This document discusses ultrasound evaluation methods for detecting fetal aneuploidy in the first and second trimesters. It describes various ultrasound markers that can be used, including nuchal translucency measurement, absent nasal bone, ductus venosus Doppler, cystic hygroma, tricuspid regurgitation, and frontomaxillary facial angle in the first trimester. In the second trimester, it discusses markers like thickened nuchal fold, absent/hypoplastic nasal bone, and hyperechoic bowel that can be assessed as part of a genetic sonogram to adjust risk for aneuploidy. The presence of these minor ultrasound findings in addition to biochemical screening can improve detection

1. ULTRASOUND EVALUATION
OF ANEUPLOIDY IN FIRST AND
SECOND TRIMESTERS
Dr.Niranjan patil
Department of radiodiagnosis
DYP Kolhapur

2. First trimester screening
combines
 measurement of the NT
First trimester serum markers
 PAPP-A
 hCG

3. Second trimester screening
Second trimester serum markers
 Unconjugated estriol
 Alpha-fetoprotein
 Inhibin A
Detection rates for aneuploidies other than trisomy 21 are lower

4.  Sonography is a noninvasive method used to perform risk assessment for fetal aneuploidy, in
addition to biochemical screening,
Minor markers or soft markers-
 In addition to the major congenital anomalies multiple other first and second trimester ultrasound
findings are associated with aneuploidy
 Typically are not structural anomalies per se and usually have no clinical significance to the fetus
except for their association with aneuploidy
 The presence or absence of these minor markers can be used to adjust a patient’s a priori risk for
aneuploidy based on biochemical screening results or maternal age.

5. • This becomes particularly important in screening for trisomy 21 - because fetuses with down
syndrome - less likely to have structural abnormalities identified by second trimester sonography.
• 75% of fetuses affected by trisomy 21 will not have ultrasound detectable major congenital
anomalies at the time of the second trimester anatomic survey.
• Fetuses with trisomies 13 and 18 have – 90% have multiple major structural anomalies.

6. FIRST TRIMESTER MARKERS OF ANEUPLOIDY
 Nuchal Translucency
 Absent Nasal Bone
 Ductus Venosus Doppler Studies
 Cystic Hygroma
 Tricuspid Regurgitation
 Frontomaxillary Facial Angle

7. Nuchal Translucency
Suggested mechanisms for increased NT-
 Increased collagen and hyaluronan content within fetal skin
 Dysfunction within the jugular-lymphatic drainage system
 Decrease in cardiac function and impaired circulation
 Increased intrathoracic pressure
 Measurements should be performed when the crown-rump length measurement is between 36 and
84 mm.

8.  Some important criteria must be fulfilled for a good quality measurement-
 The image should be magnified to occupy 75% of the screen and should show only the fetal head,
neck, and upper thorax.
 The fetus must be in the midsagittal plane.
 The fetal neck must be in a neutral position—not hyperextended or hyperflexed.
 Three echogenic lines indicating the inner and outer borders of the fetal skin and the amnion must
be displayed.
 The ultrasound calipers must be placed with the horizontal cross on the inner borders of the
echolucent space and perpendicular to the fetal axis.
 The measurement of the NT must be taken at the widest space

10.  NT increases with gestational age
 Even in the short-term window between the 10th and 14th weeks when these tests are performed
 Hence NT has been converted to multiples of the median (MoM) for gestational age
Increased NT-
 > 95th percentile for the MoM.
 >95th percentile of the delta value of the observed NT from that expected for the gestational age or crown-rump
length.
 enlarged NT (greater than 3.0 mm), regardless of gestational age correction
 These measurements are consisderd gold standard.

11. Absent nasal bone
 Nasal bone is absent in 70% of fetuses with Down syndromeal bone assessment into
 Incorporating nasal bone evaluation into screening with standard first trimester markers (NT, free β-
hCG,PAPP-A) improved the detection rate of Down syndrome.

