, intra-amniotic bleeding, CF, CMV
Further counseling
Offer CMV, CF, and aneuploidy screening or diagnostic testing

37. Aneuploidy association
Soft marker
Imaging criteria
Aneuploidy association
Management
Second trimester: choroid plexus cysts
Discrete cyst(s) in one or both choroid plexus(es)
In isolation, no aneuploidy association
Second-trimester detailed anatomic survey and fetal cardiac ultrasound
No further follow-up if isolated
Consider aneuploidy screening or diagnostic testing if other markers are present
Second trimester: short femur length
Measurement <2.5th percentile for gestational age
LR 1.2 to 2.2 for Down syndrome. Can be associated with aneuploidy, IUGR, short limb dysplasia.
Second-trimester detailed fetal anatomic evaluation for short limb dysplasia
Further detailed counseling
Consider repeat ultrasonography in third trimester for fetal growth

38. Aneuploidy association
Soft marker
Imaging criteria
Aneuploidy association
Management
Second trimester: echogenic bowel
Fetal small bowel as echogenic as bone
LR 5.5 to 6.7 for Down syndrome
Associated with aneuploidy, intra-amniotic bleeding, CF, CMV
Further counseling
Offer CMV, CF, and aneuploidy screening or diagnostic testing
Second trimester: thickened nuchal fold
≥6 mm from outer edge of the occipital bone to outer skin in the midline
LR 11 to 18.6 with 40 to 50% sensitivity and >99% specificity for Down syndrome
Most powerful second-trimester marker
Detailed anatomic survey
Further detailed genetic counseling and aneuploidy screening or diagnostic testing
Second trimester: mild ventriculomegaly
Lateral ventricular atrial measurement between 10 to 15 mm
Associated with aneuploidy
LR 25 for Down syndrome
Genetic counseling
Second-trimester detailed anatomic ultrasound evaluation
Consider diagnostic testing for aneuploidy and CMV
Repeat ultrasound in third trimester

40. Aberrant right subclavian artery
The incidence of ARSA is estimated around 1 - 2% in normal population.
Is more common in Down syndrome fetuses than euploid fetuses (prevalence 24 percent in Down syndrome versus about 1 percent in screened obstetric populations , but it is usually not an isolated finding in Down syndrome
consider the background risk after first trimester screening and the presence or absence of other sonographic markers of aneuploidies.  
Some authors offer an invasive procedure, in cases with ARSA and intermediate risk result after NT and biochemistry calculation, even if all other additional markers were normal

43. Thank you for attention