Sonographic Detection of Aneuploidy

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Sonographic Detection of Aneuploidy. Eric H. Dellinger, MD Director, Division of Maternal-Fetal Medicine Greenville Hospital System Greenville, South Carolina. Introduction. The Future of Science and Medicine: Exploring the extremes. Evolution of Ultrasound. Aneuploidy. - PowerPoint PPT Presentation

Transcript of Sonographic Detection of Aneuploidy

First Trimester Sonography

Sonographic Detection of AneuploidyEric H. Dellinger, MDDirector, Division of Maternal-Fetal MedicineGreenville Hospital SystemGreenville, South CarolinaIntroductionThe Future of Science and Medicine:Exploring the extremes

Evolution of Ultrasound


Benefits of Early DetectionPrivacy issuesDecreased maternal bondingSafer pregnancy terminationHigher detection rateNuchal TranslucencyClear space in posterior neckImaged between 11 and 14 weeks or when CRL is 36 to 84 mmNuchal thickening is associated with:AneuploidyAnomaliesInfectionsMetabolic and hematologic disordersIncidence of chromosomal defectsNuchaltranslucency (mm) Total nChromosomal defects (%)

< 3.4 95,086 0.333.5 - 4.4 568 21.124.5 - 5.4 207 33.335.5 - 6.4 97 50.51> 6.5 166 64.45Snijders et al. 1998Trisomy 21 Detection Rate96,127 patients studied NT and ageMedian age 31 years5% screen positive rate77% of affected fetuses detected

Snijders et al, Lancet 1998; 352: 343.Other AssociationsGenetic syndromes: Cornelia de Lange, Noonan, Smith-Lemli-Opitz, ApertAnomalies: Cardiac, diaphragmatic herniaAdverse outcome: Early demise

Targeted scan indicated if euploidAnomalies with Increased NTCardiac defects Diaphragmatic hernia Omphalocele Duodenal atresia Esophageal atresiaSkeletal dysplasiasLethal congenital arthryogryposis Smith-Lemli-Optiz syndrome MegacystisFryn syndrome Joubert syndrome Meckel-Gruber syndromeVATER association

NT and CHDIn 29,154 chromosomally normal fetuses, 56% of major abnormalities of the heart and great arteries were found in the subgroup with nuchal translucency above the 95th centile.

Nuchal translucency thickness at 1114 weeks may constitute the most effective method of screening for cardiac defects. Hyett JA, et al, Br Med J 1999:318:815NT and Cardiac DefectsNTCHD per 1000

< 2.0 mm1.92.0 to 2.4 mm4.82.5 to 3.4 mm6.0> 3.4 mm 23Bahado-Singh et al, Am J Obstet Gynecol. 2005 May;192(5):1357-61

NT Technique

Proper CRL is a MSLL MSLL = maximum straight line lengthEnlarge

Caliper Placement

NT Increase at 11 14 weeksNT InterpretationFrom 10 - 14 weeks, the 99th percentile remains constant at 3.5 millimeters, independent of gestational age or crown-rump length.

Nicolaides , Semin Perinatol. 2005;29(4):190.

NT measurement in 326 trisomy 21 fetuses

NT thickness and chromosomal abnormalities other than trisomy 21

Adverse Outcome with Increased NT NTPoor Outcome

3.5 - 4.4 mm 32% 4.5 - 5.4 mm 49% 5.5 - 6.4 mm 67%> 6.5 mm 89% Ultrasound Obstet Gynecol 2001;18:9-17 Cutoff3 mm threshold identifies 80% of Downs5% SPRHigh risk population

95th percentile is a better thresholdNT between 95th and 99th percentile carries 3.7% risk of aneuploidyBr J ObGyn 1994; 101:782Lancet 1998; 352: 343

PitfallsBewareNT cannot be obtained in all patients (~6%)Fetal positionMaternal body habitusTime constraints (allot 20 min)

Identify the amnion

Nuchal thickening may decrease over timeEssential for proper NTMagnify the image until the fetal head and thorax occupy the whole screen.Obtain a mid-sagittal view of the face. Minor deviations: non-visualization of the tip of the nose and visibility of the zygomatic process of the maxilla.The fetus should be in a neutral position.Essential for proper NTWidest part of NT must be measured.

The crossbar of the calliper should be such that it is hardly visible as it merges with the white line of the border, not in the nuchal fluid.

Turn the gain down. This helps avoid placing the calliper on the fuzzy edge of the line which can underestimate the nuchal measurement.Amnion vs. NT

Nasal Bone

Nasal BoneConflicting results in European vs. US studiesMay reflect the technical difficulty of imagingReview of over 35,000 nasal bone exams from 9 studies:Successful study in 94.3%Absent in 65% of Downs (0.8% of normals)Obstet Gynecol 2007; 110:300Nasal BoneThe optimum time for nasal bone assessment is at crown rump length of 65 to 74 mm (13 to 13.5 weeks of gestation).