12. Evaluation of the nasal bone
 The facial profile should be viewed in the midsagittal plane.
 The nasal bone is visualized as an echogenic line below and parallel to the overlying skin.
 When present, the nasal bone and skin appear similar to an equal sign.
 Keep the angle of insonation close to 45 degrees or 135 degrees.
 Angles less than 45 degrees or greater than 135 degrees - the nasal bone may artificially appear to be
absent.
 At 90 degrees, edges of the bone may become difficult to delineate precisely because of echo scatter,
and the measurement may be artificially large.

14. Ductus Venosus Doppler
 Doppler study of the ductus venosus normally will show triphasic, pulsatile forward flow.
 Absent or reversed a wave during atrial systole is associated with
 Fetal cardiac malformations
 Aneuploidy.
 Using ductus venosus Doppler studies as an adjunct to NT screening improves detection of downs syndrome.
 In chromosomally normal fetuses with a normal NT, abnormal ductus venosus blood flow in the first trimester
has been associated with adverse fetal outcome such as congenital heart disease and fetal growth restriction.

16. Cystic Hygroma
 Cystic hygromas represent an abnormality of the fetal lymphatic system.
 Diagnosis-
 Nuchal space is enlarged with large posterior or posterolateral fluid-filled cavities noted within the
fetal neck, with or without the presence of septations.
 Presence of a cystic hygroma in the first trimester confers a 50% risk for fetal aneuploidy.

17.  Debate continues as to whether cystic hygromas represent a continuum of thickened NT .
 Presence of either a thickened NT or cystic hygroma with or without septations, the aneuploidy risk
remains comparably very high.
 In either case, invasive diagnostic testing should be offered.

20. Tricuspid Regurgitation
 Tricuspid regurgitation has also been proposed as an adjunct to first trimester aneuploidy
screening
 Addition of tricuspid regurgitation to first trimester serum screening and NT measurement has been
shown to increase the detection rate of down syndrome
Technique
 Pulse-wave doppler imaging of the tricuspid valve in the apical four-chamber view with insonation
parallel to the ventricular septum
Diagnosis
 A regurgitant jet must be present over at least half of systole with a velocity over 60 to 80
cm/second for a diagnosis of tricuspid regurgitation

21.  https://www.youtube.com/watch?v=gIt1EV3Lttc

22. Frontomaxillary Facial Angle
 Definition
Angle between the upper surface of hard palate and a line that traverses the upper corner of the
anterior aspect of the maxilla and extends to the external surface of the frontal bone at the point of its
greatest anterior excursion in a midsagittal view of fetal face.

23.  Significantly larger in Down syndrome fetuses compared to euploid fetuses
 Incorporation of this measurement into first trimester screening increases the Down
syndrome detection rate

24. GENETIC SONOGRAM
 Targeted second trimester ultrasound study performed at the time of the anatomic survey, which
assesses for major fetal malformations as well as minor markers of aneuploidy.
 The presence or absence of these markers, either alone or in combination, can adjust a patient’s
aneuploidy risk.
 Potentially aiding in the decision as to whether or not to pursue invasive testing with amniocentesis.
 Genetic sonogram originally was targeted toward a high-risk population
 Advanced maternal age
 Positive second trimester serum screening.
 Significantly decrease the rate of invasive testing with amniocentesis.

25.  Finding of one minor marker of aneuploidy should prompt a more thorough search for other
associated markers or structural abnormalities as well as a review of the patient’s aneuploidy risk
based on age or other screening tests.

26.  LRs have been established for each individual marker
 These LRs weight the influence of each individual marker by their strength of association
with down syndrome
 These ratios can be multiplied by the patient’s prior risk for aneuploidy
 Calculated by serum screening results or age alone
to provide an age-adjusted ultrasound risk assessment [AAURA].

27. Thickened Nuchal fold
 One of the most specific second trimester markers for down syndrome (LRs ranging between 11
and 17)
 False positive rate for this sonographic marker is exceedingly low.
 Sonographic finding correlates to the ---redundant soft tissue in the posterior neck that is
characteristic of newborns affected by down syndrome
 Second trimester thickened NF does not correlate with first trimester thickened NT.

28. Measurement of NF(nuchal fold thickness)
 The NF is typically measured between 15 and 21 weeks.
 Obtain a transverse plane at the level of the biparietal diameter.
 Transducer is then angled caudally to include the cerebellum and occipital bone.
 NF is measured by placing calipers on the outer edge of skull and outer skin
 NF - 6 mm or greater is considered abnormal.

30. Absent/ Hypoplastic Nasal Bone
 The absence of the nasal bone in the first trimester have clearly shown an association with down
syndrome.
 However there is late ossification of the nasal bone in select populations.
 To minimize false positive results nasal bone screening is also suggested in the second trimester.
 Positive LR of 23.27 for absent or hypoplastic nasal bone.
 This LR is high enough to conclude “screening positive” regard less of maternal age.

31. Nasal bone hypoplasia
 Definitions --
• Fetal biparietal diameter/nasal bone length (BPD/NBL) > 11
 By utilizing this ratio, the influence of gestational age is potentially offset.
• Nasal bone MoM less than 0.75.

33. Hyperechoic Bowel
 Fetal bowel should appear as bright as surrounding bone, typically as compared to the iliac wing.
 The diagnosis of hyperechoic bowel should always be confirmed with a low frequency
transducer, less than 5 Mz.
• (LRs ranging from 1 to 6)
After thickened NF and absent nasal bone hyperechoic bowel is the next most sensitive sonographic
marker for the detection of Down syndrome.

34.  CAUSE-
 Decreased bowel motility and increased water absorption leading to subsequent dehydration of
meconium.
 Although most common chromosome abnormality associated is down syndrome.
 Hyperechoic bowel have also been reported with trisomy 18, trisomy 13, triploidy, and monosomy
x.

35.  After aneuploidy is excluded,the DD’s for hyperechoic bowel
 Cystic fibrosis
 Primary gastrointestinal disease
 Congenital infection
 Fetal swallowing of intra-amniotic blood
 Isolated hyperechoic bowel has been associated with adverse pregnancy outcomes such as fetal
growth restriction and intrauterine fetal demise

37. Femoral/Humeral Shortening
 FL and HL measurements below the 5th percentile for gestational age.
Short femur
 positive LRs of only 1.2 to1.5
Short humerus
 positive LR as high as 25
 Shortened humeral length appears to be a superior marker for detection of downs
 Combining short femur and short humeral length yields increased detection in Down syndrome risk and has a lower
false positive rate

38. Pyelectasis
 Definition-
 Anteroposterior dimension of the fluid-filled renal pelvis exceeds 4 mm prior to 32 weeks’ gestation.
 Measurements of the renal pelves should be taken with the fetal spine at either the 12 o’clock or 6 o’clock position to
ensure greatest accuracy.
 Although there is association with downs syndrome,sensitivities remain low ranging around 25%.
 When combined with other sonographic markers detection of Down syndrome can make a modest contribution, with
LRs ranging from 5.5 to 8.8.

40. Echogenic Intracardiac Focus
 Cause-
 Microcalcification and fibrosis of the papillary muscle and chordae tendineae.
Definition / Diagnosis-
 Echogenic area in the heart should be as bright as bone.
 Must be identified in two distinct cardiac planes
 EIF in the presence of other sonographic markers is useful in the detection of Down syndrome,
with positive LRs ranging from 2.8 to 8.0.

41. EIF as an isolated marker
 Should not be considered a marker for aneuploidy in patients without an elevated a priori risk
 Specifically in those under the age of 35 with negative first or second trimester screening results

43. SECOND TRIMESTER SONOGRAPHIC MARKERS
FOR OTHER ANEUPLOIDIES
 Choroid plexus cysts
 Single umbilical artery
 Abnormalities of extremities

44. Choroid Plexus Cysts
 Normal choroid plexus - fills the atrium of the lateral cerebral ventricles prior to 16 weeks
Technique-
 Transventricular view just superior to the plane of the biparietal diameter.
Diagnosis-
 Typically identified between 16 and 23 weeks and are seen as round hypoechoic structures within the
choroid plexus.
 Cysts tend to be transient, typically resolving by 26 weeks, and have no effect on structure or
neurodevelopment of the fetus.
 They can vary greatly in size and can be unilateral or bilateral, single or multiple.