Absent nasal bone earlier in gestation could reflect delayed maturation, rather than actual absence of the structure.

Ville, Am J Obstet Gynecol. 2006;195(1):1.Cystic Hygroma



Normal Tricuspid RegurgitationTricuspid Regurgitation

Anomalies and AneuploidyNormal newborns0.5% aneuploid

Structural anomalies11% aneuploid

Am J Med Genet 1988;29:289Type of Defect MattersOmphalocele with liver3 of 34 aneuploid

Omphalocele without liver12 of 14 aneuploid

AJR 1992;158:133; J Ultra Med 1989;8:299

Growth Restriction Finding Aneuploid

Isolated IUGR2 %

IUGR + anomaly20 %

Am J Obstet Gynecol 1993;168:547Detecting Down Syndrome

Major Malformation33% of Down fetuses have one or more major malformationsHeartCNSGIFace/neckHydropsPed Clin N Am 1984;31:1331Cardiovascular40-50% manifest heart anomalies


AV Canal is the Sine Qua NonOf Down SyndromeCardiovascularAV Canal defect 45 percent Ventricular septal defect 35 percent Isolated secundum ASD 8 percent Isolated persistent PDA 7 percent Isolated tetralogy of Fallot 4 percent Other 1 percent

CNSBrachycephaly, frontal hypoplasia, ventriculomegaly

GIDuodenal atresia40% risk, late finding

Face, Nuchal FoldIn 40-50% nuchal fold > 6 mm at 15-20 wksSeen in 0.5% of normals

Nuchal Thickening

Cystic Hygroma

HydropsStrong association with non-immune hydrops

Soft MarkersShort femurShort humerusEIFEchogenic bowelPyelectasisHypoplastic 5th digitSandal gapWide iliac angleShort nasal boneShort Femur and Humerus

Expected FL = -9.3105 + 0.9028 x BPDMeasured/Expected FL 0.91 is ABNORMAL

53% of Downs 5% of normals

Expected HL = -7.9404 + 0.8492 x BPDMeasured/Expected HL 4.0 mmSOFT MARKERS NOT ESTABLISHED FOR CLINICAL PRACTICESeen in many normals

Predictive value unclear

Good to know

Hypoplastic 5th Digit

Clinodactyly19% Downs3.4% normals

5th/4th ratio of 0.70

Sandal Gap

Seen in 45% of newborns with Downs

Subtle finding on scanBrachycephaly

Shortening of the frontaloccipital brain length

Smaller frontal lobes

Not an effective screen

Wide Iliac Angle

Angle of 90 degrees should be considered the upper limit of normal

Nasal Bone

Nasal Bone

Other FindingsMild ventriculomegaly (10-14 mm) Enlarged cisternal magna (> 10 mm)Small low-set earsEffusionsDuodenal bulb

Case Study31 year old G3 P2Down Syndrome risk from Quad screen is 1:430Level II scan reveals:EIFShort humerusShould she have an amniocentesis?Are You Confused?

Likelihood Ratio (LR)LR = sensitivity / false-positive rate = + test with disease / + test no disease An LR > 1 suggests a positive association with a particular finding

An LR of 10 or more suggests a strong association with a particular finding

Calculated LRs of Sonographic Findings for Fetal Down Syndrome

J Ultrasound Med 20:10531063, 2001Adjusted Aneuploidy


Trisomy 18


Choroid Plexus CystsSeen in 33% of Trisomy 18 fetusesSeen in 2-5% of normalsPerform a detailed sonogramFace, heart, great vessels, extremitiesAn open hand is significantMeta-analysisIn 748 cases of isolated CPC, risk 1/374

In 1016 cases, no cases seen (age < 35)Am J Obstet Gynecol 1995;172:83Am J Obstet Gynecol 2002;187:1246

Hands, Feet

Trisomy 18Nuchal thickeningChoroid plexus cystsNTDsCisterna magna, ACC, cerebellar hypoplasiaVentriculomegalyClenched handsRocker bottom feetStrawberry craniumFacial cleftsLow set earsDiaphragmatic herniaOmphaloceleRenal2 vessel cordCord cystsTrisomy 13

Trisomy 13Alobar holoprosencephalyCyclopia, facial cleftsAnopthalmiaPolycystic kidneysACCVentriculomegalyNTDsCardiacPolydactylyNuchal thickeningUrogenitalOmphaloceleTurner Syndrome

Turner Syndrome

Turner SyndromeSeptate cystic hygromaLymphangiectasiaCoarctationNuchal thickeningShort femur60% of fetuses become hydropicHydrops + hygroma = near 100% mortality

Triploidy69xxx (xxy)Severe asymmetric IUGRSmall calcified placenta with oligo, vs. Hydropic placenta (partial mole)Facial defectsHoloprosencephaly, Dandy-WalkerSyndactyly of 3rd and 4th digits