45.  This finding is not thought to be a sonographic marker for downs syndrome.
 Choroid plexus cysts have been associated increased risk for trisomy 18 , however as an isolated
finding choroid plexus cyst in an otherwise low-risk patient does not increase the risk of trisomy 18.
 Isolated findings, these cysts only marginally increase the risk of aneuploidy.
 Risk for aneuploidy was not related to cyst size, laterality, or regression over the course of
gestation.

47. Single Umbilical Artery
 Causes-
 Primary agenesis of umbilical artery
 Thrombotic atrophy of one of the umbilical arteries
 TECHNIQUE-
 Umbilical arteries are best viewed as they course around either side of the fetal bladder in a
transverse view of the fetal pelvis.

48.  DIAGNOSIS-
 Using color or power doppler, demonstration of an absent umbilical artery on one side of the fetal
bladder.
 A cross-sectional view of a free-floating loop of cord demonstrating only two vessels.

49.  Risk of aneuploidy-
 Association between SUA and aneuploidy is strongest in the setting of other major anomalies.
 A recent meta-analysis demonstrated no increased risk for aneuploidy in fetuses with isolated SUA.

50. Abnormalities of the Extremities
 Trisomy 18 – abnormalities of extremities
 “Rocker-bottom feet” are pathognomonic for trisomy 18.
 Clenched fists and overlapping digits.( Are one of the most common findings seen in fetuses with trisomy 18)
 Other reported extremity malformations in trisomy 18
 Hypoplastic/absent thumb
 Syndactyly of the fingers and toes,
 Radial/ulnar deviation of the hands

51. Overlapping digits in trisomy 18-
 in which the second and fifth fingers override
the third and fourth fingers.
Rocker-bottom feet-
 It is characterized by a prominent calcaneus/heel and a
convexly rounded sole

52. Talipes equinovarus (clubfoot)
 Associated with trisomy 18, trisomy 13, and
sex chromosome abnormalities.
Diagnosis
 When the foot is rotated inward and fixed in a
plantar-flexed position.
Associated risk
 As a isolated finding, it is not thought to be an
indication for invasive genetic testing in a low-
risk patient

53.  Polydactyly is diagnosed when more than five
digits are located on either the hand or foot.
 Postaxial polydactyly is diagnosed when the
digit is located on the ulnar or fibular side of
the hand or foot and has been associated
with trisomy 13.

54. THANK YOU

55. Cardiac malformations
 Cardiac malformations on prenatal sonography – risk of aneuploidy is as high as 22% to 32%
 The frequency of aneuploidy varies with the type of cardiac defect present
Higher with
 hypoplastic heart
 atrioventricular canal defects- (60% risk of aneuploidy particularly downs syndrome)
 tetralogy of Fallot
 double-outlet right ventricle
Lesser with
 isolated ventricular septal defects
 valvular stenosis

56. Trisomies and association with cardiac
malformations
 Nonspecific cardiac findings such as tricuspid regurgitation, pericardial effusion, and right-left
disproportion) were present in 76% of fetuses with down syndrome, whereas just 9% had a
characteristic atrioventricular septal defect.
 In contrast,cardiac malformations are present in more than 90% of fetuses with trisomy 18 and 13.

58. Duodenal atresia
 Duodenal atresia is rarely recognized until after 20 to 24 weeks of pregnancy.
 Characteristic features-
 Double bubble sign (dilated fluid-filled stomach and proximal duodenum)
 Polyhydramnios.
 Trisomy 21 is present in approximately one third of cases of down syndrome.

60. NIHF
 NIHF is recognized sonographically by
 Ascites
 Pericardial effusions
 Pleural effusions
 Polyhydramnios
 Thickened placenta
 Skin edema.
 Most common karyotype abnormalities associated are turner syndrome (45,x); trisomies 21, 18, and 13;
and triploidy.
 NIHF is most highly associated with aneuploidy when diagnosed earlier in pregnancy.

62.  The combination of generalized hydrops and cystic hygroma is often referred to as
lymphangiectasia, which has a very poor prognosis.
 Lymphangiectasia is associated with aneuploidy, especially Turner syndrome, in approximately two
thirds of cases.